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Abstract In the era of the global knowledge economy, the rapid advancement of new-generation information technologies has positioned digital industry at the forefront of socio-economic development. Digital industrial clusters, comprising key enterprises and related institutions, have emerged as global hubs for technological innovation, drawing recognition from governments and international organizations. However, China’s digital industry faces challenges characterized by being “large but not strong” and experiencing “industrial structure softening.” This paper explores the temporal evolution and spatial distribution of China’s digital industry, shedding light on its unique patterns. This study reveals that China’s digital industry has progressed through four distinct phases, evolving from manufacturing-oriented to service-oriented, and experiencing dynamic stability. In terms of spatial distribution, it exhibits a pattern known as the “One Core, Three Poles, and Multiple Strongholds,” with Beijing as the core and Shanghai, Shenzhen, Hangzhou, among others, serving as growth poles. The study identifies factors influencing spatial distribution, including software development, patent authorizations, mobile phone penetration, industrial parks, digital finance, and foreign investment. Manufacturing-based digital industries prioritize innovation and IP protection, while service-based sectors rely on software development, innovation, and international collaboration. The GWR model demonstrates spatial variation, emphasizing the importance of tailored development strategies. This research contributes to understanding the dynamics of China’s digital industry and provides valuable insights for policymakers aiming to create an internationally competitive digital industry cluster.

Abstract In recent years, as river-borne sediment transport has decreased, land loss in estuarine areas has become increasingly severe. Particularly from 2009 to 2022, due to the reduced sediment load from the upper reaches of the Yangtze River, significant changes in the erosion-deposition conditions at the Yangtze River Estuary have become a critical concern. The suspended sediment concentration (SSC) in the estuary is closely linked to sediment content, and against this backdrop, this study aims to thoroughly explore the response mechanisms of the Yangtze River Estuary’s SSC to changes in erosion-deposition conditions, with the goal of providing scientific bases and strategic recommendations for erosion-deposition management. To this end, this research collected historical water depth data for the Yangtze River Estuary, measured vertical distribution of SSC in September 2022, surface suspended sediment concentration (SSSC) data from 2021 to 2023, and 25 factors influencing SSSC, to analyze in detail the changes in the erosion-deposition conditions at the Yangtze River Estuary and the response mechanisms of SSC to these changes. The analysis showed that between 2009 and 2022, the mouth bar area of the Yangtze River Estuary experienced net erosion for the first time since 1958, with an annual erosion rate reaching 63.2 × 10^6 m3/yr, and the highest erosion rate occurring in the North Passage area, reaching 83.3 mm/yr. This phenomenon is likely caused by human-induced changes in underwater topography, with the Yangtze River Estuary shifting from deposition to erosion. Between 2021 and 2023, the turbidity maximum zone (TMZ) of the Yangtze River Estuary did not show regular changes in SSSC, which may be related to the frequent occurrence of typhoons and changes in sediment supply in the submerged delta of the Yangtze River Estuary.

Abstract Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded as a significant role in transcriptional regulation in many tissues. However, the role of histone lactylation in the metabolic center, the hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion of family with sequence similarity 172, member A (Fam172a) can increase histone lactylation and protect mice against diet-induced obesity (DIO) and related metabolic disorders. Conversely, overexpression of Fam172a in POMC neurons led to an obesity-like phenotype. Using RNA-seq and CUT&Tag chromatin profiling analyzes, we find that knockdown of Fam172a activates the glycolytic process and increases peptidylglycine α-amidating monooxygenase (PAM), which affects the synthesis of α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition of lactate production clearly abrogates the anti-obesity effect of PFKO (POMC-Cre, Fam172a loxP/loxP , POMC neurons Fam172a knockout). These findings highlight the importance of Fam172a and lactate in the development of obesity and our results mainly concern male mice.

Abstract Machinery operation is a major source of carbon emissions in building deconstruction. Early intervention through Design for Deconstruction (DfD) is crucial for emission reduction, yet the factors influencing these emissions are underexplored. This study integrates parametric BIM with multi-objective optimization (MOO) to assess mechanical carbon emissions in deconstruction. Using the Octopus solver in Grasshopper for Rhino, the study analyzes independent variables—possible working hours (PWH), vertical speed (VS), and horizontal speed (HS)—and dependent variables—minimum mechanical carbon emissions (MCE (min)), minimum deconstruction period (DP (min)), and maximum working efficiency (WE (max)). A lightweight steel roof truss structure is analyzed, comparing real-world deconstruction with optimized DfD schemes. Sensitivity analysis for BIM-MOO optimized results reveal that: (1) Adjusting PWH, VS, and HS significantly affects WE and DP, though with limited impact on carbon emissions; (2) VS influences WE and DP more than HS; (3) Limiting DP is essential for balancing WE, DP, and MCE, with WE adjusted to 20–60% and modifications to PWH and VS achieving balanced management. This study underscores the importance of early design and real-time adjustments for efficient, low-emission deconstruction, supporting the advancement of green building practices.

Abstract While operational stability has evolved to be the primary issue for the practical applications of perovskite solar cells (PSCs), the understanding of the origins of device degradation is still limited. Hysteresis is known as a unique and significant feature of PSCs. The hysteresis behavior of the current density-voltage (J–V) curves, governed by the interaction between the evolving ion-induced electric field and the carrier transport/recombination, offers rich and important information about the physical properties of the device. Herein, we propose to establish hysteresis as a diagnostic key to unveil and remedy degradation issues with device physics. With a custom-made ion-incorporated drift-diffusion simulator, we comprehensively investigate the relations between characteristic J–V hysteresis features and critical device issues such as bulk and surface defects, and low mobility of each layer in the PSCs. Ultimately, we derive a fundamental understanding and unveil the origins of the device degradation during the continuous operation of PSCs. This work therefore offers a new way to address and optimize PSC operational stability.

The use of nanocarbon materials to enhance the toughness of fragile cementitious materials has attracted increasing attention for investigation. This study examines the effects of incorporating graphene oxide (GO) into NaOH-activated slag (AAS) pastes and mortars, focusing on workability, phase composition, mechanical properties, and the local mechanical properties of the interfacial transition zone (ITZ) between sand and paste. The experimental results indicate that the addition of GO decreases the flowability of NaOH-AAS pastes, with noticeable aggregation at concentrations above 0.03 wt%. Furthermore, GO enhances the hydration degree of ground granulated blast furnace slag (GGBS), leading to an increased amount of C-A-S-H gel without introducing new phases. In terms of macro performance, incorporating 0.03 wt% GO significantly improves the compressive and flexural strengths of NaOH-AAS mortars by 10.6 % and 17.9 %, respectively. Additionally, the presence of GO reduces the ITZ thickness from 30 to 15 micrometres in NaOH-AAS mortars, which likely contributes to the enhanced mechanical performance.

Abstract Background Spinal cord injury (SCI) is a common neurological condition marked by damage to the spinal cord. In the field of neurological rehabilitation, virtual reality (VR) is increasingly employed for evaluating and addressing the physical limitations caused by SCI. This study aimed to describe and calculate the effect sizes of virtual reality intervention (VR) on the functional performance of SCI. Methods We searched PubMed, Embase, Web of Science, and Cochrane Library to identify articles published before October 30, 2023, that addressed the intervention of SCI using virtual reality technology. We excluded from the meta-analysis articles that did not provide enough data to evaluate the association between virtual reality intervention and spinal cord injury. The RevMan 5.4 statistical software was used for data analysis. Results We included 16 articles in the systematic review and pooled 9 for the meta-analysis, which were 5 randomized controlled trials (RCTs) and 4 non-RCTs, including 248 subjects. The outcome measure of the walking index for spinal cord injury, limits of stability testing and berg balance scale scores improved in non-RCTs. Conclusion VR has shown promise in enhancing walking ability and balance function in individuals with SCI. However, the existing evidence for VR interventions in SCI patients remains limited, highlighting the necessity for future studies in this area.

Abstract In plants, recognition between resistance gene (R) and virus induces a local hypersensitive response (HR), which is accompanied by systemic acquired resistance (SAR). The dominant resistance gene N in tobacco confers resistance to tobacco mosaic virus (TMV) at both locally inoculated tissues and systemically infected tissues. However, the mechanisms underlying HR- and SAR-mediated viral inhibition are not fully revealed. In this study, we find that Nicotiana glutinosa RNA-binding protein (NgRBP) is an RNA silencing suppressor which enhances TMV-triggered HR. Stronger HR could result in stronger local and systemic RNA silencing as well as SAR. Enhanced RNA silencing in the systemically infected leaves induced by the NgRBP gene is compromised by transient expression of NahG. These results indicate that RNA silencing is activated by HR and plays a crucial role in local and systemic virus resistance. Our results reveal a crosstalk between N gene-mediated virus resistance and RNA silencing which would deepen our understanding of the established HR and SAR models.

Abstract In order to solve the influence of the complex interaction relationships among subjects on the system solution accuracy and speed of the Multi-Microgrid system under the high penetration rate of new energy. Firstly, the paper establishes the bi-level optimal scheduling Stackelberg game model based on shared energy storage, considering the inter-subject interaction in MMG. Subsequently, based on the four improvement methods of Chaotic Map, Quantum Behavior, Gaussian Distribution, and Nonlinear Control Strategy, the Chaotic Gaussian Quantum Crayfish Optimization Algorithm is proposed to solve the optimization scheduling model. The improved algorithm exhibits superior initial solutions and enhanced search capability. In comparison to the original algorithm, the relative errors of the CGQCOA optimization outcomes are 98%, 20.96%, 98.74% and 16.55%, respectively, enhancing the model-solving accuracy and the speed of convergence to the optimal solution. Finally, the simulation demonstrates that the revenue of Microgrid 1, Microgrid 2, and Microgrid 3 have increased by 0.73%, 1.17%, and 1.04%, respectively. Concurrently, the penalty cost of pollutant emission has decreased by 5.9%, 11.5%, and 12.68%, respectively. Furthermore, the revenue of the shared storage have increased by 1.91%. These findings validate the efficacy of the methodology proposed in enhancing the revenue of the various subjects and reducing pollutant gas emission.

Abstract Background Inflammatory bowel disease (IBD) is a chronic, relapsing condition wherein biologics have improved disease prognosis but introduced elevated infection susceptibility. Vedolizumab (VDZ) demonstrates unique safety advantages; however, a comprehensive systematic comparison regarding the risk of Clostridioides difficile infection (CDI) between vedolizumab and alternative medications remains absent. Method Medline, Embase, Cochrane, and clinicaltrials.gov registry were comprehensively searched. Pooled estimates of CDI proportion, incidence, pooled risk ratio between ulcerative colitis (UC) and Crohn’s disease (CD), vedolizumab and other medications were calculated. Data synthesis was completed in R using the package “meta”. Results Of the 338 studies initially identified, 30 met the inclusion/exclusion criteria. For CDI risk, the pooled proportion was 0.013 (95% CI 0.010–0.017), as well as the pooled proportion of serious CDI was 0.004 (95% CI 0.002–0.008). The comparative pooled risk ratios revealed: UC versus CD at 2.25 (95% CI 1.73–2.92), vedolizumab versus anti-TNF agents at 0.15 (95% CI 0.04–0.63) for UC and 1.29 (95% CI 0.41–4.04) for CD. Conclusion The overall CDI risk in IBD patients exposed to vedolizumab was estimated to be 0.013. An increased risk of CDI was noted in UC patients receiving vedolizumab compared to those with CD. Vedolizumab potentially offers an advantage over anti-TNF agents for UC regarding CDI risk, but not for CD. Trial registration The study was registered on the PROSPERO registry (CRD42023465986).

Abstract The study was to evaluate the clinical outcomes of azvudine versus nirmatrelvir-ritonavir against omicron strains of coronavirus disease 2019 infections and determine their comparative effectiveness. This retrospective study included 716 patients who received nirmatrelvir-ritonavir (NR group) or azvudine (FNC group) at Peking Union Medical College Hospital between 1 November 2022 and 27 February 2023. Patients in the FNC group (n = 304) were younger, exhibited less severe symptoms, started antiviral therapy later, received corticosteroids more frequently, and used tocilizumab less frequently than patients in the NR group (n = 412). Within 28 d of therapy, 40 (9.7%) and 20 (6.6%) deaths were in the NR and FNC groups, respectively. No differences were observed between drugs and mortality rates (odds ratio [OR] 0.78, 95% CI 0.40–1.5, P = 0.45), clinical improvement (OR 0.79, 95% CI 0.79–1.3, P = 0.38), and clinical progression (OR 1.0, 95% CI 0.58–1.8, P = 0.96). More patients in the NR group experienced platelet decline than those in the FNC group (17.6% vs. 8.9%, P = 0.034). This study indicated that the effectiveness and safety of azvudine were comparable to those of nirmatrelvir-ritonavir.

Objective Increasing breast meat production is one of the primary goals of the broiler industry. Over the past few decades, tremendous progress has been made in genetic selection and the identification of candidate genes for improving the breast muscle mass. However, the molecular network contributing to muscle production traits in chickens still needs to be further illuminated. Methods A total of 150 1-day-old male 817 broilers were reared in a floor litter system. At the market age of 50 d, eighteen healthy 817 broilers were slaughtered and the left pectoralis major muscle sample from each bird was collected for RNA-seq sequencing. The birds were then plucked and eviscerated and the whole breast muscle was removed and weighed. Breast muscle yield was calculated as the ratio of the breast muscle weight to the eviscerated weight. To identify the co-expression networks and hub genes contributing to breast muscle yield in chickens, we performed weighted gene co-expression network analysis (WGCNA) based on the 18 transcriptome datasets of pectoralis major muscle from eighteen 817 broilers. Results The WGCNA analysis classified all co-expressed genes in the pectoral muscle of 817 broilers into 44 modules. Among these modules, the turquoise and skyblue3 modules were found to be most significantly positively (r = 0.78, p = 1e–04) and negatively (r = −0.57, p = 0.01) associated with breast meat yield, respectively. Further analysis identified several hub genes (e.g., DLX3, SH3RF2, TPM1, CAV3, MYF6, and CFL2) that involved in muscle structure and muscle development were identified as potential regulators of breast meat production. Conclusion The present study has advanced our understanding of the molecular regulatory networks contributing to muscle growth and breast muscle production and will contribute to the molecular breeding of chickens in the future.

SARS-CoV-2 infection may affect semen quality. However, there is limited evidence on whether this effect is reversible. Retrospective analysis was done on the same male patient’s semen quality prior to SARS-CoV-2 infection, less than 74 days following recovery from SARS-CoV-2 infection, and more than 74 days following recovery in order to confirm. Consequently, the sperm concentration (44.10 (28.00, 75.20) vs. 66.00 (47.05, 135.30) × 106/mL, p < 0.001), sperm motility ((43.22 ± 21.34)% vs. (51.65 ± 15.41)%, p = 0.0105), percentage of progressively motile sperm (PR) ((39.76 ± 20.58)% vs. (46.88 ± 15.26)%, p = 0.0243) and percentage of normal morphological sperm ((2.70 ± 1.82)% vs. (3.58 ± 2.00)%, p = 0.0299) of 45 male patients 30 to 71 days after recovery from SARS-CoV-2 infection were significantly lower than those before SARS-CoV-2 infection, while there was no significant difference in semen volume (3.20 (2.10, 4.65) mL vs. 3.20 (2.45, 4.55) mL, p = 0.4819) between them. The sperm concentration, motility and PR of 8 patients 77 to 125 days after recovery from SARS-CoV-2 infection (68.75 (31.50, 114.1) × 106/mL, (44.23 ± 25.73)% and (39.76 ± 25.23)%) were higher than those 30 to 71 days after recovery from SARS-CoV-2 infection (20.05 (13.58, 30.10) × 106/mL, (30.11 ± 22.05)% and (26.56 ± 21.55)%), and there were no significant differences from those before SARS-CoV-2 infection (50.05 (41.03, 90.35) × 106/mL, p = 0.8438; (50.24 ± 13.62)%, p = 0.5126; and (45.76 ± 12.97)%, p = 0.5251). In conclusion, SARS-CoV-2 infection may affect one spermatogenesis cycle of a male patient for about 74 days, and the patient may return to the normal state in the next spermatogenesis cycle.

Abstract Obesity has become a global health problem. In recent years, the influence of dietary microbes in the obese population has attracted the attention of scholars. Our study aimed to investigate the link between live microbe intake and obesity in adults. Participants (aged over 20 years) for this study were from the 1999–2018 National Health and Nutrition Examination Survey (NHANES). Participants were categorised into low, medium and high dietary live microbe intake groups. Linear regression was used to analyse the link between live microbe intake and body mass index (BMI) and waist circumference (WC). Logistic regression was used to analyse the link between live microbe intake and obesity and abdominal obesity prevalence. Restricted cubic spline curves (RCS) were used to check whether there was a non-linear relationship between live microbe intake and obesity. A total of 42,749 participants were included in this study and the number of obese reached 15,463. We found that live microbe intake was negatively linked to BMI and WC. In models adjusted for all confounders, the high live microbe intake group had lower obesity (OR = 0.812, 95%CI: 0.754–0.873) and abdominal obesity prevalence (OR = 0.851, 95%CI: 0.785–0.923) than the lowest intake group. Upon further quantification of live microbe intake, we found similar results. RCS analyses showed that live microbe intake was nonlinearly negatively correlated with BMI, WC, obesity, and abdominal obesity prevalence (P for non-linearity

Abstract Dried yellow chili is highly appreciated by consumers due to its excellent quality and flavor. The quality of products is determined by the drying and storage methods. In this study, dried yellow chilis were processed by natural air drying and hot air drying methods and then stored under three conditions: ambient temperature, ambient temperature with light avoidance, and at 10 °C with light avoidance for 12 months. The changes in the bioactive compounds during this period were analyzed attempting to reveal correlations between the different treatments and these compounds, with the aim of providing references for maintaining the bioactive compounds of pepper products. The results showed that samples treated with hot air had higher levels of fatty acids, resulting in a more pronounced flavor. During storage, samples stored at 10 °C with light avoidance were more effective in preserving soluble solids, total protein content, total phenols, capsaicinoids and most fatty acids.

Abstract Both plastics and CO2 are waste carbon resources, and their accumulation in nature has led to severe environmental pollution. However, simultaneously converting plastic waste and CO2 into value-added chemicals remains a challenge. Here we demonstrate a catalytic reforming process that converts plastics and CO2 into syngas over an electrified FeCrAl heating wire. The temperature of the electrified heating wire can quickly exceed 800 °C, facilitating the decomposition of polyethylene into gaseous hydrocarbons. The high-temperature heating wire promote the CO2 deoxygenation, resulting in the generation of CO, as well as the dehydrogenation of gaseous hydrocarbons. Significantly, the additional O species from CO2 and the carbon species from hydrocarbons can react to form CO, maintaining the high catalytic activity of the electrified heating wire. This novel approach is of paramount to achieving a circular economy in addressing the ongoing environmental crisis caused by the accumulation of plastic waste and excessive CO2 emissions.

Abstract Background BCR-ABL is a constitutively active tyrosine kinase that stimulates multiple downstream signaling pathways to promote the survival and proliferation of chronic myeloid leukemia (CML) cells. The clinical application of specific BCR-ABL tyrosine kinase inhibitors (TKIs) has led to significantly improved prognosis and overall survival in CML patients compared to previous treatment regimens. However, direct targeting of BCR-ABL does not eradicate CML cells expressing T315I-mutated BCR-ABL. Our previous study revealed that inhibiting CREB binding protein (CBP) is efficacious in activating β-catenin/p300 signaling, promoting cell differentiation and inducing p53/p21-dependent senescence regardless of BCR-ABL mutation status. We hypothesize that the specific inhibition of CBP may represent a novel strategy to promote β-catenin/p300-mediated differentiation and suppress cancer cell proliferation for treating CML patients. Methods The anticancer efficacy of PBA2, a novel CBP inhibitor, in CML cells expressing wild-type or T315I-mutated BCR-ABL was investigated in vitro and in vivo. Cell differentiation was determined by the nitroblue tetrazolium (NBT) reduction assay. The extent of cellular senescence was assessed by senescence-associated β-galactosidase (SA-β-Gal) activity. Cytotoxicity was measured by MTS assay. RNA interference was performed to evaluate the cell proliferation effects of CBP knockdown. The interaction of β-catenin and CBP/p300 was examined by co-immunoprecipitation assay. Results PBA2 exhibited significantly higher anticancer effects than imatinib in CML cells harboring either wild-type or T315I-mutated BCR-ABL both in vitro and in vivo. Mechanistically, PBA2 reduced CBP expression and promoted β-catenin-p300 interaction to induce cell differentiation and senescence. Conclusion Our data supported the rational treatment of CML by inhibiting the β-catenin/CBP pathway regardless of BCR-ABL mutation status.

Abstract Cardiopulmonary bypass (CPB) is often used in cardiothoracic surgery because its nonphysiological state causes pathophysiological changes in the body, causing multiorgan and multitissue damage to varying degrees. Postoperative cognitive dysfunction (POCD) is a common central nervous system complication after cardiac surgery. The etiology and mechanism of POCD are not clear. Neuroinflammation, brain mitochondrial dysfunction, cerebral embolism, ischemia, hypoxia, and other factors are related to the pathogenesis of POCD. There is a close relationship between CPB and POCD, as CPB can cause inflammation, hypoxia and reperfusion injury, and microemboli formation, all of which can trigger POCD. POCD increases medical costs, seriously affects patients' quality of life, and increases mortality. Currently, there is a lack of effective treatment methods for POCD. Commonly used methods include preoperative health management, reducing inflammation response during surgery, preventing microemboli formation, and implementing individualized rehabilitation programs after surgery. Strengthening preventive measures can minimize the occurrence of POCD and its adverse effects.

Abstract lncRNA can regulate tumorigenesis development and distant metastasis of colorectal cancer (CRC). However, the detailed molecular mechanisms are still largely unknown. Using RNA-sequencing data, RT-qPCR, and FISH assay, we found that HIF1A-AS2 was upregulated in CRC tissues and associated with poor prognosis. Functional experiments were performed to determine the roles of HIF1A-AS2 in tumor progression and we found that HIF1A-AS2 can promote the proliferation, metastasis, and aerobic glycolysis of CRC cells. Mechanistically, HIF1A-AS2 can promote FOXC1 expression by sponging miR-141-3p. SP1 can transcriptionally activate HIF1A-AS2. Further, HIF1A-AS2 can be packaged into exosomes and promote the malignant phenotype of recipient tumor cells. Taken together, we discovered that SP1-induced HIF1A-AS2 can promote the metabolic reprogramming and progression of CRC via miR-141-3p/FOXC1 axis. HIF1A-AS2 is a promising diagnostic marker and treatment target in CRC.

Abstract Introduction The efficacy of pre-exposure prophylaxis (PrEP) is highly dependent on adherence, and adherence behavior is influenced by motivation. The aim of this study was to explore the longitudinal relationship between PrEP motivation and change in adherence among men who have sex with men (MSM) in Western China. Methods From November 2019 to June 2021, we conducted a PrEP prospective cohort study. Motivation to take medicine was measured by the PrEP Motivation Scale at baseline, and was grouped into different levels of latent categories by Latent Profile Analysis (LPA). A multinomial logistic regression model was used to explore the longitudinal relationship between change in adherence (improvement, decline, no change) and different levels of PrEP motivation. Results MSM were divided into two categories of PrEP motivation, a “high motivation group” (n = 506, 69.89%) and a “low motivation group” (n = 218, 30.11%). High PrEP motivation had no significant effect on the change in short-term adherence, however, it contributed to the improvement in long-term adherence [odds ratio (OR) = 3.028 (1.100–8.332), p = 0.031]. The predictive power of the adherence model was significantly enhanced with the addition of the PrEP motivation factor. Conclusions There was a positive correlation between high PrEP motivation at baseline and an improvement in long-term adherence. Surveillance and intervention of PrEP motivation in MSM can increase their adherence, and then promote PrEP efficacy.

A crystal plasticity model based on Electron Backscatter Diffraction (EBSD) experimental data has been developed to simulate the tensile behavior of additively manufactured TiAl alloys at various temperatures. To accurately capture the activity of different slip systems and their contribution to the material's plasticity, multiple slip systems across different phases are considered. The validity of the model is verified by comparing the simulation results, such as microscopic properties, with experimental and test data. Additionally, a continuous damage model is incorporated to analyze the damage behavior of additively manufactured TiAl alloys at different temperatures. Compared to experimental data, the crystal plasticity model incorporating damage effectively simulates the tensile failure behavior of TiAl alloys across a range of temperatures.

Prostate cancer (PCa) is a multifocal disease characterized by genomic and phenotypic heterogeneity within a single gland. In this study, Visium spatial transcriptomics (ST) analysis was applied to PCa tissues with different histological structures to infer the molecular events involved in Gleason score (GS) progression. The spots in tissue sections were classified into various groups using Principal Component Analysis (PCA) and Louvain clustering analysis based on transcriptome data. Anotation of the spots according to GS revealed notable similarities between transcriptomic profiles and histologically identifiable structures. The accuracy of macroscopic GS determination was bioinformatically verified through malignancy-related feature analysis, specifically inferred copy number variation (inferCNV), as well as developmental trajectory analyses, such as diffusion pseudotime (DPT) and partition-based graph abstraction (PAGA). Genes related to GS progression were identified from the differentially expressed genes (DEGs) through pairwise comparisons of groups along a GS gradient. The proteins encoded by the representative oncogenes UQCRB and LBH were found to be highly expressed in advanced-stage PCa tissues. Knockdown of their mRNAs significantly suppressed PCa cell proliferation and invasion. These findings were validated using The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset, as well as through histological and cytological experiments. The results presented here establish a foundation for ST-based evaluation of GS progression and provide valuable insights into the GS progression-related genes UQCRB and LBH.

Abstract Day-Night imaging technology that obtains full-color and infrared images has great market demands for security monitoring and autonomous driving. The current mainstream solution relies on wide-spectrum silicon photodetectors combined with Infrared Cutfilter Removal, which increases complexity and failure rate. Here, we address these challenges by employing a perovskite photodetector based on Pb−Sn alloyed single crystal with a vertical bandgap-graded structure that presents variable-spectrum responses at different biases and extends the infrared detection range close to 1100 nm. Taking advantage of the Pb−Sn gradients in mobility and built-in field, the perovskite photodetector shows a large linear dynamic range of 177 dB. In addition, the optoelectronic characteristics feature long-term operational stability over a year. We further develop an imaging module prototype without Infrared Cutfilter Removal that exhibits excellent color fidelity with RGB color differences ranging from 0.48 to 2.46 under infrared interference and provides over 26-bit grayscale resolution in infrared imaging.

Abstract During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR. Coupled with transcriptomic analysis, we reveal a robust correlation between enhancer activation and the upregulation of the PVR-associated gene programs. Furthermore, by constructing transcription factor regulatory networks, we identify the aberrant activation of enhancer-driven RANK-NFATc1 pathway as PVR advanced. Importantly, we demonstrate that intraocular interventions, including nanomedicines inhibiting enhancer activity, gene therapies targeting NFATc1 and antibody therapeutics against RANK pathway, effectively mitigate PVR progression. Together, our findings elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offer promising therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.

Abstract Post-discharge coping difficulty presents a significant challenge for mothers of preterm infants. The readiness for hospital discharge and parenting self-efficacy are crucial factors influencing post-discharge coping difficulty. However, the pathways through which these factors impact post-discharge coping difficulty remain unclear. This study aims to investigate the impact of readiness for hospital discharge on post-discharge coping difficulty and the mediating role of parenting self-efficacy among mothers of preterm infants. A prospective study involving 462 mothers of preterm infants from six tertiary hospitals in Shandong Province was conducted. Mothers were evaluated on the day of discharge (using the Baseline characteristics and Readiness for Hospital Discharge Scale) and three weeks post-discharge (utilizing the Parenting Sense of Competence Scale-Efficacy subscale and Post-Discharge Coping Difficulty Scale). Structural equation modeling was employed to analyze the mediating effect. The results of this study revealed that readiness for hospital discharge significantly decreased post-discharge coping difficulty (β = − 0.533, P

Abstract The presence of defects at the interface between the perovskite film and the carrier transport layer poses significant challenges to the performance and stability of perovskite solar cells (PSCs). Addressing this issue, we introduce a dual host-guest (DHG) complexation strategy to modulate both the bulk and interfacial properties of FAPbI3-rich PSCs. Through NMR spectroscopy, a synergistic effect of the dual treatment is observed. Additionally, electro-optical characterizations demonstrate that the DHG strategy not only passivates defects but also enhances carrier extraction and transport. Remarkably, employing the DHG strategy yields PSCs with power conversion efficiencies (PCE) of 25.89% (certified at 25.53%). Furthermore, these DHG-modified PSCs exhibit enhanced operational stability, retaining over 96.6% of their initial PCE of 25.55% after 1050 hours of continuous operation under one-sun illumination, which was the highest initial value in the recently reported articles. This work establishes a promising pathway for stabilizing high-efficiency perovskite photovoltaics through supramolecular engineering, marking a significant advancement in the field.

Abstract Tandem repeats (TRs) are genomic regions that tandemly change in repeat number, which are often multiallelic. Their characteristics and contributions to gene expression and quantitative traits in rice are largely unknown. Here, we survey rice TR variations based on 231 genome assemblies and the rice pan-genome graph. We identify 227,391 multiallelic TR loci, including 54,416 TR variations that are absent from the Nipponbare reference genome. Only 1/3 TR variations show strong linkage with nearby bi-allelic variants (SNPs, Indels and PAVs). Using 193 panicle and 202 leaf transcriptomic data, we reveal 485 and 511 TRs act as QTLs independently of other bi-allelic variations to nearby gene expression, respectively. Using plant height and grain width as examples, we identify and validate TRs contributions to rice agronomic trait variations. These findings would enhance our understanding of the functions of multiallelic variants and facilitate rice molecular breeding.

Abstract Hepatocellular carcinoma (HCC) is a malignant tumor. It is estimated that approximately 50–80% of HCC cases worldwide are caused by hepatitis b virus (HBV) infection, and other pathogenic factors have been shown to promote the development of HCC when coexisting with HBV. Understanding the molecular mechanisms of HBV-induced hepatocellular carcinoma (HBV-HCC) is crucial for the prevention, diagnosis, and treatment of the disease. In this study, we analyzed the molecular mechanisms of HBV-induced HCC by combining bioinformatics and deep learning methods. Firstly, we collected a gene set related to HBV-HCC from the GEO database, performed differential analysis and WGCNA analysis to identify genes with abnormal expression in tumors and high relevance to tumors. We used three deep learning methods, Lasso, random forest, and SVM, to identify key genes RACGAP1, ECT2, and NDC80. By establishing a diagnostic model, we determined the accuracy of key genes in diagnosing HBV-HCC. In the training set, RACGAP1(AUC:0.976), ECT2(AUC:0.969), and NDC80 (AUC: 0.976) showed high accuracy. They also exhibited good accuracy in the validation set: RACGAP1(AUC:0.878), ECT2(AUC:0.731), and NDC80(AUC:0.915). The key genes were found to be highly expressed in liver cancer tissues compared to normal liver tissues, and survival analysis indicated that high expression of key genes was associated with poor prognosis in liver cancer patients. This suggests a close relationship between key genes RACGAP1, ECT2, and NDC80 and the occurrence and progression of HBV-HCC. Molecular docking results showed that the key genes could spontaneously bind to the anti-hepatocellular carcinoma drugs Lenvatinib, Regorafenib, and Sorafenib with strong binding activity. Therefore, ECT2, NDC80, and RACGAP1 may serve as potential biomarkers for the diagnosis of HBV-HCC and as targets for the development of targeted therapeutic drugs.

Abstract Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic Gi protein-coupled A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as an important pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.

Abstract Respiratory syncytial virus (RSV) hijacks cholesterol or autophagy pathways to facilitate optimal replication. However, our understanding of the associated molecular mechanisms remains limited. Here, we show that RSV infection blocks cholesterol transport from lysosomes to the endoplasmic reticulum by downregulating the activity of lysosomal acid lipase, activates the SREBP2–LDLR axis, and promotes uptake and accumulation of exogenous cholesterol in lysosomes. High cholesterol levels impair the VAP-A-binding activity of ORP1L and promote the recruitment of dynein–dynactin, PLEKHM1, or HOPS VPS39 to Rab7–RILP, thereby facilitating minus-end transport of autophagosomes and autolysosome formation. Acidification inhibition and dysfunction of cholesterol-rich lysosomes impair autophagy flux by inhibiting autolysosome degradation, which promotes the accumulation of RSV fusion protein. RSV-F storage is nearly abolished after cholesterol depletion or knockdown of LDLR. Most importantly, the knockout of LDLR effectively inhibits RSV infection in vivo. These findings elucidate the molecular mechanism of how RSV co-regulates lysosomal cholesterol reprogramming and autophagy and reveal LDLR as a novel target for anti-RSV drug development.

Mycena (Pers.) Roussel (1806) is a large genus of Mycenaceae known for having small to medium-sized basidiomata. It is typified by the species Mycena galericulata (Scop.) Gray. For years, many mycologists have made important contributions to understanding Mycena and several monographs have been published. Three specimens were collected from China that belonged to the genus Mycena. On the basis of morphological analysis and phylogenetic analyses employing DNA sequences, a new species is described.Mycena brunnescens sp. nov. is described as a new species from subtropical areas of China. It is characterised by its brown pileus, whitish lamellae that turns brown when bruised, orange to brown lamellae edges, the absence of pleurocystidia and cheilocystidia with simple or branched excrescences at the apex containing yellowish-brown contents. We performed phylogenetic analyses on a concatenated dataset comprising the internal transcribed spacer and large subunit regions of nuclear ribosomal RNA using Bayesian Inference and Maximum Likelihood methods. The result showed that the new taxon clustered in an independent group and is closely related to M. albiceps and M. flosoides.

Abstract Along with the constantly evolving functional microsystems toward more diversification, the more rigorous design deliberation of pursuing higher mass‐loading of electrode materials and low‐temperature fabrication compatibility have imposed unprecedented demand on integrable all‐solid‐state thin‐film microbatteries. While the classic thin‐film intercalation cathode prepared by vacuum‐based techniques inevitably encountered a post‐annealing process, tape‐casting technologies hold great merits both in terms of high‐mass loading and low‐temperature processing. In this work, a novel microbattery configuration is developed by the combination of traditional tape‐casting thick electrodes and sputtered inorganic thin‐film solid electrolytes (~3 μm lithium phosphorus oxynitride). Enabled by physically pressed or vapor‐deposited Li as an anode, solid‐state batteries with tape‐casted LiFePO4 electrodes exhibit outstanding cyclability and stability. To meet integration requirements, LiFePO4/LiPON/Si microbatteries were successfully fabricated at low temperatures and found to achieve a wide operating temperature range. This novel configuration has good prospects in promoting the thin‐film microbattery enabling a paradigm shift and satisfying diversified requirements.

Abstract Stability has been a long-standing concern for solution-processed perovskite photovoltaics and their practical applications. However, stable perovskite materials for photovoltaic remain insufficient to date. Here we demonstrate a series of ultrastable Dion−Jacobson (DJ) perovskites (1,4-cyclohexanedimethanammonium)(methylammonium) n−1Pb n I3n+1 (n ≥ 1) for photovoltaic applications. The scalable technology by blade-coated solar cells for the designed DJ perovskites (nominal n = 5) achieves a maximum stabilized power conversion efficiency (PCE) of 19.11% under an environmental atmosphere. Un-encapsulated cells by blade-coated technology retain 92% of their initial efficiencies for over 4000 hours under ~90% relative humidity (RH) aging conditions. More importantly, these cells also exhibit remarkable thermal (85 °C) and operational stability, which shows negligible efficiency loss after exceeding 5000-hour heat treatment or after operation at maximum power point (MPP) exceeding 6000 hours at 45 °C under a 100 mW cm−2 continuous light illumination.

Abstract Purpose 123I-Ioflupane SPECT is an effective tool for the diagnosis and progression assessment of Parkinson’s disease (PD). Radiomics and deep learning (DL) can be used to track and analyze the underlying image texture and features to predict the Hoehn-Yahr stages (HYS) of PD. In this study, we aim to predict HYS at year 0 and year 4 after the first diagnosis with combined imaging, radiomics and DL-based features using 123I-Ioflupane SPECT images at year 0. Methods In this study, 161 subjects from the Parkinson’s Progressive Marker Initiative database underwent baseline 3T MRI and 123I-Ioflupane SPECT, with HYS assessment at years 0 and 4 after first diagnosis. Conventional imaging features (IF) and radiomic features (RaF) for striatum uptakes were extracted from SPECT images using MRI- and SPECT-based (SPECT-V and SPECT-T) segmentations respectively. A 2D DenseNet was used to predict HYS of PD, and simultaneously generate deep features (DF). The random forest algorithm was applied to develop models based on DF, RaF, IF and combined features to predict HYS (stage 0, 1 and 2) at year 0 and (stage 0, 1 and ≥ 2) at year 4, respectively. Model predictive accuracy and receiver operating characteristic (ROC) analysis were assessed for various prediction models. Results For the diagnostic accuracy at year 0, DL (0.696) outperformed most models, except DF + IF in SPECT-V (0.704), significantly superior based on paired t-test. For year 4, accuracy of DF + RaF model in MRI-based method is the highest (0.835), significantly better than DF + IF, IF + RaF, RaF and IF models. And DL (0.820) surpassed models in both SPECT-based methods. The area under the ROC curve (AUC) highlighted DF + RaF model (0.854) in MRI-based method at year 0 and DF + RaF model (0.869) in SPECT-T method at year 4, outperforming DL models, respectively. And then, there was no significant differences between SPECT-based and MRI-based segmentation methods except for the imaging feature models. Conclusion The combination of radiomic and deep features enhances the prediction accuracy of PD HYS compared to only radiomics or DL. This suggests the potential for further advancements in predictive model performance for PD HYS at year 0 and year 4 after first diagnosis using 123I-Ioflupane SPECT images at year 0, thereby facilitating early diagnosis and treatment for PD patients. No significant difference was observed in radiomics results obtained between MRI- and SPECT-based striatum segmentations for radiomic and deep features.

Rock discontinuity information plays a key role in engineering activities. In severely fragmented and discontinuous samples, the identification accuracy of rock discontinuities can be improved with the help of geologic knowledge with identified spatial features and geoscience interaction mechanisms. Therefore, we proposed a new method – a knowledge-based intelligent recognition method for rock discontinuities that used point cloud data – to correct inaccurate identification by considering the spatial relationships of rock discontinuities. This paper integrated the geologic knowledge bases in rock discontinuity information extraction rules and combined the generative rule inference model with the region growing method for intelligent extraction. In the case study, we developed four typical rule sets as examples based on the constructed rule system to group rock discontinuities and subsume the fractured rock discontinuities. Results show that this new method is effective in identifying and classifying rock discontinuities of complex areas with a greater reduction in manual intervention.

Explosives, a type of energetic material (EM), face a high-pressure environment in the detonation process or under shock conditions. Determining their high-pressure behavior is critical to their explosion and safety. 1-Methyl-3,4,5-trinitropyrazole (MTNP), a carrier of melt-cast explosives, exhibits the potential for replacing trinitrotoluene (TNT). However, there is limited knowledge about its structural evolvement at high pressure. Using a diamond anvil cell (DAC), this study investigated the structural variation of MTNP through in situ high-pressure synchrotron angle-dispersive X-ray diffraction (ADXRD) experiments and Raman measurements. As evidenced by the results, MTNP underwent phase transition at 8.7 GPa and amorphization at 15.3 GPa due to high pressure. Through the analysis of first-principles calculations and Raman spectra, this study proposed the mechanisms behind the changes in MTNP at high pressure. Furthermore, this study systematically explored the structural evolvement of MTNP and the evolution of its weak intermolecular interactions at high pressure, gaining further understanding of MTNP's detonation and safety.

Abstract Background Jiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease. Methods BV‐2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid‐β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor‐alpha (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐10 (IL‐10) were detected using enzyme‐linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐B (NF‐κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration. Results The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL‐1β, TNF‐α, and iNOS; increased the expression level of IL‐10; and significantly decreased the phosphorylation levels of MAPK and NF‐κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL‐1β and TNF‐α in the cortex were significantly downregulated after JHP administration, whereas IL‐10 showed increased expression. Conclusions It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF‐κB signaling pathway.

Abstract Feeding behavior, the most fundamental physiological activity, is controlled by two opposing groups of factors, orexigenic and anorexigenic factors. The sulfakinin family, an insect analogue of the mammalian satiety factor cholecystokinin (CCK), has been shown to suppress food intake in various insects. Nevertheless, the mechanisms through which sulfakinin regulates feeding behavior remain a biological question. This study aimed to elucidate the signaling pathway mediated by the anorexigenic peptide sulfakinin in Bombyx mori. We identified the Bombyx mori neuropeptide G protein-coupled receptor A9 (BNGR-A9) as the receptor for sulfakinin through functional assays. Stimulation with sulfakinin triggered a swift increase in intracellular IP3, Ca2+, and a notable enhancement of ERK1/2 phosphorylation, in a manner sensitive to a Gαq-specific inhibitor. Treatment with synthetic sulfakinin resulted in decreased food consumption and average body weight. Additionally, administering synthetic sulfakinin to silkworms significantly elevated hemolymph trehalose levels, an effect markedly reduced by pre-treatment with BNGR-A9 dsRNA. Consequently, our findings establish the sulfakinin/BNGR-A9 signaling pathway as a critical regulator of feeding behavior and hemolymph trehalose homeostasis in Bombyx mori, highlighting its roles in the negative control of food intake and the positive regulation of energy balance.

Abstract Background Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment. Methods Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine. Results One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders. Conclusions Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.

Abstract Resilience is one of the main features of smart distribution networks, and a microgrid (MG) access to the distribution network provides an effective way to improve resilience. MG and distribution network belong to different interests, so it is necessary that MGs and flexible resources are actively guided through price leverage. In this way, MGs take part in the post‐disaster restoration and enhance its resilience. Firstly, this paper proposes a dynamic restoration electricity price response mechanism after extreme disasters and constructs a power response model for loads and electric vehicles within the MGs. Secondly, the optimal scheduling model of the distribution network with multiple‐microgrids (MMG) is proposed to improve the restoration rate of critical loads (RRCL). Single microgrid achieves the largest microgrid revenue and restoration contribution, and MMG uses the power headroom index to optimize the dynamic restoration electricity price to achieve the smallest power purchase cost of distribution network. Finally, the optimal scheduling method for resilience enhancement of distribution networks with MMG considering dynamic restoration electricity price response mechanism is validated by dual microgrid access to an IEEE 33‐node distribution system. The simulation results show that the proposed optimization method effectively improves the RRCL of distribution network.

Abstract In eukaryotes, the nuclear membrane that encapsulates genomic DNA is composed of an inner nuclear membrane (INM), an outer nuclear membrane (ONM), and a perinuclear space. SUN proteins located in the INM and KASH proteins in the ONM form the SUN-KASH NM-bridge, which functions as the junction of the nucleocytoplasmic complex junction. Proteins containing the SUN domain showed the highest correlation with differentially accumulated proteins (DAPs) in the wheat response to fungal stress. To understand the characteristics of SUN and its associated proteins in wheat responding to pathogen stress, here we investigated and comprehensive analyzed SUN- and KASH-related proteins among the DAPs under fungi infection based on their conserved motifs. In total, four SUN proteins, one WPP domain-interacting protein (WIP), four WPP domain-interacting tail-anchored proteins (WIT), two WPP proteins and one Ran GTPase activating protein (RanGAP) were identified. Following transient expression of Nicotiana benthamiana, TaSUN2, TaRanGAP2, TaWIT1 and TaWIP1 were identified as nuclear membrane proteins, while TaWPP1 and TaWPP2 were expressed in both the nucleus and cell membrane. RT-qPCR analysis demonstrated that the transcription of TaSUN2, TaRanGAP2 and TaWPP1 were strongly upregulated in response to fungal infection. Furthermore, using the bimolecular fluorescence complementation, the luciferase complementation and a nuclear and split-ubiquitin-based membrane yeast two-hybrid systems, we substantiated the interaction between TaSUN2 and TaWIP1, as well as TaWIP1/WIT1 and TaWPP1/WPP2. Silencing of TaSUN2, TaRanGAP2 and TaWPP1 in wheat leaves promoted powdery mildew infection and hyphal growth, and reduced the expression of TaBRI1, TaBAK1 and Ta14-3–3, indicating that these NM proteins play a positive role in resistance to fungal stress. Our study reveals the characteristics of NM proteins and propose the preliminary construction of SUN-WIP-WPP-RanGAP complex in wheat, which represents a foundation for detail elucidating their functions in wheat in future.

Abstract Background The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched. Methods Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells. Results A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy. Conclusions This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.

Abstract Background Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC. Methods Metagenomic sequencing of fecal samples was performed on matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome was profiled with 16S rRNA gene sequencing on tumor (n = 24) and tumor-adjacent normal (n = 24) tissues of CRC patients, while host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals. Results Our analysis revealed substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Of note, we observed a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues, a phenomenon notably absent in tumor tissues. Furthermore, we established consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa. Conclusions This study emphasizes the pivotal role of the gut microbiota and pathogenic bacteria in dynamically shaping DNA methylation patterns, impacting physiological homeostasis, and contributing to CRC tumorigenesis. These findings provide valuable insights into the intricate host-environment interactions in CRC development and offer potential avenues for therapeutic interventions in this disease.

ABSTRACT: Objectives: The dissemination of New Delhi metallo-β-lactamase-5 (NDM-5) among various species of Enterobacterales has attracted serious global attention. Here, we characterise the genomic characterisation of blaNDM-5-IncX3 plasmid (pNDM-KA3) in an ST4 Klebsiella aerogenes (KA3) strain isolated from a neonate with pneumonia. Methods: Antimicrobial susceptibility and multilocus sequence typing was performed for the KA3. The plasmid conjugation assay and plasmid stability of the KA3 (pNDM-KA3) were also analysed. The pNDM-KA3 plasmid was further analysed by whole-genome sequencing and comparative analysis to determine the genetic environment of blaNDM-5. Results: The KA3 strain belongs to ST4 and shows high resistance to β-lactam antibiotics, including carbapenems, but is susceptible to ciprofloxacin, amikacin, tigecycline, and colistin. The pNDM-KA3 was successfully transferred to the recipient E. coli J53 and showed strong stability in K. aerogenes. Genomic sequencing revealed that the pNDM-KA3 plasmid was assigned to plasmid incompatibility group X3 with 43367 bp, and a conserved structure sequence of △IS3000-△ISAba125-IS5-blaNDM-5-bleMBL- trpF-dsbC-IS26 was detected upstream and downstream of the blaNDM-5 gene. Further analysis revealed that insertion sequences mediated the dissemination of blaNDM-5 from other species of Enterobacterales. The pNDM-KA3 showed high similarity to blaNDM-5-harbouring plasmids in other species of Enterobacterales, with these plasmids carrying genes for replication (repB), partitioning (parA and parB), stability (hns), and conjugative transfer (virB and virD). Conclusions: Continued monitoring for the dissemination of blaNDM-5 among uncommon Enterobacterales species should be further reinforced.

Phenotypic differences between diploid parents and their allotriploid offspring are common in aquaculture breeding. Some allotriploid populations exhibit rapid growth rates and increased body weight, which are significant for supporting fisheries development. Understanding the genetic mechanisms underlying these traits is crucial for implementing diverse breeding strategies to achieve high production in fish farming. Here, we collected the following fish species for our study: red crucian carp (Carassius auratus red var., 2nRR), common carp (Cyprinus carpio L., 2nCC), and two allotriploids (3nR2C and 3 nRC2). These allotriploids were obtained through backcrossing an allotetraploid of C. auratus red var. × C. carpio L. (4nR2C2, ♂) with C. auratus red var. and C. carpio L. (♀), respectively. These allotriploids demonstrated faster growth rates compared to their diploid inbred parents, contributing to the Chinese fisheries industry for several decades. We conducted a systematic comparison of mitochondrial DNA (mtDNA) copy numbers in the liver and muscle tissues of 2nRR, 2nCC, 3nR2C, and 3 nRC2 under different seasons. When entering winter (low water temperature: 13 °C), the triploid fish (3nR2C and 3 nRC2) exhibited lower mtDNA copy numbers in the muscle, indicating a reduction in individual activity and energy expenditure to facilitate weight maintenance when food availability is limited. Furthermore, we analysed the expression levels of three nuclear-regulated mitochondrial genes (tfam, tfb1m, and tfb2m) and observed an imbalance of allelic expression in tfam and tfb1m in the two triploid fish. These findings enhance our understanding of the molecular regulatory mechanisms underlying growth trait differences among fish with different ploidy levels.

BackgroundThyroid hormones are essential for cognitive function and can impact cognitive performance even in euthyroid individuals. This study investigates how thyroid hormones influence cognitive performance in the elderly and whether body composition biomarkers moderate this relationship. The aim is to determine if lifestyle interventions should prioritize weight loss, overall body fat reduction, or abdominal fat loss.MethodsWe analyzed data from the NHANES 2011-2012 dataset, focusing on thyroid hormone levels, cognitive performance, and body composition metrics in euthyroid individuals aged 60 to 80 years. A total of 573 participants were included in the analysis. Pearson correlation analyses were conducted to evaluate the associations between thyroid hormone indicators and cognitive performance metrics. Ordinal logistic regression and linear regression analyses were used to determine the predictive capacity of thyroid hormones on cognitive functions, adjusting for potential confounders such as age, gender, and education level. Statistical analyses were performed using R Studio and Stata, utilizing Pearson correlation, ordinal logistic regression, and linear regression methods.ResultsSignificant correlations were observed between short-term memory and TT3 (r = 0.111, p = 0.018), TSHI (r = -0.121, p = 0.010), and TFQI (r = -0.107, p = 0.023); delayed memory and FT3 (r = 0.143, p = 0.003), TT3 (r = 0.146, p = 0.002), and TSHI (r = -0.125, p = 0.009); and executive function with FT4 (r = -0.141, p = 0.003) and the FT3/FT4 ratio (r = 0.137, p = 0.004). Although thyroid indicators did not independently predict short-term memory (OR = 0.006, p = 0.116), they were statistically significant for delayed memory with FT3 (OR = 0.642, p = 0.017) and TT3 (OR = 0.010, p = 0.015). Linear regression analysis indicated that FT4 (t = -2.99, p = 0.003) and the FT3/FT4 ratio (t = 2.91, p = 0.004) were significant predictors of executive function. Hierarchical regression analyses revealed that BMI and waist circumference (WWI) significantly moderated the relationship between thyroid function and short-term memory (BMI: z = 2.44, p = 0.015; WWI: z = -2.19, p = 0.029). BMI also moderated the models for delayed memory (z = 2.11, p = 0.035), while RFM and C-index did not exhibit significant moderating effects. No moderators were identified in the relationship between executive function and thyroid hormones.ConclusionThis study underscores the significant influence of higher BMI and waist circumference on the relationship between thyroid function and memory performance. In contrast, body composition indicators such as RFM and C-index do not appear to significantly affect cognitive function related to thyroid levels, highlighting the importance of fat distribution in cognitive health assessments.

Abstract Underwater imaging technology plays a pivotal role in marine exploration and reconnaissance, necessitating photodetectors (PDs) with high responsivity, fast response speed, and low preparation costs. This study presents the synergistic optimization of responsivity and response speed in self‐powered photoelectrochemical (PEC)‐type photodetector arrays based on oxygen‐vacancy‐tuned amorphous gallium oxide (a‐Ga2O3) thin films, specifically designed for solar‐blind underwater detection. Utilizing a low‐cost one‐step sputtering process with controlled oxygen flow, a‐Ga2O3 thin films with varying oxygen vacancy (VO) concentrations are fabricated. By balancing the trade‐offs among electrocatalytic reactions, charge transfer, carrier recombination, and trapping, both the responsivity and response speed of a‐Ga2O3‐based self‐powered PEC‐PDs are simultaneously improved. Consequently, the optimized PEC‐PDs demonstrated exceptional performance, achieving a responsivity of 33.75 mA W−1 and response times of 12.8 ms (rise) and 31.3 ms (decay), outperforming the vast majority of similar devices. Furthermore, a pronounced positive correlation between anomalous transient photocurrent spikes and the concentration of VO defects is observed, offering compelling evidence for VO‐mediated indirect recombination. Finally, the proof‐of‐concept solar‐blind underwater imaging system, utilizing an array of self‐powered PEC‐PDs, demonstrated clear imaging capabilities in seawater. This work provides valuable insight into the potential for developing cost‐effective, high‐performance a‐Ga2O3 thin‐film‐based PEC‐PDs for advanced underwater imaging technology.

BackgroundThe impact of a protein-rich diet and protein supplements on athletic performance remains a topic of debate. Does protein intake offer benefits for athletes? If so, which specific aspects of athletic performance are most influenced by protein?MethodsThis study aimed to explore the relationship between protein intake and athletic performance. A systematic database search was conducted to identify randomized controlled trials (RCTs) examining the effects of protein intake on athletes’ performance. The databases searched included PubMed, Scopus, Web of Science, EBSCO, and Ovid. The meta-analysis included a total of 28 studies involving 373 athletes. The meta-analysis employed both the fixed-effects model and the random-effects model to investigate the impact of protein intake on sports performance. Subgroup analyses were conducted to provide solid evidence to explain the results of the meta-analysis. Sensitive analysis and funnel plots were used to assess the risk of bias and data robustness.ResultsOverall, protein intake did not show a statistically significant improvement in athletic performance (standardized mean difference [SMD] = 0.12, 95% confidence interval [CI]: −0.01 to 0.25). However, in subgroup analysis, the protein group demonstrated a statistically significant improvement in endurance performance, as indicated by the forest plot of final values (SMD = 0.17, 95% CI: 0.02 to 0.32). Additionally, the change value in the forest plot for endurance performance showed even greater statistical significance than the final value (SMD = 0.31, 95% CI: 0.15 to 0.46). In the subgroup analysis based on physiological indices, muscle glycogen showed a statistically significant improvement in the protein group (standardized mean difference [SMD] = 0.74, 95% confidence interval [CI]: 0.02 to 0.32). Furthermore, subgroup analyses based on protein supplementation strategies revealed that co-ingestion of protein and carbohydrates (CHO) demonstrated statistically significant improvements in endurance performance (SMD = 0.36, 95% CI: 0.11 to 0.61), whereas high protein intake alone did not.ConclusionProtein intake appears to provide modest benefits to athletes in improving their performance, particularly by enhancing endurance. Subgroup analysis suggests that protein intake improves muscle glycogen levels and that the co-ingestion of protein with CHO is more effective for endurance athletes than high protein intake alone.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier CRD42024508021.