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Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

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Bladder cancer (BC) ranks as the sixth cancer in males and the ninth most common cancer worldwide. Conventional treatment modalities, including surgery, radiation, chemotherapy, and immunotherapy, have limited efficacy in certain advanced instances. The involvement of GALNT6-mediated aberrant O-glycosylation modification in several malignancies and immune evasion is a subject of speculation. However, its significance in BC has not been investigated. Through the integration of bioinformatics analysis and laboratory experimentation, we have successfully clarified the role of GALNT6 in BC. Our investigation revealed that GALNT6 has significant expression in BC, and its high expression level correlates with advanced stage and high grade, leading to poor overall survival. Moreover, both in vitro and in vivo experiments demonstrate a strong correlation between elevated levels of GALNT6 and tumor growth, migration, and invasion. Furthermore, there is a negative correlation between elevated GALNT6 levels, the extent of CD8+ T cell infiltration in the tumor microenvironment, and the prognosis of patients. Functional experiments have shown that the increased expression of GALNT6 could enhance the malignant characteristics of cancer cells by activating the epithelial-mesenchymal transition (EMT) pathway. In brief, this study examined the impact of GALNT6-mediated abnormal O-glycosylation on the occurrence and progression of bladder cancer and its influence on immune evasion. It also explored the possible molecular mechanism underlying the interaction between tumor cells and immune cells, as well as the bidirectional signaling involved. These findings offer a novel theoretical foundation rooted in glycobiology for the clinical application of immunotherapy in BC.

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Osteoporosis (OP) is a common metabolic bone disease characterized by low bone mass and microstructural deterioration of bone. Changes in the composition and structure of gut microbiota (GM) are related to changes of bone mass and bone microstructure. However, the relationship between GM and bone mineral density (BMD) is complex, and data are especially scarce for Chinese Han youth. Therefore, 62 Chinese Han youth participants were recruited. Furthermore, according to the T-score evaluation criteria of the World Health Organization (WHO), we divided the BMD levels of participants into three groups: osteoporosis\BDL, osteopenia\BDM, normal bone density\BDH, and the associations between GM community and BMD groups were conducted. According to alpha and beta diversity analysis, significant differences were found in the microbial richness and composition between groups. The dominant phyla of GM in a cohort of Chinese Han youth were Bacteroidota (50.6%) and Firmicutes (41.6%). Anaerobic microorganisms, such as g_Faecalibacterium and g_Megamonas, account for the largest proportion in the gut, which were mainly Firmicutes phylum. The dominant genera and species in the three BMD groups were g_Prevotella, g_Bacteroides, g_Faecalibacterium, g_Megamonas, s_Prevotella copri, s_unclassified_g_Faecalibacterium, s_unclassified_g_Prevotella, s_unclassified_g_Bacteroides and s_Bacteroides plebeius. g_Faecalibacterium, g_Bacteroides and g_Ruminococcus differed between the BDH and BDL groups as well as between the BDH and BDM groups. LEfSe showed three genus communities and eight species communities were enriched in the three BMD groups, respectively. The associations between microbial relative abundance and T-score was not statistically significant by Spearman and regression analysis. In conclusion, the alpha diversity indexes in the BDH group were higher than in the BDL group, and several taxa were identified that may be the targets for diagnosis and therapy of OP.

Asunto(s)

Densidad Ósea , Enfermedades Óseas Metabólicas , Microbioma Gastrointestinal , Osteoporosis , Humanos , Femenino , Osteoporosis/microbiología , Enfermedades Óseas Metabólicas/microbiología , Enfermedades Óseas Metabólicas/epidemiología , Masculino , China/epidemiología , Adolescente , Estudios de Cohortes , Adulto Joven , Pueblo Asiatico , Adulto , Pueblos del Este de Asia

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A comprehensive understanding of the evolution of soybean climate potential productivity and its response to climate change in Heilongjiang Province can offer reference and basis for further tapping soybean production potential and realizing stable and high yield of soybean in the frigid region. Based on meteorological data from 80 meteorological stations in Heilongjiang Province from 1961 to 2020, we estimated photosynthesis, light temperature, and climate potential productivity of soybean by the stepwise correction method, examined the spatiotemporal variations by spatial interpolation and statistical analysis methods, and analyzed the impact of changes in climate factors such as radiation, temperature, and precipitation on climate potential productivity. The results showed that during the study period, the average values of photosynthesis potential productivity (YQ), light-temperature potential productivity (YT), and climate potential productivity (YW) of soybean in Heilongjiang Province were 7533, 6444, and 3515 kg·hm-2, respectively. The temporal changes of those variables showed significant increasing trends, with increases of 125.9, 182.9, and 116.1 kg·hm-2·(10 a)-1, respectively. For the spatial distribution, YQ, YT, YW were characterized by high values in plains and lower in the mountains, and gradually decreased from southwest to northeast. Compared with that during 1961-1990, the high value zone of YW in period 1991-2020 expanded by 7.1%, and the low value zone decreased by 5.1%. YW showed a significant response to climate change. The potential temperature growth period was extended due to climate warming. The continuous increase in thermal resources, combined with relatively sufficient precipitation, effectively alleviated the negative impact of the decline in light resources on soybean production in Heilongjiang Province. The projected "warm and humid" climate would comprehensively boost climate potential productivity of soybean in Heilongjiang Province.

Asunto(s)

Cambio Climático , Glycine max , Glycine max/crecimiento & desarrollo , China , Fotosíntesis , Biomasa , Ecosistema , Temperatura

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BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the digestive tract with unknown etiology. It follows a relapse-remission pattern, making disease activity assessment crucial for treatment. Our study aims to evaluate the diagnostic accuracy of various imaging modalities and to validate and compare the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS), the multidetector computed tomography enterography score (MDCTEs), and the simplified endoscopic activity score for Crohn's disease (SES-CD). METHODS: We assessed diagnostic performance using the CD Activity Index (CDAI). We first categorized patients into remission and active groups. For those in the active stage, we further categorized them into mild/moderate and severe activity groups. We used Spearman rank correlation to evaluate the relationships among IBUS-SAS, bowel wall thickness (BWT), Color Doppler imaging signal (CDS), inflammatory fat (i-fat), bowel wall stratification (BWS), and clinical inflammatory indicators. RESULTS: A total of 103 CD patients were evaluated. The IBUS-SAS cut-off for remission and activity was 23.8, with an AUC of 0.923, sensitivity of 91.4%, and specificity of 84.8%. The SES-CD had an AUC of 0.801, sensitivity of 62.9%, and specificity of 84.4% at a cut-off of 4.5. The MDCTEs showed an AUC of 0.855, sensitivity of 77.1%, and specificity of 75.8% for a cut-off of 6.5. The Delong test revealed significant differences in diagnostic efficacy when comparing IBUS-SAS to SES-CD and IBUS-SAS to MDCTEs. In the group of mild or moderate-to-severe active, the IBUS-SAS had an AUC of 0.925, sensitivity of 83.7%, and specificity of 88.9% at a cut-off of 40. The SES-CD exhibited an AUC of 0.850, sensitivity of 90.7%, and specificity of 70.4% at a cut-off of 8.5. MDCTEs showed an AUC of 0.909, sensitivity of 83.7%, and specificity of 85.2% at a cut-off of 8.5. During Delong test, the IBUS-SAS, MDCTEs, and SES-CD showed no significant differences in assessing moderate-to-severe activity. Both IBUS-SAS and ultrasound parameters correlated with certain serum indicators (p < 0.05), although only weakly to moderately (all r < 0.5). CONCLUSION: The IBUS-SAS, MDCTEs and SES-CD can evaluate disease remission/active and mild/moderate-to-severe active in CD, and IBUS-SAS offers the potential to precisely define CD activity.

Asunto(s)

Enfermedad de Crohn , Tomografía Computarizada Multidetector , Índice de Severidad de la Enfermedad , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Masculino , Femenino , Adulto , Tomografía Computarizada Multidetector/métodos , Persona de Mediana Edad , Sensibilidad y Especificidad , Ultrasonografía/métodos , Adulto Joven , Ultrasonografía Doppler en Color

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PURPOSE: To develop and validate a nomogram based on 3D-PDU parameters and clinical characteristics to predict LNM and LVSI in early-stage cervical cancer preoperatively. MATERIALS AND METHODS: A total of first diagnosis 138 patients with cervical cancer who had undergone 3D-PDU examination before radical hysterectomy plus lymph dissection between 2014 and 2019 were enrolled for this study. Multivariate logistic regression analyses were performed to analyze the 3D-PDU parameters and selected clinicopathologic features and develop a nomogram to predict the probability of LNM and LVSI in the early stage. ROC curve was used to evaluate model differentiation, calibration curve and Hosmer-Lemeshow test were used to evaluate calibration, and DCA was used to evaluate clinical practicability. RESULTS: Menopause status, FIGO stage and VI were independent predictors of LNM. BMI and maximum tumor diameter were independent predictors of LVSI. The predicted AUC of the LNM and LSVI models were 0.845 (95%CI,0.765-0.926) and 0.714 (95%CI,0.615-0.813). Calibration curve and H-L test (LNM groups P = 0.478; LVSI P = 0.783) all showed that the predicted value of the model had a good fit with the actual observed value, and DCA indicated that the model had a good clinical net benefit. CONCLUSION: The proposed nomogram based on 3D-PDU parameters and clinical characteristics has been proposed to predict LNM and LVSI with high accuracy, demonstrating for the first time the potential of non-invasive prediction. The probability derived from this nomogram may have the potential to provide valuable guidance for physicians to develop clinical individualized treatment plans of FIGO patients with early cervical cancer.

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Metástasis Linfática , Nomogramas , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/diagnóstico , Metástasis Linfática/patología , Persona de Mediana Edad , Adulto , Imagenología Tridimensional/métodos , Histerectomía/métodos , Estadificación de Neoplasias , Escisión del Ganglio Linfático/métodos , Ultrasonografía/métodos , Invasividad Neoplásica , Ganglios Linfáticos/patología , Estudios Retrospectivos , Anciano , Valor Predictivo de las Pruebas

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BACKGROUND: Doxorubicin and cisplatin are both first-line chemotherapeutics for osteosarcoma (OS) treatment. However, the efficacy of doxorubicin/cisplatin chemotherapy varies considerably. Thus, identifying an efficient diagnostic biomarker to distinguish patients with good and poor responses to doxorubicin/cisplatin chemotherapy is of paramount importance. METHODS: To predict the efficacy of doxorubicin/cisplatin chemotherapy, we analyzed the differentially expressed proteins in 37 resected OS samples, which were categorized into the primary group (PG), the recurrent group (RG) and the metastatic group (MG). The characteristics of the enriched differentially expressed proteins were assessed via GO and KEGG analyses. Protein‒protein interactions were identified to determine the relationships among the differentially expressed proteins. Receiver operating characteristic (ROC) curve analyses were performed to explore the clinical significance of the differentially expressed proteins. Parallel reaction monitoring (PRM) was used to validate the candidate proteins. Immunohistochemical (IHC) staining was performed to confirm the expression of cathepsin (CTSG) in patients with good and poor response to doxorubicin/cisplatin. RESULTS: A total of 9458 proteins were identified and quantified, among which 143 and 208 exhibited significant changes (|log2FC|>1, p < 0.05) in the RG and MG compared with the PG, respectively. GO and KEGG enrichment led to the identification of neutrophil extracellular traps (NETs). ROC curve analyses revealed 74 and 86 proteins with areas under the curve greater than 0.7 in the RG and MG, respectively. PRM validation revealed the statistical significance of CTSG, which is involved in NET formation, at the protein level in both the RG and MG. IHC staining of another cohort revealed that CTSG was prominently upregulated in the poor response group after treatment with doxorubicin/cisplatin. CONCLUSION: CTSG and its associated NETs are potential biomarkers with which the efficacy of doxorubicin/cisplatin chemotherapy could be predicted in OS patients.

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Purpose: Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid ß-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD. Methods: CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys. Results: L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% ± 25.8% (P = 0.004) and 1.5% ± 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did. Conclusions: This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV. Translational Relevance: This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.

Asunto(s)

Neovascularización Coroidal , Modelos Animales de Enfermedad , Angiografía con Fluoresceína , Macaca mulatta , Ratones Endogámicos C57BL , Tomografía de Coherencia Óptica , Animales , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/patología , Ratones , Racemasas y Epimerasas/antagonistas & inhibidores , Racemasas y Epimerasas/genética , Racemasas y Epimerasas/metabolismo , Coagulación con Láser/efectos adversos , Soluciones Oftálmicas , Masculino , Coroides/efectos de los fármacos , Coroides/patología , Coroides/diagnóstico por imagen , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/uso terapéutico , Ácidos Hidroxámicos/administración & dosificación , Ácidos Hidroxámicos/farmacología , Ácidos Hidroxámicos/uso terapéutico

RESUMEN

PURPOSE: To evaluate the clinical effect of three impression methods, conventional, closed-mouth, and tissue conditioner, on complete denture fabrication. METHODS: 60 subjects (edentulous with severely resorbed alveolar ridges - Atwood classification III or IV) who visited the Prosthodontic Department of Wuxi Stomatology Hospital, China, between January 2022 and June 2023, were selected for this study. The subjects were randomly divided into three groups of 20: a conventional impression group (CI group), a closed-mouth impression group (CM group), and a tissue conditioner group (TC group). Three months after denture restoration was completed, denture quality was assessed by clinicians in terms of marginal extension, retention, and stability. In addition, patients completed the oral health impact profile-edentulous (OHIP-EDENT) questionnaire to provide subjective satisfaction evaluations of the final denture restoration outcomes. RESULTS: The comprehensive denture quality evaluation results showed that the TC group had the lowest score, which was significantly lower than that of the CM (P= 0.014) and CI (P< 0.001) groups. The average score of the CM group was also significantly lower than that of the CI group (P= 0.004), indicating that tissue conditioner restoration was the most effective method. The OHIP-EDENT scores gradually decreased across the groups from CI to CM to TC (P= 0.001), indicating patients' oral health was significantly improved using tissue conditioner. CLINICAL SIGNIFICANCE: Tissue conditioner is a suitable dynamic functional impression method. It can significantly improve the effects for edentulous patients and increase their satisfaction.

Asunto(s)

Técnica de Impresión Dental , Diseño de Dentadura , Dentadura Completa , Satisfacción del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Encuestas y Cuestionarios

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PURPOSE: Targeted axillary dissection (TAD) after neoadjuvant therapy (NAT) includes removing of marked and sentinel lymph nodes (SLNs). The aim was to investigate the optimization of TAD localization techniques after NAT among breast cancer patients. METHODS: From November 2020 to 2022, we prospectively enrolled 107 lymph node-positive breast cancer patients in XX Hospital and received complete cycles of NAT. Patients were randomly divided into the following 3 groups before treatment: group A, marked node with clip (n=34); group B, marked node with 125I seed (n=32); and group C, marked node with clip and 125I seed (n=41). Dual tracers were used to search for SLNs after NAT. The main endpoint was the detection rate of marked nodes and false-negative rate (FNR). RESULTS: The detection rates using the TAD localization technique were 82.6% (28/34), 100% (32/32), and 100% (41/41) for groups A, B, and C, respectively (P>0.05). The FNR rates were 15.8%, 5.9%, and 5.6% among group A, B, and C, respectively (P>0.05). The FNR rates in cN1 patients were 5.1%, 2.7%, and 2.6%, among these three groups, respectively (P>0.05). The change in distance between 125I seeds and clips in axillary lymph nodes was <3 mm. The FNR rates of TAD guided by dye tracer, radiolabeled tracer, and dual tracers were 5.4%, 5.2%, and 3.4%, respectively (P>0.05). The negative predictive values were 93.0%, 93.0%, and 95.2%, respectively (P>0.05). CONCLUSION: Considering inexpensive and detect rate of 125I seeds, it is recommended that placement of 125I seeds to localize metastatic nodes in neoadjuvant setting. The TAD guided by dye tracer is also feasible for axillary de-escalation surgery after NAT in countries or regions without radiolabeled colloid.

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OBJECTIVE: The Vickers ligament is thought to hinder the growth of palmar ulnar radius by tethering the lunate to the radius, leading to Madelung deformity. The purpose of this study was to clarify the nature of the Vickers ligament and investigate its pathogenesis in Madelung deformities based on our observation of the Vickers ligament. METHODS: All 22 patients (33 wrists) with Madelung deformities treated surgically between 2018 and 2022 were included. The diagnosis was confirmed radiographically in all patients. The three-dimensional computed tomography (3D-CT) data of 16 patients (19 wrists) were available. Magnetic resonance imaging (MRI) data were available for 9 patients (14 wrists). Wrist arthroscopy was used in 4 patients. The Vickers ligament was resected and submitted for histopathological examination in 8 patients. Radiographic outcomes, 3D-CT, MRI, arthroscopy, surgical findings, and histopathology of the Vickers ligament were evaluated. RESULTS: The 3D-CT revealed that the Vickers ligament originated in the metaphysis and formed a metaphyseal defect at the palmar ulnar radius. In the sequential MR coronal images, the Vickers ligament could be divided into 3 branches, extending to the lunate, triquetrum and ulnar styloid. Arthroscopy and surgical findings revealed that the nature of the Vickers ligament was the stretched palmar ligament of the wrist. The histopathology results revealed ligamentous tissue and fibrocartilaginous metaplasia with a structure similar to that of the triangular fibrocartilage complex (TFCC). CONCLUSIONS: The Vickers ligament is not a separate aberrant ligament. The nature of the Vickers ligament is a combination of the stretched TFCC ligament (palmar radioulnar ligament, ulnotriquetral ligament and ulnolunate ligament) and radiolunate ligament. The possible pathogenesis of Madelung deformity might be focal early epiphyseal closure at the middle part of the sigmoid notch, which leads to focal growth retardation of the radius and pulls palmar ligaments proximally to form the Vickers ligament.

Asunto(s)

Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Adulto , Adolescente , Tomografía Computarizada por Rayos X , Articulación de la Muñeca/diagnóstico por imagen , Articulación de la Muñeca/patología , Articulación de la Muñeca/anomalías , Adulto Joven , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/patología , Artroscopía , Niño , Ligamentos Articulares/diagnóstico por imagen , Ligamentos Articulares/patología , Imagenología Tridimensional , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/anomalías , Radio (Anatomía)/patología , Persona de Mediana Edad , Trastornos del Crecimiento

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OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). METHODS: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. RESULTS: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. CONCLUSION: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08).

Asunto(s)

Glomerulonefritis Membranosa , Hidroxicloroquina , Receptores de Fosfolipasa A2 , Humanos , Hidroxicloroquina/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Receptores de Fosfolipasa A2/inmunología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Autoanticuerpos/sangre , Proteinuria

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Patterns on polymers usually have different mechanical properties as those of the substrates, causing deformation or distortion and even detachment of the patterns from the polymer substrates. Herein, we present a wrinkling strategy, which utilizes photolithography to define the area of stress distribution by light-induced physical crosslinking of polymers and controls diffusion of residual solvent to redistribute the stress and then offers the same material for patterns as substrate by thermal polymerization, providing uniform wrinkles without worrying about force relaxation. The strategy allows the recording and hiding of up to eight switchable images in one place that can be read by the naked eye without crosstalk, applying the wrinkled polymer for optical anti-counterfeiting. The wrinkled polyimide film was also utilized to act as a substrate for the creation of fine copper circuit by a full-additive process. It generates flexible integrated circuit (IC) carrier board with copper wire density of 400% higher than that of the state-of-the-art in industry while fulfilling the standards for industrialization.

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Esophageal squamous cell carcinoma (ESCC) is a prevalent and deadly malignancy of the digestive tract. Recent research has identified long non­coding RNAs (lncRNAs) as crucial regulators in the pathogenesis of ESCC. These lncRNAs, typically exceeding 200 nucleotides, modulate gene expression through various mechanisms, including the competing endogenous RNA (ceRNA) pathway and RNA­protein interactions. The current study reviews the multifaceted roles of lncRNAs in ESCC, highlighting their involvement in processes such as proliferation, migration, invasion, epithelial­mesenchymal transition, cell cycle progression, resistance to radiotherapy and chemotherapy, glycolysis, apoptosis, angiogenesis, autophagy, tumor growth, metastasis and the maintenance of cancer stem cells. Specific lncRNAs like HLA complex P5, LINC00963 and non­coding repressor of NFAT have been shown to enhance resistance to radio­ and chemotherapy by modulating pathways such as AKT signaling and microRNA interaction, which promote cell survival and proliferation under therapeutic stress. Furthermore, lncRNAs like family with sequence similarity 83, member A antisense RNA 1, zinc finger NFX1­type containing 1 antisense RNA 1 and taurine upregulated gene 1 are implicated in enhancing invasive and proliferative capabilities of ESCC cells through the ceRNA mechanism, while interactions with RNA­binding proteins further influence cancer cell behavior. The comprehensive analysis underscores the potential of lncRNAs as biomarkers for prognosis and therapeutic targets in ESCC, suggesting avenues for future research focused on elucidating the detailed molecular mechanisms and clinical applications of lncRNAs in ESCC management.

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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , ARN Largo no Codificante/genética , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Animales , Transición Epitelial-Mesenquimal/genética , Proliferación Celular/genética

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Objective: Sleep quality can affect the performance of visual working memory. However, the effect of sleep quality on the maintenance stage, which is the key to maintain the quality and efficiency of visual working memory representation, remains unclear. This study is the first to explore the effect of sleep quality on the maintenance of visual working memory information. Method: 60 healthy college students completed the Pittsburgh Sleep Quality Index (PSQI) and color recall task of visual working memory. A mixed experimental design of sleep quality (high or low) and delay duration (1, 4, or 6 s) was used to assess the effect of sleep quality on the maintenance phase of visual working memory. Results: The main effects of sleep quality were significant on visual working memory quantity, precision and offset indexes. Among the quantity index, the interaction between sleep quality and delay duration was also significant. This suggests that prolonging the delay time in the maintenance phase leads to difficulty in maintaining attention to the task for those with lower sleep quality, which results in poorer working memory quantitative representations. Conclusion: Increases in the delay duration of the maintenance phase in visual working memory intensify the impact of sleep quality on task performance. Our study provides evidence to reveal the relationship between sleep quality and visual working memory and offers recommendations for improving sleep quality and cognitive functioning in individuals.

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We present a novel time-of-flight resolved Bessel light bullet-enabled stimulated Raman scattering (B2-SRS) microscopy for deeper tissue 3D chemical imaging with high resolution without a need for mechanical z-scanning. To accomplish the tasks, we conceive a unique method to enable optical sectioning by generating the counter-propagating pump and Stokes Bessel light bullets in the sample, in which the group velocities of the Bessel light bullets are made ultraslow (e.g., vg ≈ 0.1c) and tunable by introducing programmable angular dispersions with a spatial light modulator. We theoretically analyze the working principle of the collinear multicolor Bessel light bullet generations and velocity controls with the relative time-of-flight resolved detection for SRS 3D deep tissue imaging. We have also built the B2-SRS imaging system and present the first demonstration of B2-SRS microscopy with Bessel light bullets for 3D chemical imaging in a variety of samples (e.g., polymer bead phantoms, biological samples such as spring onion tissue and porcine brain) with high resolution. The B2-SRS technique provides a > 2-fold improvement in imaging depth in porcine brain tissue compared to conventional SRS microscopy. The method of optical sectioning in tissue using counter-propagating ultraslow Bessel light bullets developed in B2-SRS is generic and easy to perform and can be readily extended to other nonlinear optical imaging modalities to advance 3D microscopic imaging in biological and biomedical systems and beyond.

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Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.

Asunto(s)

Canales Iónicos Sensibles al Ácido , Isquemia Encefálica , Ácido Glutámico , Animales , Femenino , Humanos , Masculino , Ratones , 2-Amino-5-fosfonovalerato/efectos adversos , 2-Amino-5-fosfonovalerato/metabolismo , 2-Amino-5-fosfonovalerato/farmacología , Canales Iónicos Sensibles al Ácido/química , Canales Iónicos Sensibles al Ácido/deficiencia , Canales Iónicos Sensibles al Ácido/efectos de los fármacos , Canales Iónicos Sensibles al Ácido/genética , Canales Iónicos Sensibles al Ácido/metabolismo , Regulación Alostérica/efectos de los fármacos , Sitios de Unión/genética , Isquemia Encefálica/inducido químicamente , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Ácido Glutámico/análogos & derivados , Ácido Glutámico/metabolismo , Ácido Glutámico/farmacología , Ácido Glutámico/toxicidad , Ratones Noqueados , Mutagénesis Sitio-Dirigida , Protones , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo

RESUMEN

OBJECTIVES: Ultrasound imaging (USI) is the gold standard in the clinical diagnosis of thyroid diseases. Compared with two-dimensional (2D) USI, three-dimensional (3D) USI could provide more structural information. However, the unstable pressure generated by the hand-hold ultrasound probe scanning can cause tissue deformation, especially in soft tissues such as the thyroid. The deformation is manifested as tissue structure being compressed in 2D USI, which results in structural discontinuity in 3D USI. Furthermore, multiple scans apply pressure in different directions to the tissue, which will cause relative displacement between the 3D images obtained from multiple thyroid scans. METHODS: In this work, we proposed a framework to minimize the influence of the variation of pressure in thyroid 3D USI. To correct pressure artifacts in a single scanning sequence, an adaptive method to smooth the position of the 2D ultrasound (US) image sequence is adopted before performing volumetric reconstruction. To build a whole 3D US image including both sides of the thyroid gland, an iterative closest point (ICP) based registration pipeline is adopted to eliminate the relative displacement caused by different pressure directions. RESULTS: Our proposed method was validated by in vivo experiments, including healthy volunteers and volunteers with thyroid nodules at different grading levels. CONCLUSIONS: The thyroid gland and nodule are rendered intelligently in the whole scanning region to facilitate the observation of 3D USI results by the doctor. This work might make a positive contribution to the clinical diagnosis of diseases of the thyroid or other soft tissues.

Asunto(s)

Imagenología Tridimensional , Enfermedades de la Tiroides , Glándula Tiroides , Ultrasonografía , Humanos , Ultrasonografía/métodos , Glándula Tiroides/diagnóstico por imagen , Imagenología Tridimensional/métodos , Enfermedades de la Tiroides/diagnóstico por imagen , Femenino , Adulto , Masculino , Nódulo Tiroideo/diagnóstico por imagen

RESUMEN

Climate change may diminish biodiversity; thus, it is urgent to predict how species' ranges may shift in the future by integrating multiple factors involving more taxa. Bats are particularly sensitive to climate change due to their high surface-to-volume ratio. However, few studies have considered geographic variables associated with roost availability and even fewer have linked the distributions of bats to their thermoregulation and energy regulation traits. We used species distribution models to predict the potential distributions of 12 bat species in China under current and future greenhouse gas emission scenarios (SSP1-2.6 and SSP5-8.5) and examined factors that could affect species' range shifts, including climatic, geographic, habitat, and human activity variables and wing surface-to-mass ratio (S-MR). The results suggest that Ia io, Rhinolophus ferrumequinum, and Rhinolophus rex should be given the highest priority for conservation in future climate conservation strategies. Most species were predicted to move northward, except for I. io and R. rex, which moved southward. Temperature seasonality, distance to forest, and distance to karst or cave were the main environmental factors affecting the potential distributions of bats. We found significant relationships between S-MR and geographic distribution, current potential distribution, and future potential distribution in the 2050s. Our work highlights the importance of analyzing range shifts of species with multifactorial approaches, especially for species traits related to thermoregulation and energy regulation, to provide targeted conservation strategies.

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Patrones y correlaciones de los cambios potenciales en la distribución de las especies de murciélago de China en el contexto del cambio climático Resumen El cambio climático puede disminuir la biodiversidad, por lo que es urgente pronosticar cómo puede cambiar en el futuro la distribución de las especies mediante la integración de múltiples factores que involucren a más taxones. Los murciélagos son particularmente sensibles al cambio climático debido a que tienen una gran proporción superficie­volumen. Sin embargo, hay pocos estudios que han considerado las variables asociadas con la disponibilidad de nidos y son todavía menos los que han conectado la distribución de los murciélagos con sus rasgos de termorregulación y regulación de energía. Usamos modelos de distribución de especies para pronosticar la distribución potencial de doce especies de murciélago en China bajo escenarios actuales y futuros de emisión de gases de efecto invernadero (SSP1­2.6 y SSP5­8.5) y analizamos los factores que podrían afectar el cambio en la distribución de las especies, incluyendo las variables climáticas, geográficas, de hábitat y de actividad humana y la proporción entre la superficie del ala y la masa (P S­M). Los resultados sugieren que Ia io, Rhinolophus ferrumequinum y R. rex deberían ser la mayor prioridad de conservación para las estrategias de conservación climáticas en el futuro. Pronosticamos que la mayoría de las especies se desplazarían al norte, a excepción de I. io y R. rex, que se desplazarían hacia el sur. Los principales factores que afectaron la distribución potencial de los murciélagos fueron la estacionalidad de la temperatura, la distancia al bosque y la distancia a la cueva o al karst. Encontramos una relación significativa entre la P S­M y la distribución geográfica, la distribución potencial actual y la distribución potencial para la década de 2050. Nuestra investigación destaca la importancia del análisis de los cambios de distribución de las especies con enfoques multifactoriales, especialmente para los rasgos de especie relacionados con la termorregulación y la regulación de energía, para proporcionar estrategias de conservación focalizadas.