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Abstract Isoform 1 of DNA methyltransferase DNMT3A (DNMT3A1) specifically recognizes nucleosome monoubiquitylated at histone H2A lysine-119 (H2AK119ub1) for establishment of DNA methylation. Mis-regulation of this process may cause aberrant DNA methylation and pathogenesis. However, the molecular basis underlying DNMT3A1−nucleosome interaction remains elusive. Here we report the cryo-EM structure of DNMT3A1’s ubiquitin-dependent recruitment (UDR) fragment complexed with H2AK119ub1-modified nucleosome. DNMT3A1 UDR occupies an extensive nucleosome surface, involving the H2A-H2B acidic patch, a surface groove formed by H2A and H3, nucleosomal DNA, and H2AK119ub1. The DNMT3A1 UDR’s interaction with H2AK119ub1 affects the functionality of DNMT3A1 in cells in a context-dependent manner. Our structural and biochemical analysis also reveals competition between DNMT3A1 and JARID2, a cofactor of polycomb repression complex 2 (PRC2), for nucleosome binding, suggesting the interplay between different epigenetic pathways. Together, this study reports a molecular basis for H2AK119ub1-dependent DNMT3A1−nucleosome association, with important implications in DNMT3A1-mediated DNA methylation in development.

Abstract Background Tunlametinib (HL-085) is a novel, highly selective MEK inhibitor with substantial clinical activities in patients with NRAS-mutant melanoma. This phase I study evaluated the safety and preliminary efficacy of tunlametinib plus vemurafenib in patients with advanced BRAF V600-mutant solid tumors. Methods Patients with confirmed advanced BRAF V600-mutant solid tumors who had progressed on or shown intolerance or no available standard therapies were enrolled and received tunlametinib plus vemurafenib. This study consisted of a dose-escalation phase and a dose-expansion phase. Primary end points of this study were safety, the recommended phase II dose (RP2D), and preliminary efficacy. Results From August 17, 2018 to April 19, 2022, 72 patients were enrolled. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. The RP2D for BRAF V600-mutant non-small cell lung cancer (NSCLC) patients was tunlametinib 9 mg plus vemurafenib 720 mg, twice daily (BID, bis in die). Until the data cut-off date of December 15, 2023, of 33 NSCLC patients with evaluable disease, the objective response rate (ORR) was 60.6% (20/33; 95% confidence interval [CI], 42.1–77.1), the median progression free survival (PFS) was 10.5 months (95%CI, 5.6–14.5) and median duration of response (DoR) was 11.3 months (95%CI, 6.8-NE). At the RP2D, ORR was 60.0% (9/15; 95% CI, 32.3–83.7), the median PFS was 10.5 months (95%CI, 5.6 -NE) and median DoR was 11.3 months (95%CI, 3.9-NE). Of 24 colorectal cancer patients with evaluable disease, the ORR was 25.0% (6/24; 95% CI, 5.6-NE). All 72 patients had treatment-related adverse events (TRAEs), and the most common grade 3–4 TRAEs were anemia (n = 13, 18.1%) and blood creatine phosphokinase increased (n = 10, 13.9%). Tunlametinib was absorbed rapidly with Tmax of 0.5–1 h. Vemurafeinib did not influence the system exposure of tunlametinib and vice versa, indicating no drug-drug interaction for this combination. Conclusions Tunlametinib (HL-085) plus vemurafenib had a favorable safety profile and showed promising antitumor activity in patients with BRAF V600-mutant solid tumors. The RP2D for NSCLC was tunlametinib 9 mg BID plus vemurafeinib 720 mg BID. Trial Registration ClinicalTrials.gov, NCT03781219.

AIM: To investigate whether retinal nerve fiber layer defects (RNFLDs) is a potential risk factor for chronic kidney disease (CKD) in Chinese adults. METHODS: The Kailuan Eye Study was a population-based study that included 14 440 participants. All participants underwent detailed assessments, RNFLDs were diagnosed using color fundus photographs. RESULTS: Overall, 12 507 participants [8533 males (68.23%)] had complete systemic examination data and at least one evaluable fundus photograph. RNFLDs were found in 621 participants [5.0%; 95% confidence interval (CI): 4.6%-5.34%], and 70 cases of multiple RNFLDs were found (11.27%). After adjusting multiple factors, RNFLDs was significantly associated with CKD severity, the ORs of CKD stage 3, stage 4 and stage 5 were 1.698, 4.167, and 9.512, respectively. Multiple RNFLDs were also associated with CKD severity after adjusting multiple factors, the ORs of CKD stage 3 and stage 5 were 4.465 and 11.833 respectively. Furthermore, 2294 participants had CKD (18.34%, 95%CI: 17.68%-18.99%). After adjusting for other factors, CKD presence was significantly correlated with the presence of RNFLDs. CONCLUSION: The strongest risk factors for RNFLDs are CKD and hypertension. Conversely, RNFLDs can be an ocular feature in patients with CKD. Fundoscopy can help detect systemic diseases, and assessment for RNFLDs should be considered in CKD patients.

Abstract Background Salt stress significantly reduces soybean yield. To improve salt tolerance in soybean, it is important to mine the genes associated with salt tolerance traits. Results Salt tolerance traits of 286 soybean accessions were measured four times between 2009 and 2015. The results were associated with 740,754 single nucleotide polymorphisms (SNPs) to identify quantitative trait nucleotides (QTNs) and QTN-by-environment interactions (QEIs) using three-variance-component multi-locus random-SNP-effect mixed linear model (3VmrMLM). As a result, eight salt tolerance genes (GmCHX1, GsPRX9, Gm5PTase8, GmWRKY, GmCHX20a, GmNHX1, GmSK1, and GmLEA2-1) near 179 significant and 79 suggested QTNs and two salt tolerance genes (GmWRKY49 and GmSK1) near 45 significant and 14 suggested QEIs were associated with salt tolerance index traits in previous studies. Six candidate genes and three gene-by-environment interactions (GEIs) were predicted to be associated with these index traits. Analysis of four salt tolerance related traits under control and salt treatments revealed six genes associated with salt tolerance (GmHDA13, GmPHO1, GmERF5, GmNAC06, GmbZIP132, and GmHsp90s) around 166 QEIs were verified in previous studies. Five candidate GEIs were confirmed to be associated with salt stress by at least one haplotype analysis. The elite molecular modules of seven candidate genes with selection signs were extracted from wild soybean, and these genes could be applied to soybean molecular breeding. Two of these genes, Glyma06g04840 and Glyma07g18150, were confirmed by qRT-PCR and are expected to be key players in responding to salt stress. Conclusions Around the QTNs and QEIs identified in this study, 16 known genes, 6 candidate genes, and 8 candidate GEIs were found to be associated with soybean salt tolerance, of which Glyma07g18150 was further confirmed by qRT-PCR.

Abstract Oxygen is essential for aerobic organisms, but little is known about its role in antiviral immunity. Here, we report that during responses to viral infection, hypoxic conditions repress antiviral-responsive genes independently of HIF signaling. EGLN1 is identified as a key mediator of the oxygen enhancement of antiviral innate immune responses. Under sufficient oxygen conditions, EGLN1 retains its prolyl hydroxylase activity to catalyze the hydroxylation of IRF3 at proline 10. This modification enhances IRF3 phosphorylation, dimerization and nuclear translocation, leading to subsequent IRF3 activation. Furthermore, mice and zebrafish with Egln1 deletion, treatment with the EGLN inhibitor FG4592, or mice carrying an Irf3 P10A mutation are more susceptible to viral infections. These findings not only reveal a direct link between oxygen and antiviral responses, but also provide insight into the mechanisms by which oxygen regulates innate immunity.

Abstract Background The initial phase II stuty (NCT03215693) demonstrated that ensartinib has shown clinical activity in patients with advanced crizotinib‐refractory, anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). Herein, we reported the updated data on overall survival (OS) and molecular profiling from the initial phase II study. Methods In this study, 180 patients received 225 mg of ensartinib orally once daily until disease progression, death or withdrawal. OS was estimated by Kaplan‒Meier methods with two‐sided 95% confidence intervals (CIs). Next‐generation sequencing was employed to explore prognostic biomarkers based on plasma samples collected at baseline and after initiating ensartinib. Circulating tumor DNA (ctDNA) was detected to dynamically monitor the genomic alternations during treatment and indicate the existence of molecular residual disease, facilitating improvement of clinical management. Results At the data cut‐off date (August 31, 2022), with a median follow‐up time of 53.2 months, 97 of 180 (53.9%) patients had died. The median OS was 42.8 months (95% CI: 29.3‐53.2 months). A total of 333 plasma samples from 168 patients were included for ctDNA analysis. An inferior OS correlated significantly with baseline ALK or tumor protein 53 (TP53) mutation. In addition, patients with concurrent TP53 mutations had shorter OS than those without concurrent TP53 mutations. High ctDNA levels evaluated by variant allele frequency (VAF) and haploid genome equivalents per milliliter of plasma (hGE/mL) at baseline were associated with poor OS. Additionally, patients with ctDNA clearance at 6 weeks and slow ascent growth had dramatically longer OS than those with ctDNA residual and fast ascent growth, respectively. Furthermore, patients who had a lower tumor burden, as evaluated by the diameter of target lesions, had a longer OS. Multivariate Cox regression analysis further uncovered the independent prognostic values of bone metastases, higher hGE, and elevated ALK mutation abundance at 6 weeks. Conclusion Ensartinib led to a favorable OS in patients with advanced, crizotinib‐resistant, and ALK‐positive NSCLC. Quantification of ctDNA levels also provided valuable prognostic information for risk stratification.

Abstract We present a user-friendly molecular generative pipeline called Pocket Crafter, specifically designed to facilitate hit finding activity in the drug discovery process. This workflow utilized a three-dimensional (3D) generative modeling method Pocket2Mol, for the de novo design of molecules in spatial perspective for the targeted protein structures, followed by filters for chemical-physical properties and drug-likeness, structure–activity relationship analysis, and clustering to generate top virtual hit scaffolds. In our WDR5 case study, we acquired a focused set of 2029 compounds after a targeted searching within Novartis archived library based on the virtual scaffolds. Subsequently, we experimentally profiled these compounds, resulting in a novel chemical scaffold series that demonstrated activity in biochemical and biophysical assays. Pocket Crafter successfully prototyped an effective end-to-end 3D generative chemistry-based workflow for the exploration of new chemical scaffolds, which represents a promising approach in early drug discovery for hit identification.

Abstract Background We combined the metabolic features of 18F-FDG-PET/CT and hematological inflammatory indicators to establish a predictive model of the outcomes of patients with locally advanced non-small cell lung cancer (LA-NSCLC) receiving concurrent chemoradiotherapy. Results A predictive nomogram was developed based on sex, CEA, systemic immune-inflammation index (SII), mean SUV (SUVmean), and total lesion glycolysis (TLG). The nomogram presents nice discrimination that yielded an AUC of 0.76 (95% confidence interval: 0.66–0.86) to predict 1-year PFS, with a sensitivity of 63.6%, a specificity of 83.3%, a positive predictive value of 83.7%, and a negative predictive value of 62.9% in the training set. The calibration curves and DCA suggested that the nomogram had good calibration and fit, as well as promising clinical effectiveness in the training set. In addition, survival analysis indicated that patients in the low-risk group had a significantly longer mPFS than those in the high-risk group (16.8 months versus 8.4 months, P

Abstract Solar‐driven interfacial evaporation is an emerging desalination technology that can potentially relieve the freshwater scarcity issue. To obtain high and continuous evaporation rates for all‐weather, chemically engineered structural materials have been widely explored for simultaneous photothermal and electrothermal conversion. However, many previously reported fabrication processes involve poor integration and considerable energy loss. Herein, a scalable photo‐electro‐thermal textile is proposed to enable high efficiency, long‐term salt rejection, and solar‐driven desalination. Specifically, the photo‐electro‐thermal yarns with a core (commercial electric wire)‐shell (polypyrrole‐decorated Tencel) structure realize the integration of electrothermal and photothermal conversion. The wrapping eccentricity of 1.53 mm and pitch of 3 T cm−1 for the electric wire are rationally regulated to achieve a high surface temperature of over 52 °C at a 3 V DC input. As a result, exceptional and stable evaporation rates of 5.57 kg m−2 h−1 (pure water) and 4.89 kg m−2 h−1 (3.5 wt.% brine) under 1 kW m−2·radiation with a 3 V input voltage are realized. Practical application shows that the textiles can achieve high water collection of over 46 kg m−2 d−1 over the whole day of operation. The constructed photo‐electro‐thermal textile‐based evaporator provides an effective method for commercial and scalable photo‐electro‐thermal conversion to achieve high‐performance and salt‐resistant solar‐driven desalination.

The point-based 3D object detection method is highly advantageous due to its lightweight nature and fast inference speed, making it a valuable asset in engineering fields such as intelligent transportation and autonomous driving. However, current advanced methods solely focus on learning features from the provided point cloud, neglecting the active role of unoccupied space. This results in the problem of discontinuous receptive field (DRF), leading to the loss of semantic and geometric information of the objects. To address this issue, we propose a new end-to-end single-stage point-based model, DRF-SSD, in this paper. DRF-SSD utilizes a PointNet++-style 3D backbone to maintain fast inference capability. Then, point-wise features are projected onto a plane in the Neck structure, and local and global information are aggregated through the designed Hierarchical Encoding–Decoding (HED) and Hybrid Transformer (HT) modules. The former fills in features for unoccupied space through convolutional layers, enhancing local features by interacting with features in occupied space during the learning process. The latter further expands the receptive field using the global learning ability of transformers. The spatial transformation and learning processes in HED and HT only involve key points, and HED is designed to have a special structure that maintains the sparsity of feature maps, preserving the efficiency of the model’s inference. Finally, query features are back-projected onto points for feature enhancement and input into the detection head for prediction. Extensive experiments on the KITTI datasets demonstrate that DRF-SSD achieves superior detection accuracy compared to previous methods, with significant improvements. Specifically, the approach obtains 2.25%, 0.66%, and 0.42% improvement for the metric of 3D Average Precision (AP3D) under the easy, moderate, and hard settings, respectively. Additionally, the method enables other point-based detectors to achieve substantial gains, demonstrating its effectiveness. Our code will be made available at https://github.com/AlanLiangC/DRF-SSD.git.

Aquaculture originates from ancient Chinese wisdom, and is considered the most efficient food-producing industry. About 70 years ago, New China proposed an industrial approach to fish production and made a policy decision to begin modern aquaculture development. As one of lucky persons since the early 1980s, I have committed my scholarly career to the studies on genetics and breeding biotechnology of polyploid gibel carp (Carassius gibelio). Here, several significant recent innovations, such as the proposition of the amphitriploid concept, the association of ploidy changes with reproduction transition, the finding of a unique ameio-fusiongenesis mode, the establishment of a controllable fertility approach, the creation of intermuscular bone-free mutants, as well as the recreation of desirable goldfish, are introduced and emphasized from an active participant of these innovations. Additionally, some modern innovations and contributions are also highlighted in other aspects of aquaculture including feed development, disease control, facilities and equipment upgrading, as well as paradigm and mode changes. This comprehensive synthesis of ancient Chinese wisdom and modern innovations seeks to provide valuable insights into the field from a historical basis.

The safe and stable operation of the transformer is the key to ensure the reliable operation of the power grid. Loose windings will produce a vibration acceleration signal with twice the power supply frequency signal, i.e., 100 Hz, as the main spectral component. The realization of transformer winding vibration acceleration detection can effectively determine the operating status of the transformer winding. In this report, a dual-cantilever beam Fiber Bragg Grating (FBG) vibration acceleration sensor for transformer winding with a two-point package structure was designed based on theoretical analysis and finite element simulation of COMSOL Multiphysics software. Through the demodulation of the center wavelength change to achieve the detection of external vibration acceleration and to achieve the vibration acceleration sensitivity of 37.813 pm/g at 100 Hz, linearity up to 99.97%, cross-sensitivity is less than 17.4%. The resonant frequency of the sensor is 134 Hz, and the sensitivity of the vibration acceleration at the resonant frequency point is 425.52 pm/g. The sensor is installed under the transformer to measure the vibration acceleration of the transformer winding. The vibration component under 100 Hz frequency could be obviously captured, and the FFT of the center wavelength captured the amplitude signal to realize the measurement of the vibration acceleration of the transformer winding less than 0.02 g micro-vibration acceleration, which could satisfy the general vibration range of the transformer winding.

ObjectiveTo investigate the knowledge, attitude, and practice (KAP) towards pediatric vitamin D deficiency (VitD) among parents and explore the risk factors of their knowledge, attitude, and practice.MethodsThis cross-sectional study enrolled parents in our Hospital between November 2022 and January 2023.ResultsA total of 621 valid questionnaires were collected in this study. The knowledge, attitude, and practice scores were 6.13 ± 3.07 (theoretical score range: 0–13), 31.13 ± 6.20 (theoretical score range: 9–45), and 27.47 ± 4.21 (theoretical score range: 9–45), respectively; the mean knowledge score was

Abstract Background To investigate the sex‐based heterogeneity of immune microenvironmental feature and its impact on the response to first‐line PD‐1 blockade plus chemotherapy in patients with driver‐negative advanced or metastatic non‐small‐cell lung cancer (NSCLC). Patients and Methods A total of 439 patients with advanced NSCLC treated with first‐line PD‐1 blockade plus chemotherapy or chemotherapy were identified. Differences in clinical outcomes between female and male patients were determined using Kaplan–Meier curves. Neoantigen burden and five immune microenvironmental markers expression including PD‐L1, CD4, CD8, FOXP3, and CD68 were compared between two groups. Results Of 175 eligible patients, 89 received PD‐1 blockade plus chemotherapy and 86 received first‐line chemotherapy. Forty five were women (25.7%) and 130 were men (74.3%). Female patients received first‐line PD‐1 blockade in combination with chemotherapy had dramatically better ORR (85.2% vs. 53.2%; p = 0.009), PFS (23.7 vs. 7.3 months; p = 0.013), and OS (46.2 vs. 20.0 months; p = 0.004) than males. Treatment outcomes were similar between females and males in chemotherapy group. Multivariate analyses showed that sex was the independent prognostic factor for patients received PD‐1 blockade combined with chemotherapy. Although female patients had significantly lower tumor mutational and neoantigen burden than males, pretreatment tumor tissues of female patients had markedly higher CD4, CD4/FOXP3, and CD4/FOXP3/PD‐L1 expression level than male patients. Conclusions Female patients with untreated advanced or metastatic NSCLC would derive a larger benefit from PD‐1 blockade in combination with chemotherapy than males. The biological significances of heterogeneity of tumor immune microenvironmental features between them need further investigation.

Landfills are major emitters of greenhouse gases, especially methane (CH4). To address this, the U.S. EPA promotes utilizing landfill gas (LFG) for renewable energy. Our study in Southeast Texas compared four LFG conversion strategies: flaring, electricity generation, renewable natural gas and methanol production. Scenario analysis was conducted to reveal the influence of market conditions and incentives on profitability. While electricity generation consistently yielded the highest returns, methanol production emerged as a close contender due to the strategic advantage of its proximity to the landfill site in this industrial zone. This study highlights the promising synergy between landfills and the hydrocarbon industry for sustainable development.

Abstract Density imaging is a method that uses the inversion of the gravity and gravity gradient spectra in the wavenumber domain to create accurate 3D reconstructions of subsurface density distributions. This approach offers computational efficiency and rapid calculations. This research used preliminary inversions to examine the spectral characteristics of gravity and gravity gradient anomalies, as well as the resulting models, were scrutinized through preliminary inversions. 3D density imaging of gravity and gravity gradient was performed in the wavenumber domain using depth weighting on both noise-added and theoretical data, producing a density model that was consistent with the theoretical one. The technique was then used in the Decorah region of the United States, where 3D density imaging was performed and an examination of the properties of gravity and gravity gradient anomalies was conducted. The results showed where high-density Decorah complexes, low-density siliceous intrusive rocks, and high-density intrusive rock masses, were the distributed within the surrounding rock. Each of these provided comprehensive insights into the intrusive pathways to the rock mass. Thus, the appropriateness and effectiveness of the density imaging method were confirmed, supporting a deeper understanding of the structural division and geological evolution in the region.

Chemical resistant textiles are vital for safeguarding humans against chemical hazards in various settings, such as industrial production, chemical accidents, laboratory activities, and road transportation. However, the ideal integration of chemical resistance, thermal and moisture management, and wearer condition monitoring in conventional chemically protective textiles remains challenging. Herein, the design, manufacturing, and use of stretchable hierarchical core–shell yarns (HCSYs) for integrated chemical resistance, moisture regulation, and smart sensing textiles are demonstrated. These yarns contain helically elastic spandex, wrapped silver-plated nylon, and surface-structured polytetrafluoroethylene (PTFE) yarns and are designed and manufactured based on a scalable fabrication process. In addition to their ideal chemical resistance performance, HCSYs can function as multifunctional stretchable electronics for real-time human motion monitoring and as the basic element of intelligent textiles. Furthermore, a desirable dynamic thermoregulation function is achieved by exploiting the fabric structure with stretching modulation. Our HCSYs may provide prospective opportunities for the future development of smart protective textiles with high durability, flexibility, and scalability.

Abstract The East China Sea, situated at the intersection of the Eurasian, Philippine Sea, and Pacific plates, is characterized by complex geology influenced by tectonic phenomena such as plate movements, volcanism, faults, and uplifts. Crustal density structure inversion provides a thorough understanding of the region's geological history as well as Earth's dynamical evolution, providing critical insights into seismic disaster mitigation, resource exploration, marine environmental protection, and maritime safety. The inversion process, on the other hand, presents challenges in data quality, quantity, model complexity, uncertainty, and computational resources. With the advancement of next-generation satellite gravity measurements and developing inversion techniques, the inversion of marine crustal density structures promises to be more precise and comprehensive. We explored the density distribution in the East China Sea and surrounding areas using an innovative wavenumber domain three-dimensional density imaging method along with high-precision global satellite gravity data. By overcoming data quality and computing resource constraints, wavenumber domain three-dimensional density imaging has transformed the discipline of marine geophysics, successfully delivering accurate density distributions in the study area. We were able to get a more precise and comprehensive characterization of the crustal density structure by combining high-precision satellite gravity data and cutting-edge imaging methods. Our investigation has unveiled previously unknown details about density distribution in the East China Sea and its environs. The East China Sea shelf displays smooth low-density perturbations at 18 km depth, whereas the trench–arc–basin region exhibits increasing density perturbations. Notably, the Okinawa Trough, which is surrounded by the Tokara Volcanic Ridge and the Ryukyu Trench, displays strong positive anomalies with a north–northeastern to northeastern orientation. In contrast, the Ryukyu Ridge and the Philippine Sea Basin exhibit smaller negative values and substantial northwestward positive density trends, respectively. These findings indicate diverse material distribution, which provides important insights into the area’s geological evolution and tectonic processes. This study adds new insights into density distribution in the East China Sea and adjacent regions, offering information on the geological complexity of the region. The research lays the groundwork for future research on crustal dynamics and enhances the field of marine geophysics and related disciplines. Graphical abstract

Phospholipase C zeta (PLCζ) is a key sperm-borne oocyte-activating factor that triggers Ca2+ oscillations and the subsequent block to polyspermy following gamete fusion. Mutations in PLCZ1, the gene encoding PLCζ, cause male infertility and intracytoplasmic sperm injection (ICSI) fertilization failure; and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate (FR). However, in conventional in vitro fertilization (cIVF), whether and how sperm PLCζ affects fertilization remain unclear. Herein, we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm–zona binding and a delay in pronuclei (PN) formation. Immunofluorescence staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca2+ oscillations. ICSI with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live birth. Furthermore, we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CITIC-Xiangya (Changsha, China) between February 2019 and January 2022. We found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total FR. The optimal cutoff value below which males were likely to experience low FR (total FR ≤30%) after cIVF was 56.7% for the proportion of spermatozoa expressing PLCζ. Our study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the wider male population and not only men with ICSI failure.

Objectives: N7-methylguanosine (m7G) plays a crucial role in mRNA metabolism and other biological processes. However, its regulators' function in Primary Sjögren's Syndrome (PSS) remains enigmatic. Methods: We screened five key m7G-related genes across multiple datasets, leveraging statistical and machine learning computations. Based on these genes, we developed a prediction model employing the extreme gradient boosting decision tree (XGBoost) method to assess PSS risk. Immune infiltration in PSS samples was analyzed using the ssGSEA method, revealing the immune landscape of PSS patients. Results: The XGBoost model exhibited high accuracy, AUC, sensitivity, and specificity in both training, test sets and extra-test set. The decision curve confirmed its clinical utility. Our findings suggest that m7G methylation might contribute to PSS pathogenesis through immune modulation. Conclusions: m7G regulators play an important role in the development of PSS. Our study of m7G-realted genes may inform future immunotherapy strategies for PSS.

Summary: The development of CRISPR-Cas9 technology introduces an efficient tool for precise engineering of fish genomes. With a short reproduction cycle, zebrafish infection mode can be referenced as antiviral breeding researches in aquaculture fish. Previously we identified a crucian carp-specific gene ftrca1 as an inhibitor of interferon response in vitro. Here, we demonstrate that genome editing of zebrafish ftr42, a homolog of ftrca1, generates a zebrafish mutant (ftr42lof/lof) with an improved resistance to SVCV infection. Zebrafish ftr42 acts as a virus-induced E3 ligase and downregulates IFN antiviral response by facilitating TBK1 protein degradation and also IRF7 mRNA decay. Genome editing results in loss of function of zebrafish ftr42, which enables zebrafish to have enhanced interferon response, thus improving zebrafish survival against virus infection. Our results suggest that fine-tuning fish IFN innate immunity through genome editing of negative regulators can genetically improve viral resistance in fish.

The purpose of this study is to investigate the impact of asset status and external factors related to asset status on income distribution disparities among senior executives, employees, and shareholders. Incorporating micro-level data and theoretical analysis, the data of Chinese a-share listed companies from 2012 to 2021 are selected for panel regression analysis. Existing research has often focused on the main differences in income between employees and executives. This study reveals that the distribution of total corporate income among employees, executives, and shareholders can better reflect the fluctuating trend of income variance among different groups. It was found that asset efficiency, asset market value, and asset property rights, among other asset status factors, significantly influence the degree of inequality in income distribution. Empirical research results indicated that corporate executives can benefit similarly to shareholders from improvements in asset efficiency and other asset status factors. Following an increase in corporate cash holdings, executives tend to benefit more relative to employees. Additionally, digital inclusive finance and equity concentration both have moderating effects, mitigating the impact of asset status on inequality in income distribution.