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Abstract The quality of Recombination signal sequences (RSSs), location, and genetics of mammalian V, D, and J genes synergistically affect the recombination frequency of genes; however, the specific regulatory mechanism and efficiency have not been elucidated. By taking advantage of single-cell RNA-sequencing (scRNA-seq) and high-throughput sequencing (HTS) to investigate V(D)J rearrangement characteristics in the CDR3 repertoire, we found that the distal and proximal V genes (or J genes) “to D” gene were involved in rearrangement significantly more frequently than the middle V genes (or J genes) in the TRB locus among various species, including Primates (human and rhesus monkey), Rodentia (BALB/c, C57BL/6, and Kunming mice), Artiodactyla (buffalo), and Chiroptera (Rhinolophus affinis). The RSS quality of the V and J genes affected their frequency in rearrangement to varying degrees, especially when the V-RSSs with recombination signal information content (RIC) score < -45 significantly reduced the recombination frequency of the V gene. The V and J genes that were “away from D” had the dual advantages of recombinant structural accessibility and relatively high-quality RSSs, which promoted their preferential utilization in rearrangement. The quality of J-RSSs formed during mammalian evolution was apparently greater than that of V-RSSs, and the D-J distance was obviously shorter than that of V-D, which may be one of the reasons for guaranteeing that the “D-to-J preceding V-to-DJ rule” occurred when rearranged. This study provides a novel perspective on the mechanism and efficiency of V-D-J rearrangement in the mammalian TRB locus, as well as the biased utilization characteristics and application of V and J genes in the initial CDR3 repertoire.

The COVID-19 pandemic and large-scale administration of multiple SARS-CoV-2 vaccines have attracted global attention to the short-term and long-term effects on the human immune system. An analysis of the “traces” left by the body’s T-cell immune response is needed, especially for the prevention and treatment of breakthrough infections and long COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant infections. T-cell receptor complementarity determining region 3 (TCR CDR3) repertoire serves as a target molecule for monitoring the effects, mechanisms, and memory of the T-cell response. Furthermore, it has been extensively applied in the elucidation of the infectious mechanism and vaccine refinement of hepatitis B virus (HBV), influenza virus, human immunodeficiency virus (HIV), and SARS-CoV. Laboratories worldwide have utilized high-throughput sequencing (HTS) and scTCR-seq to characterize, share, and apply the TCR CDR3 repertoire in COVID-19 patients and SARS-CoV-2 vaccine recipients. This article focuses on the comparative analysis of the diversity, clonality, V&J gene usage and pairing, CDR3 length, shared CDR3 sequences or motifs, and other characteristics of TCR CDR3 repertoire. These findings provide molecular targets for evaluating T-cell response effects and short-term and long-term impacts on the adaptive immune system following SARS-CoV-2 infection or vaccination and establish a comparative archive of T-cell response “traces.”

The Rapid expansion of the Lanzhou–Xining (Lanxi) urban cluster in China during recent decades poses a threat to the fragile arid environment. Quantitatively assessing the impact of urban expansion on vegetation in the Lanxi urban cluster has profound implications for future sustainable urban planning. This study investigated the urban expansion dynamics of the Lanxi urban cluster and its impacts on regional vegetation between 2001 and 2021 based on time series land cover data and auxiliary remote sensing data, such as digital elevation model (DEM) data, nighttime light data, and administrative boundary data. Thereinto, urban expansion dynamics were evaluated using the annual China Land Cover Dataset (CLCD, 2001–2021). Urban expansion impacts on regional vegetation were assessed via the Vegetation Disturbance Index (VDI), an index capable of quantitatively assessing the positive and negative impacts of urban expansion at the pixel level, which can be obtained by overlaying the Enhanced Vegetation Index (EVI) and rainfall data. The major findings indicate that: (1) Over the past two decades, the Lanxi region has experienced rapid urban expansion, with the built-up area expanding from 183.50 km2 to 294.30 km2, which is an average annual expansion rate of 2.39%. Notably, Lanzhou, Baiyin, and Xining dominated the expansion. (2) Urban expansion negatively affected approximately 53.50 km2 of vegetation, while about 39.56 km2 saw positive impacts. The negative effects were mainly due to the loss of cropland and grassland. Therefore, cities in drylands should balance urban development and vegetation conservation by strictly controlling cropland and grassland occupancy and promoting intelligent urban growth.

The etiology of hemorrhagic fever with renal syndrome (HFRS) is significantly impacted by a variety of immune cells. Nevertheless, the existing techniques for sequencing peripheral blood T cell receptor (TCR) or B cell receptor (BCR) libraries in HFRS are constrained by both limitations and high costs. In this investigation, we utilized the computational tool TRUST4 to generate TCR and BCR libraries utilizing comprehensive RNA-seq data from peripheral blood specimens of HFRS patients. This facilitated the examination of clonality and diversity within immune libraries linked to the condition. Despite previous research on immune cell function, the underlying mechanisms remain intricate, and differential gene expression across immune cell types and cell-to-cell interactions within immune cell clusters have not been thoroughly explored. To address this gap, we performed clustering analysis on 11 cell subsets derived from raw single-cell RNA-seq data, elucidating characteristic changes in cell subset proportions under disease conditions. Additionally, we utilized CellChat, a tool for cell–cell communication analysis, to investigate the impact of MIF family, CD70 family, and GALECTIN family cytokines—known to be involved in cell communication—on immune cell subsets. Furthermore, hdWGCNA analysis identified core genes implicated in HFRS pathogenesis within T cells and B cells. Trajectory analysis revealed that most cell subsets were in a developmental stage, with high expression of transcription factors such as NFKB and JUN in Effector CD8+ T cells, as well as in Naive CD4+ T cells and Naive B cells. Our findings provide a comprehensive understanding of the dynamic changes in immune cells during HFRS pathogenesis, identifying specific V genes and J genes in TCR and BCR that contribute to advancing our knowledge of HFRS. These insights offer potential implications for the diagnosis and treatment of this autoimmune disease.

Background:The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development and progression have not been elucidated. In this study, the computational methods TRUST4 were used to construct a T-cell receptor (TCR) and B-cell receptor (BCR) repertoire from the peripheral blood of JIA patients via bulk RNA-seq data, after which the clonality and diversity of the immune repertoire were analyzed.Results:Our findings revealed significant differences in the frequency of clonotypes between the JIA and healthy control groups in terms of the TCR and BCR repertoires. This work identified specific V genes and J genes in TCRs and BCRs that could be used to expand our understanding of JIA. After single-cell RNA analysis, the relative percentages of CD14 monocytes were significantly greater in the JIA group. Cell-cell communication analysis revealed the significant role of the MIF signaling pathway in JIA.Conclusion:In conclusion, this work describes the immune features of both the TCR and BCR repertoires under JIA conditions and provides novel insight into immunotherapy for JIA.

ABSTRACTThe emergence and re-emergence of abundant viruses from bats that impact human and animal health have resulted in a resurgence of interest in bat immunology. Characterizing the immune receptor repertoire is critical to understanding how bats coexist with viruses in the absence of disease and developing new therapeutics to target viruses in humans and susceptible livestock. In this study, IGH germline genes of Chiroptera including Rhinolophus ferrumequinum, Phyllostomus discolor, and Pipistrellus pipistrellus were annotated, and we profiled the characteristics of Rhinolophus affinis (RA) IGH CDR3 repertoire. The germline genes of Chiroptera are quite different from those of human, mouse, cow, and dog in evolution, but the three bat species have high homology. The CDR3 repertoire of RA is unique in many aspects including CDR3 subclass, V/J genes access and pairing, CDR3 clones, and somatic high-frequency mutation compared with that of human and mouse, which is an important point in understanding the asymptomatic nature of viral infection in bats. This study unveiled a detailed map of bat IGH germline genes on chromosome level and provided the first immune receptor repertoire of bat, which will stimulate new avenues of research that are directly relevant to human health and disease.IMPORTANCEThe intricate relationship between bats and viruses has been a subject of study since the mid-20th century, with more than 100 viruses identified, including those affecting humans. While preliminary investigations have outlined the innate immune responses of bats, the role of adaptive immunity remains unclear. This study presents a pioneering contribution to bat immunology by unveiling, for the first time, a detailed map of bat IGH germline genes at the chromosome level. This breakthrough not only provides a foundation for B cell receptor research in bats but also contributes to primer design and sequencing of the CDR3 repertoire. Additionally, we offer the first comprehensive immune receptor repertoire of bats, serving as a crucial library for future comparative analyses. In summary, this research significantly advances the understanding of bats’ immune responses, providing essential resources for further investigations into viral tolerance and potential zoonotic threats.

Cuphea hookeriana Walp. is an ornamental plant belonging to the Lythraceae. In this study, we reported the complete chloroplast (cp) genome sequence here and analyzed the phylogenetic relationship among Lythraceae plants. The length of the cp genome was 158,999 bp, including a large single-copy (LSC, 89,311 bp) region and a small single-copy (SSC, 18,436 bp) region separated by a pair of inverted repeats (IRs, 25,626 bp). There were 72 unique protein-coding genes (PCGs), 30 transfer RNA (tRNA) genes, and four ribosomal RNA (rRNA) genes in the cp genome of C. hookeriana. A total of 223 simple sequence repeats (SSRs) and 34 long repeat sequences were identified. Phylogenetic analyses using maximum-likelihood (ML) revealed that C. hookeriana was close to C. hyssopifolia. In addition, the two Cuphea species were the sister group of Woodfordia fruticosa.

The GLK gene family plays a crucial role in the regulation of chloroplast development and participates in chlorophyll synthesis. However, the precise mechanism by which GLK contributes to citrus’s chlorophyll synthesis remains elusive. The GLK gene family causes variations in the photosynthetic capacity and chlorophyll synthesis of different citrus varieties. In this study, we identified tissue-specific members and the key CcGLKs involved in chlorophyll synthesis. A total of thirty CcGLK transcription factors (TFs) were discovered in the citrus genome, distributed across all nine chromosomes. The low occurrence of gene tandem duplication events and intronic variability suggests that intronic variation may be the primary mode of evolution for CcGLK TFs. Tissue-specific expression patterns were observed for various GLK family members; for instance, CcGLK12 and CcGLK15 were specifically expressed in the skin, while CcGLK30 was specific to the ovary, and CcGLK10, CcGLK6, CcGLK21, CcGLK2, CcGLK18, CcGLK9, CcGLK28, and CcGLK8 were specifically expressed in the leaves. CcGLK4, CcGLK5, CcGLK11, CcGLK23, CcGLKl7, CcGLK26, and CcGLK20 may participate in the regulation of the ALA, prochlorophylate, protoporphyrin IX, Mg-protoporphyrin IX, Chl b, T-Chl, MG-ProtoIX ME, and POR contents in citrus.

IntroductionBats are recognized as natural reservoirs for many viruses, and their unique immune system enables them to coexist with these viruses without frequently exhibiting disease symptoms. However, the current understanding of the bat adaptive immune system is limited due to the lack of a database or tool capable of processing T-cell receptor (TCR) sequences for bats.MethodsWe performed germline gene annotation in three bat species using homologous genes and RSSs (Recombinational Signal Sequences) scanning method. Then we used the conserved C gene to construct the TCRβ chain receptor library of the Intermediate Horseshoe Bat. Bats' TCRβ data will be analyzed using MiXCR and constructed reference library.ResultsRegarding the annotation results, we found that the Pale Spear-nosed Bat has 37 members in the TRBV12 family, which is more than the total number of TRBV genes in the Greater Horseshoe Bat. The average number of unique TCRβ chain receptor sequences in each Intermediate Horseshoe Bat sample reached 24,904.DiscussionThe distinct variations in the distribution of TRBV genes among the three types of bats could have a direct impact on the diversity of the TCR repertoire, as evidenced by the presence of conserved amino acids that indicate the T-cell recognition of antigens in bats is MHC-restricted. The bats’ TCRβ repertoire is formed through the rearrangement of the V-D-J-C genes, with D-J/V-D deletions and insertions resulting in high diversity.

Precipitation, as one of the main components of the hydrological cycle, is known to be significantly impacted by global climate change. In recent years, the frequency of extreme precipitation has increased, resulting in greater destructiveness. Atmospheric circulation has a significant impact on extreme precipitation in a region. This study aims to investigate the prospective changes in extreme precipitation and their relationship with large-scale atmospheric circulation in the Haihe River Basin. The Haihe River Basin is located in the North China Plain. Mountains and plains can be found in both the eastern and western parts of the study region. The summer seasons experience the most precipitation. The monthly and extreme precipitation (based on daily precipitation) results from the Coupled Model Intercomparison Project Phase 6 (CMIP6) models were evaluated using observed precipitation data, which was utilized as a reference. The CMIP6 models were used to assess future changes in the characteristics of extreme precipitation in the study region. The relationship between extreme precipitation and large-scale atmospheric circulation was also analyzed using historical observation data. Remote sensing results regarding land cover and soil erosion were used to analyze the risks of extreme precipitation and their influences in the study region. According to the results, their multi-model ensembles (MME) and BCC-CSM2-MR models, respectively, outperformed all other CMIP6 models in simulating monthly and extreme (based on daily precipitation) precipitation over the study region. Extreme precipitation demonstrated a rising degree of contribution and future risk under numerous scenarios. The degrees of contribution of R95p and R99p are anticipated to increase in the future. BCC-CSM2-MR predicted that Rx1day and Rx5day would decline in the future. Generally, extreme precipitation increased to a greater degree under SSP585 than under SSP245. Both the El Niño–Southern Oscillation and the Pacific Decadal Oscillation displayed substantial resonance with the extreme precipitation from 1962 to 1980 and around 1995, respectively. This study not only improves our understanding of the occurrence of extreme precipitation, but it also serves as a reference for flood control and waterlogging prevention in the Haihe River Basin.

Lagerstroemia indica has great economic value due to its ecological, medicinal, and ornamental properties. Because its bloom color is one of the most essential characteristics, research into its color development is a hot topic. In this study, five representative colored cultivars were chosen, each representing a different color, such as white, red, pink, violet, and purple. Fully bloomed flowers were used to detect flavonoids in the petals. Anthocyanin is the main factor for the color formation of L. indica. 14 anthocyanins were discovered among the 299 flavonoids. Among 14 anthocyanins, malvidin-3,5-di-O-glucoside varied greatly among four colored samples and is the main contributor to color diversity. Transcriptome sequencing revealed that compared to white flowers, Anthocyanin pathway genes appear to be more active in colored samples. Analyzing the correlation network between metabolites and differential expressed genes, 53 key structural genes, and 24 TFs were detected that may play an essential role in the formation of color in L. indica flowers. Among these, the differential expression of F3′5′H and F3′H between all samples are contributors to color diversity. These findings lay the foundation for discovering the molecular mechanism of L. indica flower color diversity.

Tree peony (Paeonia suffruticosa) is a traditional Chinese flower that is not resistant to high temperatures, and the frequent sunburn during summer limits its normal growth. The lack of understanding of the molecular mechanisms in tree peony has greatly restricted the improvement of novel heat-tolerant varieties. Therefore, we treated tree peony cultivar “Yuhong” (P. suffruticosa “Yuhong”) at normal (25°C) and high temperatures (40°C) and sequenced the transcriptomes, to investigate the molecular responsive mechanisms to heat stress. By comparing the transcriptomes, a total of 7,673 differentially expressed genes (DEGs) were detected comprising 4,220 upregulated and 3,453 downregulated genes. Functional annotation showed that the DEGs were mainly related to the metabolic process, cells and binding, carbon metabolism, and endoplasmic reticulum protein processing. qRT-PCR revealed that three sHSP genes (PsHSP17.8, PsHSP21, and PsHSP27.4) were upregulated in the response of tree peony to heat stress. Tissue quantification of the transgenic lines (Arabidopsis thaliana) showed that all three genes were most highly expressed in the leaves. The survival rates of transgenic lines (PsHSP17.8, PsHSP21, and PsHSP27.4) restored to normal growth after high-temperature treatment were 43, 36, and 31%, respectively. In addition, the activity of superoxide dismutase, accumulation of free proline, and chlorophyll level was higher than those of the wild-type lines, while the malondialdehyde content and conductivity were lower, and the membrane lipid peroxidation reaction of the wild-type plant was more intense. Our research found several processes and pathways related to heat resistance in tree peony including metabolic process, single-organism process, phenylpropane biosynthesis pathway, and endoplasmic reticulum protein synthesis pathway. PsHSP17.8, PsHSP21, and PsHSP27.4 improved heat tolerance by increasing SOD activity and proline content. These findings can provide genetic resources for understanding the heat-resistance response of tree peony and benefit future germplasm innovation.

Drought is a major environmental condition that inhibits the development and cultivation of Heimia myrtifolia. The molecular processes of drought resistance in H. myrtifolia remain unknown, which has limited its application. In our study, transcriptome analyzes were compared across three treatment groups (CK, T1, and T2), to investigate the molecular mechanism of drought resistance. Plant leaves wilted and drooped as the duration of drought stress increased. The relative water content of the leaves declined dramatically, and relative electrolyte leakage rose progressively. Using an RNA-Seq approach, a total of 62,015 unigenes with an average length of 1730 bp were found, with 86.61% of them annotated to seven databases, and 14,272 differentially expressed genes (DEGs) were identified in drought stress. GO and KEGG enrichment analyzes of the DEGs revealed significantly enriched KEGG pathways, including photosynthesis, photosynthetic antenna proteins, plant hormone signal transduction, glutathione metabolism, and ascorbate and aldarate metabolism. Abscisic acid signal transduction was the most prevalent in the plant hormone signal transduction pathway, and other plant hormone signal transductions were also involved in the drought stress response. The transcription factors (including MYB, NAC, WRKY, and bHLH) and related differential genes on significantly enriched pathways all played important roles in the drought process, such as photosynthesis-related genes and antioxidant enzyme genes. In conclusion, this study will provide several genetic resources for further investigation of the molecular processes that will be beneficial to H. myrtifolia cultivation and breeding.

The core technology to realize the development of unconventional oil and gas resources is the large-scale volume transformation of shale reservoirs, but volume fracturing is a complex physical and mechanical process, and its mechanism remains to be further studied. In this paper, starting from the current research status of shale volumetric fracturing, the perforation orientation of volumetric fracturing is numerically simulated by using the finite element software. The following conclusions are drawn: ① when the ground stress conditions are equal, with the increase of perforation angle, the maximum principal stress at the front of perforation decreases gradually; that is, when the perforation is along the horizontal minimum principal stress, the maximum principal stress at the front of perforation is the largest, which is most conducive to fracturing of shale reservoirs. ② When the perforation is along the direction of the horizontal minimum principal stress and the horizontal stress difference is zero, the smaller the horizontal stress, the greater the maximum principal stress at the front of the perforation. Therefore, the smaller the horizontal stress, the more conducive to the rupture of shale reservoirs. ③ When the perforation is along the horizontal minimum principal stress, the maximum principal stress at the front of the perforation increases with the increase of the horizontal stress difference. Therefore, the larger the horizontal stress difference, the more favorable for the fracture of shale reservoirs.

Calmodulin-binding transcription factor (CAMTA) is an important component of plant hormone signal transduction, development, and drought resistance. Based on previous transcriptome data, drought resistance genes of the Heimia myrtifolia CAMTA transcription factor family were predicted in this study. The physicochemical characteristics of amino acids, subcellular localization, transmembrane structure, GO enrichment, and expression patterns were also examined. The results revealed that H. myrtifolia has a total of ten members (HmCAMTA1~10). Phylogenetic tree analysis of the HmCAMTA gene family revealed four different branches. The amino acid composition of CAMTA from H. myrtifolia and Punica granatum was quite similar. In addition, qRT-PCR data showed that the expression levels of HmCAMTA1, HmCAMTA2, and HmCAMTA10 genes increased with the deepening of drought, and the peak values appeared in the T4 treatment. Therefore, it is speculated that the above four genes are involved in the response of H. myrtifolia to drought stress. Additionally, HmCAMTA gene expression was shown to be more abundant in roots and leaves than in other tissues according to tissue-specific expression patterns. This study can be used to learn more about the function of CAMTA family genes and the drought tolerance response mechanism in H. myrtifolia.

Alfalfa (Medicago sativa) is one of the most important legume forage species in the world. It is often affected by several abiotic stressors that result in reduced yields and poor growth. Therefore, it is crucial to study the resistance of M. sativa to abiotic stresses. Heat shock transcription factors (HSF) are key players in a number of transcriptional regulatory pathways. These pathways play an essential role in controlling how plants react to different abiotic stressors. Studies on the HSF gene family have been reported in many species but have not yet undergone a thorough analysis in M. sativa. Therefore, in order to identify a more comprehensive set of HSF genes, from the genomic data, we identified 16 members of the MsHSF gene, which were unevenly distributed over six chromosomes. We also looked at their gene architectures and protein motifs, and phylogenetic analysis allowed us to divide them into 3 groups with a total of 15 subgroups. Along with these aspects, we then examined the physicochemical properties, subcellular localization, synteny analysis, GO annotation and enrichment, and protein interaction networks of amino acids. Finally, the analysis of 16 MsHSF genes’ expression levels across all tissues and under four abiotic stresses using publicly available RNA-Seq data revealed that these genes had significant tissue-specific expression. Moreover, the expression of most MsHSF genes increased dramatically under abiotic stress, further validating the critical function played by the MsHSF gene family in abiotic stress. These results provided basic information about MsHSF gene family and laid a foundation for further study on the biological role of MsHSF gene in response to stress in M. sativa.

Introduction Mutations in the filaggrin ( FLG ) gene are known to cause ichthyosis vulgaris. Methods We used whole-genome sequencing (WGS) technology to investigate the genetic causes of rare and complex inherited diseases including rheumatoid arthritis, ichthyosis, and congenital fibrosis of the extraocular muscles type 1 (CFEOM1) in a Chinese family. WGS was performed in four topics, and the identified candidate mutations were further verified through Sanger sequencing. Results We identified a mutation in FLG gene (g.152280098 C>A, p.E2422∗) that may be associated with ichthyosis and arthritis. Moreover, a mutation in KIF21A (g.39726207 G>A, p.R954 W) was also determined in affected members as the cause of CFEOM1. The gene interaction network demonstrated an interesting correlation between FLG and genes associated with arthritis and ichthyosis. Functional enrichment analysis of these interacting genes revealed several possible pathways that might be linked to arthritis and ichthyosis. Conclusion In general, we confirmed a loss of function mutation in the FLG gene associated with ichthyosis vulgaris and rheumatoid arthritis in this family.

Abstract Mitochondrial epigenetics is rising as intriguing notion for its potential involvement in aging and diseases, while the details remain largely unexplored. Here it is shown that among the 13 mitochondrial DNA (mtDNA) encoded genes, NADH‐dehydrogenase 6 (ND6) transcript is primarily decreased in obese and type 2 diabetes populations, which negatively correlates with its distinctive hypermethylation. Hepatic mtDNA sequencing in mice unveils that ND6 presents the highest methylation level, which dramatically increases under diabetic condition due to enhanced mitochondrial translocation of DNA methyltransferase 1 (DNMT1) promoted by free fatty acid through adenosine 5’‐monophosphate (AMP)‐activated protein kinase (AMPK) activation. Hepatic knockdown of ND6 or overexpression of Dnmt1 similarly impairs mitochondrial function and induces systemic insulin resistance both in vivo and in vitro. Genetic or chemical targeting hepatic DNMT1 shows significant benefits against insulin resistance associated metabolic disorders. These findings highlight the pivotal role of ND6 epigenetic network in regulating mitochondrial function and onset of insulin resistance, shedding light on potential preventive and therapeutic strategies of insulin resistance and related metabolic disorders from a perspective of mitochondrial epigenetics.

ObjectiveTo experimentally determine the involvement and mechanism of long non-coding RNA (lncRNA) HCP5 in the development of gastric cancer (GC).MethodsDetection of HCP5, miR-186-5p, and WNT5A expression in clinical GC tissues and adjacent healthy tissues was performed, followed by Pearson correlation analysis. BGC-823 and AGS cells, with interferences of HCP5, miR-186-5p, and WNT5A, were cultured under hypoxia. MTT, colony formation assay, Caspase-3 activity assay, and transwell assay were applied for the determination of cell proliferation, viability, apoptosis, and invasion, respectively. Expressions of WNT5A and protein markers of epithelial-mesenchymal transition (EMT) in cells were detected by western blotting. And the binding of HCP5 and WNT5A to miR-186-5p was validated using dual-luciferase reporter assay.ResultsIn GC tissues, an increase in HCP5 and WNT5A expressions and a reduction in miR-186-5p expression were found, and the negative correlation between miR-186-5p and HCP5/WNT5A was proven. Subsequently, under hypoxia, an increase in HCP5 and WNT5A expressions and a decrease in miR-186-5p expression in GC cells were confirmed. In addition, in GC cells under hypoxia, the inhibition of HCP5 suppressed cell biological activity and EMT, while the inhibition of miR-186-5p or the overexpression of WNT5A led to the opposite changes.ConclusionAn upregulation of WNT5A expression by HCP5 competitively binding to miR-186-5p promotes GC cell development.

Lagerstroemia indica is a widely used ornamental plant in summer gardens because of its desirable plant shape. The weeping traits of plants are related to secondary cell wall thickness and hormone signaling. NAC (NAM-ATAF1/2-CUC2), as one of the plant-specific transcription factors, is a switch for the secondary cell wall and also involved in leaf senescence, phytohormone signaling, and other growth processes. We identified a total of 21 LiNAC genes from the transcriptome data, which we divided into 14 subgroups and 2 groups. The physicochemical characteristics of amino acids, subcellular localization, transmembrane structure, GO and KEGG enrichment, and expression patterns were also examined. The qRT-PCR analysis showed that the expressions of LiNAC8 and LiNAC13 in upright L. indica ‘Shaoguifei’ and weeping L. indica ‘Xiariwuniang’ were significantly higher from the beginning to the end of growth stage (S1–S3), and the expressions of ‘Shaoguifei’ were always higher than those of ‘Xiariwuniang’. However, LiNAC2 showed a downward trend in S1–S3 and the relative expression level of ‘Shaoguifei’ was lower than that of ‘Xiariwuniang’. It is hypothesized that these LiNAC genes may be involved in the regulation of weeping traits in L. indica. The results of this study provide a basis for analyzing the functions of LiNAC genes and help to explore the molecular regulatory mechanisms related to the weeping traits in L. indica.

Background. B7 family members and ligands have been identified as critical checkpoints in orchestrating the immune response during sepsis. V-domain Ig suppressor of T cell activation (VISTA) is a new inhibitory immune checkpoint involved in restraining T cell response. Previous studies demonstrated that VISTA engagement on T cells and myeloid cells could transmit inhibitory signals, resulting in reduced activation and function. The current study was designed to determine the potential therapeutic effects of a high-affinity anti-VISTA antibody (clone MH5A) in a murine model of sepsis. Methods. Polymicrobial sepsis was induced in male C57BL/6 mice via cecal ligation and puncture. Expression profiles of VISTA on T lymphocytes and macrophage were examined at 24 and 72 h postsurgery. The effects of anti-VISTA mAb on the 7-day survival, lymphocyte apoptosis, cytokine expression, bacterial burden, and vital organ damage were determined. Furthermore, the effects of anti-VISTA mAb on CD3+ T cell apoptosis and macrophage activation were determined in vitro. Results. VISTA was substantially expressed on T cells and macrophages in sham-operated mice; septic peritonitis did not induce significant changes in the expression profiles. Treatment with MH5A improved the survival of septic mice, accompanied by reduced lymphocyte apoptosis, decreased cytokine expression, and enhanced bacterial clearance. Engagement of VISTA receptor with MH5A mitigated CD3+ T cell apoptosis cultured from CLP mice and suppressed LPS-induced cytokine production by macrophage in vitro. Conclusion. The present study identified VISTA as a novel immune checkpoint in the regulation of T cell and macrophage response during sepsis. Modulation of the VISTA pathway might offer a promising opportunity in the immunotherapy for sepsis.

The formation of the B cell receptor (BCR) heavy chain variable region is derived from the germline V(D)J gene rearrangement according to the “12/23” rule and the “beyond 12/23” rule. The usage frequency of each V(D)J gene in the peripheral BCR repertoires is related to the initial recombination, self-tolerance selection, and the clonal proliferative response. However, their specific differences and possible mechanisms are still unknown. We analyzed in-frame and out-of-frame BCR-H repertoires from human samples with normal physiological and various pathological conditions by high-throughput sequencing. Our results showed that IGHJ gene frequency follows a similar pattern which is previously known, where IGHJ4 is used at high frequency (>40%), IGHJ6/IGHJ3/IGHJ5 is used at medium frequencies (10∼20%), and IGH2/IGHJ1 is used at low frequency (

Gut microbes play a crucial role in the occurrence and development of autoimmune diseases. The diversity of intestinal microorganisms affected by the living environment, regulate the immune function of peripheral immune organs and local tissues. In the study, the diversity of intestinal microorganisms of Germ-free (GF), Specific Pathogen-free (SPF), and Clean (CL) BALB/c mice were conducted by 16S rDNA sequencing. High-throughput sequencing technology was used to analysis the composition and characterization of TCR β chain CDR3 repertoires in Regulatory T cells (Treg) in intestine and spleen of GF, SPF, and CL mice, so as to investigate the effects of differential composition of intestinal microorganisms on the CD4+CD25+Foxp3+Treg TCR β CDR3 repertoire of intestine and spleen. We observed that GF, SPF, and CL mice have different gut microorganism composition, and the abundance and quantity of microorganisms are positively correlated with the level of feeding environment. Interestingly, incomplete structure of spleen and small intestine in GF mice was found. Moreover, a significant difference in the usage of high frequency unique CDR3 amino acid sequences was detected in the intestinal Treg TCRβ CDR3 repertoire among GF, SPF and CL mice, and there were a greater heterogeneity in the usage frequency of TRBV, TRBJ, and TRBV-TRBJ combinations gene segments. However, the effect of different feeding environment on the mice Treg TCRβ CDR3 repertoire of spleen was weak, implying that the different composition of intestinal microbiota may primarily affect the diversity of the local Treg TCRβ CDR3 repertoire and does not alter the overall properties of the circulating immune system. These results provide basic data to further analyze the mechanism of gut microbes regulating the intestinal mucosal immune system.

Although persistent hepatitis B virus (HBV) infection is associated with natural killer (NK) cell dysfunction, it remains obscure whether HBV viral antigens are responsible for NK cell dysfunction in patients with chronic hepatitis B (CHB) infection. In this study, we found that the percentage of NK cells expressing the inhibitory receptor, NKG2A, was increased in CHB patients, and NKG2A blockade restored NK cell function. Furthermore, in CHB patients, the frequency of NK cells expressing NKG2A positively correlated with the number of regulatory T cells (Tregs) and production of interleukin-10 (IL-10) in these Tregs. Moreover, exposure of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls to sera from CHB patients resulted in increased proportion of NKG2A+ NK cells; IL-10 blockade reduced the frequency of NKG2A+ NK cells while increasing the percentage of IFN-γ+ NK cells. In addition, stimulation of NK cells and Tregs from healthy controls with CHB sera together with anti-IL-10 antibody increased IFN-γ production in the culture supernatant. The frequencies of NKG2A+ NK cells and IL-10+ Tregs, along with serum levels of alanine transferase and HBV DNA, were significantly increased in CHB patients positive for the Hepatitis B e antigen (HBeAg, a marker of viral replication) when compared to HBeAg-negative CHB patients. Importantly, exposure of PBMCs from healthy controls to HBeAg resulted in increased IL-10 production but reduced levels of TNF and IFN-γ, and IL-10 blockade rescued the generation of TNF and IFN-γ in this assay. The reduced production of TNF and IFN-γ was also observed in NK cells and Tregs from healthy controls that were stimulated with HBeAg, while IL-10 blockade increased the secretion of these two cytokines. We conclude that HBeAg induces IL-10 production in Tregs, thereby leading to increased expression of NKG2A on NK cells, which contributes to NK cell dysfunction during CHB infection. These data suggest that HBeAg is associated with NK cell dysfunction in CHB.

Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disorder and the leading genetic cause of infant mortality. Early detection of SMA through newborn screening (NBS) is essential to selecting pre-symptomatic treatment and ensuring optimal outcome, as well as, prompting the urgent need for effective screening methods. This study aimed to determine the feasibility of applying an Agena iPLEX SMA assay in NBS for SMA in China.Methods: We developed an Agena iPLEX SMA assay based on the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and evaluated the performance of this assay through assessment of 167 previously-genotyped samples. Then we conducted a pilot study to apply this assay for SMA NBS. The SMN1 and SMN2 copy number of screen-positive patients were determined by multiplex ligation-dependent probe amplification analysis.Results: The sensitivity and specificity of the Agena iPLEX SMA assay were both 100%. Three patients with homozygous SMN1 deletion were successfully identified and conformed by multiplex ligation-dependent probe amplification analysis. Two patients had two SMN2 copies, which was correlated with severe SMA type I phenotype; both of them exhibited neurogenic lesion and with decreased muscle power. Another patient with four SMN2 copies, whose genotype correlated with milder SMA type III or IV phenotype, had normal growth and development without clinical symptoms.Conclusions: The Agena iPLEX SMA assay is an effective and reliable approach for population-based SMA NBS. The first large-scale pilot study using this assay in the Mainland of China showed that large-scale implementation of population-based NBS for SMA is feasible.

Hepatic glycolipid metabolism disorder is considered as one of the key factors in the pathogenesis of many chronic diseases. The objective of this study was to investigate the protective effect and underlying mechanisms of Rhus chinensis Mill. fruits against hepatic glycolipid metabolic disorders in rats induced by a high fat/high sugar diet. Results showed that ethanol extract, especially at a dose of 600 mg/kg b.w., could effectively ameliorate glycolipid metabolic disorders in rats. The biochemical indexes, including CAT, GSH and HOMA-IR, were significantly improved by the administration of ethanol extract. Immunohistochemistry and Western blot analysis revealed that ethanol extract up-regulated the expression levels of PI3K/AKT, PPAR-α, and the phosphorylation of IRS1 and AMPK proteins, and down-regulated the expressions of SREBP-1 and FAS proteins in the liver, which are closely related to hepatic glycolipid metabolism. Those findings suggested that R. chinensis Mill. fruits could be developed as functional foods and/or nutraceuticals for preventing or controlling some chronic diseases related to hepatic glycolipid metabolism disorder.

Lactic acid bacteria (LAB) are widely used as probiotics in the food industry owing to their beneficial effects on human health. However, numerous antibiotic resistance genes have been found in LAB strains, especially tetracycline resistance genes. Notably, the potential transferability of these genes poses safety risks. To comprehensively evaluate tetracycline resistance in LAB, we determined the tetracycline susceptibility patterns of 478 LAB strains belonging to four genera and eight species. By comparing phenotypes with genotypes based on genome-wide annotations, five tetracycline resistance genes, tet(M), tet(W/N/W), tet(L), tet(S), and tet(45), were detected in LAB. Multiple LAB strains without tetracycline resistance genes were found to be resistant to tetracycline at the currently recommended cutoff values. Thus, based on the minimum inhibitory concentrations of tetracycline for these LAB strains, the species-specific microbiological cutoff values for Lactobacillus (para)gasseri, Lactobacillus johnsonii, and Lactobacillus crispatus to tetracycline were first developed using the Turnidge, Kronvall, and eyeball methods. The cutoff values for Lactiplantibacillus plantarum were re-established and could be used to better distinguish susceptible strains from strains with acquired resistance. Finally, we verified that these five genes play a role in tetracycline resistance and found that tet(M) and tet(W/N/W) are the most widely distributed tetracycline resistance genes in LAB.

The necrotrophic fungus Botrytis cinerea causes devastating pre- and post-harvest yield losses in grapevine (Vitis vinifera L.). Although B. cinerea has been well-studied in different plant species, there is limited information related to the resistance and susceptibility mechanisms of Vitis genotypes against B. cinerea infection. In the present study, leaves and berries of twenty four grape genotypes were evaluated against B. cinerea infection. According to the results, one genotype (Ju mei gui) was highly resistant (HR), one genotype (Kyoho) was resistant (R), eight genotypes were susceptible (S), and fourteen genotypes were highly susceptible (HS) against infection of B. cinerea in leaves. Whereas in the case of B. cinerea infection in grape berry, three genotypes were found to be highly resistant, three resistant, eleven genotypes susceptible, and seven were highly susceptible. To further explore the mechanism of disease resistance in grapevine, we evaluated “Ju mei gui” and “Summer black” in terms of B. cinerea progression, reactive oxygen species reactions, jasmonic acid contents, and the activities of antioxidant enzymes in leaf and fruit. We surmise that the resistance of “Ju mei gui” is due to seized fungal growth, minor reactive oxygen species (ROS) production, elevated antioxidant enzyme activity, and more jasmonic acid (JA) contents. This study provides insights into the resistance and susceptibility mechanism of Vitis genotypes against B. cinerea. This will help for the selection of appropriate germplasm to explore the molecular basis of disease resistance mechanisms in grapevine.

In order to analyze variable-mass permeation characteristics of broken rock mass under different cementation conditions and reveal the water inrush mechanism of geological structures containing broken rock masses like karst collapse pillars (KCPs) in the coal mine, the EDEM-FLUENT coupling simulation system was used to implement a numerical simulation study of variable-mass permeation of broken rock mass under different cementation conditions and time-dependent change laws of parameters like porosity, permeability, and mass loss rate of broken rock specimens under the erosion effect were obtained. Study results show that (1) permeability change of broken rock specimens under the particle migration effect can be divided into three phases, namely, the slow-changing seepage phase, sudden-changing seepage phase, and steady seepage phase. (2) Specimen fillings continuously migrate and run off under the water erosion effect, porosity and permeability rapidly increase and then tend to be stable, and the mass loss rate firstly rapidly increases and then gradually decreases. (3) Cementation degree has an important effect on permeability of broken rock mass. As cementing force of the specimen is enhanced, its maximum mass loss rate, mass loss, porosity, and permeability all continuously decrease. The study approach and results not only help enhance coal mining operations safety by better understanding KCP water inrush risks. It can also be extended to other engineering applications such as backfill paste piping and tailing dam erosion.

Immunization with recombinant HBV vaccine induces specific immune responses in human causing B lymphocytes to produce protective HBsAb, and to form memory B lymphocytes, thereby facilitating HBV immunity in the body. However, B lymphocytes heterogeneity and characteristics are not fully elucidated. In this study, we conducted high-throughput sequencing of BCR heavy chain CDR3 repertoires in 3 healthy volunteers before and after the third immunization with recombinant HBV vaccine. We used Roche 454 Genome Sequencer FLX system to perform a comparative analysis of IgM and IgG H chain CDR3 repertoires. First, we found that the diversity of IgG H chain CDR3 repertoires was 1/6 of IgM on average. Moreover, after the third immunization with HBV vaccine, the diversity of IgG H chain CDR3 repertoires was 1/26 of IgM on average. Second, we detected relatively high levels of HBsAbs in all the healthy volunteers after immunization with HBV vaccine. The volunteers shared a small number of CDR3 sequences before and after immunization, and among each other. However, we did not find completely identical BCR H chain CDR3 amino acid sequences in these volunteers. Lastly, after immunization with recombinant HBV vaccine, the volunteers showed high frequency of IgG H chain CDR3 amino acid sequences mostly resulting from rearrangements of IGHV, IGHD and IGHJ, suggesting that the mechanism of high frequency CDR3 generation might be associated with the maturation of IgG affinity (somatic hypermutation) during the recombinant HBV vaccine-induced B lymphocyte responses. This study identified the characteristics and changes of BCR CDR3 repertoires before and after immunization with HBV vaccine, and evaluated the performance of the sequencing technology for this application. Our findings provide a basis for further research in B lymphocyte generated HBsAb heterogeneity and monitoring the maintenance of memory B lymphocytes.

Based on the analysis of epidermal growth factor receptor (EGFR) complexes with gefitinib with molecular docking, the scaffold-hopping strategy, combination of the active substructures, and structural optimization of EGFR inhibitors, a novel series of benzo[4,5]imidazo[2,1-b]thiazole derivatives was designed, synthesized, and evaluated for antitumor activity in human cancer cell lines and cellular toxicity against human normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and EGFR inhibitory activities in vitro. Some target compounds such as 2-(benzo[4,5]imidazo[2,1-b]thiazol-3-yl)-N-(2-hydroxyphenyl)acetamide (D04) and 2-(benzo[4,5]imidazo[2,1-b]thiazol-3-yl)-N-(naphthalen-1-yl)acetamide (D08) have shown significant antitumor activity against the EGFR high-expressed human cell line HeLa. All the target compounds showed hardly any antitumor activity against the EGFR low-expressed human cell line HepG2, and nearly no cellular toxicity against the human normal cell lines HL7702 and human umbilical vein endothelial cell lines (HUVEC). The inhibitory activities against EGFR kinase in vitro of the three target compounds were greatly consistent with the anti-proliferative activities. The preliminary structure⁻activity relationships of the target compounds were summarized. Conclusively, the novel benzo[4,5]imidazo[2,1-b]thiazole derivatives as novel potential EGFR inhibitors may be used as the potential lead compounds for the development of antitumor agents.

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Abstract Background The formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum. Methods In the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum. Results In maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia. Conclusion In conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

Abstract LLMs can accomplish specialized medical knowledge tasks, however, equitable access is hindered by the extensive fine-tuning, specialized medical data requirement, and limited access to proprietary models. Open-source (OS) medical LLMs show performance improvements and provide the transparency and compliance required in healthcare. We present OpenMedLM, a prompting platform delivering state-of-the-art (SOTA) performance for OS LLMs on medical benchmarks. We evaluated OS foundation LLMs (7B-70B) on medical benchmarks (MedQA, MedMCQA, PubMedQA, MMLU medical-subset) and selected Yi34B for developing OpenMedLM. Prompting strategies included zero-shot, few-shot, chain-of-thought, and ensemble/self-consistency voting. OpenMedLM delivered OS SOTA results on three medical LLM benchmarks, surpassing previous best-performing OS models that leveraged costly and extensive fine-tuning. OpenMedLM displays the first results to date demonstrating the ability of OS foundation models to optimize performance, absent specialized fine-tuning. The model achieved 72.6% accuracy on MedQA, outperforming the previous SOTA by 2.4%, and 81.7% accuracy on MMLU medical-subset, establishing itself as the first OS LLM to surpass 80% accuracy on this benchmark. Our results highlight medical-specific emergent properties in OS LLMs not documented elsewhere to date and validate the ability of OS models to accomplish healthcare tasks, highlighting the benefits of prompt engineering to improve performance of accessible LLMs for medical applications.

Flower bud differentiation is a key component of plant blooming biology and understanding how it works is vital for flowering regulation and plant genetic breeding, increasing the number and quality of flowering. Red soil is the most widely covered soil type in the world, and it is also the most suitable soil type for crape myrtle planting. The flower buds of crape myrtle (Lagerstroemia indica) planted in red soil were employed as experimental materials in this study, and the distinct periods of differentiation were identified using stereomicroscopy and paraffin sectioning. We optimized the steps of dehydration, transparency, embedding, sectioning and staining when employing paraffin sections. When seen under a microscope, this optimization can make the cell structure of paraffin sections obvious, the tissue structure complete, and the staining clear and natural. The flower bud differentiation process is divided into 7 periods based on anatomical observations of the external morphology and internal structure during flower bud differentiation: undifferentiated period, start of differentiation period, inflorescence differentiation period, calyx differentiation period, petal differentiation period, stamen differentiation period, and pistil differentiation period. The differentiation time is concentrated from the end of May to mid-June. Crape myrtle flower bud differentiation is a complicated process, and the specific regulatory mechanism and affecting elements need to be investigated further. [ABSTRACT FROM AUTHOR]

BackgroundGeographic distribution of dietary inflammatory index (DII) in China has not been thoroughly evaluated and evidence on the association between DII and hypertension among Chinese middle-aged and older population was inadequate.ObjectiveTo investigate the geographic disparities of DII and its association with hypertension among Chinese middle-aged and elders.MethodsData was from the China Adults Chronic Diseases and Nutrition Surveillance (CACDNS 2015) for middle-aged and older participants. The DII for each participant was determined through a combination of 3 days 24 h dietary recall interviews and a food frequency questionnaire. Spatial analysis was employed to investigate the geographic distribution of DII in China. Restricted cubic spline models and binary logistic regression analysis were used to assess the relationship between DII and hypertension. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key hypertension-related factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) being built to evaluate its discriminatory power for hypertension.ResultsA total of 52,087 middle-aged and older participants were included in the study, among whom 36.6% had hypertension. it revealed that a clear spatial correlation in the national distribution of DII scores (Moran I: 0.252, p = 0.001), with higher DII scores concentrated in the northwest region and lower DII scores concentrated in the southeast region. Hypertensive participants had higher DII scores compared to those without hypertension (OR: 1.507 vs. 1.447, p = 0.003). Restricted cubic spline models and binary logistic regression analysis demonstrated a positive association between DII and hypertension after adjusting for potential confounding factors. There was a significant increasing trend in the proportion of hypertensive individuals as DII scores increase (p for trend = 0.004). The nomogram model, constructed using key factors identified through LASSO regression, demonstrated a robust discriminative capacity, with an area under the curve (AUC) of 73.2% (95% CI, 72.4–74.0%). Decision curve analysis confirmed the reliability and effectiveness of the nomogram model. Sensitivity analysis conducted within the subpopulation aged under 45 years yielded results consistent with the primary analysis.ConclusionIn Chinese adults middle-aged and older, geographic disparities in dietary inflammatory potential are notable, with lower levels observed in the southeastern coastal regions of China and higher levels in the northwestern regions. Meanwhile, there is a positive association between the inflammatory potential of the diet and hypertension. Additional research is needed to investigate regional disparities in dietary inflammatory potential and pinpoint specific dietary patterns associated with lower inflammation.

Abstract Sepsis is one of the possible outcomes of severe trauma, and it poses a dire threat to human life, particularly in immunocompromised people. The most prevalent pathogens are bacteria and fungi, but viruses should not be overlooked. For viral metagenomic analysis, we collected blood samples from eight patients with post-traumatic sepsis before and seven days after treatment. The results demonstrated that Anellovirus predominated the viral community, followed by Siphoviridae and Myoviridae, and that the variations in viral community and viral load before and after treatment were not statistically significant. This study allows us to investigate methods for establishing NGS-based viral diagnostic instruments for detecting viral infections in the blood of sepsis patients so that antiviral therapy can be administered quickly.

Acetate is an important metabolite in metabolic fluxes. Its presence in biological entities originates from both exogenous inputs and endogenous metabolism. Because the change in blood acetate level has been associated with both beneficial and adverse health outcomes, blood acetate analysis has been used to monitor the systemic status of acetate turnover. The present study examined the use of urinary N-acetyltaurine (NAT) as a marker to reflect the hyperacetatemic status of mice from exogenous inputs and endogenous metabolism, including triacetin dosing, ethanol dosing, and streptozotocin-induced diabetes. The results showed that triacetin dosing increased serum acetate and urinary NAT but not other N-acetylated amino acids in urine. The co-occurrences of increased serum acetate and elevated urinary NAT were also observed in both ethanol dosing and streptozotocin-induced diabetes. Furthermore, the renal cortex was determined as an active site for NAT synthesis. Overall, urinary NAT behaved as an effective marker of hyperacetatemia in three experimental mouse models, warranting further investigation into its application in humans.

In order to solve the problems that are difficult to deal with by traditional prediction methods, such as non-linear, time-series and random, and strong diversity of micro correlation factors, a prediction method of construction waste in urban underground pipe gallery based on Deep BeliefNetwork(DBN) is proposed. Firstly, the Nadam momentum optimization algorithm is used to train the DBN and obtain the best DBN parameters, a learning framework for construction waste prediction is formed. Secondly, PLSR was used to replace gradient fine-tuning method in conventional DBN for improving prediction accuracy. Meanwhile, a Lyapunov function was constructed to prove convergence of the proposed method in the learning process. Finally, the proposed method is applied to underground pipeline gallery construction waste prediction. The experimental results show that the method has a fast convergence rate and a high prediction accuracy, which can meet the demands for waste prediction. [ABSTRACT FROM AUTHOR]

Abstract Background Certain foods and food groups could positively or negatively impact serum uric acid (SUA) levels. However, evidence on the holistic dietary strategy to prevent and control hyperuricemia (HUA) development remains limited. Objective The aim of this research work was to explore the association of dietary approaches to stop hypertension (DASH) diet with SUA levels and odds of HUA among Chinese adults. Methods This research premise included 66,427 Chinese adults aged 18 and above who were part of the China Adult Chronic Disease and Nutrition Surveillance in 2015. Dietary consumptions were assessed via the household condiment weighing approach and a three-day, 24-hour dietary recall. Total fat, saturated fat, calcium, protein, potassium, cholesterol, magnesium, fiber, and sodium were all adopted to calculate the DASH score (score range, 0–9). The associations of DASH score with SUA levels and odds of HUA were evaluated using multiple linear and logistic regression models, respectively. Results We established that a higher DASH score was linked with a lower SUA levels (β = − 0.11; 95% CI: − 0.12, − 0.1; p

Abstract Background Applied behavioral analysis (ABA) is regarded as the gold standard treatment for autism spectrum disorder (ASD) and has the potential to improve outcomes for patients with ASD. It can be delivered at different intensities, which are classified as comprehensive or focused treatment approaches. Comprehensive ABA targets multiple developmental domains and involves 20–40 h/week of treatment. Focused ABA targets individual behaviors and typically involves 10–20 h/week of treatment. Determining the appropriate treatment intensity involves patient assessment by trained therapists, however, the final determination is highly subjective and lacks a standardized approach. In our study, we examined the ability of a machine learning (ML) prediction model to classify which treatment intensity would be most suited individually for patients with ASD who are undergoing ABA treatment. Methods Retrospective data from 359 patients diagnosed with ASD were analyzed and included in the training and testing of an ML model for predicting comprehensive or focused treatment for individuals undergoing ABA treatment. Data inputs included demographics, schooling, behavior, skills, and patient goals. A gradient-boosted tree ensemble method, XGBoost, was used to develop the prediction model, which was then compared against a standard of care comparator encompassing features specified by the Behavior Analyst Certification Board treatment guidelines. Prediction model performance was assessed via area under the receiver-operating characteristic curve (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results The prediction model achieved excellent performance for classifying patients in the comprehensive versus focused treatment groups (AUROC: 0.895; 95% CI 0.811–0.962) and outperformed the standard of care comparator (AUROC 0.767; 95% CI 0.629–0.891). The prediction model also achieved sensitivity of 0.789, specificity of 0.808, PPV of 0.6, and NPV of 0.913. Out of 71 patients whose data were employed to test the prediction model, only 14 misclassifications occurred. A majority of misclassifications (n = 10) indicated comprehensive ABA treatment for patients that had focused ABA treatment as the ground truth, therefore still providing a therapeutic benefit. The three most important features contributing to the model’s predictions were bathing ability, age, and hours per week of past ABA treatment. Conclusion This research demonstrates that the ML prediction model performs well to classify appropriate ABA treatment plan intensity using readily available patient data. This may aid with standardizing the process for determining appropriate ABA treatments, which can facilitate initiation of the most appropriate treatment intensity for patients with ASD and improve resource allocation.