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ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality of cerebrovascular diseases are increasing year by year. Cerebral ischemia-reperfusion injury (CIRI) is common in patients with ischemic stroke. Naoxintong (NXT) is composed of a variety of Chinese medicines and has the ability to treat CIRI. AIM OF THE STUDY: The aim of this study is to investigate whether NXT regulates mitophagy in CIRI based on network pharmacology analysis and experimental validation. MATERIALS AND METHODS: Oxygen and glucose deprivation/re-oxygenation (OGD/R, 2/22 h) model of PC12 cells and transient middle cerebral artery occlusion (tMCAO, 2/22 h) model of rats were established. Pharmacodynamic indicators include neurological deficit score, 2,3,5-triphenyte-trazoliumchloride (TTC) staining, hematoxylin-eosin (HE) staining and cell viability. Network pharmacology was used to predict pharmacological mechanisms. Pharmacological mechanism indexes include transmission electron microscopy (TEM), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), immunohistochemistry (IHC), western blot (WB) and immunofluorescence (IF). Kevetrin (an agonists of p53) and pifithrin-α (an inhibitor of p53) used to detect the key role of p53 in mitophagy of NXT. RESULTS: NXT (1% serum containing NXT and 110 mg/kg) improved the damage of OGD/R PC12 cells and tMCAO rats, and this protective effect was related to the anti-oxidation and ability to promote mitophagy of NXT. NXT and pifithrin-α increased the expression of promoting-mitophagy targets (PINK1, PRKN and LC3B) and inhibited the expression of inhibiting-mitophagy targets (p52) via restraining p53, and finally accelerated mitophagy caused by CIRI. CONCLUSION: This study demonstrates that NXT promotes mitophagy in CIRI through restraining p53 and promoting PINK1/PRKN in vivo and in vitro.

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Medicamentos de Ervas Chinesas , Mitofagia , Farmacologia em Rede , Proteínas Quinases , Traumatismo por Reperfusão , Proteína Supressora de Tumor p53 , Animais , Masculino , Ratos , Isquemia Encefálica/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/patologia , Mitofagia/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Células PC12 , Proteínas Quinases/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases

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Mercury ion (Hg2+), a heavy metal cation with greater toxicity, is widely present in the ecological environment and has become a serious threat to human health and environmental safety. Currently, developing a solution to simultaneously visualize and monitor Hg2+ in environmental samples, including water, soil, and plants, remains a great challenge. In this work, we created and synthesized a near-infrared fluorescent probe, BBN-Hg, and utilized Hg2+ to trigger the partial cleavage of the carbon sulfate ester in BBN-Hg as a sensing mechanism, and the fluorescence intensity of BBN-Hg was significantly enhanced at 650 nm, thus realizing the visualization of Hg2+ with good selectivity (detection limit, 53 nM). In live cells and zebrafish, the probe BBN-Hg enhances the red fluorescence signal in the presence of Hg2+, and successfully performs 3D imaging on zebrafish, making it a powerful tool for detecting Hg2+ in living systems. More importantly, with BBN-Hg, we are able to detect Hg2+ in actual water samples, soil and plant seedling roots. Furthermore, the probe was prepared as a test strip for on-site determination of Hg2+ with the assistance of a smartphone. Therefore, this study offers an easy-to-use and useful method for tracking Hg2+ levels in living organisms and their surroundings.

Assuntos

Corantes Fluorescentes , Mercúrio , Peixe-Zebra , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Mercúrio/análise , Animais , Humanos , Espectrometria de Fluorescência/métodos , Limite de Detecção

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The plasmid-mediated tet(X4) gene has exhibited a high-level resistance to tigecycline (TGC), which has raised concerns globally regarding antibiotic resistance. Although the widespread tet(X4) has been found widely in Escherichia coli, it is scarcely found in other Enterobacteriaceae. This study aimed to characterize a ST469 Salmonella enterica serovar Rissen (S. Rissen) isolate harboring tet(X4) from pork, which was identified and characterized via antimicrobial susceptibility testing, conjugation assays, plasmid curing testing, whole-genome sequencing, and bioinformatic analysis. Ten ST469 S. Rissen isolates of 223 Salmonella spp. isolates were isolated from food samples in China during 2021-2023. One of 10 S. Rissen isolates, SM2301, carrying tet(X4) conferred high-level resistance to TGC (minimum inhibitory concentration > 8 µg/mL). The tet(X4) could be conjugated into different recipients, including E. coli, S. enteritidis, and K. pneumoniae isolates. Plasmid curing confirmed that tet(X4) was plasmid-mediated. Genetic analysis revealed that the tet(X4) in the SM2301 isolate was located in the IncFIA(HI1)-IncHI1A-IncHI1B(R27) hybrid plasmid, and the structure of tet(X4) was abh-tet(X4)-ISCR2. To the best of our knowledge, this is the first report of a tet(X4)-positive food-derived S. Rissen isolate. The extending bacterial species of tet(X4)-bearing plasmids suggested the increasing transmission risk of the mobile TGC resistance gene tet(X4) beyond E. coli. This study highlights the emerging and evolution risk of novel resistance genes across various bacterial species. Therefore, further surveillance is warranted to monitor the prevalence of tet(X4) in Salmonella spp. and other bacterial species.

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To date, there have been no reports on tertiary lymphoid structures (TLS) in primary adenocarcinoma of jejunum and ileum. In this study, we employed digital pathology image analysis software to classify and quantify TLS, and evaluated the maturity of TLS using immunohistochemistry. Molecular genetics and immunotherapy biomarker detection were performed using next-generation sequencing technology, such as tumor mutational burden (TMB) and microsatellite instability (MSI). The aim of this study was to investigate the presence, location, maturity, association with immunotherapy biomarkers, and prognostic value of TLS in primary adenocarcinoma of jejunum and ileum. Compared to secondary follicle-like TLS (SFL-TLS), intra-tumoral TLS (IT-TLS) were more likely to manifest as early TLS (E-TLS) (P = 0.007). Compared to IT-TLS, SFL-TLS had a higher propensity to occur at the invasive margin (IM) (P = 0.032) and showed a trend towards being more prevalent at the tumor periphery (P = 0.057). In terms of immunotherapy biomarkers, there was a higher trend of IM-TLS density in PD-L1(22C3) score CPS < 1 group compared to PD-L1(22C3) score CPS ≥ 1 group (P = 0.071). TMB-H was significantly associated with MSI-H (P = 0.040). Univariate survival analysis demonstrated a correlation between high SFL-TLS group and prolonged disease free survival (DFS) (P = 0.047). There was also a trend towards prolonged DFS in the E-TLS-high group compared to the E-TLS-low group (P = 0.069). The peri-tumoral TLS (PT-TLS)-high group showed a trend of prolonged overall survival (OS) compared to the PT-TLS-low group (P = 0.090). In conclusion, the majority of TLS were located at the invasive margin and tumor periphery, predominantly consisting of mature TLS, while IT-TLS were mainly immature. Notably, TMB was closely associated with MSI and PD-L1, indicating potential predictive value for immunotherapy in primary adenocarcinoma of jejunum and ileum.

Assuntos

Adenocarcinoma , Biomarcadores Tumorais , Neoplasias do Íleo , Neoplasias do Jejuno , Estruturas Linfoides Terciárias , Humanos , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/imunologia , Prognóstico , Masculino , Feminino , Estruturas Linfoides Terciárias/patologia , Estruturas Linfoides Terciárias/imunologia , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias do Íleo/patologia , Neoplasias do Íleo/mortalidade , Neoplasias do Jejuno/patologia , Taxa de Sobrevida , Seguimentos , Instabilidade de Microssatélites , Adulto , Estudos Retrospectivos

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AIMS: Previous proteomics studies in dysferlinopathy muscle have been limited in scope, often utilizing 2D-electrophoresis and yielding only a small number of differential expression calls. To address this gap, this study aimed to employ high-resolution proteomics to explore the proteomic landscapes of dysferlinopathy and analyze the correlation between muscle pathological changes and alterations in protein expression in muscle biopsies. METHODS: We conducted a comprehensive approach to investigate the proteomic profile and disease-associated changes in the muscle tissue proteome from 15 patients with dysferlinopathy, exhibiting varying degrees of dystrophic pathology, alongside age-matched controls. Our methodology encompasses tandem mass tag (TMT)-labeled liquid chromatography-mass spectrometry (LC-MS/MS)-based proteomics, protein-protein interaction (PPI) network analysis, weighted gene co-expression network analysis, and differential expression analysis. Subsequently, we examined the correlation between the expression of key proteins and the clinical characteristics of the patients to identify pathogenic targets associated with DYSF mutations in dysferlinopathy. RESULTS: A total of 1600 differentially expressed proteins were identified, with 1321 showing high expression levels and 279 expressed at lower levels. Our investigation yields a molecular profile delineating the altered protein networks in dysferlinopathy-afflicted skeletal muscle, uncovering dysregulation across numerous cellular pathways and molecular processes, including mRNA metabolic processes, regulated exocytosis, immune response, muscle system processes, energy metabolic processes, and calcium transmembrane transport. Moreover, we observe significant associations between the protein expression of ANXA1, ANXA2, ANXA4, ANXA5, LMNA, PYGM, and the extent of histopathologic changes in muscle biopsies from patients with dysferlinopathy, validated through immunoblotting and immunofluorescence assays. CONCLUSIONS: Through the aggregation of expression data from dysferlinopathy-impacted muscles exhibiting a range of pathological alterations, we identified multiple key proteins associated with the dystrophic pathology of patients with dysferlinopathy. These findings provide novel insights into the pathogenesis of dysferlinopathy and propose promising targets for future therapeutic endeavors.

Assuntos

Biomarcadores , Progressão da Doença , Músculo Esquelético , Distrofia Muscular do Cíngulo dos Membros , Proteômica , Humanos , Masculino , Distrofia Muscular do Cíngulo dos Membros/patologia , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/metabolismo , Feminino , Adulto , Adulto Jovem , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , Adolescente , Biomarcadores/metabolismo , Criança , Disferlina/genética , Disferlina/metabolismo , Pessoa de Meia-Idade , Pré-Escolar , Mapas de Interação de Proteínas , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Espectrometria de Massas em Tandem

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BACKGROUND: Radiomics has been used in the diagnosis of cirrhosis and prediction of its associated complications. However, most current studies predict the risk of esophageal variceal bleeding (EVB) based on image features at a single level, which results in incomplete data. Few studies have explored the use of global multi-organ radiomics for non-invasive prediction of EVB secondary to cirrhosis. AIM: To develop a model based on clinical and multi-organ radiomic features to predict the risk of first-instance secondary EVB in patients with cirrhosis. METHODS: In this study, 208 patients with cirrhosis were retrospectively evaluated and randomly split into training (n = 145) and validation (n = 63) cohorts. Three areas were chosen as regions of interest for extraction of multi-organ radiomic features: The whole liver, whole spleen, and lower esophagus-gastric fundus region. In the training cohort, radiomic score (Rad-score) was created by screening radiomic features using the inter-observer and intra-observer correlation coefficients and the least absolute shrinkage and selection operator method. Independent clinical risk factors were selected using multivariate logistic regression analyses. The radiomic features and clinical risk variables were combined to create a new radiomics-clinical model (RC model). The established models were validated using the validation cohort. RESULTS: The RC model yielded the best predictive performance and accurately predicted the EVB risk of patients with cirrhosis. Ascites, portal vein thrombosis, and plasma prothrombin time were identified as independent clinical risk factors. The area under the receiver operating characteristic curve (AUC) values for the RC model, Rad-score (liver + spleen + esophagus), Rad-score (liver), Rad-score (spleen), Rad-score (esophagus), and clinical model in the training cohort were 0.951, 0.930, 0.801, 0.831, 0.864, and 0.727, respectively. The corresponding AUC values in the validation cohort were 0.930, 0.886, 0.763, 0.792, 0.857, and 0.692. CONCLUSION: In patients with cirrhosis, combined multi-organ radiomics and clinical model can be used to non-invasively predict the probability of the first secondary EVB.

Assuntos

Varizes Esofágicas e Gástricas , Hemorragia Gastrointestinal , Cirrose Hepática , Nomogramas , Humanos , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/diagnóstico por imagem , Varizes Esofágicas e Gástricas/epidemiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/diagnóstico , Estudos Retrospectivos , Feminino , Fatores de Risco , Idoso , Medição de Risco/métodos , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Baço/diagnóstico por imagem , Valor Preditivo dos Testes , Esôfago/diagnóstico por imagem , Esôfago/patologia , Adulto , Curva ROC , Radiômica

RESUMO

The widespread distribution of antibiotics in natural waters is a great threat to human health. Photocatalytic degradation is an environmentally friendly technology to remediate antibiotic-polluted waters, driven by endless solar energy. Herein, a Z-scheme Ag2S-Ag-In2O3 heterostructure photocatalyst is prepared to remove antibiotics under environmental conditions. Under natural sunlight (light intensity: ∼78 mW/cm2) irradiation, the optimal Ag2S-Ag-In2O3 (10-ASAIO) exhibits considerable performance for decomposing diverse antibiotics, including norfloxacin (NOR), tetracycline hydrochloride, sulfisoxazole, ciprofloxacin, chlortetracycline hydrochloride, and ofloxacin. The NOR photodegradation rate constant of 10-ASAIO reaches 0.025 min-1, which is 12.50, 5.00, and 6.25 times higher than that of In2O3 (0.002 min-1), Ag-In2O3 (0.005 min-1), and Ag2S-In2O3 (0.004 min-1), respectively. This performance of the 10-ASAIO photocatalyst for decomposing NOR under natural sunlight exceeds most of the previously reported photocatalysts under a xenon lamp. Particularly, due to the intermittency of natural sunlight, a light-emitting diode (LED) lamp (light intensity: 5.1 mW/cm2) is also used as a light source, and 72.20% of NOR can be degraded with irradiation for 12 h. The effects of many water characteristics (water bodies, coexisting inorganic anions, pH, and humic acid) on the degradation performance of 10-ASAIO have been investigated, which exhibits stable degradation efficiency in variable aquatic environments. A 10-ASAIO catalyst-coated frosted glass sheet is fabricated to settle the problem of recovery of powder photocatalysts, and the immobilized catalyst shows outstanding activity and stability to decompose NOR. The photocatalytic mechanism and pathway of degrading NOR over 10-ASAIO have also been systemically investigated and proposed. The ecotoxicity (phytotoxicity and biotoxicity) of the 10-ASAIO photocatalyst and treated NOR solution have been tested by their toxic effects on cabbage seeds and Staphylococcus aureus (S. aureus). This work provides a feasible photocatalytic system for environmental pollutant remediation under natural sunlight or an LED lamp.

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Conductive gels have greatly facilitated the development of flexible energy storage devices, including supercapacitors, batteries, and triboelectric nanogenerators. However, it is challenging for gel electrolytes to tackle the trade-off issues between mechanical properties and conductivity. Herein, a strategy of all inorganic salt-driven supramolecular networks is presented to construct gel electrolytes with high conductivity and reliable mechanical performance for flexible supercapacitors. The salt gel is successfully fabricated by combining a salt supramolecular network constructed by NH4Mo7O24·4H2O and FeCl3·6H2O and a polymer network of poly(vinyl alcohol). The inorganic salt supramolecular network serves as a rigid self-supporting framework in the hydrogel system for improving the mechanical properties and providing abundant active sites for accelerating ion transport. Furthermore, the salt gel-enabled supercapacitors are equipped and exhibit a high specific capacitance (199.4 mF cm-2) and excellent energy density (27.69 µWh cm-2). Moreover, the flexible supercapacitors not only present remarkable cyclic stability after 3000 charging/discharging cycles but also exhibit good electrochemical stability even under severe deformation conditions. The strategy of salt-gel-driven flexible supercapacitors would provide fresh thinking for the development of advanced flexible energy storage fields.

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Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract, and chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from chemotherapy in the long term, which ultimately leads to tumor recurrence, metastasis, and patient death. Elucidating the detailed mechanism of chemoresistance in GC and identifying specific therapeutic targets will help to solve the difficult problem of chemoresistance and improve the prognosis of patients with GC. This review summarizes and clarifies the cellular and molecular mechanisms underlying chemoresistance for GC.

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In recent decades, global aquaculture has expanded rapidly, raising concerns about coastal environmental degradation due to unregulated or poorly regulated discharge of aquaculture tailwater. Despite the crucial role of dissolved organic matter (DOM) in biogeochemical processes and aquatic biodiversity, the influence of aquaculture type on the molecular characteristics of DOM remains largely unexplored. Herein, this study investigated the variations in chemical and spectroscopic properties as well as molecular characteristics and composition of DOM across different aquaculture types including crustacean, fish and shellfish. Our findings revealed notable differences in DOM quantities among different aquaculture types, with crustacean and fish aquaculture water containing higher DOM amount compared to shellfish aquaculture water. This disparity can be attributed to the more frequent formulated feeds of crustacean and fish in contrast to shellfish aquaculture. Furthermore, distinct differences were also observed in the characteristics and composition of DOM among the different aquaculture waters. Specifically, DOM in shellfish aquaculture water exhibited a higher abundance of unsaturated and reduced molecules as well as increased aromaticity compared to the other two aquaculture waters. Conversely, DOM from fish aquaculture water showed a greater contribution from terrestrial origin characterized by elevated levels of plant-based components such as lignin-like and tannin-like compounds. Interestingly, DOM from shellfish aquaculture water contained lower levels of microbial-derived components such as lipid-like and protein-like compounds, likely due to reduced microorganism populations resulting from lower nutrients availability and higher salinity. Overall, these significant variations in characteristics and composition of DOM underscore the potential impacts of aquaculture type on the DOM biogeochemical cycle and the environmental quality in aquatic ecosystems.

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BACKGROUND: Newly graduated nurses' lack of professional competence is associated with inadequate preparation during their clinical placement as nursing students. Clinical placement is a critical stage in the development of nursing students' professional preparedness. However, research on the trajectory of nursing students' professional preparedness during clinical placement has not yielded findings with the same specificity. OBJECTIVES: The aim of this study is to estimate differences in professional preparedness levels at different clinical placement stages, to identify distinct patterns of professional preparedness trajectories during clinical placement, and to evaluate predictors of these trajectory group memberships. DESIGN: A quantitative longitudinal study. SETTINGS: Participants were recruited on a voluntary basis using convenience sampling at a tertiary hospital in Nanning, China. PARTICIPANTS: 224 senior nursing students were initially invited to participate in the study. A total of 178 nursing students successfully completed the follow-up assessments at baseline, as well as at 1 month, 4 months, and 8 months into their clinical placement. METHODS: Participants completed four online surveys, during which their professional preparedness level was measured using the Perceived Professional Preparedness questionnaire for senior nursing students. Professional preparedness scores at different time points were compared using one-way repeated measures ANOVA and latent growth model. Group-based trajectory model was applied to identify professional preparedness trajectories. Multiple logistic regression was adopted to determine the predictors of trajectory group memberships. RESULTS: The entire sample of Senior nursing students experienced a significant increase in professional preparedness during clinical placement. The best-fitting group-based trajectory model delineated three distinct trajectories: low-slowly increase trajectory (27.53 % of sample), moderate-rapidly increase trajectory (47.19 % of sample) and a high-stably increase trajectory (25.28 % of sample). Male, good and excellent academic performance, and very high degree of professional interest are the predictors of the moderate-rapidly increase trajectory. While male, good and excellent academic performance, high and very high degree of professional interest and participating in medical-related part-time employment are the predictors of the high-stable increase trajectory. CONCLUSIONS: Senior nursing students exhibit different levels of professional preparedness throughout their clinical placement. Simultaneously, three different trajectories were identified among the sample of nursing students. Therefore, in future research, greater attention should be directed towards the professional preparedness levels of nursing students with different trajectories, and early identification and targeted interventions should be prioritized.

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Pregnancy outcomes in women with recurrent implantation failure (RIF) undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI): does treatment with lipiodol flush matter? In this propensity score-matched study, we recruited 966 RIF patients who underwent IVF/ICSI from two tertiary hospitals. These patients were divided into groups based on whether they received lipiodol flush or not. Further stratification was applied to investigate the effect of lipiodol flush on pregnancy outcomes in RIF patients with different cycle type of embryo transferred. Then, patients subjected to lipiodol flush were categorized into three groups based on the duration of the interval: short interval (≤ 3 months), moderate interval (3-6 months), and long interval (≥ 6 months). The groups were well-matched at baseline. The lipiodol flush group exhibited a significantly lower incidence of biochemical pregnancy (46.27% vs. 56.22%, p = 0.046) and live birth (25.87% vs. 37.31%, p = 0.014). Subgroup analysis for fresh embryo transfer cycles revealed no significant differences in pregnancy outcomes. Among RIF patients underwent frozen-thawed embryo transfer cycle, a statistically significant difference in the live birth rate was observed in the lipiodol flush group when compared to the control group (26.40% vs. 37.21%, p = 0.030). Analysis of different lipiodol flush intervals demonstrated a significantly lower live birth rate in the lipiodol flush group. Our results challenge the value of lipiodol use in clinical practice for the treatment of RIF.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900024273. Registered 4 July 2019.

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The discovery of the bone-gut axis linking bone metabolism to gut microbiota (GM) dysbiosis has revolutionized our understanding of managing degenerative skeletal diseases. Targeting GM regulation has emerged as a promising approach to osteoporosis treatment. Herein, we develop propolis nanoemulsions (PNEs) with enhanced gastrointestinal stability and oral bioavailability for GM-based osteoporosis therapy. Orally administered PNEs exhibit superior antiosteoporosis efficacy in an ovariectomized (OVX) mouse model by modulating the GM structure and metabolites and restoring the intestinal barrier function. Multiomics analysis reveals that a reduction in Streptococcus abundance and an increase in the GM metabolite l-arginine are key factors in osteoporosis management. These changes suppress osteoclast activity and enhance osteoblast function, leading to balanced bone remodeling and, thus, significant antiosteoporotic effects via the gut-bone axis. Our results deepen insights into the intricate relationship between GM and bone remodeling, suggesting a promising strategy that maintains the homeostasis of the GM structure and metabolite for osteoporosis treatment.

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We discover a connection between a Gauss sum of number theory and the degree of coherence (DOC) of the field in a transverse plane of structured speckled light beams. We theoretically demonstrate and experimentally validate that prime number factorization can be achieved by manipulating the source beam's DOC in Young's double-slit experiment. The determination of whether a number can be factored is based solely on the visibility of the resulting interference patterns. Our findings offer new insights into information encryption and decryption, data compression, etc.

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The widespread utilization of straw return was a popular practice straw disposal for highly intensive agriculture in China, which has brought about some negative impacts such as less time for straw complete biodegradation, aggravation of greenhouse gas evolution, and lower efficient of carbon accumulation. It was urgent to find an eco-friendly N-rich organic fertilizer instead of mineral N as activator to solve the above problems and lead a carbon accumulation in long tern management. Besides, microbial necromass was considered as a crucial contributor to persistent soil carbon (C) and nitrogen (N) pool. How organic fertilizer activators influence microbial residue under different amount of crop residues input remained unclear. Thus, soils incorporating moderate and high rate of rice straw residue with additions of half and full of organic activators (fish protein hydrolysates vs. manure) were incubated for measuring carbon dioxide (CO2) and nitrous oxide (N2O) emission, microbial community and necromass. It was found that soil CO2 emission was rapidest during the first 13 days of straw decomposition but remained lowest in the treatments of 50% mineral N substituted by fish protein hydrolysate. There were that 81%-89% of total CO2 release and 59%-65% of total N2O emission occurred within 60 days of incubation period, and bacterial community and nitrate positively affected soil CO2 and N2O release respectively. Straw incorporation amount and organic activator application interactively influenced soil CO2 emission but not affected soil N2O emission. After 360 days of incubation, the difference of bacterial necromass was noticeable but fungal necromass remained almost unaltered across all treatments. All treatments showed generally comparable contribution of microbial necromass N to the total N pool. The treatment of 50% mineral N substituted by fish protein hydrolysate under high rate of straw input (HSF50) promoted the highest proportion of microbial necromass C in soil organic C because of alleviating N limitation for microorganisms. Finally, HSF50 was recommended as an eco-friendly strategy for enhancing microbial necromass C and N storage and climate benefits in agroecosystems.

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OBJECTIVE: To investigate the value of serum markers in assessing mucosal healing (MH) and inflammatory activity in patients with inflammatory bowel disease (IBD). METHODS: In this retrospective analysis, we examined data from 320 IBD patients, including 176 with ulcerative colitis (UC) and 144 with Crohn's disease (CD), alongside 100 healthy controls during the same period. Serum levels of various markers, including white blood cell (WBC), platelet count (PLT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) were evaluated. These indices were analyzed for their diagnostic value in endoscopic MH in IBD patients. The independent influencing factors affecting MH in IBD patients were identified by univariate and multivariate analyses. RESULTS: The levels of WBC, PLT, ESR, CRP, PLR, and NLR were significantly higher in IBD patients, UC patients, and CD patients than in healthy controls (all P < 0.05). For those achieving MH, their WBC, PLT, ESR, CRP, PLR, and NLR levels were significantly lower than patients who did not achieve MH (all P < 0.05). The AUCs of WBC, PLT, ESR, CRP, PLR, and NLR for the diagnosis of MH were 0.729, 0.756, 0.673, 0.707, 0791, and 0.724, respectively. A multifactorial analysis found that the presence of abdominal pain (OR: 2.155, 95% CI: 1.081-4.297, P < 0.05), higher WBC (OR: 3.927, 95% CI: 2.008-7.681, P < 0.001), higher PLT (OR: 4.181, 95% CI: 2.078-8.412, P < 0.001), higher ESR (OR: 2.221, 95% CI: 1.082-4.562, P < 0.05), higher CRP (OR: 3.874, 95% CI: 1.861-8.065, P < 0.001), higher PLR (OR: 4.087, 95% CI: 1.586-10.534, P < 0.01), and higher NLR ( OR: 2.688, 95% CI: 1.292-5.592, P < 0.01) were independent risk factors for failure in achieving MH. CONCLUSION: WBC, PLT, ESR, CRP, PLR, and NLR can be used as noninvasive markers for predicting MH in patients with IBD, and they hold promise for clinical application.

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Anthocyanins are plant secondary metabolites belonging to the polyphenol class of natural water-soluble phytopigments. The accumulation of anthocyanins in different plant tissues can improve plant survival under adverse conditions. In addition, plants with the resulting colorful morphology can be utilized as landscape plants. Triticum boeoticum (syn. Triticum monococcum ssp. aegilopoides, 2n=2x=14, AbAb) serves as a valuable genetic resource for the improvement of its close relative common wheat in terms of enhancing resilience to various biotic and abiotic stresses. In our previous study, the EMS-mutagenized mutant Z2921 with a red glume, stem, and rachis was generated from T. boeoticum G52, which has a green glume, stem, and rachis. In this study, the F1, F2, and F2:3 generations of a cross between mutant-type Z2921 and wild-type G52 were developed. A single recessive gene, tentatively designated RgM4G52, was identified in Z2921 via genetic analysis. Using bulked segregant exome capture sequencing (BSE-Seq) analysis, RgM4G52 was mapped to chromosome 6AL and was flanked by the markers KASP-58 and KASP-26 within a 3.40-cM genetic interval corresponding to 1.71-Mb and 1.61-Mb physical regions in the Chinese Spring (IWGSC RefSeq v1.1) and Triticum boeoticum (TA299) reference genomes, respectively, in which seven and four genes related to anthocyanin synthesis development were annotated. Unlike previously reported color morphology-related genes, RgM4G52 is a recessive gene that can simultaneously control the color of glumes, stems, and rachis in wild einkorn. In addition, a synthetic Triticum dicoccum-T. boeoticum amphiploid Syn-ABAb-34, derived from the colchicine treatment of F1 hybrids between tetraploid wheat PI 352367 (T. dicoccum, AABB) and Z2921, expressed the red stems of Z2921. The flanking markers of RgM4G52 developed in this study could be useful for developing additional common wheat lines with red stems, laying the foundation for marker-assisted breeding and the fine mapping of RgM4G52.

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The effect of Chlorella pyrenoidosa (CP) and Spirulina platensis (SP) at concentrations of 0 %-12 % on the properties of rice starch (RS) was investigated. Compared with pure RS, the addition of CP and SP powder decreased the viscosity, increased the gelatinization temperature, and promoted the retrogradation of RS gel. However, when CP was added at 12 % and SP at 8 %, retrogradation inhibition was reduced. At these concentrations, the relative crystallinity of the CP mixture increased by 57.37 %, whereas that of SP increased by 48.13 %. Scanning electron microscopy revealed that the addition of low amount of CP and SP reduced porosity. CP and SP powder facilitated the conversion of bound water to free water and contributed to the weakening of the viscoelasticity of the RS gel. CP powder likely had a more detrimental effect on the short-term storage properties of RS than SP powder. These results provide theoretical support for the development of RS-based products and the innovative utilization of microalgae.

RESUMO

Microbes have been demonstrated to be closely linked to diseases that pose a major threat to human health. Computing technologies can help researchers find potential microbe-drug associations more quickly and precisely. In this study, we introduced a novel computational prediction model called GLNNMDA based on global and local features of microbes and drugs to infer possible microbe-drug correlations. In GLNNMDA, we first constructed a heterogeneous network based on known microbe-drug relationships by integrating multiple similarity metrics of drugs and microbes. Subsequently, low-dimensional features will be extracted for nodes in the heterogeneous network by adopting the graph attention encoder. Next, based on combining these low-dimensional features with multiple properties of microbes and drugs to form a new comprehensive feature matrix, we would utilize the GLF module to extract the global and local features for microbes and drugs respectively, and then, we would further fuse these global and local features to come up with predictions of possible microbe-drug associations. Moreover, in order to evaluate the prediction performance of GLNNMDA, under the framework of fivefold cross-validation, intensive comparative experiments and case studies were done on different well-known public databases. The results showed that GLNNMDA obtained the highest AUC values as well as AUPR values of 0.9802 ± 0.0011, 0.9773 ± 0.0021 and 0.8586 ± 0.0004, 0.8008 ± 0.0031 in the two databases, MDAD and aBiofilm, respectively, compared to the state-of-the-art competing prediction methods. In addition, case studies of well-known microorganisms and drugs have demonstrated the effectiveness of GLNNMDA in inferring potential microbial drug associations, which implies that GLNNMDA may be a useful tool for microbe-drug association prediction in the future. The source code is available at: " https://github.com/KuangHaiYue/GLNNMDA.git ".

Assuntos

Biologia Computacional , Humanos , Biologia Computacional/métodos , Algoritmos , Bactérias/genética , Preparações Farmacêuticas

RESUMO

AIM: Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. METHODS: The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. RESULTS: Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/ß-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. CONCLUSION: Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/ß- catenin pathway.