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Abstract Recent advancements in hyperspectral imaging (HSI) for early disease detection have shown promising results, yet there is a lack of validated high-resolution (spatial and spectral) HSI data representing the responses of plants at different stages of leaf disease progression. To address these gaps, we used bacterial leaf spot (Xanthomonas perforans) of tomato as a model system. Hyperspectral images of tomato leaves, validated against in planta pathogen populations for seven consecutive days, were analyzed to reveal differences between infected and healthy leaves. Machine learning models were trained using leaf-level full spectra data, leaf-level Vegetation index (VI) data, and pixel-level full spectra data at four disease progression stages. The results suggest that HSI can detect disease on tomato leaves at pre-symptomatic stages and differentiate bacterial disease spots from abiotic leaf spots. Using VI data as features for machine learning improved overall classification performance by 26–37% compared to the direct use of raw data. Critical wavelength bands and VIs varied across disease progression stages, suggesting that pre-symptomatic disease detection relied more on changes in leaf water content (1400 nm) and plant defense hormone‐mediated responses (750 nm) rather than changes in leaf pigments or internal structure (800–900 nm), which may become more crucial during symptomatic stages. In conclusion, this study provides valuable insights into the dynamics of bacterial spot disease, revealing the potential benefits of leaf structure segmentation and VI group pattern analysis in HSI studies for the early detection of leaf diseases.

Abstract Engineering the electronic band structures upon doping is crucial to improve the thermoelectric performance of materials. Understanding how dopants influence the electronic states near the Fermi level is thus a prerequisite to precisely tune band structures. Here, we demonstrate that the Sn-s states in SnTe contribute to the density of states at the top of the valence band. This is a consequence of the half-filled p-p σ-bond (metavalent bonding) and its resulting symmetry of the orbital phases at the valence band maximum (L point of the Brillouin zone). This insight provides a recipe for identifying superior dopants. The overlap between the dopant s- and the Te p-state is maximized, if the spatial overlap of both orbitals is maximized and their energetic difference is minimized. This simple design rule has enabled us to screen out Al as a very efficient dopant to enhance the local density of states for SnTe. In conjunction with doping Sb to tune the carrier concentration and alloying with AgBiTe2 to promote band convergence, as well as introducing dislocations to impede phonon propagation, a record-high average ZT of 1.15 between 300 and 873 K and a large ZT of 0.36 at 300 K is achieved in Sn0.8Al0.08Sb0.15Te-4%AgBiTe2.

Lung cancer is primarily classified as NSCLC, which is distinguished by a wide range of genetic variations. This study focused on RNF144A-AS1, a relatively unexplored lncRNA, to explore the impact of its genetic polymorphisms on the susceptibility to NSCLC. We detected RNF144A-AS1 expression and its correlation with prognosis and clinical pathological features using bioinformatics analysis. The association between RNF144A-AS1 polymorphism and NSCLC susceptibility was evaluated using case-control methods. This investigation featured a cohort of 700 NSCLC individuals and 700 healthy controls. The genotype of genetic variation was detected by PCR-RFLP and iMLDR, followed by subsequent calculation of OR and 95 % CI. Our data show that RNF144A-AS1 exhibits high expression levels in LUAD tissues and its expression is closely linked to LUAD progression and prognosis. Carrier of RNF144A-AS1 rs3806609 TT genotype increased NSCLC susceptibility compared to carrier of rs3806609 CC genotype (OR = 2.21, 95%CI = 1.57–3.13). Our study identifies RNF144A-AS1 genetic variants as potential susceptibility markers in NSCLC. RNF144A-AS1 promotes cell proliferation and migration in LUAD through the IFN-γ/JAK2/STAT1 signalling pathway. Collectively, these findings pave the way for developing targeted therapies and diagnostic tools based on RNF144A-AS1 and its variants.

Penaeus vannamei is an important shrimp species that is farmed globally, owing to its fast growth and good environmental adaptability. However, vibriosis outbreaks, such as acute hepatopancreatic necrosis disease and translucent post-larva disease, have become a considerable constraint on the development of the shrimp aquaculture industry globally in recent years. Due to the negative consequences associated with the use of antibiotics to control bacterial diseases, alternative technologies, such as improving shrimp immunity, the nutrition level of shrimp diets, and the ecological environment of shrimp ponds by using probiotics, have been developed. Owing to the limitations related to the sourcing and cost of fish meal, a large amount of vegetable protein is often used as a fish meal substitute in shrimp artificial feed, which is not only difficult for the shrimp to digest and absorb but can also lead to nutritional antagonism. In order to improve the health status of aquaculture animals by providing high-quality feed, the development and optimization of fermented feed have received extensive attention. Probiotics in fermented feed can produce exogenous cellulase, protease, amylase, and other digestive enzymes in the digestive tract of farmed animals, which can improve the feed utilization rate, promote growth performance, and enhance the immunity of shrimp.In this study, in order to explore the application effects of shrimp feed fermented by different probiotic bacteria, probiotic strains, including Bacillus subtilis, Saccharomyces cerevisiae, and Lactobacillus acidophilus, were used individually and in combination for the fermentation of commercial feed and fed to shrimp (P. vannamei) for 28 days. The survival, body length growth, specific growth, and feed conversion rates of the shrimp were analyzed, and the density of Vibrio in vitro and in vivo, as well as relevant immune indicators in the serum, were analyzed. Furthermore, ammonia nitrogen and nitrite nitrogen concentrations in the water column were compared between the groups.The results demonstrated that the survival rates of shrimp in the fermented feed groups of B. subtilis, L. acidophilus, and complex bacteria were 8.54%, 8.54%, and 9.76%, respectively, which were significantly higher than that of the control group (P < 0.05). The body length growth rates in the B. subtilis and L. acidophilus groups were significantly higher than that of the control group (P < 0.05), while the feed conversion rate in the L. acidophilus group was significantly decreased compared with that of the control group (P < 0.05). There was no significant difference in the specific growth rate of shrimp between the experimental groups and the control group (P > 0.05). Fermented feed can affect the composition of bacteria in the hepatopancreas of shrimp. The density of Vibrio in the hepatopancreas of shrimp in each experimental group was significantly lower than that in the control group on days 14 and 21 of the experiment (P < 0.05). The feeding of different fermented feed in the short term (within 14 days) had no significant effect on reducing the total density of Vibrio in the water. However, feeding B. subtilis and L. acidophilus fermented feed significantly reduced the Vibrio density in the water body on day 21 (P < 0.05). In addition, the serum total protein concentration in each experimental group was significantly higher than that in the control group (P < 0.05). The activities of serum peroxidase, superoxide dismutase, and phenoloxidase in the L. acidophilus fermented feed group increased significantly compared with those of the other experimental and control groups (P < 0.05). The activities of serum peroxidase and phenoloxidase in the serum of shrimp fed S. cerevisiae fermented feed were significantly higher than those of the control group (P < 0.05). Complex bacteria-fermented feed could significantly increase the activities of serum lysozyme, peroxidase, and phenoloxidase (P < 0.05). However, the activity of the detected immune-related enzymes in the B. subtilis group did not increase significantly compared with that of the control group (P > 0.05), except for the activity of total serum protein, which was higher than that of the control group. The results also revealed that the concentration of ammonia nitrogen and nitrite nitrogen in the water group of each experimental group at the end of the experiment was significantly lower compared to that of the control group. S. cerevisiae and L. acidophilus groups had the best effect in reducing the concentration of ammonia nitrogen and nitrite nitrogen in the water, respectively.In summary, shrimp feed fermented by B. subtilis, S. cerevisiae, and L. acidophilus singly or in combination could improve the survival rate, growth performance, and immunity of shrimp to a degree, and reduce the concentration of ammonia nitrogen and nitrite nitrogen in aquaculture water. Moreover, L. acidophilus shows great potential as a candidate probiotic for shrimp feed fermentation. The results of this study provide a theoretical basis for the development of shrimp fermentation feed, which can improve the feed utilization and survival rates of shrimp in aquaculture.

Abstract Background Colon cancer remains a major health concern worldwide, with genetic factors playing a crucial role in its development. Toll-like receptors (TLRs) has been implicated in various cancers, but their role in colon cancer is not well understood. This study aims to identify functional polymorphisms in the promoter and 3′UTR regions of TLRs and evaluate their association with colon cancer susceptibility. Methods We conducted a case-control study involving 410 colon cancer patients and 410 healthy controls from the Chinese population. Genotyping of polymorphisms in TLR3, TLR4, TLR5 and TLR7 was performed using PCR-RFLP and TaqMan MGB probes. Using logistic regression analysis, we evaluated the association of TLRs polymorphisms and the susceptibility to colon cancer. To understand the biological implications of the TLR4 rs1927914 polymorphism, we conducted functional assays, including luciferase reporter assay and electrophoretic mobility shift assay (EMSA). Results Our results demonstrated that the G-allele of the TLR4 rs1927914 polymorphism is significantly associated with a decreased risk of colon cancer (OR = 0.68, 95%CI = 0.50–0.91). Stratified analysis showed that TLR4 rs1927914 AG or GG genotype contributed to a decreased risk of colon cancer among younger individuals (OR = 0.52, 95%CI = 0.34–0.81), males (OR = 0.58, 95%CI = 0.38–0.87), non-smokers (OR = 0.58, 95%CI = 0.41–0.83) and non-drinker with OR (95%CI) of 0.66 (0.46–0.93). Functional assays demonstrated that in HCT116 and LOVO colon cancer cells, the luciferase activity driven by the TLR4 promoter with the rs1927914A allele was 5.43 and 2.07 times higher, respectively, compared to that driven by the promoter containing the rs1927914G allele. Electrophoretic mobility shift assay (EMSA) results indicated that the rs1927914G allele enhanced transcription factor binding. Using the transcription factor prediction tool, we found that the G allele facilitates binding of the repressive transcription factor Oct1, while the A allele does not. Conclusion The TLR4 rs1927914 polymorphism influence the susceptibility to colon cancer, with the G allele offering a protective effect through modulation of gene expression. These insights enhance our understanding of the genetic determinants of colon cancer risk and highlight TLR4 as a promising target for cancer prevention strategies.

Abstract Background Lung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population. Methods A hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses. Results Baseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype. Conclusions CD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

Low Earth Orbit (LEO) stands as the primary access point for deep space exploration endeavors, encompassing a variety of space missions such as communication satellites, Earth observation platforms, and scientific research missions. In light of the expanding scope of human activities in space, the cost associated with accessing LEO has emerged as a critical focal point for spacecraft designers. Within the spectrum of proposed solutions, laser-powered vehicle has emerged as a viable avenue toward achieving cost-effective launch options. In order to significantly augment the payload capacity of laser-powered launch vehicles destined for LEO, this study introduced a novel Relay Solution Trajectory Flight Scheme. Central to this scheme was the implementation of a relay mirror system affixed to a satellite, which served to stabilize the incident angle of the laser beam directed toward the laser-powered vehicle, thereby ensuring continuous alignment between the laser beam and the vehicle’s axis throughout the duration of the flight. Following the development of comprehensive structural, propulsive, aerodynamic, and trajectory models tailored for the laser-powered vehicle, an optimization of its flight trajectory was conducted, comparing this innovative strategy with two conventional flight strategies. The outcomes of this analysis showcased a notable enhancement of 269.29% in payload capacity compared to conventional strategies that lacked a relay satellite system, within a designated 400 km LEO flight scenario. This endeavor underscored the transformative potential of advanced relay systems in reshaping payload delivery mechanisms and elevating mission feasibility levels, notwithstanding the intricate coordination challenges posed by intricate satellite systems.

Abstract Background This study aimed to investigate the effects of immune checkpoint inhibitors (ICIs) versus chemotherapy on the prognosis of real‐world diffuse pleural mesothelioma patients in China. Methods Clinical data of 90 patients with diffuse pleural mesothelioma from 2019 to 2022 were collected from Harbin Medical University Cancer Hospital. Patients were divided into two groups: the ICIs‐treated group (n = 46) and the chemotherapy‐only group (n = 44). The efficacy and safety of immunotherapy relative to chemotherapy at different treatment stages were explored. Results The median progression‐free survival (PFS) was 10.0 and 7.0 months, and the median overall survival (OS) was 24.7 and 15.8 months in the ICIs‐treated group and the chemotherapy group, respectively. The ICIs‐treated group showed an 11% increase in objective response rate (ORR) (52.2% vs. 41.0%) and an 8.0% increase in disease control rate (DCR) (78.3% vs. 70.0%) compared to the chemotherapy group. The Kaplan–Meier curves demonstrated significant PFS (HR: 0.61; 95% CI: 0.38–0.98; p = 0.038) and OS (HR: 0.47; 95% CI: 0.26–0.86; p = 0.011) benefits of receiving immunotherapy over chemotherapy alone. Subgroup analysis according to treatment timing showed the same trend. Conclusion In patients with nonsurgical diffuse pleural mesothelioma, immunotherapy achieved better survival benefits compared to chemotherapy in both first‐ and second‐/third‐line treatments. The early addition of immunotherapy improved survival in patients with nonsurgical diffuse pleural mesothelioma.

The detoxified pneumolysin derivative ΔA146Ply has been proven to have a direct anti-triple negative breast cancer effect by our group, but its work model remains unclear. In this study, we focused on its ability to inhibit triple-negative breast cancer metastasis. We found that ΔA146Ply suppressed the migration and invasion of triple-negative breast cancer cells by activating mannose receptor and toll-like receptor 4. Their activation triggers the activation of the mammalian target of rapamycin signalling, sequentially leading to autophagy, transforming growth factor-β1, and epithelial-mesenchymal transition inhibition. Furthermore, the combination of doxorubicin and ΔA146Ply significantly inhibited triple-negative breast cancer progression and prolonged survival in tumour-bearing mice. Taken together, our study provides an alternative microbiome-based mannose receptor-targeted therapy for triple-negative breast cancer and a novel theoretical and experimental basis for the downstream signalling pathway of the mannose receptor.

In conjunction with the aggregates, bitumen is commonly applied for surface and base layers of asphalt pavements. A large number of studies concentrated more on the surface layer performance influenced by different types of bitumen and service time. However, the performance evolution of base layer bitumen properties influenced by surface layer bitumen over time remains understudied. To contribute to this gap, this study aims to investigate the influence of surface layer bitumen type on base layer performance with varying service time. Four road segments with two-layer structure (surface layer and base layer) serviced for 4, 6, 7 and 9 years were studied. The surface layer was paved with neat bitumen with Pen 70/100 and polymer modified bitumen (PMB), and the base layer was applied with soft bitumen with Pen 160/220. Physical properties, chemical structure, intermediate-temperature rheological properties, permanent deformation resistance, anti-rutting ability and recovery properties of the field bitumen were analysed and compared with the reference bitumen. The temperature- and frequency-dependent characteristics of asphaltic core samples, as well as the reference mixtures, were characterised. The statistical analyses were performed to quantitatively evaluate the significance of service time and bitumen type of surface layer to base layer performance using mean absolute percentage errors (MAPEs), Pearson correlation coefficient and eta squared. The results showed that the performance of the surface layer was greatly related to service time, and PMB presented better durability and anti-ageing properties than 70/100. Notably, the bitumen type of the surface layer played an important role in base layer performance except for service time, especially in penetration, phase angle and Jnr with eta squared of 0.925, 0.976 and 0.988. Moreover, the ageing speed of the base layer was highly determined by the bitumen type of the surface layer. The findings imply that a better bitumen type of surface layer can enhance the durability of both surface and base layers, resulting in significant improvement in lifespan of asphalt pavement.

IntroductionThis research examines the coupling coordinated development dynamics between marine ecological governance and marine economic development in China’s coastal provinces. The marine ecological governance and economic development data of China’s 11 coastal provinces were comprehensively analyzed from 2011 to 2021.MethodsWe established a multi-dimensional evaluation index system for marine ecological governance and economic development, employing the global entropy weight method for quantification. Furthermore, the research examines and analyzes the trends in coordinated development and divergence between these two systems by constructing a coupled coordination degree(CCD) model, utilizing the Theil index decomposition method, and employing the geodetector detector.ResultsThe Northern marine economic circle outperforms the Eastern and Southern ones regarding marine ecological governance, while the Eastern marine economic circle is the most advanced in marine economic development. The results of the CCD model indicate that Guangdong, Shandong, Hebei, and Jiangsu have the best coupling coordinated development, while Hainan, Tianjin, and Guangxi are at the bottom. The results of the Theil index decomposition method indicate that intra-regional disparities are the primary cause of coupling coordinated regional development variations. At the same time, the results of the geographic detector further substantiate that energy structure, degree of industrial agglomeration, and foreign overseas direct investment are the principal influencing factors.DiscussionThe study presents policy recommendations derived from the findings intended to foster the integrated advancement of marine ecology and economy in coastal provinces, reduce regional development disparities, and establish a scientific foundation for achieving a sustainable marine economy.

Summary: Constructing electric vehicle charging piles (EVCPs) is crucial for promoting electric vehicle (EV) sales. Yet, empirical evidence on the bidirectional relationship between EV sales and public EVCPs is limited, with most related works relying on simulations. We empirically investigate this relationship using panel vector autoregression (PVAR) across 95 Chinese cities from 2018 to 2022. Results show EVCPs significantly boost EV sales, especially in colder regions. Higher air pollution and purchase subsidies inhibit the promoting impact of EV sales on EVCPs. The propelling effect of EVCPs on EV sales is impaired in higher housing prices regions. A significant and positive bidirectional relationship exists between EVCPs and battery electric vehicles (BEVs) sales exists, but not with plug-in hybrid electric vehicles (PHEVs) present. Our findings have implications for stakeholders, such as the construction of fast charging infrastructure under lower temperatures, and differentiated charging demands of EVs with different powertrains need to be addressed.

BackgroundAnlotinib, a highly selective inhibitor of VEGFR2, has demonstrated significant anti-tumor effects in various cancers. However, its potential synergistic effects with DDP (cisplatin) in breast cancer (BRCA) remain to be fully elucidated. This study aims to discover the therapeutic efficacy of anlotinib on BRCA, specifically the synergistic effects with DDP, and to elucidate the underlying molecular mechanisms.MethodsBRCA cells were treated with anlotinib and/or DDP. The proliferation, migration and invasion capabilities of BRCA cells were evaluated using CCK-8 assays, cell cycle distribution, clone formation assays, wound healing assays and transwell assays. Cell apoptosis was detected by flow cytometry technique and Hoechst33342 fluorescence staining. The potential mechanism of anlotinib in the development of BRCA was predicted through bioinformatics analysis, and the mRNA or protein levels were subsequently quantified using qPCR, immunofuorescence and western blot. The anti-breast cancer efficacy of anlotinib was evaluated in vivo using a xenograft tumor model.ResultsOur findings reveal that increased VEGFA expression in BRCA patients is associated with poorer prognosis, underscoring the need for targeted therapeutic strategies. We also demonstrate that both anlotinib and DDP independently inhibit BRCA cell growth, migration, and invasion, while their combination exhibits a synergistic effect, significantly enhancing the inhibition of these oncogenic processes. This synergy is further evident through the induction of apoptosis and autophagy in BRCA cells. Mechanistically, anlotinib’s effectiveness is linked to its inhibition of the JAK2/STAT3 pathway, a critical axis in BRCA progression. In vivo study further support these results, showing that anlotinib markedly inhibits tumor growth in xenografted mice.ConclusionThis study confirms the efficacy of anlotinib or in combination with DDP and elucidates the mechanism behind anlotinib’s effectiveness, highlighting its role in inhibiting the JAK2/STAT3 pathway.

Fusarium species are the dominant cause of maize ear rot, but they also inflict serious damage to the roots and stalks. Theoretically, the organ where the host interacts with the pathogen most frequently should exhibit the highest degree of symptom-genotype correlation. Because that symptom-genotype correlation is an indicator reflecting the degree of coevolution between pathogen and its hosts. We wonder which organ is the main battlefield for the antagonism between maize and Fusarium. For this purpose, 43 isolates of Fusarium were isolated from infected maize ears. Fusarium verticillioides and F. graminearum are the two dominant pathogens, accounting for 44% and 30%, respectively. Furthermore, 14 elite maize inbreds were exposed to 43 Fusarium isolates and the symptoms of ear rot, stalk rot and root rot were investigated. In general, symptoms caused by F. graminearum were significantly more severe than those caused by other Fusarium species. Surprisingly, the genotype of F. verticillioides showed a strong correlation with stalk and root rot, but not with ear rot. Accordingly, our study may provide the first evidence that the stalk and root of maize, rather than the ear, is the main battlefield for the coevolution between maize and F. verticillioides.

Current pneumococcal vaccines, including the pneumococcal polysaccharide (PPV23) and conjugate (PCV13) vaccines, offer protection against specific serotypes but pose risks of serotype replacement that can alter the composition of the nasopharyngeal microbiota. To address this challenge, a novel strategy has been proposed to provide effective protection without disrupting the colonization of other bacterial populations. In our study, we found that subcutaneous immunization with recombinant peptidoglycan N-acetylglucosamine deacetylase A (rPgdA) elicited robust humoral and cellular immune responses, significantly reducing the invasion of Streptococcus pneumoniae in the lungs without affecting nasopharyngeal carriage. Furthermore, rPgdA antisera were shown to diminish bacterial invasion of lung epithelial cells in vitro. Notably, sera from patients with invasive pneumococcal infections exhibited higher levels of antibodies against the PgdA protein compared to sera from healthy adults, suggesting that a natural immune response to this protein occurs during infection. These results suggest a promising new target for the development of pneumococcal vaccines.

PurposeTo develop a predictive model for orthokeratology (Ortho-K) lens decentration 1 month after wear.MethodsThis study included myopic children who were fitted with Ortho-K lenses at Fujian Provincial Hospital between December 2022 and May 2024. Corneal topography parameters and other relevant metrics were collected pre- and post-treatment. Feature selection was conducted using univariate logistic regression and Lasso regression analysis. A machine learning approach was used to develop multiple predictive models, including Decision Tree, Logistic Regression, Multilayer Perceptron, Random Forest, and Support Vector Machine. Model performance was evaluated using accuracy, sensitivity, specificity, ROC curves, DCA curves, and calibration curves. SHAP values were employed to interpret the models.ResultsThe Logistic Regression model demonstrated the best predictive performance, with an AUC of 0.82 (95% CI: 0.69–0.95), accuracy of 77.59%, sensitivity of 85%, and specificity of 61.11%. The most significant predictors identified were age, 8 mm sag height difference, 5 mm Kx1, and 7 mm Kx2. SHAP analysis confirmed the importance of these features, particularly the 8 mm sag height difference.ConclusionsThe Logistic Regression model successfully predicted the risk of Ortho-K lens decentration using key corneal morphological metrics and age. This model provides valuable support for clinicians in optimizing Ortho-K lens fitting strategies, potentially reducing the risk of adverse outcomes and improving the quality of vision for patients. Further validation in clinical settings is recommended.

Abstract Background Chondroitin sulfate proteoglycan 4 pseudogene 12 (CSPG4P12) has been implicated in the pathogenesis of various cancers. This study aimed to evaluate the association of the CSPG4P12 polymorphism with esophageal squamous cell carcinoma (ESCA) risk and to explore the biological impact of CSPG4P12 expression on ESCA cell behavior. Methods A case-control study was conducted involving 480 ESCA patients and 480 healthy controls to assess the association between the rs8040855 polymorphism and ESCA risk. The CSPG4P12 rs8040855 genotype was identified using the TaqMan-MGB probe method. Logistic regression model was used to evaluate the association of CSPG4P12 SNP with the risk of ESCA by calculating the odds ratios (OR) and 95% confidence intervals (95%CI ). The effects of CSPG4P12 overexpression on cell proliferation, migration, and invasion were examined in ESCA cell lines. Co-expressed genes were identified via the CBioportal database, with pathway enrichment analyzed using SangerBox. The binding score of CSPG4P12 to P53 was calculated using RNA protein interaction prediction (RPISeq). Additionally, Western Blot analysis was performed to investigate the impact of CSPG4P12 overexpression on the P53/PI3K/AKT signaling pathway. Results The presence of at least one rs8040855 G allele was associated with a reduced susceptibility to ESCA compared to the CC genotype (OR = 0.51, 95%CI = 0.28–0.93, P = 0.03). Stratification analysis revealed that the CSPG4P12 rs8040855 C allele significantly decreased the risk of ESCA among younger individuals (≤ 57 years) and non-drinkers (OR = 0.31, 95%CI = 0.12–0.77, P = 0.01; OR = 0.42, 95%CI=0.20–0.87, P = 0.02, respectively). CSPG4P12 expression was found to be downregulated in ESCA tissues compared to adjacent normal tissues. Overexpression of CSPG4P12 in ESCA cells inhibited their proliferation, migration, and invasion capabilities. Furthermore, Western Blot analysis indicated that CSPG4P12 overexpression led to a reduction in PI3K and p-AKT protein expression levels. P53 silencing rescues the inhibitory effect of CSPG4P12 on p-AKT. Conclusion The CSPG4P12 rs8040855 variant is associated with reduced ESCA risk and the overexpression of CSPG4P12 inhibited the migration and invasion of ESCA cells by P53/PI3K/AKT pathway. These findings suggest that CSPG4P12 may serve as a novel biomarker for ESCA susceptibility and a potential target for therapeutic intervention.

Abstract The Quercus L. species is widely recognized as a significant group in the broad-leaved evergreen forests of tropical and subtropical East Asia. These plants hold immense economic value for their use as firewood, furniture, and street trees. However, the identification of Quercus species is considered challenging, and the relationships between these species remain unclear. In this study, we sequenced and assembled the chloroplast (cp.) genomes of four Quercus section Cyclobalanopsis species (Quercus disciformis, Quercus dinghuensis, Quercus blackei, and Quercus hui). Additionally, we retrieved six published cp. genome sequences of Cyclobalanopsis species (Quercus fleuryi, Quercus pachyloma, Quercus ningangensis, Quercus litseoides, Quercus gilva, and Quercus myrsinifolia). Our aim was to perform comparative genomics and phylogenetic analyses of the cp. whole genome sequences of ten Quercus section Cyclobalanopsis species. The results revealed that: (1) Quercus species exhibit a typical tetrad structure, with the cp. genome lengths of the newly sequenced species (Q. disciformis, Q. dinghuensis, Q. blakei, and Q. hui) being 160,805 bp, 160,801 bp, 160,787 bp, and 160,806 bp, respectively; (2) 469 SSRs were detected, among which A/T base repeats were the most common; (3) no rearrangements or inversions were detected within the chloroplast genomes. Genes with high nucleotide polymorphism, such as rps14-psaB, ndhJ-ndhK, rbcL-accD, and rps19-rpl2_2, provided potential reference loci for molecular identification within the Cyclobalanopsis section; (4) phylogenetic analysis showed that the four sections of Cyclobalanopsis were grouped into sister taxa, with Q. hui being the first to diverge from the evolutionary branch and Q. disciformis being the most closely related to Q. blackei. The results of this study form the basis for future studies on taxonomy and phylogenetics.

Abstract The intestinal lumen acts as a critical interface connecting the external environment with the body’s internal state. It’s essential to prevent the passage of harmful antigens and bacteria while facilitating nutrient and water absorption. The intestinal barriers encompass microbial, mechanical, immunological, and chemical elements, working together to maintain intestinal balance. Numerous studies have associated m6A modification with intestinal homeostasis. This review comprehensively outlines potential mechanisms through which m6A modification could initiate, exacerbate, or sustain barrier damage from an intestinal perspective. The pivotal role of m6A modification in preserving intestinal equilibrium provides new insights, guiding the exploration of m6A modification as a target for optimizing preventive and therapeutic strategies for intestinal homeostasis.

Abstract N-type polycrystalline SnSe is considered as a highly promising candidates for thermoelectric applications due to facile processing, machinability, and scalability. However, existing efforts do not enable a peak ZT value exceeding 2.0 in n-type polycrystalline SnSe. Here, we realized a significant ZT enhancement by leveraging the synergistic effects of divacancy defect and introducing resonance level into the conduction band. The resonance level and increased density of states resulting from tungsten boost the Seebeck coefficient. The combination of the enhanced electrical conductivity (achieved by increasing carrier concentration through WCl6 doping and Se vacancies) and large Seebeck coefficient lead to a high power factor. Microstructural analyses reveal that the co-existence of divacancy defects (Se vacancies and Sn vacancies) and endotaxial W- and Cl-rich nanoprecipitates scatter phonons effectively, resulting in ultralow lattice conductivity. Ultimately, a record-high peak ZT of 2.2 at 773 K is achieved in n-type SnSe0.92 + 0.03WCl6.

Abiotic stress reduces plant yield and quality. WRKY transcription factors play key roles in abiotic stress responses in plants, but the molecular mechanisms by which WRKY transcription factors mediate responses to drought and osmotic stresses in apple (Malus × domestica Borkh.) remain unclear. Here, we functionally characterized the apple Group III WRKY gene MdWRKY115. qRT-PCR analysis showed that MdWRKY115 expression was up-regulated by drought and osmotic stresses. GUS activity analysis revealed that the promoter activity of MdWRKY115 was enhanced under osmotic stress. Subcellular localization and transactivation assays indicated that MdWRKY115 was localized to the nucleus and had a transcriptional activity domain at the N-terminal region. Transgenic analysis revealed that the overexpression of MdWRKY115 in Arabidopsis plants and in apple callus markedly enhanced their tolerance to drought and osmotic stresses. DNA affinity purification sequencing showed that MdWRKY115 binds to the promoter of the stress-related gene MdRD22. This binding was further verified by an electrophoretic mobility shift assay. Collectively, these findings suggest that MdWRKY115 is an important regulator of osmotic and drought stress tolerance in apple.

Abstract Nasopharyngeal carcinoma (NPC) is a distinct malignancy primarily prevalent in Southern China and Southeast Asia. Circular RNAs (circRNAs), a class of non-coding RNAs, are evolutionarily conserved and exhibit remarkable stability. Their dysregulation has been observed in various cancers, including NPC. In this review, we investigate the pivotal role of circRNAs in NPC, focusing specifically on their involvement in tumor proliferation, apoptosis, metastasis, angiogenesis, stemness, metabolism, and the tumor microenvironment. We highlight the diagnostic and prognostic potential of circRNAs in NPC, emphasizing their utility as biomarkers for early detection, disease monitoring, and prediction of treatment outcomes. Additionally, we explore the therapeutic implications of circRNAs in NPC, highlighting their potential for targeted therapies.

Abstract Background Ciliary body tumor is extremely rare and treatment is challenging. The aim of this study is to present our experience in treating this rare entity, especially large tumors with more than 5 clock hours of involvement, and to evaluate the surgical outcomes and complications of local resection via partial lamellar sclerouvectomy in four cases of ciliary body tumors in China. Methods Four patients with ciliary body tumors underwent partial lamellar sclerouvectomy between October 2019 and April 2023 in Shanghai General Hospital, China. Tumor features, histopathologic findings, complications, visual acuity, and surgical outcomes were reviewed at a mean follow-up of 20.8 months. Results Four patients with a mean age of 31.8 years were included in this study. The histopathological diagnosis was adenoma of non-pigmented ciliary epithelium (ANPCE), schwannoma, and multiple ciliary body pigment epithelial cysts. The mean largest tumor base diameter was 6.00 mm (range: 2.00–10.00) and the mean tumor thickness was 3.50 mm (range: 2.00–5.00). Preoperative complications included cataract in 3 (75%) eyes, lens dislocation in 2 (50%), and secondary glaucoma in 1 (25%). Temporary ocular hypotonia was observed in one case and no other postoperative complications were observed. At a mean follow-up of 20.8 months, the best corrected visual acuity increased in 3 eyes and was stable in 1 eye. Tumor recurrence was absent in all eyes. All patients were alive at the end of follow-up. Conclusions Local tumor resection via PLSU is useful in the treatment of ciliary body tumors, including large tumors occupying more than five clock hours of pars plicata. Surgery-related complications were manageable with adequate preoperative assessment and careful operation during surgery.

Abstract Cross-dehydrogenative coupling of C(sp3)-H bonds is an ideal approach for C(sp3)-C(sp3) bond construction. However, conventional approaches mainly rely on a single activation mode by either stoichiometric oxidants or electrochemical oxidation, which would lead to inferior selectivity in the reaction between similar C(sp3)-H bonds. Herein we describe our development of a paired electrocatalysis strategy to access an unconventional selectivity in the cross-dehydrogenative coupling of alcoholic α C(sp3)-H with allylic (or benzylic) C-H bonds, which combines hydrogen evolution reaction catalysis with hydride transfer catalysis. To maximize the synergistic effect of the catalyst combinations, a HER catalyst pentacoordinated Co-salen is disclosed. The catalyst displays a large redox-potential gap (1.98 V) and suitable redox potential. With the optimized catalyst combination, an electrochemical cross-dehydrogenative coupling protocol features unconventional chemoselectivity (C-C vs. C-O coupling), excellent functional group tolerance (84 examples), valuable byproduct (hydrogen), and high regio- and site-selectivity. A plausible reaction mechanism is also proposed to rationalize the experimental observations.

The measured thermobaric adsorption of anthracite coal “Vmeas” contains 12 pairs of testing results at different temperatures (18∼72 °C) and corresponding pressures (1∼19 MPa), simulating the buried depth of 100∼1900 meter has been published by Zhang Qingling in 2008. A temperature-pressure-adsorption equation (TPAE) has been used to regress the measured data, then to calculate the 12 pairs of thermobaric adsorption data “Vcal”. The relative error and the standard deviation between the Vmeas and the Vcal are calculated and used to verify TPAE's applicability for thermobaric adsorption data. The 3-dimensional TPAE surface is also used for verification. The other 3 sets of optimized thermobaric adsorptions (10 pairs, 8 pairs, and 6 pairs) have been created. To cover a range of temperature (18∼72 °C) and pressure (1∼19 MPa), there must be at least the minimum 6 pairs of thermobaric adsorptions including the lowest temperature 18 °C and pressure 1 MPa, and the highest temperature 72 °C and pressure 19 MPa.

AimsMesenchymal stem cells (MSCs) are key components in promoting glioblastoma (GBM) progression. This study aimed to explore new therapeutic targets and related pathogenic mechanisms based on different MSCs infiltration levels in GBM patients.MethodsWe estimated the relationship between cell infiltration and prognosis of GBM. Subsequently, key risk genes were identified and prognostic models were constructed by LASSO-Cox analysis. The risk genes were validated by five independent external cohorts, single-cell RNA analysis, and immunohistochemistry of human GBM tissues. TIDE analysis predicted responsiveness to immune checkpoint inhibitors in different risk groups.ResultsThe MSCs infiltration level was negatively associated with survival in GBM patients. LOXL1, LOXL4, and GUCA1A are key risk genes that promote GBM progression and may act through complex intercellular communication.ConclusionThis research has provided a comprehensive study for exploring the MSCs infiltration environment on GBM progression, which could shed light on novel biomarkers and mechanisms involved in GBM progression.

The genus Quercus L. is widely acknowledged as a significant assemblage within East Asia tropical and subtropical broadleaf evergreen forests, possessing considerable economic importance. Nevertheless, the differentiation of Quercus species is deemed arduous, and the interrelations among these species remain enigmatic. Leveraging Illumina sequencing, we undertook the sequencing and assembly of the chloroplast (cp) genomes of seven species belonging to Quercus section Cyclobalanopsis (Quercus argyrotricha, Q. augustinii, Q. bambusifolia, Q. bella, Q. edithiae, Q. jenseniana, and Q. poilanei). Furthermore, we collated three previously published cp genome sequences of Cyclobalanopsis species (Q. litseoides, Q. obovatifolia, and Q. saravanensis). Our primary objective was to conduct comparative genomics and phylogenetic analyses of the complete cp genomes of ten species from Quercus section Cyclobalanopsis. This investigation unveiled that Quercus species feature a characteristic circular tetrad structure, with genome sizes ranging from 160,707 to 160,999 base pairs. The genomic configuration, GC content, and boundaries of inverted repeats/single copy regions exhibited marked conservation. Notably, four highly variable hotspots were identified in the comparative analysis, namely trnK-rps16, psbC-trnS, rbcL-accD, and ycf1. Furthermore, three genes (atpF, rpoC1, and ycf2) displayed signals of positive selection pressure. Phylogenetic scrutiny revealed that the four sections of Cyclobalanopsis clustered together as sister taxa. The branch support values ranged from moderate to high, with most nodes garnering 100% support, underscoring the utility of cp genomic data in elucidating the relationships within the genus. Divergence time analysis revealed that Section Cyclobalanopsis represents the earliest type of Quercus genus. The outcomes of this investigation establish a foundation for forthcoming research endeavors in taxonomy and phylogenetics.

Asphalt surface layer as one of the significant pavement layers is directly withstanding traffic loading and external service conditions, and its performance highly determines the life cycle cost of asphalt pavements. Bitumen ageing is an unavoidable process for asphalt surface layer, and it shortens the service life and increases the risk of distress of asphalt pavements. A large number of studies have been conducted on the consequences of asphalt surface layer ageing under ambient environmental conditions. However, the development of asphalt mixture performance under Norwegian conditions and ageing model for the in-service bitumen have not been extensively investigated. Therefore, this work aims to investigate asphalt surface layer performance over service time and establish ageing model for the in-service bitumen. To achieve this goal, core samples acquired from the field and bitumen extracted from in-service field cores were analysed by comparing them with reference bitumen and asphalt mixtures. The physical, chemical, viscoelastic and performance grade variables of the bitumen were characterised, as well as the dynamic modulus and density of asphalt mixtures. The ageing models for bitumen property parameters were established using bitumen type, service time and average annual temperature as independent variables after statistical data processing. As a result, a good agreement between predicted values and measured values of property parameters was achieved because of the high accuracy of prediction of the ageing model. The proposed ageing model for bitumen under Norwegian conditions is beneficial for predicting bitumen properties at specific service time.

The M6.2 earthquake in Jishishan, Gansu Province, on December 18, 2023, caused extraordinary earthquake disasters. It was located in the northern part of the north−south seismic zone, which is a key area for earthquake monitoring in China. The newly built dense strong motion stations in this area provide unprecedented conditions for high-precision earthquake relocation, especially the earthquake focal depth. This paper uses the newly built strong motion and traditional broadband seismic networks to relocate the source locations of the M3.0 and above aftershocks and to invert their focal mechanisms. The horizontal error of earthquake location is estimated to be 0.5−1 km, and the vertical error is 1−2 km. The focal depth range of aftershocks is 9.6−14.6 km, distributed in a 12-km-long strip with SSE direction. Aftershocks in the south are more concentrated horizontally and vertically, while aftershocks in the north are more scattered. The focal mechanisms of the main shock and aftershocks are relatively consistent, and the P-axis orientation is consistent with the regional strain direction. There is a seismic blank area of M3.0 and above, about 3−5 km between the main shock and aftershocks. It is suggested that the energy released by the main shock rupture is concentrated in this area. Based on the earthquake location and focal mechanism of the main shock, it is inferred that the Northern Lajishan fault zone is the seismogenic structure of the main shock, and the main shock did not occur on the main fault, but on a secondary fault. The initial rupture depth and centroid depth of the main shock were 12.8 and 14.0 km, respectively. The source rupture depth may not be the main reason for the severe earthquake disaster.

The collaborative governance of inclusive preschool education (IPE) is a process in which multiple subjects work together to promote the advancement and development of IPE by taking a series of governance measures. Based on precise identification of multiple stakeholders in collaborative governance of integrated preschool education, it applied the quadrilateral evolutionary game model and Lyapunov's first law to analyze the stability of behavioral strategy choice by multiple subjects in promoting the practice of collaborative governance of IPE and the possible equilibrium points in the system. The influence of key elements on the system evolution is analyzed using MATLAB 2019 simulation. The study reveals that the evolution and trend of one game agent's behavior are closely related to the strategy choice of others. The willingness of the main body of kindergarten, social organization, and parents to participate in the collaborative governance of IPE are related to the government's active promotion to perform its leading functions at the government level. The willingness for collaborative governance of integrated education can help improve mutual trust and the main body's benefits, thus promoting the collaborative behavior of multiple subjects. Complementary resources, strict supervision, reasonable rewards and punishments can promote the collaborative behavior of multiple subjects.

Abstract Background The use of handgrip strength (HGS) in clinical cancer research is surging. The association between HGS and outcomes in patients with cancer varied across studies, which might be due to the different measurement protocols for HGS. We aimed to answer three questions: (1) Did the use of various protocols for HGS, along with different numbers of repetitions, lead to significant differences in maximum HGS values? (2) If yes, were these differences clinically significant? (3) Did the differences in HGS protocols and repetitions affect the identification of HGS weakness or HGS asymmetry? Methods We continuously recruited adult patients with solid tumours. Two protocols were used to measure HGS: Method A, following the American Society of Hand Therapists guidelines, and Method B, following the National Health and Nutrition Examination Survey guidelines. To analyse HGS, we used the maximal value obtained from either two or three repetitions of the dominant hand or four or six repetitions of both hands. Results We included 497 patients (326 men and 171 women, median age: 58 years). The maximal HGS values, measured with Method B, were significantly higher than those measured by Method A in both men and women, despite repetitions (all P

Introduction: Allotetraploid upland cotton (Gossypium hirsutum L.) is native to the Mesoamerican and Caribbean regions, had been improved in the southern United States by the mid-eighteenth century, was then dispersed worldwide. However, a Hainan Island Native Cotton (HIC) has long been grown extensively on Hainan Island, China. Objectives: Explore HIC’s evolutionary relationship and genomic diversity with other tetraploid cottons, its origin and whether it was used for YAZHOUBU (Yazhou cloth, World Intangible Cultural Heritage) weaving, and the role of structural variations (SVs) in upland cotton domestication. Methods: We assembled a high-quality genome of one HIC plant. We performed phylogenetic analysis, divergence time estimation, principal component analysis and population differentiation estimation using cotton assemblies and/or resequencing data. SVs were detected by whole-genome comparison. A F2 population was used for linkage analysis and to study effects of SVs. Buoyancy and salt water tolerance tests for seeds were conducted. Results: We found that the HIC belongs to G. purpurascens. G. purpurascens is best classified as a primitive race of G. hirsutum. The potential for long range transoceanic dispersal of G. purpurascens seeds was proved. A set of SVs, selective sweep regions between G. hirsutum races and cultivars, and quantitative trait loci (QTLs) of eleven agronomic traits were obtained. SVs, especially large-scale SVs, were found to have important effects on cotton domestication and improvement. Of them, eight large-scale inversions strongly associated with yield and fiber quality have probably undergone artificial selection in domestication. Conclusion: G. purpurascens including HIC is a primitive race of G. hirsutum, probably disperse to Hainan from Central America by floating on ocean currents, may have been partly domesticated, planted and was likely used for YAZHOUBU weaving in Hainan much earlier than the Pre-Columbian period. SV plays an important role in cotton domestication and improvement.

Abstract Background In cellular activities, essential proteins play a vital role and are instrumental in comprehending fundamental biological necessities and identifying pathogenic genes. Current deep learning approaches for predicting essential proteins underutilize the potential of gene expression data and are inadequate for the exploration of dynamic networks with limited evaluation across diverse species. Results We introduce ECDEP, an essential protein identification model based on evolutionary community discovery. ECDEP integrates temporal gene expression data with a protein–protein interaction (PPI) network and employs the 3-Sigma rule to eliminate outliers at each time point, constructing a dynamic network. Next, we utilize edge birth and death information to establish an interaction streaming source to feed into the evolutionary community discovery algorithm and then identify overlapping communities during the evolution of the dynamic network. SVM recursive feature elimination (RFE) is applied to extract the most informative communities, which are combined with subcellular localization data for classification predictions. We assess the performance of ECDEP by comparing it against ten centrality methods, four shallow machine learning methods with RFE, and two deep learning methods that incorporate multiple biological data sources on Saccharomyces. Cerevisiae (S. cerevisiae), Homo sapiens (H. sapiens), Mus musculus, and Caenorhabditis elegans. ECDEP achieves an AP value of 0.86 on the H. sapiens dataset and the contribution ratio of community features in classification reaches 0.54 on the S. cerevisiae (Krogan) dataset. Conclusions Our proposed method adeptly integrates network dynamics and yields outstanding results across various datasets. Furthermore, the incorporation of evolutionary community discovery algorithms amplifies the capacity of gene expression data in classification.

Abstract Background Protein phosphatases type 2C (PP2C) are heavily involved in plant growth and development, hormone-related signaling pathways and the response of various biotic and abiotic stresses. However, a comprehensive report identifying the genome-scale of PP2C gene family in ginger is yet to be published. Results In this study, 97 ZoPP2C genes were identified based on the ginger genome. These genes were classified into 15 branches (A-O) according to the phylogenetic analysis and distributed unevenly on 11 ginger chromosomes. The proteins mainly functioned in the nucleus. Similar motif patterns and exon/intron arrangement structures were identified in the same subfamily of ZoPP2Cs. Collinearity analysis indicated that ZoPP2Cs had 33 pairs of fragment duplicated events uniformly distributed on the corresponding chromosomes. Furthermore, ZoPP2Cs showed greater evolutionary proximity to banana’s PP2Cs. The forecast of cis-regulatory elements and transcription factor binding sites demonstrated that ZoPP2Cs participate in ginger growth, development, and responses to hormones and stresses. ZoERFs have plenty of binding sites of ZoPP2Cs, suggesting a potential synergistic contribution between ZoERFs and ZoPP2Cs towards regulating growth/development and adverse conditions. The protein–protein interaction network displayed that five ZoPP2Cs (9/23/26/49/92) proteins have robust interaction relationship and potential function as hub proteins. Furthermore, the RNA-Seq and qRT-PCR analyses have shown that ZoPP2Cs exhibit various expression patterns during ginger maturation and responses to environmental stresses such as chilling, drought, flooding, salt, and Fusarium solani. Notably, exogenous application of melatonin led to notable up-regulation of ZoPP2Cs (17/59/11/72/43) under chilling stress. Conclusions Taken together, our investigation provides significant insights of the ginger PP2C gene family and establishes the groundwork for its functional validation and genetic engineering applications.

Radiation-induced intestinal injury is a common complication of radiotherapy for abdominal and pelvic malignancies. Due to its rapid proliferation, the small intestine is particularly sensitive to radiation, making it a critical factor limiting treatment. Ferulic acid (FA), a derivative of cinnamic acid, exhibits antioxidant, anti-inflammatory, and anti-radiation properties. In this study, we established a mouse model of radiation-induced intestinal injury using a dose of 11 Gy at a rate of 96.62 cGy/min. Our findings indicate that FA’s protective effects against radiation-induced intestinal injury may be mediated through the parkinsonism-associated deglycase (DJ-1) nuclear factor erythroid 2-related factor 2 (Nrf2) and silent mating type information regulation 2 homolog 1 (Sirt1) nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) NOD-like receptor family, pyrin domain containing 3 (NLRP3). FA was found to mitigate changes in oxidative stress indices and inflammatory factors induced by radiation, as well as to attenuate radiation-induced pathological alterations in the small intestine. Furthermore, FA enhanced the expression of DJ-1 and Nrf2 at both the transcriptional and protein levels, inhibited NLRP3 protein fluorescence intensity, and reduced the expression of NLRP3, interleukin-18 (IL-18), and interleukin-1 beta (IL-1β). Additionally, FA suppressed the transcription and translation of NF-κB, NLRP3, cysteine-aspartic acid protease-1 (Caspase-1), IL-18, and IL-1β by upregulating Sirt1, thereby alleviating radiation-induced inflammatory injury in the small intestine. Thus, FA holds promise as an effective therapeutic agent for ameliorating radiation-induced intestinal injury.

Abstract A novel catalytic system for radical cross‐coupling reactions based on copper and chiral Pyridyl‐bis(imidazole) (PyBim) ligands is described. It overcomes the challenges of chemoselectivity and enantioselectivity, achieving a highly enantioselective vicinal sulfonyl‐esterification reaction of alkenes involving sulfur dioxide. This strategy involves the use of earth‐abundant metal catalyst, mild reaction conditions, a broad range of substrates (84 examples), high yields (up to 97% yield), and exceptional control over enantioselectivity. The reaction system is compatible with different types of radical precursors, including O‐acylhydroxylamines, cycloketone oxime esters, aryldiazonium salts, and drug molecules. Chiral ligand PyBim is identified as particularly effective in achieving the desired high enantioselectivity. Mechanistic studies reveal that copper/PyBim system plays a vital role in C─O coupling, employing an outer‐sphere model. In addition, the side arm effect of ligand is observed.

Tubby-like proteins (TLPs) constitute a diverse multigene family found across a broad range of eukaryotic organisms, from single-celled to multicellular eukaryotes. Despite their importance, the existence of TLPs in walnuts (Juglans regia L.) has not been reported until now. In this study, we identified 12 members of the JrTLP gene family in the walnut genome, revealing a pattern of gene replication events. Notably, all JrTLPs exhibited a split gene structure, containing two to eight introns, and these genes could be divided into five distinct categories based on their evolutionary relationships. The majority of TLP proteins possess two signature domains: the F-box and Tubby domains. Subcellular localization prediction and experiments confirmed that JrTLP2 was located in the nucleus and membrane. Expression profiling revealed that multiple JrTLPs respond to a range of stimuli, including pathogen infection, hormonal treatment (such as auxin, ABA, MeJA, and GA), and abiotic stress conditions such as cold, heat, and salt. This study represents the first comprehensive identification of the walnut TLP family, providing valuable insights into the function and regulation of TLP in walnut and laying the foundation for future functional dissection, particularly in the context of stress tolerance.

Mitochondria are semi-autonomous organelles in eukaryotic cells with their own genome. Plant mitogenomes differ from animal mitogenomes in size, structure, and repetitive DNA sequences. Despite larger sizes, plant mitogenomes do not have significantly more genes. They exhibit diverse structures due to variations in size, repetitive DNA, recombination frequencies, low gene densities, and reduced nucleotide substitution rates. In this study, we analyzed the mitochondrial genome of Stemona sessilifolia using Nanopore and Illumina sequencing. De-novo assembly and annotation were conducted using Unicycler, Geseq, tRNAscan-SE and BLASTN, followed by codon usage, repeat sequence, RNA-editing, synteny, and phylogenetic analyses. S. sessilifolia’s mitogenome consisted of one linear contig and six circular contigs totaling 724,751 bp. It had 39 protein-coding genes, 27 tRNA genes, and 3 rRNA genes. Transfer of chloroplast sequences accounted for 13.14% of the mitogenome. Various analyses provided insights into genetic characteristics, evolutionary dynamics, and phylogenetic placement. Further investigations can explore transferred genes’ functions and RNA-editing’s role in mitochondrial gene expression in S. sessilifolia.

This study investigates the relationship between institutional investor association and stock price crash risk, using data from all listed non-financial sector companies in the Chinese capital market. The findings indicate a significant positive correlation between institutional investor association and stock price crash risk. Moreover, property rights and agency costs play significant moderating roles in this relationship. Specifically, the impact of institutional investors on stock price crash risk is more pronounced in non-state-owned enterprises (non-SOEs) than in state-owned enterprises (SOEs). Furthermore, this impact is more pronounced in firms with high agency costs and prominent agency problems compared to firms with low agency costs. This research contributes to financial regulators being able to identify better and prevent stock price crashes, ensuring the stability of investors' returns from their invested enterprises.

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation. Using a fragment of tacL regulatory probe as bait in a DNA pulldown assay, we successfully identified several regulatory proteins, including ComE. Electrophoretic mobility shift assays revealed that phosphomimetic ComE, but not wild-type ComE, exhibited specific binding to the probe. DNase I footprinting assays revealed the specific binding sequences encompassing around 30 base pairs located 31 base pairs upstream from the start codon of tacL. Expression of tacL was found to be upregulated in the ΔcomE strain, and the addition of exogenous competence-stimulating peptide repressed the tacL transcription in the wild-type strain but not the ΔcomE mutant, indicating that ComE exerted a negative regulatory effect on the transcription of tacL. Mutation in the JH2 region of tacL upstream regulatory sequence led to increased LTAs abundance and displayed higher transformation efficiency. Collectively, our work identified the regulatory mechanisms that control LTAs biosynthesis during competence and thereby unveiled a repression mechanism underlying pneumococcal transformation.

Due to the rise in temperature and sea level caused by climate change, the detection rate of aflatoxin B1 (AFB1) in food crops has increased dramatically, and the frequency and severity of aflatoxicosis in humans and animals are also increasing. AFB1 has strong hepatotoxicity, causing severe liver damage and even cancer. However, the mechanism of AFB1 hepatotoxicity remains unclear. By integrating network toxicology, molecular docking and in vivo experiments, this research was designed to explore the potential hepatotoxicity mechanisms of AFB1. Thirty-three intersection targets for AFB1-induced liver damage were identified using online databases. PI3K/AKT1, MAPK, FOXO1 signaling pathways, and apoptosis were significantly enriched. In addition, the proteins of ALB, AKT1, PIK3CG, MAPK8, HSP90AA1, PPARA, MAPK1, EGFR, FOXO1, and IGF1 exhibited good affinity with AFB1. In vivo experiments, significant pathological changes occurred in the liver of mice. AFB1 induction increased the expression levels of EGFR, ERK, and FOXO1, and decreased the expression levsls of PI3K and AKT1. Moreover, AFB1 treatment caused an increase in Caspase3 expression, and a decrease in Bcl2/Bax ratio. By combining network toxicology with in vivo experiments, this study confirms for the first time that AFB1 promotes the FOXO1 signaling pathway by inactivating PI3K/AKT1 and activating EGFR/ERK signaling pathways, hence aggravating hepatocyte apoptosis. This research provides new strategies for studying the toxicity of environmental pollutants and new possible targets for the development of hepatoprotective drugs.

Abstract Background Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined. Methods BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages. Results We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg. Conclusion Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.

Abstract Monitoring extent and severity is vital in the ulcerative colitis (UC) follow-up, however, current assessment is complex and low cost-effectiveness. We aimed to develop a routine blood-based clinical decision support tool, Jin’s model, to investigate the extent and severity of UC. The multicentre retrospective cohort study recruited 975 adult UC inpatients and sub-grouped into training, internal validation and external validation set. Model was developed by logistics regression for the extent via Montreal classification and for the severity via Mayo score, Truelove and Witts score (TWS), Mayo endoscopic score (MES) and Degree of Ulcerative colitis Burden of Luminal Inflammation (DUBLIN) score. In Montreal classification, left-sided and extensive versus proctitis model achieved area under the receiver operating characteristic curve (AUROC) of 0.78 and 0.81 retrospectively. For severity, Mayo score model, TWS model, MES model and DUBLIN score model achieved an AUROC of 0.81, 0.70, 0.74 and 0.70 retrospectively. The models also were evaluated with satisfactory calibration and clinical unity. Jin’s model was free with open access at http://jinmodel.com:3000/ . Jin’s model is a noninvasive, convenient, and efficient approach to assess the extent and severity of UC.

Abstract Background and purpose Chronic gastritis, especially that caused by helicobacter pylori (HP) infection, has been associated with increased risk of ischemic stroke. But the relationship between chronic gastritis and cerebral small vessel disease (CSVD) remains largely undetermined. This study aimed to determine the potential predictors for CSVD, with chronic gastritis and its proxies as alternatives. Method Patients aged 18 years or older with indications for electronic gastroscopy were enrolled. Presence of CSVD was evaluated with brain magnetic resonance imaging (MRI) results. Degree of CSVD was scored according to established criteria. Logistic regression analysis was used for identifying possible risk factors for CSVD. Results Of the 1191 enrolled patients, 757 (63.6%) were identified as with, and 434 (36.4%) as without CSVD. Multivariate analysis indicated that patients with chronic atrophic gastritis had an increased risk for CSVD than those without (adjusted odds ratio = 1.58; 95% CI, 1.08–2.32; P

ABSTRACTChinese onion is a common vegetable in daily diet, especially in Southwest China. We collected 184 samples from farm and market in Chongqing Municipality during 2020–2021 and established a multi-residue method for analysis of 79 pesticide residues on Chinese onion. Sixty-three of 184 samples were found pesticide resdues, accounting for 34.2%. A total of 31 pesticides were detected, and 6 pesticides in 11 samples have exceeded the Chinese MRLs, 5.98% of all samples. The chronic and acute dietary exposure assessment showed the %ADI and the %ARfD value were 0.005%–5.46% and 0.03%–297.95%, respectively. The %ARfD of most pesticides were acceptable except for cyhalothrin (297.95%, children; 140.17%, adults) and carbofuran (107.94%, children). The study indicated that pesticide residues on Chinese onion had different concentration levels which were low commonly. The establishment of MRLs for several pesticides (cyfluthrin, carbendazim, propamocarb) in Chinese onion is required for better estimation of dietary risk.

Abstract Background The efficacy of current surgery and chemotherapy for triple negative breast cancer (TNBC) is limited due to heterogenous and immunosuppressive tumor microenvironment (TME). Tumor associated macrophages (TAMs), which are regarded as an M2 tumor-promoting phenotype, are crucial in the development of the immunosuppressive TME. Targeting TAM reprograming is a promising strategy in anti-tumor therapy since reprogramming techniques provide the opportunity to actively enhance the antitumor immunological activity of TAM in addition to eliminating their tumor-supportive roles, which is rarely applied in TNBC clinically. However, how to drive M2 macrophages reprogramming into M1 with high potency remains a challenge and the molecular mechanisms how M2 macrophages polarized into M1 are poorly understood. Here, we identified a new immunoregulatory molecular PepO that was served as an immunoregulatory molecule governed the transformation of tumor-promoting M2 to tumor-inhibitory M1 cells and represented an effective anti-tumor property. Results At the present study, we identified a new immunoregulatory molecular PepO, as a harmless immunoregulatory molecule, governed the transformation of tumor-promoting M2 to tumor-inhibitory M1 cells efficiently. PepO-primed M2 macrophages decreased the expression of tumor-supportive molecules like Arg-1, Tgfb, Vegfa and IL-10, and increased the expression of iNOS, Cxcl9, Cxcl10, TNF-α and IL-6 to inhibit TNBC growth. Moreover, PepO enhanced the functions of macrophages related to cell killing, phagocytosis and nitric oxide biosynthetic process, thereby inhibiting the development of tumors in vivo and in vitro. Mechanistically, PepO reprogramed TAMs toward M1 by activating PI3K-AKT-mTOR pathway via TLR4 and suppressed the function of M2 by inhibiting JAK2-STAT3 pathway via TLR2. The PI3K inhibitor LY294002 abrogated the role of PepO in switching M2 macrophages into M1 and in inhibiting TNBC growth in vivo. And PepO failed to govern the M2 macrophages to reprogram into M1 macrophages and inhibit TNBC when TLR2 or TLR4 was deficient. Moreover, PepO enhanced the antitumor activity of doxorubicin and the combination exerted a synergistic effect on TNBC suppression. Conclusions Our research identified a possible macrophage-based TNBC immunotherapeutic approach and suggested a novel anticancer immunoregulatory molecular called PepO.

Abstract Background RAS mutations affect prognosis in patients with metastatic colorectal cancer (mCRC) and have been identified as strong negative predictive markers for anti-epidermal growth factor receptor monoclonal antibody (anti-EGFR mAb) therapy, but many tumors containing wild-type RAS genes still do not respond to these therapies. Some additional biomarkers may have prognostic or predictive roles, but conclusions remain controversial. Methods We performed a meta-analysis and systematic review of randomized controlled trials comparing anti-EGFR mAb therapy with alternative therapy that investigated the prognostic and predictive impact of additional biomarkers in RAS wild-type (wt) mCRC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) for objective response rate (ORR) were calculated. The prognostic value of biomarkers was investigated by separately pooling HR and OR for different treatment groups in an individual study. The predictive value was assessed by pooling study interactions between treatment effects and biomarker subgroups. Results Thirty publications reporting on eighteen trials were selected, including a total of 13,507 patients. In prognostic analysis, BRAF mutations were associated with poorer PFS [HRs = 3.76 (2.47–5.73) and 2.69 (1.82–3.98)] and OS [HRs = 2.66 (1.95–3.65) and 2.45 (1.55–3.88)] in both the experimental and control arms; low miR-31-3p expression appeared to have longer PFS and OS. In terms of predictive effect, a lack of response to anti-EGFR therapy was observed in patients with BRAF mutant tumors (P interaction

Abstract The identification in Quercus L. species was considered to be difficult all the time. The fundamental phylogenies of Quercus have already been discussed by morphological and molecular means. However, the morphological characteristics of some Quercus groups may not be consistent with the molecular results (such as the group Helferiana), which may lead to blurring of species relationships and prevent further evolutionary researches. To understand the interspecific relationships and phylogenetic positions, we sequenced and assembled the CPGs (160,715 bp-160842 bp) of four Quercus section Cyclobalanopsis species by Illumina pair-end sequencing. The genomic structure, GC content, and IR/SC boundaries exhibited significant conservatism. Six highly variable hotspots were detected in comparison analysis, among which rpoC1, clpP and ycf1 could be used as molecular markers. Besides, two genes (petA, ycf2) were detected to be under positive selection pressure. The phylogenetic analysis showed: Trigonobalanus genus and Fagus genus located at the base of the phylogeny tree; The Quercus genus species were distincted to two clades, including five sections. All Compound Trichome Base species clustered into a single branch, which was in accordance with the results of the morphological studies. But neither of group Gilva nor group Helferiana had formed a monophyly. Six Compound Trichome Base species gathered together in pairs to form three branch respectively (Quercus kerrii and Quercus chungii; Quercus austrocochinchinensis with Quercus gilva; Quercus helferiana and Quercus rex). Due to a low support rate (0.338) in the phylogeny tree, the interspecies relationship between the two branches differentiated by this node remained unclear. We believe that Q. helferiana and Q. kerrii can exist as independent species due to their distance in the phylogeny tree. Our study provided genetic information in Quercus genus, which could be applied to further studies in taxonomy and phylogenetics.