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Extreme hydrological events such as droughts and floods have been increasingly influenced by abnormal atmospheric disturbances caused by human activity and global warming. The Dongting Lake Basin (DLB) has experienced challenging circumstances over the past 20 years due to complex climatic variations, leading to extreme flooding and drought. This study aims to investigate the spatiotemporal variation in terrestrial water storage anomalies (TWSA) over the DLB using data from the GRACE/GRACE-FO and GLDAS spanning the latest two decades. A significant decline trend in TWSA is unveiled from July 2019 to May 2023, with the rate of change determined as −1.94 cm/year and −1.99 cm/year based on the GRACE/GRACE-FO and GLDAS, respectively. The GRACE- Drought Severity Index (DSI) is employed to identify and evaluate the severity and spatiotemporal evolution of the 2022 drought event in the DLB. The results accurately capture the drought event, which began in July 2022 and continued until March 2023, with the most severe conditions occurring in October 2022, when the GRACE-DSI value stood at −2.06 and the TWSA decreased by 15.24 cm and 33.51 cm relative to the same month in 2021 and 2020, respectively. Additionally, the daily water level variation at the Chenglingji hydrological gauging station in 2022 broke previous records, reaching a minimum of only 19 m. Comparing the 2022 drought event with the drought events in 2006 and 2011, the impact of drought on vegetation growth conditions was relatively small, but there was still significant vegetation degradation across the DLB.

Peanut (Arachis hypogaea L.) is a globally important oil crop. Web blotch is one of the most important foliar diseases affecting peanut, which results in serious yield losses worldwide. Breeding web blotch-resistant peanut varieties is the most effective and economically viable method for minimizing yield losses due to web blotch. In the current study, a bulked segregant analysis with next-generation sequencing was used to analyze an F2:3 segregating population and identify candidate loci related to web blotch resistance. Based on the fine-mapping of the candidate genomic interval using kompetitive allele-specific PCR (KASP) markers, we identified a novel web blotch resistance-related locus spanning approximately 169 kb on chromosome 16. This region included four annotated genes, of which only Arahy.35VVQ3 had a non-synonymous single nucleotide polymorphism in the coding region between the two parents. Two markers (Chr.16.12872635 and Chr.16.12966357) linked to this gene were shown to be co-segregated with the resistance of peanut web blotch by 72 randomly selected recombinant inbred lines (RIL), which could be used in marker-assisted breeding of resistant peanut varieties.

Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Abstract Catalyst design relies heavily on electronic metal‐support interactions, but the metal‐support interface with an uncontrollable electronic or coordination environment makes it challenging. Herein, we outline a promising approach for the rational design of catalysts involving heteroatoms as anchors for Pd nanoparticles for ethanol oxidation reaction (EOR) catalysis. The doped B and N atoms from dimethylamine borane (DB) occupy the position of the Ti3C2 lattice to anchor the supported Pd nanoparticles. The electrons transfer from the support to B atoms, and then to the metal Pd to form a stable electronic center. A strong electronic interaction can be produced and the d‐band center can be shifted down, driving Pd into the dominant metallic state and making Pd nanoparticles deposit uniformly on the support. As‐obtained Pd/DB–Ti3C2 exhibits superior durability to its counterpart (∼14.6% retention) with 91.1% retention after 2000 cycles, placing it among the top single metal anodic catalysts. Further, in situ Raman and density functional theory computations confirm that Pd/DB–Ti3C2 is capable of dehydrogenating ethanol at low reaction energies.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Background Impaired ventilatory efficiency during exercise is a predictor of mortality in chronic obstructive pulmonary disease. However, little is known about the clinical features and associated factors of impaired ventilatory efficiency in China.Methods We conducted a cross-sectional community-based study in China and collected demographic and clinical information, cardiopulmonary exercise testing, spirometry, and CT data. Impaired ventilatory efficiency was defined by a nadir ventilatory equivalent for CO2 production above the upper limit of normal. Multivariable linear and logistic regression models were used to explore the clinical features and associated factors of impaired ventilatory efficiency.Results The final analyses included 941 subjects, 702 (74.6%) of whom had normal ventilatory efficiency and 239 (25.4%) had impaired ventilatory efficiency. Participants with impaired ventilatory efficiency had more chronic respiratory symptoms, poorer lung function and exercise capacity, and more severe emphysema (natural logarithm transformation of the low-attenuation area of the lung with attenuation values below −950 Hounsfield units, logLAA−950: 0.19±0.65 vs −0.28±0.63, p

Abstract Background The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR. Methods Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio

Abstract Background Bacterial wilt caused by Ralstonia solanacearum severely affects peanut (Arachis hypogaea L.) yields. The breeding of resistant cultivars is an efficient means of controlling plant diseases. Therefore, identification of resistance genes effective against bacterial wilt is a matter of urgency. The lack of a reference genome for a resistant genotype severely hinders the process of identification of resistance genes in peanut. In addition, limited information is available on disease resistance-related pathways in peanut. Results Full-length transcriptome data were used to generate wilt-resistant and -susceptible transcript pools. In total, 253,869 transcripts were retained to form a reference transcriptome for RNA-sequencing data analysis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of differentially expressed genes revealed the plant-pathogen interaction pathway to be the main resistance-related pathway for peanut to prevent bacterial invasion and calcium plays an important role in this pathway. Glutathione metabolism was enriched in wilt-susceptible genotypes, which would promote glutathione synthesis in the early stages of pathogen invasion. Based on our previous quantitative trait locus (QTL) mapping results, the genes arahy.V6I7WA and arahy.MXY2PU, which encode nucleotide-binding site-leucine-rich repeat receptor proteins, were indicated to be associated with resistance to bacterial wilt. Conclusions This study identified several pathways associated with resistance to bacterial wilt and identified candidate genes for bacterial wilt resistance in a major QTL region. These findings lay a foundation for investigation of the mechanism of resistance to bacterial wilt in peanut.

Purpose: To evaluate regional changes in the posterior corneal elevation after three laser refractive surgeries for correction of myopia of different degrees. Settings and Design: Retrospective, comparative, and non-randomized study. Methods: Two hundred patients (200 eyes) who underwent laser epithelial keratoplasty (LASEK), femtosecond-assisted laser in-situ keratomileusis (FS-LASIK), and small-incision lenticule extraction (SMILE) were included in this study. According to preoperative spherical equivalent (SE), each surgical group was divided into two refractive subgroups: low-to-moderate myopia (LM group) and high myopia (H group). The posterior corneal elevation from Pentacam Scheimpflug tomography was analyzed preoperatively and at 1 month, 3 months, 6 months, and 12 months postoperatively. Three subregions of the posterior cornea were divided in this study as the central, paracentral, and peripheral regions. Statistical Analysis Used: Generalized Estimating Equations (GEE). Results: For all three surgical groups, similar changing trends were seen in the two refractive subgroups. H group presented a larger changing magnitude than the LM group in FS-LASIK over time (P < 0.05), whereas no significant difference was noted in the two refractive subgroups of LASEK or SMILE (P > 0.05). At 12 months postoperatively, the central posterior corneal elevation returned to the preoperative level in LASEK (P > 0.05) but shifted forward significantly in FS-LASIK and SMILE (P < 0.05). Conclusion: Different posterior corneal regions respond differently to corneal refractive surgeries. LASEK, FS-LASIK, and SMILE demonstrate different trends in the regional changes in posterior corneal elevation. The corneal shape seems more stable in LASEK than in FS-LASIK and SMILE.

Abstract Background A significant association between women’s reproductive traits and the risk of schizophrenia (SCZ) has been discovered, but the causalities remain unclear. We designed a two-sample univariate Mendelian randomization (MR) study using female-specific SNPs collected from a large-scale genome-wide association study as a genetic tool to explore the causal effect of female reproductive traits on the risk of SCZ, and conducted a multivariate MR study to re-validate the above findings. Methods From extensive genome-wide association studies (GWAS) of people with European ancestry (n = 176,881 to 418,758 individuals), summary-level data on five female reproductive variables were extracted. Summary-level information on SCZ was taken from a GWAS meta-analysis involving 320,404 people with European ancestry. The inverse variance weighting estimations for both univariable MR (UVMR) and multivariable MR (MVMR) were presented as the primary results. MR-Egger, weighted median, simple mode, and weighted mode regression methods for UVMR, and MVMR-Egger, MVMR-Lasso, and MVMR-median methods for MVMR were used for sensitivity analyses. Results The UVMR produced compelling proof for a connection between genetically predicted later age at first sexual intercourse (AFS) (OR, 0.632; 95% CI, 0.512–0.777; P 0.05). Consistent, substantial causal effects of AFS (OR, 0.592; 95%CI, 0.407–0.862; P

Abstract Background Pod shell thickness (PST) is an important agronomic trait of peanut because it affects the ability of shells to resist pest infestations and pathogen attacks, while also influencing the peanut shelling process. However, very few studies have explored the genetic basis of PST. Results An F2 segregating population derived from a cross between the thick-shelled cultivar Yueyou 18 (YY18) and the thin-shelled cultivar Weihua 8 (WH8) was used to identify the quantitative trait loci (QTLs) for PST. On the basis of a bulked segregant analysis sequencing (BSA-seq), four QTLs were preliminarily mapped to chromosomes 3, 8, 13, and 18. Using the genome resequencing data of YY18 and WH8, 22 kompetitive allele-specific PCR (KASP) markers were designed for the genotyping of the F2 population. Two major QTLs (qPSTA08 and qPSTA18) were identified and finely mapped, with qPSTA08 detected on chromosome 8 (0.69-Mb physical genomic region) and qPSTA18 detected on chromosome 18 (0.15-Mb physical genomic region). Moreover, qPSTA08 and qPSTA18 explained 31.1–32.3% and 16.7–16.8% of the phenotypic variation, respectively. Fifteen genes were detected in the two candidate regions, including three genes with nonsynonymous mutations in the exon region. Two molecular markers (Tif2_A08_31713024 and Tif2_A18_7198124) that were developed for the two major QTL regions effectively distinguished between thick-shelled and thin-shelled materials. Subsequently, the two markers were validated in four F2:3 lines selected. Conclusions The QTLs identified and molecular markers developed in this study may lay the foundation for breeding cultivars with a shell thickness suitable for mechanized peanut shelling.

Background There are limited data on the clinical features and longitudinal prognosis of variable obstruction, particularly among never smokers and different variable obstruction types. Therefore, we aimed to evaluate the clinical characteristics of the participants with variable obstruction and determine the relationship between variable obstruction and the development of chronic obstructive pulmonary disease (COPD) and the decline of lung function in a community-dwelling study of Chinese, especially among never smokers and different variable obstruction subtypes.Methods Participants with preserved spirometry (postbronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.70) at baseline from the Early COPD cohort were included in our analysis. Participants with variable obstruction (prebronchodilator FEV1/FVC

Abstract Background Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored. Methods We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells. Results We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking. Conclusion Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.

To reduce the random error of microelectromechanical system (MEMS) gyroscope, a hybrid method combining improved empirical mode decomposition (EMD) and least squares algorithm (LS) is proposed. Firstly, based on the multiple screening mechanism, intrinsic mode functions (IMFs) from the first decomposition are divided into noise IMFs, strong noise mixed IMFs, weak noise mixed IMFs and signal IMFs. Secondly, according to their characteristics, they are processed again. IMFs from the second decomposition are divided into noise IMFs and signal IMFs. Finally, useful signal is gathered to obtain the final denoising signal. Compared with some other denoising methods proposed in recent years, the experimental results show that the proposed method has obvious advantages in suppressing random error, greatly improving the signal quality and improving the accuracy of inertial navigation.

Objective: To investigate the optimal process for preparing peppermint essential oil/β-cyclodextrin (β-CD) inclusion complex using high-speed shearing combined with freeze-drying. Methods: The effects of freeze-drying and vacuum drying, high-speed shearing, and stirring on the encapsulation process were compared. Based on single-factor experiments, the ratio of β-CD to essential oil, encapsulation temperature, and mass fraction of β-CD were considered as influencing factors. The comprehensive score of oil content and encapsulation efficiency was used as an evaluation index to investigate the Box-Behnken response surface method for optimizing the encapsulation process. The content of pulegone in the inclusion complex was measured by high-performance liquid chromatography (HPLC). Fourier transform infrared spectroscopy (FTIR) was used to characterize the inclusion complex. Results: The yield of inclusion complex prepared by freeze-drying was higher, with an average yield of 97.6%. The oil content and encapsulation efficiency by the high-speed shearing method were relatively high, being about 3% and 19% higher than those by the stirring method, respectively. The optimized conditions were as follows: The weight ratio of β-CD to volatile oil was 9:1 (g/mL), the encapsulation temperature was 55 ℃, and the mass fraction of β-CD was 17%. Under these conditions, the essential oil content was 10.9%, the encapsulation efficiency was 97.6%, the comprehensive score was 99.7, the RSD value was 1.59%, and the optimized process was stable and feasible. The content of pulegone in the inclusion complex was found to be 2.465 mg/g by HPLC. The formation of the peppermint oil/β-CD inclusion complex was confirmed by analysis using FTIR. Conclusion: The combination of high-speed shearing and freeze-drying for the preparation of peppermint essential oil inclusion complex had the advantages of high efficiency, simple process, and it improved theyield, would provide guidance for the production process.

Abstract Background Peanut is an important oil crop worldwide. Peanut web blotch is a fungal disease that often occurs at the same time as other leaf spot diseases, resulting in substantial leaf drop, which seriously affects the peanut yield and quality. However, the molecular mechanism underlying peanut resistance to web blotch is unknown. Results The cytological examination revealed no differences in the conidium germination rate between the web blotch-resistant variety ZH and the web blotch-susceptible variety PI at 12–48 hpi. The appressorium formation rate was significantly higher for PI than for ZH at 24 hpi. The papilla formation rate at 36 hpi and the hypersensitive response rate at 60 and 84 hpi were significantly higher for ZH than for PI. We also compared the transcriptional profiles of web blotch-infected ZH and PI plants at 0, 12, 24, 36, 48, 60, and 84 hpi using an RNA-seq technique. There were more differentially expressed genes (DEGs) in ZH and PI at 12, 36, 60, and 84 hpi than at 24 and 48 hpi. Moreover, there were more DEGs in PI than in ZH at each time-point. The analysis of metabolic pathways indicated that pantothenate and CoA biosynthesis; monobactam biosynthesis; cutin, suberine and wax biosynthesis; and ether lipid metabolism are specific to the active defense of ZH against YY187, whereas porphyrin metabolism as well as taurine and hypotaurine metabolism are pathways specifically involved in the passive defense of ZH against YY187. In the protein-protein interaction (PPI) network, most of the interacting proteins were serine acetyltransferases and cysteine synthases, which are involved in the cysteine synthesis pathway. The qRT-PCR data confirmed the reliability of the transcriptome analysis. Conclusion On the basis of the PPI network for the significantly enriched genes in the pathways which were specifically enriched at different time points in ZH, we hypothesize that serine acetyltransferases and cysteine synthases are crucial for the cysteine-related resistance of peanut to web blotch. The study results provide reference material for future research on the mechanism mediating peanut web blotch resistance.

Congenital birth defects contribute significantly to preterm birth, stillbirth, perinatal death, infant mortality, and adult disability. As a first step to exploring the mechanisms underlying this major clinical challenge, we analyzed the embryonic phenotypes of lethal strains generated by random mutagenesis. In this study, we report the gross embryonic and perinatal phenotypes of 55 lethal strains randomly picked from a collection of mutants that carry piggyBac (PB) transposon inserts. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested most of the analyzed mutations hit genes involved in heart and nervous development, or in Notch and Wnt signaling. Among them, 12 loci are known to be associated with human diseases. We confirmed 53 strains as embryonic or perinatal lethal, while others were subviable. Gross morphological phenotypes such as body size abnormality (29/55, 52.73%), growth or developmental delay (35/55, 63.64%), brain defects (9/55, 16.36%), vascular/heart development (31/55, 56.36%), and other structural defects (9/55, 16.36%) could be easily observed in the mutants, while three strains showed phenotypes similar to those of human patients. Furthermore, we detected body weight or body composition alterations in the heterozygotes of eight strains. One of them was the TGF-β signaling gene Smad2. The heterozygotes showed increased energy expenditure and a lower fat-to-body weight ratio compared to wild-type mice. This study provided new insights into mammalian embryonic development and will help understand the pathology of congenital birth defects in humans. In addition, it expanded our understanding of the etiology of obesity.

Summary: China has committed to eradicating the forage-livestock conflict (FLC) by 2035 to restore degraded rangelands. This commitment is accompanied by China’s rapid socioeconomic development, highlighting the necessity to analyze the effects of socioeconomic transition on FLC changes. Here, we uncover multi-regional socioeconomic drivers of China’s FLC changes. The results show that during 2005–2015, the economic structure transition of China has cumulatively driven 24 Mt of FLC reductions. In particular, the FLC reduction driven by the final demand structure transition of pastoral provinces is three times that of non-pastoral provinces. The mitigation effects of the final demand structure transition of external regions generally decrease with increasing distance from the certain pastoral province. The FLC reduction caused by the production structure transition of non-pastoral provinces is twice that of pastoral provinces. This study highlights the significance of interregional cooperation and economic structure optimization to achieve China’s “Forage-Livestock Balance Goal 2035.” Science for society: Forage-livestock conflict (FLC) is a major anthropogenic driver of rangeland degradation in China. It poses serious threats to environmental, economic, and social sustainability due to its harmful impacts on ecosystem services, livestock development, and pastoralists’ well-being. To combat rangeland degradation, China has adopted a series of in situ FLC control measures and set a goal to eradicate FLC by 2035. Grazing in pastoral areas and associated FLCs are significantly affected by local and remote socioeconomic development. Using a numerical model that accounts for multi-regional socioeconomic changes, we find that the national economic structure transition has led to FLC reductions during 2005–2015. The final demand structure change of non-pastoral provinces and production structure change of pastoral provinces have mitigation potentials to be tapped. The outcome can support interregional cooperation and economic structure transition to achieve China’s zero-FLC goal.

Abstract Precise design and control of molecular self‐assembly as living creatures are exciting ideas in the field of nanotechnology. Characterized with predesigned geometries and accurate spatial addressability, programmable DNA origami nanostructures have been recognized as optimized tools for assembling multiple functional components. A variety of biomolecules can be attached to the nanoscale drawing boards in a site‐specific fashion, thus facilitating the precise construction of DNA origami‐based materials for studies on biological interface. In this minireview, we highlight the recent advances in the precise construction of DNA origami‐based materials with artificial bio‐structures and/or biomimicking functions. The regulation of biological functions by these DNA origami‐engineered assemblies at the bio‐interface has been summarized and discussed.

Abstract Natural molecular chaperones utilize spatially ordered multiple molecular forces to effectively regulate protein folding. However, synthesis of such molecules is a big challenge. The concept of “aggregate science” provides insights to construct chemical entities (aggregates) beyond molecular levels to mimic both the structure and function of natural chaperone. Inspired by this concept, herein we fabricate a novel multi‐interaction (i.e., electrostatic and hydrophobic interaction) cooperative nanochaperone (multi‐co‐nChap) to regulating protein folding. This multi‐co‐nChap is fabricated by rationally introducing electrostatic interactions to the surface (corona) and confined hydrophobic microdomains (shell) of traditional single‐hydrophobic interaction nanochaperone. We demonstrate that the corona electrostatic attraction facilitates the diffusion of clients into the hydrophobic microdomains, while the shell electrostatic interaction balances the capture and release of clients. By finely synergizing corona electrostatic attraction with shell electrostatic repulsion and hydrophobic interaction, the optimized multi‐co‐nChap effectively facilitated de novo folding of nascent polypeptides. Moreover, the synergy between corona electrostatic attraction, shell electrostatic attraction and shell hydrophobic interaction significantly enhanced the capability of multi‐co‐nChap to protect native proteins from denaturation at harsh temperatures. This work provides important insights for understanding and design of nanochaperone, which is a kind of ordered aggregate with chaperone‐like activity that beyond the level of single molecule.

BackgroundEpidemiological studies have demonstrated a comorbid association between migraine and epilepsy. However, despite the long history of this association, the exact nature of the relationship between migraine and epilepsy remains largely unresolved. Therefore, it is crucial to conduct a meta-analysis in order to thoroughly investigate the relationship between migraine and epilepsy.MethodsOdds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs) regarding association between migraine and epilepsy were summarized using STATA 12.0 software.ResultsThere was an 80% increase in the lifetime prevalence of migraine among patients with epilepsy, compared to those without epilepsy with a random effects model (OR/RR: 1.80, 95% CI: 1.35 to 2.40, I2 = 97.5%, p < 0.001). There was an 80% increase in the lifetime prevalence of epilepsy among patients with migraine, compared to those without migraine with a random effects model (OR/RR: 1.80, 95% CI: 1.43 to 2.25, I2 = 80.6%, p < 0.001).ConclusionsIt is important to note the comorbid association between migraine and epilepsy examined in the study.

Abstract The tyrosine kinase inhibitor (TKI) Sunitinib is one the therapies approved for advanced renal cell carcinoma. Here, we undertake proteogenomic profiling of 115 tumors from patients with clear cell renal cell carcinoma (ccRCC) undergoing Sunitinib treatment and reveal the molecular basis of differential clinical outcomes with TKI therapy. We find that chromosome 7q gain-induced mTOR signaling activation is associated with poor therapeutic outcomes with Sunitinib treatment, whereas the aristolochic acid signature and VHL mutation synergistically caused enhanced glycolysis is correlated with better prognosis. The proteomic and phosphoproteomic analysis further highlights the responsibility of mTOR signaling for non-response to Sunitinib. Immune landscape characterization reveals diverse tumor microenvironment subsets in ccRCC. Finally, we construct a multi-omics classifier that can detect responder and non-responder patients (receiver operating characteristic–area under the curve, 0.98). Our study highlights associations between ccRCC molecular characteristics and the response to TKI, which can facilitate future improvement of therapeutic responses.

Talaromyces, a filamentous fungus widely distributed across terrestrial and marine environments, can produce a diverse array of natural products, including alkaloids, polyketones, and polyketide-terpenoids. Among these, chrodrimanins represented a typical class of natural products. In this study, we isolated three previously undescribed pentaketide-sesquiterpenes, 8,9-epi-chrodrimanins (1–3), along with eight known compounds (4–11). The structures of compounds 1–3 were elucidated using nuclear magnetic resonance (NMR) and mass spectrometry (MS), while their absolute configurations were determined through X-ray crystallography and electronic circular dichroism (ECD) computations. The biosynthetic pathways of compounds 1–3 initiate with 6-hydroxymellein and involve multiple stages of isoprenylation, cyclization, oxidation, and acetylation. We selected four strains of gastrointestinal cancer cells for activity evaluation. We found that compound 3 selectively inhibited MKN-45, whereas compounds 1 and 2 exhibited no significant inhibitory activity against the four cell lines. These findings suggested that 8,9-epi-chrodrimanins could serve as scaffold compounds for further structural modifications, potentially leading to the development of targeted therapies for gastric cancer.

The quest for efficient and safe trajectory planning in robotic manipulation poses significant challenges, particularly in complex obstacle environments where the risk of encountering singularities and obstacles is high. Addressing this critical issue, our study presents a novel enhancement of the Fast Marching Tree (FMT) algorithm, ingeniously designed to navigate the complex terrain of Cartesian space with an unprecedented level of finesse. At the heart of our approach lies a sophisticated two-stage path point sampling strategy, ingeniously coupled with a singularity avoidance mechanism that leverages geometric perception to assess and mitigate the risk of encountering problematic configurations. This innovative method not only facilitates seamless obstacle navigation but also adeptly circumvents the perilous zones of singularity, ensuring a smooth and uninterrupted path for the robotic arm. To further refine the trajectory, we incorporate a quasi-uniform cubic B-spline curve, optimizing the path for both efficiency and smoothness. Our comprehensive simulation experiments underscore the superiority of our algorithm, showcasing its ability to consistently achieve shorter, more efficient paths while steadfastly avoiding obstacles and singularities. The practical applicability of our method is further corroborated through successful implementation in real-world robotic arm trajectory planning scenarios, highlighting its potential to revolutionize the field with its robustness and adaptability.

Alternative polyadenylation (APA) contributes to transcriptome complexity and gene expression regulation and has been implicated in various cellular processes and diseases. Single-cell RNA sequencing (scRNA-seq) has enabled the profiling of APA at the single-cell level; however, the spatial information of cells is not preserved in scRNA-seq. Alternatively, spatial transcriptomics (ST) technologies provide opportunities to decipher the spatial context of the transcriptomic landscape. Pioneering studies have revealed potential spatially variable genes and/or splice isoforms; however, the pattern of APA usage in spatial contexts remains unappreciated. In this study, we developed a toolkit called stAPAminer for mining spatial patterns of APA from spatially barcoded ST data. APA sites were identified and quantified from the ST data. In particular, an imputation model based on the k-nearest neighbors algorithm was designed to recover APA signals, and then APA genes with spatial patterns of APA usage variation were identified. By analyzing well-established ST data of the mouse olfactory bulb (MOB), we presented a detailed view of spatial APA usage across morphological layers of the MOB. We compiled a comprehensive list of genes with spatial APA dynamics and obtained several major spatial expression patterns that represent spatial APA dynamics in different morphological layers. By extending this analysis to two additional replicates of the MOB ST data, we observed that the spatial APA patterns of several genes were reproducible among replicates. stAPAminer employs the power of ST to explore the transcriptional atlas of spatial APA patterns with spatial resolution. This toolkit is available at https://github.com/BMILAB/stAPAminer and https://ngdc.cncb.ac.cn/biocode/tools/BT007320.

1α,25-Dihydroxyvitamin D3 (VitD3) is the active form of vitamin D, and it regulates gene expression and protein synthesis in mammalian follicle development. However, the function of VitD3 in the follicular development of layers remains unclear. This study investigated, through in vivo and in vitro experiments, the effects of VitD3 on follicle development and steroid hormone biosynthesis in young layers. In vivo, ninety 18-week-old Hy-Line Brown laying hens were randomly divided into three groups for different treatments of VitD3 (0, 10, and 100 μg/kg). VitD3 supplementation promoted follicle development, increasing the number of small yellow follicles (SYFs) and large yellow follicles (LYFs) and the thickness of the granulosa layer (GL) of SYFs. Transcriptome analysis revealed that VitD3 supplementation altered gene expression in the ovarian steroidogenesis, cholesterol metabolism, and glycerolipid metabolism signaling pathways. Steroid hormone-targeted metabolomics profiling identified 20 steroid hormones altered by VitD3 treatment, with 5 being significantly different among the groups. In vitro, it was found that VitD3 increased cell proliferation, promoted cell-cycle progression, regulated the expression of cell-cycle-related genes, and inhibited the apoptosis of granulosa cells from pre-hierarchical follicles (phGCs) and theca cells from prehierarchical follicles (phTCs). In addition, the steroid hormone biosynthesis-related genes, estradiol (E2) and progesterone (P4) concentrations, and vitamin D receptor (VDR) expression level was significantly altered by VitD3. Our findings identified that VitD3 altered the gene expression related to steroid metabolism and the production of testosterone, estradiol, and progesterone in the pre-hierarchical follicles (PHFs), resulting in positive effects on poultry follicular development.

Abstract Aims Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all‐cause and cause‐specific mortality in patients with type 2 diabetes. Methods All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999–2002. Death status and its causes were ascertained for National Death Index based on International Classification of Diseases, Tenth Revision code. Cox proportional hazards regression models were established to estimate the hazard ratios (HRs) of LTL associating with all‐cause and cause‐specific mortality. Results The study enrolled 804 diabetic patients with the mean follow‐up of 14.9 ± 2.59 years. There were 367 (45.6%) all‐cause deaths, 80 (10.0%) cardiovascular deaths, and 42 (5.2%) cancer‐related deaths. Longer LTL was associated with reduced all‐cause mortality, whereas this association disappeared after adjusting for other variables. Compared with the lowest tertiles of LTL, the multivariable‐adjusted hazard ratio of cardiovascular mortality was 2.11 (95% confidence interval [CI] 1.31–3.39; p

Background Evidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals with NOCB in the Chinese population.Methods We obtained data on participants in the Early Chronic Obstructive Pulmonary Disease Study who had normal spirometry (post-bronchodilator forced expiratory volume in 1 s/forced vital capacity ≥0.70). NOCB was defined as chronic cough and sputum production for at least 3 months for two consecutive years or more at baseline in participants with normal spirometry. We assessed the differences in demographics, risk factors, lung function, impulse oscillometry, CT imaging and frequency of acute respiratory events between participants with and without NOCB.Results NOCB was present in 13.1% (149/1140) of participants with normal spirometry at baseline. Compared with participants without NOCB, those with NOCB had a higher proportion of men and participants with smoke exposure, occupational exposure, family history of respiratory diseases and worse respiratory symptoms (all p

Background The relationship between airway inflammation in chronic obstructive pulmonary disease (COPD) and clinical characteristics remains unclear. This study aimed to investigate the airway inflammatory phenotypes in COPD and their association with clinical characteristics.Methods 895 patients with COPD were recruited from Guangdong Province, China in this study. Each patient underwent questionnaire interviews, spirometry testing, CT scans and induced sputum examination. Classification of airway inflammation phenotypes was based on sputum inflammatory cell counts. Covariance analysis was applied to assess associations with airway inflammation phenotypes.Results In this study, we found that neutrophilic phenotype (NP, 58.0%) was the most common airway inflammation phenotype in patients with COPD, followed by mixed granulocytic phenotype (MGP, 32.6%), eosinophilic phenotype (EP, 5.4%) and paucigranulocytic phenotype (PP, 4.0%). Compared with NP patients, those with MGP exhibited more frequent chronic respiratory symptoms, and a higher proportion of individuals classified under Global Initiative for Chronic Obstructive Lung Disease stages 3 and 4. After adjusting for confounding factors, MGP patients had lower lung function, and more severe emphysema and air trapping. On the contrary, patients with PP had the best pulmonary function and less emphysema and air trapping.Conclusions NP was the most common airway inflammation phenotype in patients with COPD. Patients with MGP had more respiratory symptoms, greater loss of lung function, and more severe emphysema and gas trapping compared with those with NP. Meanwhile, PP may be a phenotype of mild damage to lung structure in patients with COPD.

Lonicera japonica flos (LJF) is a common clinical herb with outstanding medicinal and nutritional value. This study aimed to evaluate the antidepressant effects of LJF’s active extract and compound chlorogenic acid (CGA) around brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B (TrkB) pathway. The results showed that LJF’s extracts and CGA had significant antidepressant effects, and the antidepressant effects of different extracts of LJF were highly positively correlated with the content of CGA (forced swimming test, r = 0.998; tail suspension test, r = 0.934). Moreover, LJF-70% ethanolic extract and CGA improved chronic unpredictable mild stress-induced depressive behavior, upregulated protein expression levels of BDNF and p-TrkB in the hippocampus, restored the damage of hippocampal neurons, and protected liver from damage. In summary, this study demonstrated for the first time that LJF-70% ethanolic extract was the active extract of LJF in antidepressant and CGA was its active compound, and the antidepressant mechanisms mainly involved the upregulation of BDNF-TrkB signaling pathway in the hippocampus of mice.

Interplay between energy-storing white adipose cells and thermogenic beige adipocytes contributes to obesity and insulin resistance. Irrespective of specialized niche, adipocytes require the activity of the nuclear receptor PPARγ for proper function. Exposure to cold or adrenergic signaling enriches thermogenic cells though multiple pathways that act synergistically with PPARγ; however, the molecular mechanisms by which PPARγ licenses white adipose tissue to preferentially adopt a thermogenic or white adipose fate in response to dietary cues or thermoneutral conditions are not fully elucidated. Here, we show that a PPARγ/long noncoding RNA (lncRNA) axis integrates canonical and noncanonical thermogenesis to restrain white adipose tissue heat dissipation during thermoneutrality and diet-induced obesity. Pharmacologic inhibition or genetic deletion of the lncRNA Lexis enhances uncoupling protein 1–dependent (UCP1-dependent) and -independent thermogenesis. Adipose-specific deletion of Lexis counteracted diet-induced obesity, improved insulin sensitivity, and enhanced energy expenditure. Single-nuclei transcriptomics revealed that Lexis regulates a distinct population of thermogenic adipocytes. We systematically map Lexis motif preferences and show that it regulates the thermogenic program through the activity of the metabolic GWAS gene and WNT modulator TCF7L2. Collectively, our studies uncover a new mode of crosstalk between PPARγ and WNT that preserves white adipose tissue plasticity.

Background: This research was designed to investigate Algorithm Guided Treatment (AGT) and clinical traits for the prediction of antidepressant treatment outcomes in Chinese patients with major depressive disorder (MDD). Methods: This study included 581 patients who had reached treatment response and 406 patients remained non-responded observed after three months of treatment. Sociodemographic factors, clinical traits, and psychiatric rating scales for evaluating therapeutic responses between the two groups were compared. Logistic regression analysis was adopted to determine the risk factors of unresponsive to antidepressant (URA) in MDD. Kaplan-Meier survival analysis was utilized to compare the therapeutic response between AGT and treatment as usual (TAU). Results: Compared to the MDD responsive to antidepressant (RA) group, the URA group had significantly lower rates of the following clinical traits: married status, anxious distress, moderate to severe depressive symptoms, and higher rates of comorbidity (p-value < 0.05). Logistic Regression Analysis showed that eight clinical traits from psychiatric rating scales, such as anxious characteristics, were correlated positively with URA, while the other eight symptoms, such as autonomic symptoms, were negatively correlated. Time to symptomatic remission was longer in TAU without statistically significant (p-value = 0.11) by log-rank testing. Conclusions: The factors may affect the therapeutic responses and compliance of patients, increasing the non-response risk for antidepressants. Therapeutic responses might be improved by increasing the clarification and elucidation of different symptom clusters of patients. Benefits on treatment response to AGT were not found in our study, indicating a one-size-fits-all approach may not work.Trial Registration: We registered as a clinical trial at the International Clinical Trials Registry Platform (No. NCT01764867) and obtained ethical approval 2012-42 from SMHC.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a general term for a class of diseases that are mostly caused by intrauterine genetic development limitation. Without timely intervention, certain children with CAKUT may experience progressive decompensation and a rapid decline in renal function, which will ultimately result in end-stage renal disease. At present, a comprehensive understanding of the pathogenic signaling events of CAKUT is lacking. The role of long noncoding RNAs (lncRNAs) in renal development and disease have recently received much interest. In previous research, we discovered that mice overexpressing the lncRNA 4933425B07Rik (Rik) showed a range of CAKUT phenotypes, primarily renal hypoplasia. The current study investigated the molecular basis of renal hypoplasia caused by Rik overexpression. We first used Rapid Amplification of cDNA ends (RACE) to obtain the full-length sequence of Rik in Rik+/+;Hoxb7 mice. Mouse proximal renal tubule epithelial cells (MPTCs) line with Rik overexpression was constructed using lentiviral methods, and mouse metanephric mesenchyme cell line (MK3) with Rik knockout was then constructed by the CRISPR‒Cas9 method. We performed RNA-seq on the Rik-overexpressing cell line to explore possible differentially expressed molecules and pathways. mRNA expression was confirmed by qRT‒PCR. Reduced levels of Wnt10b, Fzd8, and β-catenin were observed when Rik was expressed robustly. On the other hand, these genes were more highly expressed when Rik was knocked out. These results imply that overabundance of Rik might inhibit the Wnt/β-catenin signaling pathway, which may result in renal hypoplasia. In general, such research might help shed light on CAKUT causes and processes and offer guidance for creating new prophylactic and therapeutic strategies.

Alternative polyadenylation (APA) plays important roles in modulating mRNA stability, translation, and subcellular localization, and contributes extensively to shaping eukaryotic transcriptome complexity and proteome diversity. Identification of poly(A) sites (pAs) on a genome-wide scale is a critical step toward understanding the underlying mechanism of APA-mediated gene regulation. A number of established computational tools have been proposed to predict pAs from diverse genomic data. Here we provided an exhaustive overview of computational approaches for predicting pAs from DNA sequences, bulk RNA sequencing (RNA-seq) data, and single-cell RNA sequencing (scRNA-seq) data. Particularly, we examined several representative tools using bulk RNA-seq and scRNA-seq data from peripheral blood mononuclear cells and put forward operable suggestions on how to assess the reliability of pAs predicted by different tools. We also proposed practical guidelines on choosing appropriate methods applicable to diverse scenarios. Moreover, we discussed in depth the challenges in improving the performance of pA prediction and benchmarking different methods. Additionally, we highlighted outstanding challenges and opportunities using new machine learning and integrative multi-omics techniques, and provided our perspective on how computational methodologies might evolve in the future for non-3′ untranslated region, tissue-specific, cross-species, and single-cell pA prediction.

Abstract Background The role of airway impairment assessed by impulse oscillometry (IOS) in patients with chronic obstructive pulmonary disease (COPD) remains unclear. Therefore, this study aimed to analyze the proportion and clinical characteristics of airway impairment assessed by IOS across COPD severities, and explore whether airway impairment is a subtype of COPD. Methods This study was based on cross-sectional data from the ECOPD cohort in Guangdong, China. Subjects were consecutively recruited from July 2019 to August 2021. They filled out questionnaires and underwent lung function tests, IOS and computed tomography (CT). COPD was defined as post-bronchodilator forced expiratory volume in one second/forced vital capacity upper limit of normal or

The strategic development of reverse logistics networks is crucial for addressing the common challenge of low recovery rates for end-of-life vehicles (ELVs) in China. To minimize the total cost of the reverse logistics network for ELVs, this paper proposes a mixed-integer linear programming (MILP) model. The model considers the recycling volume of different vehicle types, facility processing capacity, and the proportions of parts and materials. Building on this foundation, a fuzzy mixed-integer nonlinear programming (FMINLP) model is developed to account for the inherent uncertainty associated with recycling volumes and facility processing capacities. The model was solved using Lingo, and its effectiveness was validated using Jiangsu Province of China as a case study, followed by a sensitivity analysis. The results indicate that dismantling and machining centers incur the highest processing costs. Variations in recycling volume and facility handling capacity significantly impact total costs and site selection, with the former having a more pronounced effect. Increasing facility processing capacity effectively increases the recovery rate. Moreover, a higher confidence level corresponds to higher total costs and a greater demand for facilities.

Inspired by the practice of urban distribution of fresh products, we introduce a new electric vehicle routing problem with soft time windows. In this problem, goods with different temperature layers can be distributed in ordinary electric vehicles simultaneously based on the cold storage insulation box. The primary objective is to devise optimized distribution routes for logistics companies to minimize distribution costs, including transportation, refrigeration, and charging costs. To address this, we present a mathematical model for the problem and propose an improved ant colony optimization algorithm combined with a 2-opt algorithm. Based on Solomon dataset, we conduct numerical experiments to verify the effectiveness of the proposed model and algorithm. The numerical results demonstrate that multi-temperature co-distribution can lead to a reduction in distribution cost and an improvement in distribution efficiency.

The molecular landscape of microphthalmia transcription factor family translocation renal cell carcinoma tumours remain to be characterised. Here, the authors perform proteogenomic analysis and reveal dysregulation of DNA repair, mTOR signalling and metabolic processes.

The mechanisms of resistance to therapy in gastric cancer remain to be explored. Here, proteomic profiling of 206 tumour tissues from patients treated with chemotherapy and anti-HER2-based therapy results in the identification of four molecular subtypes and the development of prognostic models.

Abstract Background Aging has been evidenced to bring about some structural and functional lung changes, especially in COPD. However, whether aging affects SAD, a possible precursor of COPD, has not been well characterized. Objective We aimed to comprehensively assess the relationship between aging and SAD from computed tomography, impulse oscillometry, and spirometry perspectives in Chinese. Methods We included 1859 participants from ECOPD, and used a linear-by-linear association test for evaluating the prevalence of SAD across various age subgroups, and multivariate regression models for determining the impact of age on the risk and severity of SAD. We then repeated the analyses in these subjects stratified by airflow limitation. Results The prevalence of SAD increases over aging regardless of definitional methods. After adjustment for other confounding factors, per 10-yrs increase in age was significantly associated with the risk of CT-defined SAD (OR 2.57, 95% CI 2.13 to 3.10) and the increase in the severity of air trapping (β 2.09, 95% CI − 0.06 to 4.25 for LAA-856), airway reactance (β − 0.02, 95% CI − 0.04 to − 0.01 for X5; β 0.30, 95% CI 0.13 to 0.47 for AX; β 1.75, 95% CI 0.85 to 2.66 for Fres), as well as the decrease in expiratory flow rates (β − 3.95, 95% CI − 6.19 to − 1.71 for MMEF%predicted; β − 5.42, 95% CI − 7.88 to − 2.95 for FEF50%predicted) for SAD. All these associations were generally maintained in SAD defined by IOS or spirometry. After stratification of airflow limitation, we further found that the effect of age on LAA-856 was the most significant among almost all subgroups. Conclusions Aging is significantly associated with the prevalence, increased risk, as well as worse severity of SAD. CT may be a more optimal measure to assess aging-related SAD. The molecular mechanisms for the role of aging in SAD need to be explored in the future. Trial registration Chinese Clinical Trial Registry ChiCTR1900024643. Registered on 19 July 2019

The glass transition temperature (Tg) is used to determine thermophysical properties of polymer materials and is often considered one of the most important descriptors. Methods for predicting various physical properties of materials based on machine learning algorithms and key molecular descriptors are efficient and accurate. However, it still needs improvements because an overly complex model is less practical and difficult to generalize. In addition, obtaining a large number of samples to achieve accurate predictions remains a challenge due to the complex and lengthy experimental process. In this work, based on Tg of 100 polymers, we use a feature selection algorithm combining FeatureWiz and the least absolute shrinkage and selection operator to quickly select molecular descriptors that are minimally redundant and maximally relevant to Tg. The processed dataset is interpolated from the original dataset using the nearest neighbor interpolation algorithm to solve the data deficiency problem. Finally, the synthetic minority oversampling technique algorithm is used to solve the data imbalance problem. The augmented dataset is used to construct the extreme gradient boosting prediction model to achieve good prediction accuracy. The experimental results demonstrate the robustness of the proposed model and the accuracy of its prediction results.

Metal-organic frameworks (MOFs) are porous materials, which possess a large specific surface area, various coordination types and modes, and versatile and adaptable morphologies and characteristics. MOFs have drawn much interest recently because of their appealing structure and potential for extensive use. With excellent characteristics, including high sensitivity, a low detection limit, and robust stability, nickel (Ni)-based MOFs have several benefits in electrochemical sensing. However, the weak conductivity of pure Ni-based MOFs limits their electrochemical applications. It is essential to further improve the characteristics and enhance the electrical conductivity of pure Ni-based MOFs aiming at enhancing their performance in electrochemical sensing. Herein, the three preparation methods of pure Ni-based MOFs are introduced, then the most recent advancements of pure Ni-based MOFs in electrochemical sensing applications are detailed in this work. In addition, it described how to adapt pure Ni-based MOFs to improve their electrochemical characteristics in three ways. In the introduction of these processes, the structures and morphologies of the prepared pure or modified Ni-based MOF are also described. It is envisaged that this work may give some extending techniques for future research of Ni-based MOFs materials in this burgeoning sector.

Abstract Organic montmorillonite/brominated butyl rubber nanocomposites are prepared by improved solution blending, i.e., preparation of organic clay suspension and suspension blending with brominated butyl rubber solution by adding polytetramethylene ether glycol as interface agent. Scanning electron microscopy and atomic force microscopy show that polytetramethylene ether glycol has good dispersing effect on organic clay. Transmission electron microscopy and X‐ray diffraction analysis demonstrates that both intercalated and exfoliated structures are obtained in organic montmorillonite/brominated butyl rubber nanocomposites. The mechanical performances and the gas barrier properties of the organic montmorillonite/brominated butyl rubber nanocomposites are improved greatly, which proves that the high‐performance clay/rubber nanocomposites are prepared in nonpolar solvent.

The gut microbiome is critically involved in maintaining normal physiological function in the host. Recent studies have revealed that alterations in the gut microbiome contribute to the development and progression of cerebrovascular disease via the microbiota-gut-brain axis (MGBA). As a broad communication network in the human body, MGBA has been demonstrated to have significant interactions with various factors, such as brain structure and function, nervous system diseases, etc. It is also believed that the species and composition of gut microbiota and its metabolites are intrinsically linked to vascular inflammation and immune responses. In fact, in fecal microbiota transplantation (FMT) research, specific gut microbiota and downstream-related metabolites have been proven to not only participate in various physiological processes of human body, but also affect the occurrence and development of cerebrovascular diseases directly or indirectly through systemic inflammatory immune response. Due to the high mortality and disability rate of cerebrovascular diseases, new treatments to improve intestinal dysbacteriosis have gradually attracted widespread attention to better ameliorate the poor prognosis of cerebrovascular diseases in a non-invasive way. This review summarizes the latest advances in the gut microbiome and cerebrovascular disease research and reveals the profound impact of gut microbiota dysbiosis and its metabolites on cerebrovascular diseases. At the same time, we elucidated molecular mechanisms whereby gut microbial metabolites regulate the expression of specific interleukins in inflammatory immune responses. Moreover, we further discuss the feasibility of novel therapeutic strategies targeting the gut microbiota to improve the outcome of patients with cerebrovascular diseases. Finally, we provide new insights for standardized diagnosis and treatment of cerebrovascular diseases.

The shear connection joint is an important component of the prefabricated shear wall structure system, which plays a dual role in ensuring reasonable force transmission and structural integrity. A new type of steel shear-connection horizontal joint was proposed in this study. In order to verify the effectiveness of the proposed new joint, the established numerical model and its constitutive relationship were first verified based on the existing experimental results. Then, the influence effect on the mechanical behaviors of this new type of joint was further investigated with 20 computational cases. The corresponding influencing laws were established, and optimal parameter ranges were suggested. Finally, a simplified constitutive model—namely, a bilinear constitutive model based on the M-θ relationship—of the new steel shear-connection joint is further advanced and deduced. The results show that the proposed new joint can provide stable shear capacity and superior energy dissipation capacity. The interlocking slot in the new steel shear-connection joint is suggested to be designed with a slot length of 20~30 mm, a slot number of two or three, and a slot thickness of 20~30 mm so as to guarantee superior mechanical behaviors. The advanced bilinear constitutive model can effectively capture the mechanical characteristics of the new joints, in which the maximum error is only 7.67% between theory and simulation.

In micron or nano smart sensing systems, piezoelectric cantilever beams are distributed as major components in microsensors, actuators, and energy harvesters. This paper investigates the performance of four cantilever beam devices with “electric-force” conversion based on the inverse piezoelectric effect of lithium niobate (LiNbO3, LN) single-crystal materials. A new compact piezoelectric smart device model is proposed, designed as a single mass block connected by four beams, where devices exhibit smaller lateral errors (0.39–0.41%). The relationship between the displacement characteristics of cantilever beams and driving voltage was researched by applying excitation signals. The results show that the device has the maximum displacement at a first-order intrinsic frequency (fosc = 11.338 kHz), while the displacement shows a good linear relationship (R2 = 0.998) with driving voltage. The square wave signals of the same amplitude have greater “electrical-force” conversion efficiency. The output displacement can reach 12 nm, which is much higher than the output displacement with sinusoidal excitation. In addition, the relative displacement deviation of devices can be maintained within ±1% under multiple cycles of electrical signal loading. The small size, high reliability, and ultra-stability of Si–LN ferroelectric single-crystal cantilever beam devices with lower vibration amplitudes are promising for nanopositioning techniques in microscopy, diagnostics, and high-precision manufacturing applications.

Clear cell renal cell carcinoma is an aggressive form of renal cancer, with differences in genomic mutations reported between Western and Eastern populations. In this study, the authors have compiled proteogenomic analysis of Chinese ccRCC to reveal genomic alterations and dysregulation of immune and metabolic responses.

Blood-brain barrier (BBB) leakage is an important cause of the exacerbation of pathological features of cerebral ischemia reperfusion injury (CIRI). However, the specific mechanism of BBB leakage is not clear. It was found that the CIRI resulted in RIPK1 activation and subsequent RIPK1-dependent apoptosis (RDA). Inhibition of RIPK1 significantly reduced BBB breakdown and brain damage. The aim of this study is to investigate the mechanism of RIPK1 in the BBB leakage during CIRI. It was discovered by proteomics that autophagy activation resulting from ischemia and reperfusion significantly downregulated the level of A20 protein. A20 is an important protein that regulates RIPK1 and RDA. It was hypothesized that activation of autophagy caused by ischemic reperfusion led to a decrease in A20 protein, which, in turn, caused the activation of RIPK1 and the occurrence of RDA, leading to leakage of the BBB. The findings in this study revealed the role of RIPK1 in the cell death and BBB leakage upon cerebral ischemia reperfusion injury, and these findings provide a novel perspective for the treatment of ischemic reperfusion.

Plant-based functional foods have attracted increasing research interest to validate their use in preventing metabolic disease. Since it is increasingly recognized that inflammation, oxidative stress, and circadian rhythm play vital roles in various metabolic diseases, including diabetes, obesity and non-alcoholic liver disease, plant proteins, protein hydrolysates, and food extracts that intervene in these biological processes are promising dietary supplements to prevent metabolic diseases. Here, we reviewed the recent research on plant-based foods used for metabolic disease prevention and provided new perspectives regarding the current study gaps and future directions in this field.