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AIMS: With the wide application of trastuzumab deruxtecan (T-DXd), the survival of HER2-low breast cancer patients is dramatically improved. However, resistance to T-DXd still exists in a subset of patients, and the molecular mechanism remains unclear. METHODS: An in vivo shRNA lentiviral library functional screening was performed to identify potential circular RNA (crRNA) that mediates T-DXd resistance. RNA pull-down, mass spectrometry, RNA immunoprecipitation, and co-immunoprecipitation assays were conducted to investigate the molecular mechanism. Ferroptosis was detected using C11-BODIPY, Liperfluo, FerroOrange staining, glutathione quantification, malondialdehyde quantification, and transmission electron microscopy. Molecular docking, virtual screening, and patient-derived xenograft (PDX) models were used to validate therapeutic agents. RESULTS: VDAC3-derived crRNA (crVDAC3) ranked first in functional shRNA library screening. Knockdown of crVDAC3 increased the sensitivity of HER2-low breast cancer cells to T-DXd treatment. Further mechanistic research revealed that crVDAC3 specifically binds to HSPB1 protein and inhibits its ubiquitination degradation, leading to intracellular accumulation and increased levels of HSPB1 protein. Notably, suppression of crVDAC3 dramatically increases excessive ROS levels and labile iron pool accumulation. Inhibition of crVDAC3 induces ferroptosis in breast cancer cells by reducing HSPB1 expression, thereby mediating T-DXd resistance. Through virtual screening and experimental validation, we identified that paritaprevir could effectively bind to crVDAC3 and prevent its interaction with HSPB1 protein, thereby increasing ubiquitination degradation of HSPB1 protein to overcome T-DXd resistance. Finally, we validated the enhanced therapeutic efficacy of T-DXd by paritaprevir in a HER2-low PDX model. CONCLUSION: This finding reveals the molecular mechanisms underlying T-DXd resistance in HER2-low breast cancer. Our study provides a new strategy to overcome T-DXd resistance by inhibiting the interaction between crVDAC3 and HSPB1 protein.

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Solanum commersonii (2n = 2x = 24, 1EBN, Endosperm Balance Number), native to the southern regions of Brazil, Uruguay, and northeastern Argentina, is the first wild potato germplasm collected by botanists and exhibits a remarkable array of traits related to disease resistance and stress tolerance. In this study, we present a high-quality haplotype-resolved genome of S. commersonii. The two identified haplotypes demonstrate chromosome sizes of 706.48 and 711.55 Mb, respectively, with corresponding chromosome anchoring rates of 94.2 and 96.9%. Additionally, the contig N50 lengths are documented at 50.87 and 45.16 Mb. The gene annotation outcomes indicate that the haplotypes encompasses a gene count of 39 799 and 40 078, respectively. The genome contiguity, completeness, and accuracy assessments collectively indicate that the current assembly has produced a high-quality genome of S. commersonii. Evolutionary analysis revealed significant positive selection acting on certain disease resistance genes, stress response genes, and environmentally adaptive genes during the evolutionary process of S. commersonii. These genes may be related to the formation of diverse and superior germplasm resources in the wild potato species S. commersonii. Furthermore, we utilized a hybrid population of S. commersonii and S. verrucosum to conduct the mapping of potato freezing tolerance genes. By combining BSA-seq analysis with traditional QTL mapping, we successfully mapped the potato freezing tolerance genes to a specific region on Chr07, spanning 1.25 Mb, with a phenotypic contribution rate of 18.81%. In short, current research provides a haplotype-resolved reference genome of the diploid wild potato species S. commersonii and establishes a foundation for further cloning and unraveling the mechanisms underlying cold tolerance in potatoes.

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OBJECTIVE: To explore the effectiveness of HPV 16/18 E7 oncoprotein in detecting high-grade cervical intraepithelial neoplasia (CIN) and predicting disease outcomes in HPV 16/18-positive patients. METHODS: The present study was a cross-sectional study with a 2-year follow up. We collected 915 cervical exfoliated cell samples from patients who tested positive for HPV 16/18 in gynecologic clinics of three tertiary hospitals in Beijing from March 2021 to October 2022 for HPV 16/18 E7 oncoprotein testing. Subsequently, 2-year follow up of 408 patients with baseline histologic CIN1 or below were used to investigate the predictive role of HPV 16/18 E7 oncoprotein in determining HPV persistent infection and disease progression. RESULTS: The positivity rate of the HPV 16/18 E7 oncoprotein assay was 42.06% (249/592) in the inflammation/CIN 1 group and 85.45% (277/324) in the CIN2+ group. For CIN2+ detection, using the HPV 16/18 E7 oncoprotein assay combined with HPV 16/18 testing, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 85.45%, 57.94%, 52.57%, and 87.95%, respectively. During the 2-year follow up, the sensitivity, specificity, PPV, and NPV for predicting persistent HPV infection were 48.44%, 58.21%, 34.64%, and 71.18% in the baseline inflammation and CIN1 group. CONCLUSIONS: As a triage method for high-grade CIN screening in HPV 16/18-positive patients, HPV 16/18 E7 oncoprotein demonstrated a relatively high NPV, making it suitable for clinical use in triaging HPV 16/18-positive cases and potentially reducing the colposcopic referral rate. HPV 16/18 E7 oncoprotein exhibited a preferably predictive value in determining HPV infection outcomes and disease progression.

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The perovskite materials are broadly incorporated into optoelectronic devices due to a number of advantages. Their rapid technological progress is related to the relatively simple fabrication process, low production cost and high efficiency. Significant improvement is made in the light emitting, detection performance and device design especially operating in the visible and near-infrared regions. This review presents the status and possible future development of the perovskite devices such as solar cells, photodetectors, and light-emitting diodes. The fundamental properties of perovskite materials related to their effective device applications are summarized. Since the development of the perovskite technology is mainly driven by the revolutionary evolution of the semiconductor perovskite solar cell as a robust candidate for next-generation solar energy harvesting, this topic is considered first. The device engineering of various perovskite photodetector structures, including perovskite quantum dot photodetectors, is then discussed in detail. Their performance is compared with the current commercial photodetectors available on the global market together with their challenges. Finally, the considerable progress in the fabrication of the perovskite light-emitting diodes with external quantum efficiency exceeding 20% is presented. The paper is completed in an attempt to determine the development of perovskite optoelectronic devices in the future.

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Introduction: Exogenous melatonin (MT) can promote horticultural crops growth under stress conditions. Methods: In this study, the effects of exogenous MT on the accumulation of selenium (Se) in grape were studied under Se stress. Results and discussion: Under Se stress, exogenous MT increased the biomass, content of photosynthetic pigments and antioxidant enzyme activity of grapevines. Compared with Se treatment, MT increased the root biomass, shoot biomass, chlorophyll a content, chlorophyll b content, carotenoids, superoxide dismutase activity, and peroxidase activity by 18.11%, 7.71%, 25.70%, 25.00%, 25.93%, 5.73%, and 9.41%, respectively. Additionally, MT increased the contents of gibberellin, auxin, and MT in grapevines under Se stress, while it decreased the content of abscisic acid. MT increased the contents of total Se, organic Se and inorganic Se in grapevines. Compared with Se treatment, MT increased the contents of total Se in the roots and shoots by 48.82% and 135.66%, respectively. A transcriptome sequencing analysis revealed that MT primarily regulated the cellular, metabolic, and bioregulatory processes of grapevine under Se stress, and the differentially expressed genes (DEGs) were primarily enriched in pathways, such as aminoacyl-tRNA biosynthesis, spliceosome, and flavonoid biosynthesis. These involved nine DEGs and nine metabolic pathways in total. Moreover, a field experiment showed that MT increased the content of Se in grapes and improved their quality. Therefore, MT can alleviate the stress of Se in grapevines and promote their growth and the accumulation of Se.

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BACKGROUND: Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms of m6A-related regulators in HCC cell ferroptosis remain unclear. METHODS: By examining a series of m6A modification enzymes upon ferroptosis induction or inhibition, we identified METTL16 as a novel ferroptotic repressor in HCC cells. The roles of METTL16 on ferroptosis and HCC development were investigated in multiple cell lines, human HCC organoids, subcutaneous xenografts and MYC/Trp53-/- HCC model in hepatocyte-specific Mettl16 knockout and overexpression mice. The underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay and Mass Spectrometry. The clinical significance and relevance were evaluated in human samples. RESULTS: High METTL16 expression confers ferroptosis resistance in HCC cells and mouse models, and promotes cell viability and tumor progression. Mechanistically, METTL16 collaborates with IGF2BP2 to modulate SENP3 mRNA stability in an m6A-dependent manner, and the latter impedes the proteasome-mediated ubiquitination degradation of Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF expression facilitates the chelation of free iron and reduces liable iron pool level. SENP3 and LTF are implicated in METTL16-mediated HCC progression and anti-ferroptotic effects both in vivo and in vitro. Clinically, METTL16 and SENP3 expression were positively correlated, and high METTL16 and SENP3 expression predicts poor prognosis in human HCC samples. CONCLUSIONS: Our study reveals a new METTL16-SENP3-LTF signaling axis regulating ferroptosis and driving HCC development. Targeting this axis is a promising strategy for sensitizing ferroptosis and against HCC.

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Carcinoma Hepatocelular , Ferroptosis , Neoplasias Hepáticas , Metiltransferasas , Proteínas de Unión al ARN , Animales , Humanos , Ratones , Carcinogénesis/metabolismo , Carcinogénesis/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Cisteína Endopeptidasas , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Proteínas de Unión al ARN/metabolismo , Proteínas de Unión al ARN/genética

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Natural bone tissue has the certain function of self-regeneration and repair, but it is difficult to repair large bone damage. Recently, although autologous bone grafting is the "gold standard" for improving bone repair, it has high cost, few donor sources. Besides, allogeneic bone grafting causes greater immune reactions, which hardly meet clinical needs. The bone tissue engineering (BTE) has been developed to promote bone repair. Gelatin, due to its biocompatibility, receives a great deal of attention in the BTE research field. However, the disadvantages of natural gelatin are poor mechanical properties and single structural property. With the development of BTE, gelatin is often used in combination with a range of natural, synthetic polymers, and inorganic materials to achieve synergistic effects for the complex physiological process of bone repair. The review delves into the fundamental structure and unique properties of gelatin, as well as the excellent properties necessary for bone scaffold materials. Then this review explores the application of modified gelatin three-dimensional (3D) scaffolds with various structures in bone repair, including 3D fiber scaffolds, hydrogels, and nanoparticles. In addition, the review focuses on the excellent efficacy of composite bone tissue scaffolds consisting of modified gelatin, various natural or synthetic polymeric materials, as well as bioactive ceramics and inorganic metallic/non-metallic materials in the repair of bone defects. The combination of these gelatin-based composite scaffolds provides new ideas for the design of scaffold materials for bone repair with good biosafety.

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We present a case study highlighting prenatal ultrasound findings in monozygotic twins with chromosome 17q12 deletion syndrome. Fetus A exhibited bilateral fetal pyelectasis and talipes equinovarus, while fetus B showed hyperechogenic kidneys. Despite sharing the same de novo variant, the twins displayed distinct clinical phenotypes, suggesting the presence of non-genetic factors influencing the phenotypic variability of this syndrome. This case represents the first documented instance of prenatally identified identical twins affected by 17q12 deletion syndrome.

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TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of A-910, a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign. The lead compound exhibits favorable oral bioavailability, exceptional kinome selectivity, and significantly improved in vivo target engagement. These findings support the use of A-910 as an orally bioavailable in vivo tool compound for investigating the immunotherapy potential of dual MerTK/Axl inhibition.

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Holometabolous insects undergo morphological remodeling from larvae to pupae and to adults with typical changes in the cuticle; however, the mechanism is unclear. Using the lepidopteran agricultural insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the transcription factor RUNT-like (encoded by Runt-like) regulates the development of the pupal cuticle via promoting a pupal cuticle protein gene (HaPcp) expression. The HaPcp was highly expressed in the epidermis and wing during metamorphosis and was found being involved in pupal cuticle development by RNA interference (RNAi) analysis in larvae. Runt-like was also strongly upregulated in the epidermis and wing during metamorphosis. Knockdown of Runt-like produced similar phenomena, a failure of abdomen yellow envelope and wing formation, to those following HaPcp knockdown. The insect molting hormone 20-hydroxyecdysonen (20E) upregulated HaPcp transcription via RUNT-like. 20E upregulated Runt-like transcription via nuclear receptor EcR and the transcription factor FOXO. Together, RUNT-like and HaPCP are involved in pupal cuticle development during metamorphosis under 20E regulation.

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Regulación del Desarrollo de la Expresión Génica , Proteínas de Insectos , Metamorfosis Biológica , Pupa , Animales , Pupa/crecimiento & desarrollo , Pupa/genética , Pupa/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Metamorfosis Biológica/genética , Larva/crecimiento & desarrollo , Larva/genética , Larva/metabolismo , Alas de Animales/crecimiento & desarrollo , Alas de Animales/metabolismo , Ecdisterona/metabolismo , Interferencia de ARN , Mariposas Nocturnas/crecimiento & desarrollo , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Epidermis/metabolismo , Epidermis/crecimiento & desarrollo , Muda/genética

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Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7-78.9%) and the DCR was 76% (95% CI: 54.9-90.6%). The mPFS was 6.0 months (95% CI: 5.4-9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Indoles , Neoplasias Pulmonares , Quinolinas , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Anciano , Indoles/administración & dosificación , Indoles/uso terapéutico , Indoles/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Estadificación de Neoplasias , Albúminas

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Phase engineering is an effective strategy for modulating the electronic structure and electron transfer mobility of cobalt selenide (CoSe2) with remarkable sodium storage. Nevertheless, it remains challenging to improve fast-charging and cycling performance. Herein, a heterointerface coupling induces phase transformation from cubic CoSe2 to orthorhombic CoSe2 accompanied by the formation of MoSe2 to construct a CoSe2/MoSe2 heterostructure decorated with N-doped carbon layer on a 3D graphene foam (CoSe2/MoSe2@NC/GF). The incorporated Mo cations in the bridged o-CoSe2/MoSe2 not only act an electron donor to regulate charge-spin configurations with more active electronic states but also trigger the upshift of d/p band centers and a decreased ∆d-p band center gap, which greatly enhances ion adsorption capability and lowers the ion diffusion barrier. As expected, the CoSe2/MoSe2@NC/GF anode demonstrates a high-rate capability of 447 mAh g-1 at 2 A g-1 and an excellent cyclability of 298 mAh g-1 at 1 A g-1 over 1000 cycles. The work deepens the understanding of the elaborate construction of heterostructured electrodes for high-performance SIBs.

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Objectives: No study has reported secular trends in dementia prevalence, all-cause mortality, and survival status in rural China. Methods: We established two cohorts (XRRCC1 and XRRCC2) in the same region of China, 17 years apart, to compare dementia prevalence, all-cause mortality, and survival status, and performed regression analysis to identify associated factors. Results: Dementia prevalence was 3.49% in XRRCC1 and 4.25% in XRRCC2, with XRRCC2 showing a significantly higher prevalence (OR = 1.79, 95%CI: 1.2-2.65). All-cause mortality rates for dementia patients were 62.0% in XRRCC1 and 35.7% in XRRCC2. Mortality in the normal population of XRRCC2 decreased by 66% compared to XRRCC1, mainly due to improved survival rates in women with dementia. Dementia prevalence was positively associated with age >65, spouse-absent status, and stroke, and negatively associated with ≥6 years of education. Conclusion: Dementia prevalence in rural China increased over 17 years, while mortality decreased. Major risk factors include aging, no spouse, and stroke, with higher education offering some protection.

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Demencia , Población Rural , Humanos , China/epidemiología , Demencia/epidemiología , Demencia/mortalidad , Femenino , Masculino , Prevalencia , Anciano , Población Rural/estadística & datos numéricos , Persona de Mediana Edad , Factores de Riesgo , Anciano de 80 o más Años , Mortalidad/tendencias , Factores de Edad , Causas de Muerte

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Blood lactate concentration is an established circulating biomarker for measuring muscle acidity and can be evaluated for monitoring endurance, training routines, or athletic performance. Sweat is an alternative biofluid that may serve similar purposes and offers the advantage of noninvasive collection and continuous monitoring. The relationship between blood lactate and dynamic sweat biochemistry for wearable engineering applications in physiological fitness remains poorly defined. Here, we developed a microfluidic wearable band with an integrated colorimetric timer and biochemical assays that temporally captures sweat and measures pH and lactate concentration. A colorimetric silver nanoplasmonic assay was used to measure the concentration of lactate, and dye-conjugated SiO2 nanoparticle-agarose composite materials supported dynamic pH analysis. We evaluated these sweat biomarkers in relation to blood lactate in human participant studies during cycling exercise of varying intensity. Iontophoresis-generated sweat pH from regions of actively working muscles decreased with increasing heart rate during exercise and was negatively correlated with blood lactate concentration. In contrast, sweat pH from nonworking muscles did not correlate with blood lactate concentration. Changes in sweat pH and blood lactate were observed in participants who did not regularly exercise but not in individuals who regularly exercised, suggesting a relationship to physical fitness and supporting further development for noninvasive, biochemical fitness evaluations.

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Ejercicio Físico , Ácido Láctico , Piel , Sudor , Humanos , Sudor/química , Sudor/metabolismo , Ejercicio Físico/fisiología , Concentración de Iones de Hidrógeno , Piel/metabolismo , Ácido Láctico/sangre , Ácido Láctico/metabolismo , Microfluídica/métodos , Masculino , Adulto , Femenino , Biomarcadores/metabolismo , Biomarcadores/sangre , Dispositivos Electrónicos Vestibles

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BACKGROUND: Contiguous gene deletion in the short arm of chromosome 4 is linked to various neurodevelopmental disorders. METHODS: In this study, we conducted peripheral blood chromosome G-banding karyotyping and whole-exome sequencing (WES) on a proband presenting with anal atresia, global developmental delay, lymphocytosis, and other multisystem anomalies. Additionally, chromosome G-banding karyotyping was also carried out on the proband's parents and brother. RESULTS: The 7-month-old proband was found to have a 26.738 Mb 4p15.33-p14 deletion as identified by chromosome G-banding karyotyping and WES. CONCLUSION: We identified a patient with proximal 4p deletion syndrome by karyotype and WES analysis, which might explain some of his phenotypes. Our research enhances clinicians' knowledge of this rare condition, and offers valuable genetic counseling to the affected family. Further research is necessary to identify the causative gene or critical region associated with proximal 4p deletion syndrome.

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Anomalías Múltiples , Deleción Cromosómica , Cromosomas Humanos Par 4 , Humanos , Masculino , Lactante , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Cromosomas Humanos Par 4/genética , Fenotipo , Trastornos de los Cromosomas/genética , Trastornos de los Cromosomas/patología , Cariotipificación , Secuenciación del Exoma

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P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3ß domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3-/-, mice, indicating that the 1α3ß, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.

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Sitio Alostérico , Dominios Proteicos , Receptores Purinérgicos P2X3 , Animales , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X3/química , Receptores Purinérgicos P2X3/genética , Humanos , Ratones , Células HEK293 , Adenosina Trifosfato/metabolismo , Masculino , Ratones Endogámicos C57BL , Regulación Alostérica

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Bismuth germanate (Bi4Ge3O12, BGO) is a widely used optical sensing material with a high electro-optic coefficient, ideal for optical electric field sensors. Achieving high precision in electric field sensing requires fabricating optical waveguides on BGO. Traditional waveguide writing methods face challenges with this material. This study explores using femtosecond laser writing technology for preparing waveguides on BGO, leveraging ultrafast optical fields for superior material modification. Our experimental analysis shows that a cladding-type waveguide, written with a femtosecond laser at 200 kHz repetition frequency and 10.15 mW average power (pulse energy of 50.8 nJ), exhibits excellent light-guiding characteristics. Simulations of near-field optical intensity distribution and refractive index variations using the refractive index reconstruction method demonstrate that the refractive index modulation ensures single-mode transmission and effectively confines light to the core layer. In situ refractive index characterization confirms the feasibility of fabricating a waveguide with a refractive index reduction on BGO. The resulting waveguide has a loss per unit length of approximately 1.2 dB/cm, marking a successful fabrication. Additionally, we design an antenna electrode, analyze sensor performance indicators, and integrate a preparation process plan for the antenna electrode. This achievement establishes a solid experimental foundation for future studies on BGO crystal waveguides in electric field measurement applications.

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Air pollutants combined with Hg, Cd, Cr, Pb, etc. in many global populated areas were studied comprehensively, while our understanding towards thallium (Tl), an extremely toxic heavy metal, remains very limited. Further, the knowledge on atmospheric emissions, distribution, and the hidden risks associated with Tl is of great scarcity. Hence, this work aims to review recent data on significant sources of ambient Tl resulting from industrial activities, including Pb/Zn/Cu/Fe sulfide ore smelting, steel-making, coal burning, and cement production that involves the use of Tl-bearing wastes. Through the examination of Tl emissions and transfer pathways in the atmosphere, it is found that Tl is present at lower than ng/m3 in aerosols and air particulates but can increase to much higher levels even at 1000 µg/m3 in atmospheric fine particulate matters near the mining and smelting industrialized zones located near populated areas. This study highlights the importance of creating a comprehensive emission inventory for Tl, particularly in developing countries where this data is currently lacking. The time has come to develop a precise national emission inventory for Tl in order to prevent and mitigate the risks associated with ambient exposure to this element. This review offers novel insights for the scientific community and policy-makers in establishing effective control and management strategies to curb hidden Tl hazards derived from industrial activities.

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Brain asymmetries are hypothesized to reduce functional duplication and thus have evolutionary advantages. The goal of this study was to examine whether early brain lateralization contributes to skill development within the speech-language domain. To achieve this goal, 25 infants (2-13 months old) underwent behavioral language examination and fMRI during sleep while listening to forward and backward speech, and then were assessed on various language skills at 55-69 months old. We observed that infant functional lateralization of the superior temporal gyrus (STG) for forward > backward speech was associated with phonological, vocabulary, and expressive language skills 4 to 5 years later. However, we failed to observe that infant language skills or the anatomical lateralization of STG were related to subsequent language skills. Overall, our findings suggest that infant functional lateralization of STG for speech perception may scaffold subsequent language acquisition, supporting the hypothesis that functional hemisphere asymmetries are advantageous.