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The mass transfer from a stagnant CO2 gas pocket to the flowing water in a horizontal pipe was investigated experimentally, considering the application of pH adjustment by injecting gaseous CO2 for raw water in water treatment industries. In the experiments, the variation of the CO2 gas pocket volume and the corresponding pH values of the pipe flow with time under different conditions were recorded. The mass transfer coefficient of the CO2 gas pocket in the pipe flow was then calculated. The results showed that the injection of gaseous CO2 into the pipe flow could effectively adjust the pH. The volume of the CO2 gas pocket decreased exponentially. Different from most studies on bubble mass transfer, it was found that the ambient CO2 concentration could not be neglected in this study due to the large volume of the gas pocket and the restricted space in the pipe. The mass transfer coefficient increased with the increasing ratio of the CO2 injection rate to the water flow rate and exhibited a sharp reduction as the volume of the CO2 gas pocket decreased by about 80%. The outcomes of this paper can contribute to a better understanding of gas bubble mass transfer in pipe flows. HIGHLIGHTS The mass transfer of a large CO2 gas pocket in the horizontal pipe flow was investigated, which has been hardly reported before.; During mass transfer processes, the pH variation of the pipe flow could be divided into three regimes, and the volume of the gas pocket was reduced exponentially.; The CO2 concentration in the pipe flow is important to mass transfer due to the large volume of the gas pocket and the restricted space in the pipe.;

Abstract This study aimed to investigate the epidemiological characteristics and trends over time of carbapenemase-producing (e.g., KPC, NDM, VIM, IMP, and OXA-48) Gram-negative bacteria (CPGNB). Non-duplicated multi-drug resistant Gram-negative bacteria (MDRGNB) were collected from the First Affiliated Hospital of Zhengzhou University from April 2019 to February 2023. Species identification of each isolate was performed using the Vitek2 system and confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry according to the manufacturer's instructions. PCR detected carbapenem resistance genes in the strains, strains carrying carbapenem resistance genes were categorized as CPGNB strains after validation by carbapenem inactivation assay. A total of 5705 non-repetitive MDRGNB isolates belonging to 78 different species were collected during the study period, of which 1918 CPGNB were validated, with the respiratory tract being the primary source of specimens. Epidemiologic statistics showed a significant predominance of ICU-sourced strains compared to other departments. Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa were the significant CPGNB in Henan, and KPC and NDM were the predominant carbapenemases. Carbapenem-resistant infections in Henan Province showed an overall increasing trend, and the carriage of carbapenemase genes by CPGNB has become increasingly prevalent and complicated. The growing prevalence of CPGNB in the post-pandemic era poses a significant challenge to public safety.

Abstract Age-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.

With the wide application of artificial intelligence (AI) in the medical field, more and more AI-based clinical decision support systems have been applied in the clinical diagnosis, screening, and other fields. Early-stage clinical evaluation is important for evaluating the clinical performance, safety, and human factors of AI-based clinical decision support systems, and laying the foundation for large-scale trials. However, the transparency and integrity of the clinical reports need to be improved. The Developmental and Exploratory Clinical Investigations of DEcision Support Systems Driven by Artificial Intelligence (DECIDE-AI) was officially published online in May 2022. Based on this guideline and relative literature, this paper explores the transparent reporting of early-stage clinical evaluation of AI-based clinical decision support systems, in order to help developers and researchers better understand and apply the relevant guidelines, and improve the reporting transparency of early-stage clinical evaluation of AI-based clinical decision support systems.

Data-driven material research for property prediction and material design using machine learning methods requires a large quantity, wide variety, and high-quality materials data. For battery materials, which are commonly polycrystalline, ceramics, and composites, multiscale data on substances, materials, and batteries are required. In this work, we develop a data network composed of three interlinked databases, from which we can obtain comprehensive data on substances such as crystal structures and electronic structures, data on materials such as chemical composition, structure, and properties, and data on batteries such as battery composition, operation conditions, and capacity. The data are extracted from research papers on solid electrolytes and cathode materials, selected by screening more than 330 thousand papers using natural language processing tools. Data extraction and curation are carried out by editors specialized in material science and trained in data standardization.

ObjectivePulmonary artery hypertension (PAH) poses a significant challenge due to its limited therapeutic options and high mortality rates. The ACE2-Ang-(1-7)-Mas axis plays a pivotal role in regulating blood pressure and inhibiting myocardial remodeling. However, the precise mechanistic links between the ACE2-Ang-(1-7)-Mas axis and PAH remain poorly understood. This study aimed to elucidate the involvement of the ACE2-Ang-(1-7)-Mas axis in the development of PAH.MethodsPAH was induced in mice using Sugen5416/hypoxia, PAAT/PET ratio and PA were detected using cardiac ultrasound; inflammation related factors such as MCP-1, TNF, IL-10and IL-12p70 were detected in intestines using cytometric bead array (CBA) kits; histopathological and morphological changes in lung and intestinal tissues were assessed via HE staining and Masson staining to evaluate the progression of PAH. Immunohistochemistry and western blotting were employed to determine the expression levels of two tight junction proteins, occludin and ZO-1, in intestinal tissues. Additionally, 16rRNA sequencing and non-targeted metabolomics by LC-MS/MS techniques were utilized to investigate the impact of the ACE2-Ang-(1-7)-Mas axis on microbial diversity and metabolomics of intestinal contents.ResultsActivation of the ACE2-Ang-(1-7)-Mas axis improves heart function, reduces intestines inflammatory factors and ameliorates pathological and histological alterations in SuHx mice. This activation notably upregulated the expression of occludin and ZO-1 proteins in intestinal tissues and promoted the proliferation of SCFA-producing bacteria genera, such as g_Candidatus_Saccharimonas. Furthermore, it enhanced the abundance of beneficial metabolites, including tryptophan and butyric acid.ConclusionThe findings suggest that modulation of the ACE2-Ang-(1-7)-Mas axis can alleviate PAH by regulating intestinal microbes and metabolites. These results highlight the potential of the ACE2-Ang-(1-7)-Mas axis as a promising therapeutic target for clinical management of PAH.

Here we report an ultrafast quadruplex RT-qPCR assay with robust diagnostic ability to detect and distinguish pan-SARS-CoVs and influenza A/B viruses within 35 min. This quadruplex RT-qPCR assay comprised of one novel RNA-based internal control targeting human β2-microglobulin (B2M) for process accuracy and three newly-designed primers-probe sets targeting the envelope protein (E) of pan-SARS-CoV, matrix protein (MP) of influenza A virus and non-structural (NS) region of influenza B virus. This quadruplex assay exhibited a sensitivity comparable to its singleplex counterparts and a slightly higher to that of the Centers for Disease Control and Prevention-recommended SARS-CoV-2 and influenza A/B assays. The novel assay showed no false-positive amplifications with other common respiratory viruses, and its 95 % limits of detection for pan-SARS-CoV and influenza A/B virus was 4.26–4.52 copies/reaction. Moreover, the assay was reproducible with less than 1 % coefficient of variation and adaptable testing different clinical and environmental samples. Our ultrafast quadruplex RT-qPCR assay can serve as an attractive tool for effective differentiation of influenza A/B virus and SARS-CoV-2, but more importantly prognose the reemergence/emergence of SARS and novel coronaviruses or influenza viruses from animal spillover.

PurposeAlthough the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis.MethodsA high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton (Gossypium hirsutum L.), and its parental lines, CRI12 and J8891. This atlas allowed us to identify gene expression differences between the parents and to characterize the transcriptomic reprogramming that occurs in the hybrid.ResultsOur analysis revealed abundant gene expression differences between the parents, with pronounced tissue specificity; a total of 1,112 genes exhibited single-parent expression in at least one tissue. It also illuminated transcriptomic reprogramming in the hybrid XZM2, which included both additive and non-additive expression patterns. Coexpression networks between parents and hybrid constructed via weighted gene coexpression network analysis identified modules closely associated with fiber development. In particular, key regulatory hub genes involved in fiber development showed high-parent dominant or over dominant patterns in the hybrid, potentially driving the emergence of heterosis. Finally, high-depth resequencing data was generated and allele-specific expression patterns examined in the hybrid, enabling the dissection of cis- and trans-regulation contributions to the observed expression differences.ConclusionParental transcriptional differences and transcriptomic reprogramming in the hybrid, especially the non-additive upregulation of key genes, play an important role in shaping heterosis. Collectively, these findings provide new insights into the molecular basis of heterosis in cotton.

Objectives: To investigate cases of five Campylobacter jejuni outbreaks and describe laboratory characteristics of these infections. Methods: Whole-genome sequencing and conventional methods were combined to thoroughly investigate the outbreaks, and data of contemporaneous sporadic cases was included for comparison. Results: Seven sequence types (STs) of C. jejuni caused 83 cases, including ST9079 which recurred across 2 years. Trace-back investigation could not identify any food items of infection but detected identical campylobacters from food contacts. Phylogenetic analysis unveiled genetic closeness between outbreak strains and some concurrent sporadic strains, indicating local campylobacteriosis may not be wholly sporadic but rather a series of linked cases. Virulence genes disclosed species/case-specific signatures to differentiate outbreaks from truly non-outbreak strains. Resistance to fluoroquinolones and/or macrolides was prevalent (90.8%, 108/119), with a noteworthy portion exhibiting multidrug resistance (31.1%, 37/119). Five types of plasmids were harbored among outbreak isolates, of which one plasmid harboring anti-stress and resistant genes was rarely found in C. jejuni. Conclusions: This is the first reported sequential outbreak of C. jejuni in China. Our observations help to define the genomic landscape and antimicrobial resistance patterns of Campylobacter, emphasizing the need for a broader ‘One Health’ perspective to combat the threats posed by campylobacteriosis.

Abstract Background Although phytoplankton are important primary producers in food webs, they are relatively less studied in large rivers compared to other types of systems. To fill this research gap, we studied phytoplankton taxonomic and functional composition and their relationships with water quality, habitat, climate, and land use across 30 river sections in the middle and lower reaches of the Yangtze River during 2017–2018. Results Major observed phytoplankton groups were cyanobacteria, bacillariophyta, and chlorophyta. Phytoplankton total abundance, total biomass, and species richness significantly decreased in the dry season compared to the wet season, with the species and functional composition differing significantly between seasons. Phytoplankton species differences between seasons were mainly contributed by Oscillatoria sp., Pseudanabaena sp., and Melosira granulata. The dfferences in phytoplankton functional groups between seasons were mainly contributed by P (including Closterium sp., Melosira sp.), Lo (including Merismopedia sp., Peridinium sp., Ceratium sp., and Gymnodinium sp.), and J (including Pediastrum sp., Tetraedron sp., Crucigenia sp., Scenedesmus sp., and Coelastrum sp.). The variance partitioning showed that water quality (NO3-N, total suspended solids, turbidity) and habitat (water flow, river bank and river channel conditions) were critical factors in shaping phytoplankton patterns, followed by climate and land use. Conclusions Results indicated that there was significant seasonal variation of phytoplankton in the Yangtze River, with water quality and habitat primarily driving phytoplankton patterns. Our study contributes to the understanding of natural and anthropogenic factors that drive seasonal successional processes of phytoplankton in the Yangtze River. These findings have important implications for environmental management as well as towards the ecological restoration of large rivers.

Abstract Background Multi-drug-resistant organisms (MDROs) in gram-negative bacteria have caused a global epidemic, especially the bacterial resistance to carbapenem agents. Plasmid is the common vehicle for carrying antimicrobial resistance genes (ARGs), and the transmission of plasmids is also one of the important reasons for the emergence of MDROs. Different incompatibility group plasmid replicons are highly correlated with the acquisition, dissemination, and evolution of resistance genes. Based on this, the study aims to identify relevant characteristics of various plasmids and provide a theoretical foundation for clinical anti-infection treatment. Methods 330 gram-negative strains with different antimicrobial phenotypes from a tertiary hospital in Henan Province were included in this study to clarify the difference in incompatibility group plasmid replicons. Additionally, we combined the information from the PLSDB database to elaborate on the potential association between different plasmid replicons and ARGs. The VITEK mass spectrometer was used for species identification, and the VITEK-compact 2 automatic microbial system was used for the antimicrobial susceptibility test (AST). PCR-based replicon typing (PBRT) detected the plasmid profiles, and thirty-three different plasmid replicons were determined. All the carbapenem-resistant organisms (CROs) were tested for the carbapenemase genes. Results 21 plasmid replicon types were detected in this experiment, with the highest prevalence of IncFII, IncFIB, IncR, and IncFIA. Notably, the detection rate of IncX3 plasmids in CROs is higher, which is different in strains with other antimicrobial phenotypes. The number of plasmid replicons they carried increased with the strain resistance increase. Enterobacterales took a higher number of plasmid replicons than other gram-negative bacteria. The same strain tends to have more than one plasmid replicon type. IncF-type plasmids tend to be associated with MDROs. Combined with PLSDB database analysis, IncFII and IncX3 are critical platforms for taking bla KPC−2 and bla NDM. Conclusions MDROs tend to carry more complex plasmid replicons compared with non-MDROs. The plasmid replicons that are predominantly prevalent and associated with ARGs differ in various species. The wide distribution of IncF-type plasmids and their close association with MDROs should deserve our attention. Further investigation into the critical role of plasmids in the carriage, evolution, and transmission of ARGs is needed.

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.

Freshwater biodiversity is increasingly threatened by dams and many other anthropogenic stressors, yet our understanding of the complex responses of different biotas and their multiple facets remains limited. Here, we present a multi-faceted and integrated-indices approach to assess the differential responses of freshwater biodiversity to multiple stressors in the Yangtze River, the third longest and most dam-densely river in the world. By combining individual biodiversity indices of phytoplankton, zooplankton, periphyton, macroinvertebrates, and fish with a novel integrated aquatic biodiversity index (IABI), we disentangled the effects of hydrology, water quality, land use, and natural factors on both α and β diversity facets in taxonomic, functional, and phylogenetic dimensions. Our results revealed that phytoplankton and fish species and functional richness increased longitudinally, while fish taxonomic and phylogenetic β diversity increased but phytoplankton and macroinvertebrate β diversity remained unchanged. Hydrology and water quality emerged as the key drivers of all individual biodiversity indices, followed by land use and natural factors, with fish and phytoplankton showed the strongest responses. Importantly, we found that natural, land use, and hydrological factors indirectly affected biodiversity by altering water quality, which in turn directly influenced taxonomic and phylogenetic IABIs. Our findings highlight the complex interplay of multiple stressors in shaping freshwater biodiversity and underscore the importance of considering both individual and integrated indices for effective conservation and management. We propose that our multi-faceted and integrated-indices approach can be applied to other large, dam-modified river basins globally.

Background To investigate the association between gestational weight gain (GWG) and preterm birth (PTB) according to pre-pregnancy body mass index (pp-BMI) and glycated haemoglobin (HbA1c) within the normal range.Methods We conducted a population-based retrospective cohort study between July 2017 and January 2020 at Women’s Hospital, Zhejiang University School of Medicine. Women were classified into three groups (inadequate GWG, appropriate GWG, and excessive GWG). In addition, women were divided into different subgroups according to pp-BMI and HbA1c. We estimated the odds ratios (OR) with 95% confidence intervals (CI) to assess the associations between GWG and the risk of PTB. Meanwhile, we adjusted for possible confounding factors, including maternal age, infant sex, family history of diabetes, education, pregnancy mode, delivery mode, parity, and gravidity.Results The study involved 23,699 pregnant women, of which 1124 (4.70%) were PTB. Women who had inadequate GWG were found to have a significantly higher risk of PTB compared to women with appropriate GWG. In contrast, women with excessive GWG had a reduced risk of PTB. Similarly, GWG and PTB had similar risk associations in the HbA1c and pp-BMI subgroups. Among women with pp-BMI

Marine protected areas (MPAs) across various countries have contributed to safeguarding coastal and marine environments. Despite these efforts, marine non-native species (NNS) continue to threaten biodiversity and ecosystems, even within MPAs. Currently, there is a lack of comprehensive studies on the inventories, distribution patterns, and effect factors of NNS within MPAs. Here we show a database containing over 15,000 occurrence records of 2714 marine NNS across 16,401 national or regional MPAs worldwide. To identify the primary mechanisms driving the occurrence of NNS, we utilize model selection with proxies representing colonization pressure, environmental variables, and MPA characteristics. Among the environmental predictors analyzed, sea surface temperature emerged as the sole factor strongly associated with NNS richness. Higher sea surface temperatures are linked to increased NNS richness, aligning with global marine biodiversity trends. Furthermore, human activities help species overcome geographical barriers and migration constraints. Consequently, this influences the distribution patterns of marine introduced species and associated environmental factors. As global climate change continues to alter sea temperatures, it is crucial to protect marine regions that are increasingly vulnerable to intense human activities and biological invasions.

Cotton fiber, the mainstay of the world’s textile industry, is formed by the differentiation of epidermal cells on the outer peridium of the ovule. The TBL gene family is involved in the regulation of epidermal hair development as well as response to abiotic stress. However, the function of TBL genes in cotton has not been systematically studied yet. Here, we identified 131 and 130 TBL genes in TM-1 (Gossypium hirsutum) and Hai7124 (Gossypium barbadense), respectively. Phylogenetic, gene structure, expression pattern and cis-element of promoter analysis were performed and compared. Single gene association analysis indicated that more TBL genes related to fiber quality traits were found in G. barbadense, whereas more genes associated with yield traits were found in G. hirsutum. One gene, GhTBL84 (GH_D04G0930), was induced by treatment at 4°C for 12 and 24 h in G. hirsutum and silencing of the GhTBL84 gene by VIGS technology in TM-1 can significantly improve the resistance of cotton seedlings to low temperature stress. In sum, our study conducted a genome-wide identification and comparative analysis of TBL family genes in G. hirsutum and G. barbadense and demonstrated a group of TBL genes significantly associated with fiber quality and excavated cold stress responsive gene, such as GhTBL84, providing a theoretical basis for further improving cotton agronomic traits.

Background: To refine the methods of developing clinical practice guidelines (CPGs) for integrative Chinese-Western medicine (ICWM), promoting the formation of trustworthy, implementable recommendations that integrate the strengths of Chinese and Western medicine. Methods: Using a nominal group technique (NGT) approach, a multidisciplinary expert panel was established. The panel identified key methodological issues in ICWM-CPG development through literature review and iterative discussions, and formulated methodological proposals to address these issues. The final set of proposals was achieved through consensus among the panel members. Results: The collaborative effort resulted in the identification of five pivotal methodological issues and the subsequent establishment of 22 specific recommendations. These encompass strict adherence to renowned standards, such as those proposed by the Institute of Medicine (IOM) and Guidelines International Network (G-I-N), the employment of methodologies like the GRADE approach and RIGHT statement, the strategic constitution of a balanced development group, the adept identification of ICWM-focused clinical inquiries, the nuanced integration of diverse evidence sources, and the detailed crafting of transparent, implementable recommendations. Conclusions: This study concentrates on the most crucial and prevalent methodological issues in ICWM-CPG development, proposing a series of recommendations. These suggestions result from a multidisciplinary expert consensus, aiming to provide methodological guidance for ICWM-CPG developers, building upon the current foundational methodologies.

Members of the Malvaceae family, including Corchorus spp., Gossypium spp., Bombax spp., and Ceiba spp., are important sources of natural fibers. In the past decade, the genomes of several Malvaceae species have been assembled; however, the evolutionary history of Malvaceae species and the differences in their fiber development remain to be clarified. Here, we report the genome assembly and annotation of two natural fiber plants from the Malvaceae, Bombax ceiba and Ceiba pentandra, whose assembled genome sizes are 783.56 Mb and 1575.47 Mb, respectively. Comparative analysis revealed that whole-genome duplication and Gypsy long terminal repeat retroelements have been the major causes of differences in chromosome number (2n = 14 to 2n = 96) and genome size (234 Mb to 2676 Mb) among Malvaceae species. We also used comparative genomic analyses to reconstruct the ancestral Malvaceae karyotype with 11 proto-chromosomes, providing new insights into the evolutionary trajectories of Malvaceae species. MYB-MIXTA-like 3 is relatively conserved among the Malvaceae and functions in fiber cell-fate determination in the epidermis. It appears to perform this function in any tissue where it is expressed, i.e. in fibers on the endocarp of B. ceiba and in ovule fibers of cotton. We identified a structural variation in a cellulose synthase gene and a higher copy number of cellulose synthase-like genes as possible causes of the finer, less spinnable, weaker fibers of B. ceiba. Our study provides two high-quality genomes of natural fiber plants and offers insights into the evolution of Malvaceae species and differences in their natural fiber formation and development through multi-omics analysis.

Background and aimTraumatic brain injury (TBI), a leading cause of high morbidity and mortality, represents a significant global public health challenge. Currently, no effective treatment for TBI exists. Curcumin, an active compound extracted from the root of Curcuma longa, has demonstrated neuroprotective properties both in vitro and in vivo. Notably, it has shown potential in reducing oxidative stress and inflammation and enhancing redox balance. This paper conducts a systematic review and meta-analysis to explore curcumin’s role in TBI animal models extensively. The findings offer valuable insights for future human clinical trials evaluating curcumin as a therapeutic supplement or nutraceutical in TBI management.MethodsComprehensive literature searches were conducted across MEDLINE, Embase, Cochrane, Web of Science, and Google Scholar databases. These searches aimed to identify relevant manuscripts in all languages, utilizing the keywords “curcumin” and “traumatic brain injury.”ResultsThe final quantitative analysis included 18 eligible articles corresponding to animal studies. The analysis revealed that curcumin significantly reduced inflammatory cytokines, including IL-1β (p = 0.000), IL-6 (p = 0.002), and TNF-α (p = 0.000), across various concentrations, time points, and administration routes. Additionally, curcumin markedly enhanced the activity of oxidative stress markers such as SOD (p = 0.000), Sir2 (p = 0.000), GPx (p = 0.000), and Nrf2 (p = 0.000), while reducing MDA (p = 0.000), 4-HNE (p = 0.001), and oxyprotein levels (p = 0.024). Furthermore, curcumin improved cerebral edema (p = 0.000) and upregulated neuroprotective factors like synapsin I (p = 0.019), BDNF (p = 0.000), and CREB (p = 0.000), without reducing mNSS (p = 0.144). About autophagy and apoptosis, curcumin increased the activity of Beclin-1 (p = 0.000) and Bcl-2 (p = 0.000), while decreasing caspase-3 (p = 0.000), the apoptosis index (p = 0.000), and P62 (p = 0.002).ConclusionCurcumin supplementation positively affects traumatic brain injury (TBI) by alleviating oxidative stress and inflammatory responses and promoting neuroprotection. It holds potential as a therapeutic agent for human TBI. However, this conclusion necessitates further substantiation through high-quality literature and additional randomized controlled trials (RCTs).Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/. The registration number of PROSPERO: CRD42023452685.

Morphology of bivalves, a kind of quantitative character, is closely connected with the ecological and physiological behaviors of bivalves, including growth, survival, metabolism and reproduction. In this study, a multivariate statistical method was used to analyze seven indices for shell shape evaluation of Ruditaps philippinarum (R. philippinarum). Polymorphism of R. philippinarum shell shape across seven geographical populations from the southern and northern regions of China was revealed, and decisive effect of shell shape in determining the trait of weight was discussed. In total, three types of R. philippinarum shell shape were observed: globular, flat, and lateral-view round. The Laizhou (LZ) population from the north of China displayed an approximately globular shell shape, with a shell-width-to-shell-length ratio of 0.5496 and an ellipse index ventral view (EIV) value of 0.9543. The Lianjiang (LJ) population from the south of China displayed a flat shell shape, with a shell-width-to-shell-length ratio of 0.4044, an ellipse index lateral view (EIL) value of 1.2518, and an EIV value of 0.7063. The Zhangzidao (ZZD) population from the north of China displayed a lateral view round shell shape, with a shell-width-to-shell-length ratio of 0.7476 and a circle index lateral view (CIL) value of 0.7195. According to the results of principal component analysis (PCA), discriminant analysis and cluster analysis on shell shape parameters, LJ population and LZ population could be grouped separately. However, despite the long geographical distance, Rongcheng (RC) population was highly similar with ZZD population in terms of shell shape traits, implying that these two populations might be more closely related. Lowest degree of divergence in shell shape was observed in Beihai (BH) population and Yingkou (YK) population, both of which belonged to Zuidong (ZD) population. Weight of globular Manila clams was significantly higher than that of flat clams (P < 0.05). This study not only lays a foundation for conservation of R. philippinarum germplasm resources, but also highlights the importance of considering shell morphology in the breeding and culture of R. philippinarum.

Abstract Background Kirsten rat sarcoma (KRAS) and mutant KRASG12D have been implicated in human cancers, but it remains unclear whether their activation requires ubiquitination. This study aimed to investigate whether and how F-box and leucine-rich repeat 6 (FBXL6) regulates KRAS and KRASG12D activity in hepatocellular carcinoma (HCC). Methods We constructed transgenic mouse strains LC (LSL-Fbxl6 KI/+ ;Alb-Cre, n = 13), KC (LSL-Kras G12D/+ ;Alb-Cre, n = 10) and KLC (LSL-Kras G12D/+ ;LSL-Fbxl6 KI/+ ;Alb-Cre, n = 12) mice, and then monitored HCC for 320 d. Multiomics approaches and pharmacological inhibitors were used to determine oncogenic signaling in the context of elevated FBXL6 and KRAS activation. Co‑immunoprecipitation (Co-IP), Western blotting, ubiquitination assay and RAS activity detection assay were employed to investigate the underlying molecular mechanism by which FBXL6 activates KRAS. The pathological relevance of the FBXL6/KRAS/extracellular signal-regulated kinase (ERK)/mammalian target of rapamycin (mTOR)/proteins of relevant evolutionary and lymphoid interest domain 2 (PRELID2) axis was evaluated in 129 paired samples from HCC patients. Results FBXL6 is highly expressed in HCC as well as other human cancers (P

Pepper (Capsicum annuum L.) is an economically important crop containing capsaicinoids in the seed and placenta, which has various culinary, medical, and industrial applications. Late embryogenesis abundant (LEA) proteins are a large group of hydrophilic proteins participating in the plant stress response and seed development. However, to date there have been no genome‐wide analyses of the LEA gene family in pepper. In the present study, 82 LEA genes were identified in the C. annuum genome and classified into nine subfamilies. Most CaLEA genes contain few introns (≤ 2) and are unevenly distributed across 10 chromosomes. Eight pairs of tandem duplication genes and two pairs of segmental duplication genes were identified in the LEA gene family; these duplicated genes were highly conserved and may have performed similar functions during evolution. Expression profile analysis indicated that CaLEA genes exhibited different tissue expression patterns, especially during embryonic development and stress response, particularly in cold stress. Three out of five CaLEA genes showed induced expression upon cold treatment. In summary, we have comprehensively reviewed the LEA gene family in pepper, offering a new perspective on the evolution of this family.

Abstract The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Throughout the human lifespan, from conception to the end of life, small molecules have an intrinsic relationship with numerous physiological processes. The investigation into small-molecule targets holds significant implications for pharmacological discovery. The determination of the action sites of small molecules provide clarity into the pharmacodynamics and toxicological mechanisms of small-molecule drugs, assisting in the elucidation of drug off-target effects and resistance mechanisms. Consequently, innovative methods to study small-molecule targets have proliferated in recent years, with chemical proteomics standing out as a vanguard development in chemical biology in the post-genomic age. Chemical proteomics can non-selectively identify unknown targets of compounds within complex biological matrices, with both probe and non-probe modalities enabling effective target identification. This review attempts to summarize methods and illustrative examples of small-molecule target identification via chemical proteomics. It delves deeply into the interactions between small molecules and human biology to provide pivotal directions and strategies for the discovery and comprehension of novel pharmaceuticals, as well as to improve the evaluation of drug safety.

Bacterial foodborne diseases caused by Vibrio parahaemolyticus pose persistent challenges to coastal cities in China. In this study, we employed multiple logistic regression analysis and distributed lag non-linear models (DLNM) to investigate the epidemiological characteristics and associated risk factors of vibriosis in the metropolitan area of Hangzhou from 2014 to 2018. Analysis of foodborne cases indicated that certain demographics and occupational factors, including age between 16 and 44 years; houseworkers or unemployed individuals; preference for aquatic and meat products; and dining in collective canteens or catering services contribute to an increased likelihood of V. parahaemolyticus infection. Moreover, a higher per capita GDP and exposure to high temperatures were identified as risk factors for vibriosis. This study highlights the significance of the daily mean temperature as a meteorological factor influencing V. parahaemolyticus infection, with varying lag effects observed depending on temperature conditions. At low temperatures, the risk of infection occurs after a lag of 21 days, whereas at high temperatures, the risk is highest on the same day, while the second infection risk period occurs after a lag of 21 days. These findings provide a spatiotemporal perspective of the risk analysis of foodborne diseases, with a daily timescale and street spatial scale, which contributes to the development of public health strategies and food safety protocols in coastal cities.

Forests in the wildland-urban interface (WUI) are of high value but vulnerable to wildland fires due to abundant fire ignitions and flammable forest fuels. Restoring the post-fire Wildland-Urban Interface (WUI) forest landscape is of utmost importance in order to maintain ecosystem service provision. The near-natural restoration strategy is widely employed in vegetation restoration as it enables the formation of healthy, stable, and diverse artificial mixed forests that resemble natural forests. To evaluate the long-term effects of near-natural restoration on the WUI forest landscape, which are largely unclear, we used a wildfire in 2019 near Shenyang City in northeast China as an example and investigated the post-fire forest dynamics under two different scenarios (i.e., natural succession and near-natural restoration) based on the forest landscape model. The results demonstrated that near-natural restoration can significantly accelerate the restoration process in terms of forest biomass, species biodiversity, and age structure. Under the near-natural restoration scenario, the biomass of the burned area can be quickly restored within 20 years after the fire. At the species level, the biomass and proportion of pioneer tree species such as Pinus tabuliformis and Robinia pseudoacacia decreased under the near-natural restoration scenario, while other species started to increase. Then post-fire near-natural planting accelerated the restoration of forest biodiversity, by 2070, the Shannon–Wiener index was predicted to be 1.49 under natural succession and remained at 2.02 under near-natural restoration. In terms of age structure, near-natural restoration shortens the recovery time of fire trails to mature forests. In summary, near-natural restoration accelerates forest recovery in post-fire WUI areas. Our results highlighted the impact of near-natural restoration on forest conservation to inform post-fire forest planning and management practices.

Background: Although many circulating miRNAs (c-miRNAs) are associated with coronary artery disease (CAD), they are far from being the biomarker for CAD diagnosis or risk prediction. Therefore, novel c-miRNAs discovery and validation are still required, especially evaluating their prediction capacity. Objectives: Identify novel CAD-related c-miRNAs and evaluate its risk prediction capacity for CAD. Methods: miRNAs associated with CAD were preliminarily investigated in three paired samples representing pre-CAD stage and CAD stage of three female individuals using the Applied Biosystems miRNA TaqMan® Low-Density Array (TLDA). Then, the candidate miRNAs were further verified in an independent case-control study including 129 CAD patients and 76 controls, and their potential practical value in prediction for CAD was evaluated using a machine learning (ML) algorithm. The accuracy of classification and prediction was assessed with the area under the receiver operating characteristic curve (AUC). Results: TLDA analysis shows that miR-140-3p decreased significantly in CAD-stage (FC = −3.01, P = 0.007). Further study shows that miR-140-3p was significantly lower in CAD group [1.26 (0.68, 2.01)] than in control group [2.07 (1.19, 3.21)] (P

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS, with a case fatality rate of up to 30 %. The innate immune system plays a crucial role in the defense against SFTSV; however, the impact of viral propagation of STFSV on the innate immune system remains unclear. Although proteomics analysis revealed that the expression of the downregulator of transcription 1 (DR1) increased after SFTSV infection, the specific change trend and the functional role of DR1 during viral infection remain unelucidated. In this study, we demonstrate that DR1 was highly expressed in response to SFTSV infection in HEK 293T cells using qRT-PCR and Western blot analysis. Furthermore, viral replication significantly increased the expression of various TLRs, especially TLR9. Our data indicated that DR1 positively regulated the expression of TLRs in HEK 293T cells, DR1 overexpression highly increased the expression of numerous TLRs, whereas RNAi-mediated DR1 silencing decreased TLR expression. Additionally, the myeloid differentiation primary response gene 88 (MyD88)-dependent or TIR-domain-containing adaptor inducing interferon-β (TRIF)-dependent signaling pathways were highly up- and downregulated by the overexpression and silencing of DR1, respectively. Finally, we report that DR1 stimulates the expression of TLR7, TLR8, and TLR9, thereby upregulating the TRIF-dependent and MyD88-dependent signaling pathways during the SFTSV infection, attenuating viral replication, and enhancing the production of type I interferon and various inflammatory factors, including IL-1β, IL-6, and IL-8. These results imply that DR1 defends against SFTSV replication by inducing the expression of TLR7, TLR8, and TLR9. Collectively, our findings revealed a novel role and mechanism of DR1 in mediating antiviral responses and innate immunity.

Abstract Metastatic hepatocellular carcinoma (HCC) is the most lethal malignancy and lacks effective treatment. FBXL6 is overexpressed in human hepatocellular carcinoma (HCC), but whether this change drives liver tumorigenesis and lung metastasis in vivo remains unknown. In this study, we aimed to identify FBXL6 (F-Box and Leucine Rich Repeat Protein 6) as a key driver of HCC metastasis and to provide a new paradigm for HCC therapy. We found that elevated FBXL6 expression in hepatocytes drove HCC lung metastasis and was a much stronger driver than Kras mutation (Kras G12D/+ ;Alb-Cre), p53 haploinsufficiency (p53 +/- ) or Tsc1 loss (Tsc1 fl/fl ;Alb-Cre). Mechanistically, VRK2 promoted Thr287 phosphorylation of TKT and then recruited FBXL6 to promote TKT ubiquitination and activation. Activated TKT further increased PD-L1 and VRK2 expression via the ROS-mTOR axis, leading to immune evasion and HCC metastasis. Targeting or knockdown of TKT significantly blocked FBXL6-driven immune evasion and HCC metastasis in vitro and in vivo. Notably, the level of active TKT (p-Thr287 TKT) was increased and was positively correlated with the FBXL6 and VRK2 expression levels in HCC patients. Our work provides novel mechanistic insights into FBXL6-driven HCC metastasis and suggests that targeting the TKT-ROS-mTOR-PD-L1/VRK2 axis is a new paradigm for treating patients with metastatic HCC with high FBXL6 expression.

Abstract Native mass spectrometry (MS) is a powerful technique for interrogating membrane protein complexes and their interactions with other molecules. A key aspect of the technique is the ability to preserve native-like structures and noncovalent interactions, which can be challenging depending on the choice of detergent. Different strategies have been employed to reduce charge on protein complexes to minimize activation and preserve non-covalent interactions. Here, we report the synthesis of a class of polyamine detergents tailored for native MS studies of membrane proteins. These detergents, a series of spermine covalently attached to various alkyl tails, are exceptional charge-reducing molecules, exhibiting a ten-fold enhanced potency over spermine. Addition of polyamine detergents to proteins solubilized in maltoside detergents results in improved, charge-reduced native mass spectra and reduced dissociation of subunits. Polyamine detergents open new opportunities to investigate membrane proteins in different detergent environments that have thwarted previous native MS studies.

Abstract Aim To examine how the effects of hardiness, self‐efficacy and positive academic emotion related to the SRL ability of undergraduate nursing students. Design A cross‐sectional survey was designed. Methods A total of 395 Chinese undergraduate nursing students from two undergraduate colleges filled out the questionnaires from May to June 2019. The relationships between hardiness, self‐efficacy, positive academic emotion and SRL ability were analysed by structural equation modelling. Results The response rate was 94.05%. SRL ability was significantly positive correlated with hardiness, self‐efficacy and positive academic emotion in undergraduate nursing students. Self‐efficacy (β = 0.417, p

Abstract Objectives The present study aims to investigate the efficacy of utilizing three-dimensional (3D) printing technology in concert with Problem-Based Learning (PBL) and Case-Based Learning (CBL) pedagogical approaches in educating senior undergraduate clinical medical students on respiratory diseases. Methods A cohort of 422 fourth-year clinical medicical students of from Anhui Medical University, pursuing a five-year program, were arbitrarily segregated into two distinct groups. The experimental group was subjected to a combined pedagogical approach, which included 3D printing technology, PBL and CBL (referred to as DPC). Conversely, the control group was exposed to conventional teaching methodologies for respiratory disease education. The effectiveness of the teaching methods was subsequently appraised using both theoretical test scores and custom questionnaires. Results Post-quiz scores indicated a statistically significant improvement in the DPC group as compared to the traditional group (P 0.05). Conclusion The deployment of the DPC pedagogical approach may confer unique experiential learning opportunities for students, potentially enhancing theoretical test scores and promoting self-evaluation and satisfaction in the context of respiratory disease education. Hence, it may be instrumental in augmenting the overall teaching efficacy.

Abstract Strength training is recommended by the American Physical Therapy Association to improve muscle strength, mobility, and balance following knee replacement. Few studies have focused on the direct effects of strength training on functional ambulation, and potential dose–response relationships between strength training parameters and the effect remain unclear. The aim of this systematic review, meta-analysis, and meta-regression was to evaluate the effects of strength training on functional ambulation following knee replacement (KR). We also aimed to explore potential dose–response relationships between strength training parameters and performance in functional ambulation. A systematic literature search of eight online databases was performed on March 12, 2023, for randomized controlled trials evaluating the effects of strength training on functional ambulation by six-minute walk test (6MWT) or timed-up and go test (TUG) after KR. Data were pooled by random-effect meta-analyses and presented as weighted mean difference (WMD). A random-effect meta-regression was performed for four predetermined training parameters, namely, duration (weeks), frequency (sessions per week), volume (time per session), and initial time (after surgery) separately to explore dose–response relationships with WMD. Fourteen trials encompassing 956 participants were included in our study. Meta-analyses showed an improvement in 6MWT performance after strength training (WMD: 32.15, 95% CI 19.44–44.85) and a decrease in time to complete TUG (WMD: − 1.92, 95% CI − 3.43 to − 0.41). Meta-regression revealed a dose–response relationship only between volume and 6MWT, with a decreasing trend (P = 0.019, 95% CI − 1.63 to − 0.20). Increasing trends of improvement in 6MWT and TUG were observed with increasing training duration and frequency. A slight decreasing trend of improvement was observed in 6MWT with postponed initial time, while an opposite trend was observed in TUG. Based on existing studies, moderate-certainty evidence suggests that strength training could increase 6MWT distance, and low-certainty evidence shows that strength training could decrease the time to complete TUG after KR. Meta-regression results only suggested a dose–response relationship between volume and 6MWT with a decreasing trend. Registration: PROSPERO: CRD42022329006.

Abstract A reasonable geometric transformation model is the key to image registration. When the relative motion direction between the line-scan camera and the object is strictly parallel to the planar object, it is possible to align the image by using the eight-parameter geometric transformation model of the line-scan image. However, it will be invalid when the relative motion direction is arbitrary. Therefore, a new general geometric transformation model of line-scan images is proposed for line-scan image registration in this paper. Considering the different initial poses and motion directions of the line-scan camera, the proposed model is established based on the imaging model of the line-scan camera. In order to acquire line-scan images to verify the proposed model, a line-scan image acquisition system was built. The method based on feature points is used to register the line-scan images. The experimental results show that the proposed geometric transformation model can align the line-scan image collected under arbitrary relative motion direction, not just the parallel case. Besides, the statistical errors of the image feature point coordinates are the best performance after registration. The accuracy of the registration results is better than that of other existing geometric transformation models, which verifies the correctness and generality of the geometric transformation model of the line-scan camera proposed in this paper.

Inland aquaculture ponds, as an important land use type, have brought great economic benefits to local people but at the same time have caused many environmental problems threatening regional ecology security. Therefore, understanding the spatiotemporal pattern of aquaculture ponds and its potential influence on water quality is vital for the sustainable development of inland lakes. In this study, based on Landsat5/8 images, three types of land features, namely spectral features, index features, and texture features, and five machine learning algorithms, namely random forest (RF), extreme gradient boosting (XGBoost), artificial neural network (ANN), k-nearest neighbor (KNN), and Gaussian naive Bayes (GNB), were combined to identify aquaculture ponds and some other primary land use types around a typical inland lake of China. The results demonstrated that the XGBoost algorithm that integrated the three features performed the best among all groups of the five machine learning algorithms and the three features, with an overall accuracy of up to 96.15%. In particular, the texture features provided additional useful information besides the spectral features to allow more accurately separation of aquaculture ponds from other land use types and thus improve the land use mapping ability in complex inland lakes. Next, this study examined the tendency of aquaculture ponds and found a segmented increase mode, namely sharp increase during 1984–2003 and then slow elevation since 2003. Further positive correlation detected between the area of aquaculture ponds and the phytoplankton population dynamics suggest a likely influence of aquaculture activity on the lake water quality. This study provides an important scientific basis for the sustainable management and ecological protection of inland lakes.

Net Primary Productivity (NPP) is a critical metric for assessing terrestrial carbon sequestration and ecosystem health. While advancements in NPP modeling have enabled estimation at various scales, hidden anomalies within NPP time series necessitate further investigation to understand the driving forces. This study focuses on Shandong Province, China, generating a high-resolution (250 m) monthly NPP product for 2000–2019 using the Carnegie–Ames–Stanford Approach (CASA) model, integrated with satellite remote sensing and ground observations. We employed the Seasonal Mann–Kendall (SMK) Test and the Breaks For Additive Season and Trend (BFAST) algorithm to differentiate between gradual declines and abrupt losses, respectively. Beyond analyzing land use and land cover (LULC) transitions, we utilized Random Forest models to elucidate the influence of environmental factors on NPP changes. The findings revealed a significant overall increase in annual NPP across the study area, with a moderate average of 503.45 gC/(m2·a) during 2000–2019. Although 69.67% of the total area displayed a substantial monotonic increase, 3.89% of the area experienced abrupt NPP losses, and 8.43% exhibited gradual declines. Our analysis identified LULC transitions, primarily driven by urban expansion, as being responsible for 55% of the abrupt loss areas and 33% of the gradual decline areas. Random Forest models effectively explained the remaining areas, revealing that the magnitude of abrupt losses and the intensity of gradual declines were driven by a complex interplay of factors. These factors varied across vegetation types and change types, with explanatory variables related to vegetation status and climatic factors—particularly precipitation—having the most prominent influence on NPP changes. The study suggests that intensified land use and extreme climatic events have led to NPP diminishment in Shandong Province. Nevertheless, the prominent positive vegetation growth trends observed in some areas highlight the potential for NPP enhancement and carbon sequestration through targeted management strategies.

In this research, the CuFeS2/MXene-modified polyvinylidene fluoride (PVDF) membrane was prepared to activate peroxymonosulfate (PMS) to remove moxifloxacin (MOX) and its morphology; surface functional groups and hydrophilicity were also studied. The parameters of the catalytic membrane/PMS system were optimized, with an optimal loading of 4 mg/cm2 and a PMS dosage of 0.20 mM. High filtration pressure, alkaline conditions, and impurities in water could inhibit MOX removal. After continuous filtration, the removal efficiency of MOX using the catalytic membrane/PMS system and PVDF membrane was 68.2% and 9.9%, respectively. Batch filtration could remove 87.8% MOX by the extra 10 min contact time between the catalytic membrane and solution. During the filtration process, CuFeS2/MXene on the surface of the catalytic membrane activated PMS to produce SO4•−, HO•, and 1O2, and MOX was removed through adsorption and degradation. Taking humic acid (HA) as the model foulant, reversible fouling resistance in the catalytic membrane/PMS system was 22.8% of the PVDF membrane. The catalytic membrane/PMS system weakened the formation of the cake layer by oxidizing HA into smaller pollutants and followed the intermediate blocking cake filtration model. The novelty of this research was to develop a CuFeS2/MXene–PVDF membrane-activated PMS system and explore its application in antibiotics removal.

Chikungunya virus, a mosquito-borne virus that causes epidemics, is often misdiagnosed due to symptom similarities with other arboviruses. Here, a portable and integrated nucleic acid-based diagnostic device, which combines reverse transcription-loop-mediated isothermal amplification and lateral-flow detection, was developed. The device is simple to use, precise, equipment-free, and highly sensitive, enabling rapid chikungunya virus identification. The result can be obtained by the naked eye within 40 min. The assay can effectively distinguish chikungunya virus from dengue virus, Japanese encephalitis virus, Zika virus, and yellow fever virus with high specificity and sensitivity as low as 598.46 copies mL−1. It has many benefits for the community screening and monitoring of chikungunya virus in resource-limited areas because of its effectiveness and simplicity. The platform has great potential for the rapid nucleic acid detection of other viruses.

Abstract Retrosynthesis is an important task in organic chemistry. Recently, numerous data-driven approaches have achieved promising results in this task. However, in practice, these data-driven methods might lead to sub-optimal outcomes by making predictions based on the training data distribution, a phenomenon we refer as frequency bias. For example, in template-based approaches, low-ranked predictions are typically generated by less common templates with low confidence scores which might be too low to be comparable, and it is observed that recorded reactants can be among these low-ranked predictions. In this work, we introduce RetroRanker, a ranking model built upon graph neural networks, designed to mitigate the frequency bias in predictions of existing retrosynthesis models through re-ranking. RetroRanker incorporates potential reaction changes of each set of predicted reactants in obtaining the given product to lower the rank of chemically unreasonable predictions. The predicted re-ranked results on publicly available retrosynthesis benchmarks demonstrate that we can achieve improvement on most state-of-the-art models with RetroRanker. Our preliminary studies also indicate that RetroRanker can enhance the performance of multi-step retrosynthesis.

Abstract Background Panax quinquefolius L. (American ginseng) is widely used in medicine due to its wealth of diverse pharmacological effects. Endophytes colonize within P. quinquefolius in multiple tissue types. However, the relationship between endophytes and the production of their active ingredients in different parts of the plant is not clear. Results In this study, the relationship of endophytic diversity and the metabolites produced in different plant tissues of P. quinquefolius were analyzed using metagenomic and metabolomic approaches. The results showed relatively similar endophyte composition in roots and fibrils, but obvious differences between endophyte populations in stems and leaves. Species abundance analysis showed that at the phylum level, the dominant bacterial phylum was Cyanobacteria for roots, fibrils, stems and leaves, Ascomycota forroots and fibrils roots, and Basidiomycota for stems and leaves. LC-MS/MS technology was used to quantitatively analyze the metabolites in different tissues of P. quinquefolius. A total of 398 metabolites and 294 differential metaboliteswere identified, mainly organic acids, sugars, amino acids, polyphenols, and saponins. Most of the differential metabolites were enriched in metabolic pathways such as phenylpropane biosynthesis, flavonoid biosynthesis, citric acid cycle, and amino acid biosynthesis. Correlation analysis showed a positive and negative correlation between the endophytes and the differential metabolites. Conexibacter significantly enriched in root and fibril was significantly positively correlated with saponin differential metabolites, while cyberlindnera significantly enriched in stem and leaf was significantly negatively correlated with differential metabolites (p

Abstract Background Pseudorabies virus (PRV) was thought to only infect animals. Recent studies have shown that it can also infect human. Case presentation We report a case of pseudorabies virus encephalitis and endophthalmitis, diagnosed 89 days after onset, confirmed with intraocular fluid metagenomic next generation sequencing (mNGS) after the result of two cerebrospinal fluid (CSF) mNGS tests were negative. Although treatment with intravenous acyclovir, foscarnet sodium, and methylprednisolone improved the symptoms of encephalitis, significant diagnostic delay resulted in permanent visual loss. Conclusions This case suggests that pseudorabies virus (PRV) DNA in the intraocular fluid may have a higher positivity than that in the CSF. PRV may persist in the intraocular fluid for an extended period and may thus require extended antiviral therapy. Patients with severe encephalitis and PRV should be examined with the focus on pupil reactivity and light reflex. A fundus examination should be performed in patients with a central nervous system infection, specifically, those in a comatose state, to help reduce eye disability.

Abstract Retrosynthesis analysis is an important task in organic chemistry with numerous industrial applications. Previously, machine learning approaches employing natural language processing techniques achieved promising results in this task by first representing reactant molecules as strings and subsequently predicting reactant molecules using text generation or machine translation models. Chemists cannot readily derive useful insights from traditional approaches that rely largely on atom-level decoding in the string representations, because human experts tend to interpret reactions by analyzing substructures that comprise a molecule. It is well-established that some substructures are stable and remain unchanged in reactions. In this paper, we developed a substructure-level decoding model, where commonly preserved portions of product molecules were automatically extracted with a fully data-driven approach. Our model achieves improvement over previously reported models, and we demonstrate that its performance can be boosted further by enhancing the accuracy of these substructures. Analyzing substructures extracted from our machine learning model can provide human experts with additional insights to assist decision-making in retrosynthesis analysis.

Abstract Bone defects are encountered substantially in clinical practice, and bionic scaffolds represent a promising solution for repairing bone defects. However, it is difficult to fabricate scaffolds with bionic structures and reconstruct the microenvironment to fulfill the satisfying repair effects. In this review article, we first discuss various strategies for the design and construction of bionic scaffolds to promote bone defect repair, especially including the structural construction of the scaffold and the integration of bioactive substances together with the application of external stimuli. We then discuss the roles of artificial intelligence and medical imaging in aiding clinical treatment. Finally, we point out the challenges and future outlooks in developing multifunctional bone repair scaffolds, aiming to provide insights for improving bone regeneration efficacy and accelerating clinical translation.

Climate change and rapid urbanization have exacerbated the occurrence and impact of floods. It is essential to carry out a quantitative flood risk assessment and manage the flood risk before a disaster occurs. This article presents a combined riverine flood risk model to obtain the exceedance probability loss (EPL) curve and expected annual damage (EAD) under the current climate. This model includes a rapid flood model and a flood damage model. It aims to simulate the flood risk and evaluate the flood damage at 10-, 30-, 50-, 100-, and 200-year return period events. The results show that: (1) The total inundation areas will sharply increase when the flood return periods are over 30 years. (2) The EAD is 1,476 million dollars in the Jiulong River Basin (JRB). When the flood return period is over 30 years, the total damage increases sharply. (3) The flood risk in the lower reaches of the JRB is higher than in the upper reaches when the flood event is beyond a 20-year return period. (4) Industrial sector damage is the largest, followed by tertiary industry, transportation, construction, agriculture, and infrastructure. The combined model chain can quickly assess the flood risk in the river basin and judge the flood risk in a watershed compared to the national level. In addition, it can be applied to other river basins, and it will provide actionable information for future flood risk management.

Abstract Background Ammonium (NH4 +) is a key nitrogen source supporting plant growth and development. Proteins in the ammonium transporter (AMT) family mediate the movement of NH4 + across the cell membrane. Although several studies have examined AMT genes in various plant species, few studies of the AMT gene family have been conducted in chili pepper. Results Here, a total of eight AMT genes were identified in chili pepper, and their exon/intron structures, phylogenetic relationships, and expression patterns in response to arbuscular mycorrhizal (AM) colonization were explored. Synteny analyses among chili pepper, tomato, eggplant, soybean, and Medicago revealed that the CaAMT2;1, CaAMT2.4, and CaAMT3;1 have undergone an expansion prior to the divergence of Solanaceae and Leguminosae. The expression of six AMT2 genes was either up-regulated or down-regulated in response to AM colonization. The expression of CaAMT2;1/2;2/2;3 and SlAMT2;1/2;2/2;3 was significantly up-regulated in AM fungi-inoculated roots. A 1,112-bp CaAMT2;1 promoter fragment and a 1,400-bp CaAMT2;2 promoter fragment drove the expression of the β-glucuronidase gene in the cortex of AM roots. Evaluation of AM colonization under different NH4 + concentrations revealed that a sufficient, but not excessive, supply of NH4 + promotes the growth of chili pepper and the colonization of AM. Furthermore, we demonstrated that CaAMT2;2 overexpression could mediate NH4 + uptake in tomato plants. Conclusion In sum, our results provide new insights into the evolutionary relationships and functional divergence of chili pepper AMT genes. We also identified putative AMT genes expressed in AM symbiotic roots.

Many transcriptomic pathways in the liver show circadian rhythms, which have been reported to be disrupted in aged mice. Here the authors report that the expression of transcription factor Egr-1 decreases and its rhythm is shifted with age in the liver of male mice, and that deletion of Egr-1 results in increased liver fat accumulation.

To reveal the microscopic pore characteristics and strength weakening mechanism of rock under the influence of cyclic freeze-thaw treatment, uniaxial compression tests and MIP (mercury intrusion porosimetry) were conducted on red sandstone specimens with different numbers of freeze-thaw cycles (0, 20, 40, 60, and 80). The experimental results showed that cyclic F-T (freeze-thaw) treatment can lead to an increase in porosity and the expansion of the pore structure. Specifically, the porosity increased by nearly 30.22% from 8.467% without freeze-thaw to 11.026% after 80 freeze-thaw cycles. The distribution ratios of mesopores (2–10 μm) and micropores (less than 0.1 μm) changed from 0.7% to 19.9% without freeze‒thaw to 12.6% and 11.6% after 80 freeze‒thaw cycles, which showed an expansion trend from small to large pores. For the PFD (pore fractal dimension) of sandstone, three fractal models (capillary pressure model, Menger sponge model and thermodynamic model) were used to calculate the pore fractal dimension of different freeze-thaw cycles, which gradually increased with the increase in freeze‒thaw cycles. Specifically, the PFD increased by 3.02, 3.01 and 2.65% after 20, 40, 60, and 80 freeze-thaw cycles, respectively. Additionally, the PFD calculated by the capillary pressure model and Menger sponge model had piecewise characteristics, which can better characterize pore fractal characteristics with pore diameters less than 2 μm. In summary, based on thermodynamic theory and pore water frost heaving deformation theory, a freeze-thaw damage degradation model based on the porosity of a fractured rock mass was established, and the theoretical value obtained was in good agreement with the experimental results.

To reduce the construction risk of prefabricated building projects, a prefabricated building construction risk assessment index system with five first-level indicators and 21 second-level indicators was established based on human, machine, material, management, and environmental factors. By combining the analytic hierarchy process (AHP), CRiteria Importance through Intercriteria Correlation (CRITIC), and catastrophe theory, a risk assessment model of prefabricated building construction based on a combination weighting and catastrophe progression method was constructed. The effectiveness of the assessment model using the combination weighting and catastrophe progression method was verified through case analysis. The results show the following: (1) The quality of the prefabricated components, the standardization degree of the prefabricated components, and the environment of the installation working space in the construction risk assessment indicators of prefabricated buildings obtained by the AHP-CRITIC weighting method have higher weights. (2) Four prefabricated construction enterprises under China State Construction Corporation are evaluated, and the evaluation results effectively evaluate the project risk situation before an accident occurred, achieving the goal of improving the risk management efficiency. (3) The AHP-CRITIC weighting method can reflect the fuzziness of the construction risk of the evaluated project, effectively reduce information loss, and thus make the evaluation results more accurate. The conclusions have important practical significance for improving the construction risk management of prefabricated buildings.