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Abstract Sepsis, caused by uncontrollable infection and inflammatory response, leads to more than 30 million infected patients and results in high morbidity worldwide every year. Currently, no efficient approaches have been developed for sepsis therapy due to antimicrobial resistance and inflammatory storm. Here, we report macrophages loaded with aggregated carbon dots (ACDs) in the lysosome, termed MCDs, to treat sepsis in immunosuppressive mice. The ACDs are constructed by negative CDs and amine‐abundant polyethyleneimine (PEI), enabling them to bear the strong antibacterial ability and enhanced photoluminescent efficacy. The ACDs are specifically located in the macrophage lysosomes, efficiently enhancing the multidrug‐resistant bacteria‐killing ability of MCDs. More importantly, the MCDs possess superior anti‐inflammatory effects such as reducing the number of pro‐inflammatory (M1) and stimulating anti‐inflammatory (M2) macrophages. These effects upregulate the inflammatory cytokines (TNF‐α, IL‐1β, IL‐4, and IL‐10), ultimately resulting in increased sepsis survival. Our work provides an intelligent approach to overcoming multidrug‐resistant bacteria‐induced infection from sepsis patients and paves a new avenue on employing nanoparticle‐loaded cells for combating inflammation‐related infection.

Time-restricted feeding (TRF) is an emerging dietary intervention that improves metabolic disorders such as obesity, insulin resistance and dyslipidemia. Inflammatory bowel disease (IBD) is a chronic inflammatory disorder affecting the gastrointestinal tract, where nutrition plays an important role in its pathogenesis. Although numerous strategies of nutritional intervention have been reported, whether TRF can improve IBD has been elusive. In this study, we investigated the effect of two cycles of 7-day TRF intervention in a dextran sulfate sodium-induced IBD mouse model. We found that TRF was able to reduce the disease activity index and ameliorate the IBD-associated symptoms, as well as increase the number of colonic crypts and decrease the histological score in the colon. Furthermore, TRF lowered the percentage of CD4+ T cells in the peripheral blood and mesenteric lymph node, and increased the number of CD4+CD25+ T cells in the mesenteric lymph nodes. Additionally, TRF reduced the infiltration of leukocytes and macrophages around the crypt base in the colon. However, unlike the intermittent caloric restriction with fasting-mimicking diet, TRF was not able to increase the markers of progenitor and cell proliferation in the colon. Collectively, these results demonstrated that TRF is able to improve IBD in mice via reduction in intestinal inflammation.

Abstract Background Although the experiences of mothers with mental illness are well researched in Western countries, little is known about the experiences of Chinese mothers. This study aims to explore the experiences of family life and parenting of Chinese mothers, in the context of their mental illness. Methods Fourteen Chinese mothers with mental illness undertook in-depth, semi-structured interviews. Interpretative Phenomenological Analysis was employed to guide the data analysis. Results Seven themes were identified: motherhood as a central identity, the stigma associated with being a mother with mental illness, participants’ perceptions about the impact of mental illness on parenting and their children, experiences of talking to children about mental illness, how having children impacts mothers’ illness and recovery, and support obtained and needed. Similar to Western mothers, Chinese mothers experienced stigma and fluctuating mental illness symptoms which impacted on parenting. Unlike mothers based in Western countries, the mothers interviewed in this study highlighted complicated co-caring relationships with parents-in-law and did not raise child custody concerns. Conclusions Mental health professionals need to have the skills to identify and recognize the mothering role of their clients. Culturally sensitive interventions are required to assist Chinese families where mothers have a mental illness. Future research is required to investigate family experiences of parental mental illness from the perspectives of children, partners, and mental health professionals.

Abstract Triple-negative breast cancer (TNBC) is one of the most daunting diseases, low toxicity and efficient approaches are in urgent demand. Herein, we developed degradable mesoporous manganese carbonate nanocubes (MnCO3 NCs), incorporated with survivin shRNA-expressing plasmid DNA (iSur-pDNA) and riboflavin (Rf), namely MRp NCs, for synergistic TNBC therapy. The MnCO3, itself, could generate O2 and CO2 under H2O2 and thus relieve the hypoxia and acidic tumor microenvironment (TME). Furthermore, the MnCO3 NCs exhibited high Rf loading capacity and iSur-pDNA delivery ability after polyethyleneimine modification. Specifically, MRp NCs decompose in TME, meanwhile they deprived the endogenous expression of survivin gene and significantly amplified the generation of reactive oxygen species after exposure to LED light, resulting in serious tumor destruction. The multifunctional MRp NCs with LED light-driven characters are able to provide a high efficiency, low toxicity and promising strategy for TNBC therapy.

African swine fever (ASF) is a contagious and lethal hemorrhagic disease in pigs; its spread results in huge economic losses to the global pig industry. ASF virus (ASFV) is a large double-stranded DNA virus encoding >150 open reading frames. Among them, ASFV-encoded D1133L was predicted to be a helicase but its specific function remains unknown. Since virus-host protein interactions are key to understanding viral protein function, we used co-immunoprecipitation combined with liquid chromatography-mass spectrometry to investigate D1133L. This study describes the interaction network of ASFV D1133L protein in porcine kidney PK-15 cells. Overall, 1,471 host proteins that potentially interact with D1133L are identified. Based on these host proteins, a protein–protein network was constructed. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that cellular D1133L-interacted proteins are involved in the ribosome, spliceosome, RNA transport, oxidative phosphorylation, proteasome, and DNA replication. Vimentin (VIM), tripartite motif-containing protein 21 (TRIM21), and Tu translation elongation factor (TUFM) were confirmed to interact with D1133L in vitro. VIM or TRIM21 overexpression significantly promoted ASFV replication, but TUFM overexpression significantly inhibited ASFV replication. These results help elucidate the specific functions of D1133L and the potential mechanisms underlying ASFV replication.

Radiotherapy is one of the mainstream treatment modalities for several malignancies. However, radiation-induced injury to surrounding normal tissues limits its efficacy. The NLRP3 inflammasome is an essential mechanism of innate immunity that reacts to challenges from endogenous danger signals and pathological microbes. A growing body of evidence has demonstrated a key role of NLRP3 inflammasome in the pathogenesis of radiation-induced tissue injury. Despite accumulating evidence, the potential value of the NLRP3 inflammasome in the management of radiation-induced tissue injury is not adequately recognized. We conducted a literature review to characterize the relationship between NLRP3 inflammasome and radiation injury. By analyzing recent evidence, we identify NLRP3 inflammasome as one of the executioners of radiation-induced injury, since it responds to the challenges of radiation, induces cell pyroptosis and tissue dysfunction, and initiates non-resolving inflammation and fibrosis. Based on these concepts, we propose early intervention/prevention strategies targeting NLRP3 inflammasome in a radiation context, which may help resolve imperative clinical problems.

Obesity represents a major health challenge because it substantially increases the risk of metabolic diseases. Capsaicin, the major active ingredient of Capsicum spp., has been reported to possess anti-obesity activity. Hereon, the effect of capsaicin on glucose uptake and consumption in hepatocytes was extensively studied. Capsaicin was shown to accelerate the glucose uptake/consumption and the ATP production of hepatocytes. The elevation of intracellular Ca2+ was thought to be a potential mechanism. By transcriptome analysis, 78, 146 and 507 differentially expressed genes (DEGs) were identified between capsaicin and the control group for 4 h, 12 h and 24 h treatments. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that most of the DEGs were involved in canonical pathways, like MAPK and PI3K-AKT signaling pathways. Clustering analysis showed that many DEGs were associated with glucose and amino acid metabolism. The variation trend in genes related to glucose and amino acid metabolism (like CTH, VEGFA, PCK2 and IGFBP3) in the quantitative PCR (q-PCR) assay was consistent with the transcriptome data. These results demonstrated that capsaicin efficiently accelerated the glucose uptake and consumption of hepatocytes.

Abstract Human mitochondrial chaperonin mHsp60 is essential for mitochondrial function by assisting folding of mitochondrial proteins. Unlike the double-ring bacterial GroEL, mHsp60 exists as a heptameric ring that is unstable and dissociates to subunits. The structural dynamics has been implicated for a unique mechanism of mHsp60. We purified active heptameric mHsp60, and determined a cryo-EM structure of mHsp60 heptamer at 3.4 Å. Of the three domains, the equatorial domains contribute most to the inter-subunit interactions, which include a four-stranded β sheet. Our structural comparison with GroEL shows that mHsp60 contains several unique sequences that directly decrease the sidechain interactions around the β sheet and indirectly shorten β strands by disengaging the backbones of the flanking residues from hydrogen bonding in the β strand conformation. The decreased inter-subunit interactions result in a small inter-subunit interface in mHsp60 compared to GroEL, providing a structural basis for the dynamics of mHsp60 subunit association. Importantly, the unique sequences are conserved among higher eukaryotic mitochondrial chaperonins, suggesting the importance of structural dynamics for eukaryotic chaperonins. Our structural comparison with the single-ring mHsp60-mHsp10 shows that upon mHsp10 binding the shortened inter-subunit β sheet is restored and the overall inter-subunit interface of mHsp60 increases drastically. Our structural basis for the mHsp10 induced stabilization of mHsp60 subunit interaction is consistent with the literature that mHsp10 stabilizes mHsp60 quaternary structure. Together, our studies provide structural bases for structural dynamics of the mHsp60 heptamer and for the stabilizing effect of mHsp10 on mHsp60 subunit association.

Abstract Early detection and diagnosis are vitally important in reducing the mortality rate of fatal diseases but require highly sensitive detection of biomarkers. Presently, detection methods with the highest sensitivity require in vitro processing, while in vivo compatible fluorescence detections require a much higher concentration of biomarkers or limit of detection (LOD). In this paper, a fundamentally new strategy for ultrasensitive detection based on color‐switchable lasing with a cavity‐enhanced reduction of LOD is demonstrated, down to 1.4 × 10−16 mg ml−1 for a quantitative detection, lower than both the fluorescence method and plasmonic enhanced method. For a qualitative or a yes/no type of detection, the LOD is as low as 10–17 mg ml−1. The approach in this work is based on a dye‐embedded, in vivo compatible, polystyrene‐sphere cavity, penetrable by biomarkers. A polystyrene sphere serves the dual roles of a laser cavity and an in vivo bio‐reactor, in which dye molecules react with a biomarker, reporting biomarker information through lasing signals. The cavity‐enhanced emission and lasing with only a single biomarker molecule per cavity allow improved visual distinguishability via color changes. Furthermore, when combined with a narrow‐band filter, the color‐switchable lasers act as an “on‐off” logic signal and can be integrated into multiplexing detection assay biochips.

Abstract Background The development of factor VIII (FVIII) inhibitor is a severe complication during replacement therapy for hemophilia A patients. Objectives We investigated the potential risk factors for FVIII inhibitor formation based on genome‐wide RNA‐sequencing and whole‐genome bisulfite sequencing analysis. Methods RNA‐sequencing and whole‐genome bisulfite sequencing analysis were applied on 17 blood samples with F8 intron 22 inversion, including seven with inhibitors and 10 without. Results Altogether, 344 mRNA transcripts and 20 long noncoding RNAs (lncRNA) transcripts were differentially expressed. Among the differentially expressed transcripts, 200 mRNAs and 12 lncRNAs were upregulated, and 144 mRNAs and eight lncRNAs were downregulated. Gene ontology enrichment analysis of differentially expressed mRNAs showed that genes involved in immune stimulation, especially those for T‐cell activation, were upregulated, whereas genes involved in negative immune response regulation were downregulated. Coexpression analysis revealed that the targeted upregulated genes of differentially expressed lncRNA were similarly closely related to immune activation, especially T‐cell activation. Methylation analysis showed inhibitor patients exhibited a slightly lower methylation status in the CpG islands, 5′ untranslated region, and exon regions (p

Abstract Background To what extent hospital use and medical resources are used on hemophilia care in China's health care system is unknown. Objectives This study was based on a single center in China and was conducted to comprehensively assess the resource use for hospitalization of people with hemophilia. Methods We analyzed clinical characteristics, diagnosis, inhibitor status, reasons, length of stay, and hospital costs of 323 hospitalizations in which hemophilia must be considered as the main factor for hospitalization from January 2009 to December 2020 at the Institute of Hematology and Blood Diseases Hospital in Tianjin, China. Results There were 265 hospitalizations for people with hemophilia A (HA) and 58 with hemophilia B (HB). Seventy‐eight hospitalizations (24%) were for patients with inhibitor (INH+). Minor bleeding (eg, hemarthrosis, hematuria) was the most common reason for hospitalization. The cost of clotting factor concentrates was the major burden of inpatients with hemophilia. Total cost in a single hospitalization of a person with HA (median, 21,281 Chinese yuan [¥]) was about twice that for HB (median, ¥11,060). Expenditure of drugs in HA (median ¥14,157) was two to three times more than that in HB (median, ¥5707). Total cost and drug cost in hospitalizations of people with inhibitors were about two times more than these without (INH–) (median cost in INH+ hospitalizations: total cost, ¥27,303; drug cost, ¥20,445. Median cost in INH– hospitalizations: total cost, ¥17,743; drug cost, ¥11,973.). Conclusions For hemophilia, the most dominant cost during hospitalization was on clotting factor concentrates. Diagnosed HA and inhibitor positivity increased the global cost.

ABSTRACT Ralstonia solanacearum (Rs), a soilborne phytopathogen, causes bacterial wilt disease in a broad range of hosts. Common approaches, for example, the direct reduction of the pathogen using classic single broad-spectrum probiotics, suffer from poor colonization efficiency, interference by resident microbiota, and nonnative-microorganism invasion. The soil microbiota plays an important role in plant health. Revealing the intrinsic linkage between the microbiome and the occurrence of disease and then applying it to agroecosystems for the precise control of soilborne diseases should be an effective strategy. Here, we surveyed the differences in the microbiome between healthy and diseased soils used for tomato planting across six climatic regions in China by using 16S rRNA amplicon and metagenomic sequencing. The roles of species associated with disease symptoms were further validated. Healthy soil possessed more diverse bacterial communities and more potential plant probiotics than diseased soil. Healthy soil simultaneously presented multiple strategies, including specifically antagonizing Rs, decreasing the gene expression of the type III secretion system of Rs, and competing for nutrition with Rs. Bacteria enriched in diseased samples promoted the progression of tomato bacterial wilt by strengthening the chemotaxis of pathogens. Therefore, Rs and its collaborators should be jointly combatted for disease suppression. Our research provides integrated insights into a multifaceted strategy for the biocontrol of tomato bacterial wilt based on the individual network of local microbiota. IMPORTANCE In the current work, the relationship between the soil microbiota and tomato bacterial wilt on a large scale offered us a comprehensive understanding of the disease. The delicate strategy of the microbiota in soil used for growing tomatoes to conquer the strong competitor, Rs, was revealed by microbiome research. The collaborators of Rs that coexist in a common niche with Rs strengthened our understanding of the pathogenesis of bacterial wilt. Bacteria enriched in healthy soil that antagonized pathogens with high specificity provide a novel view for ecofriendly probiotics mining. Our study offers new perspectives on soilborne-pathogen biocontrol in agroecosystems by decoding the rule of the natural ecosystem.

BackgroundDietary restriction has a profound effect in altering immune system and promoting metabolic health and aging. However, how dietary restriction impacts erythroid system is largely unknown. We found that a short-term caloric restriction (CR) stimulates expression of KLF1, a master regulator of erythroid development, in the spleen of mouse, and thus explored the potential effect of CR on erythropoiesis.MethodsWe analyzed the effects of intermittent CR and continuous CR for different lengths of time on parameters of peripheral blood and erythroid profiles in the spleen and bone marrow in C57BL/6 mice. We next assessed how different types of CR affect phenylhydrazine-induced anemia in the mice. Colony formation assay was also used to analyze LK + progenitors and BFU-E in the bone marrow.ResultsIntermittent CR for 2 weeks raised the number of reticulocytes in the blood, while continuous CR for 2 weeks elevated red blood cells and hemoglobin level. Intermittent CR for 2 weeks promoted extramedullary hematopoiesis in the spleen, while continuous CR mainly promoted erythropoiesis in the bone marrow. Interestingly, a short-term intermittent CR but not continuous CR was able to ameliorate phenylhydrazine-induced anemia. Intermittent CR reduced early-stage erythroblasts and increased late-stage erythroblasts/mature RBCs in the spleen, indicating an accelerated transition from early-stage to late-stage erythroblasts/mature red blood cells. Furthermore, a short-term intermittent CR elevated LK + progenitors and the committed erythroid progenitor cells BFU-E in the bone marrow.ConclusionOur study demonstrated that a short-term intermittent CR, but not continuous CR, has a significant effect to promote hematopoiesis and such activity can ameliorate phenylhydrazine-induced acute anemia in the mouse.

Tellurium (Te) nanomaterials (NMs) have emerged as a new antibacterial candidate to respond to the complex global health challenge of bacterial resistance. Herein, Te nanoneedles (NNs) that act both chemically and physically on bacteria are synthesized by a facile method using Na2TeO3, urea and glucose. It is found that the prepared Te NNs have a strong affinity to the cell membrane of bacteria and subsequently promote the generation of reactive oxygen species (ROS) in bacteria, resulting in an excellent antibacterial effect toward Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). What's more, this needle-like morphology also can physically damage the bacterial cell membranes. The Te NNs per se are inert in mammalian cells to produce ROS at a proper concentration, indicating considerable biocompatibility of this material. As a proof-of-concept, the antibacterial Te NNs were used as an anti-inflammatory reagent for promoting bacteria-infected wound healing in vivo, during which Te NNs caused no evident side effects to major organs in mice. Additionally, the antibacterial activity is maintained in the presence of surface oxidation of Te NNs after long-term dispersion in phosphate buffered saline solution. The needle-like Te NMs with long-term antibacterial stability and good biocompatibility have great potential for the treatment of associated infectious diseases.

Abstract Background Growing evidence suggests that the pluripotent state of mesenchymal stem cells (MSCs) relies on specific local microenvironmental cues such as adhesion molecules and growth factors. Fibronectin (FN), fibroblast growth factor 2 (FGF2), and bone morphogenetic protein 4 (BMP4) are the key players in the regulation of stemness and lineage commitment of MSCs. Therefore, this study was designed to investigate the pluripotency and multilineage differentiation of bone marrow-derived MSCs (BMSCs) with the introduction of FN, FGF-2, and BMP4 and to identify the metabolic and proteomic cues involved in stemness maintenance. Methods To elucidate the stemness of BMSCs when treated with FN, FGF-2, and BMP4, the pluripotency markers of OCT4, SOX2, and c-MYC in BMSCs were monitored by real-time PCR and/or western blot. The nuclear translocation of OCT4, SOX2, and c-MYC was investigated by immunofluorescence staining. Multilineage differentiation of the treated BMSCs was determined by relevant differentiation markers. To identify the molecular signatures of BMSC stemness, gas chromatography-mass spectrometry (GC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and bioinformatics analysis were utilized to determine the metabolite and protein profiles associated with stem cell maintenance. Results Our results demonstrated that the expression of stemness markers decreased with BMSC passaging, and the manipulation of the microenvironment with fibronectin and growth factors (FGF2 and BMP4) can significantly improve BMSC stemness. Of note, we revealed 7 differentially expressed metabolites, the target genes of these metabolites may have important implications in the maintenance of BMSCs through their effects on metabolic activity, energy production, and potentially protein production. We also identified 21 differentially abundant proteins, which involved in multiple pathways, including metabolic, autophagy-related, and signaling pathways regulating the pluripotency of stem cells. Additionally, bioinformatics analysis comfirned the correlation between metabolic and proteomic profiling, suggesting that the importance of metabolism and proteome networks and their reciprocal communication in the preservation of stemness. Conclusions These results indicate that the culture environment supplemented with the culture cocktail (FN, FGF2, and BMP4) plays an essential role in shaping the pluripotent state of BMSCs. Both the metabolism and proteome networks are involved in this process and the modulation of cell-fate decision making. All these findings may contribute to the application of MSCs for regenerative medicine.

Adding time delay to nonlinear systems can significantly improve their performance, making it possible to construct image-encryption algorithms with higher security. In this paper, we propose a time-delayed nonlinear combinatorial hyperchaotic map (TD-NCHM) with a wide hyperchaotic interval. Based on TD-NCHM, we develop a fast and secure image-encryption algorithm that includes a plaintext-sensitive key-generation method and a simultaneous row-column shuffling-diffusion encryption process. Plenty of experiments and simulations demonstrate the superiority of the algorithm in terms of efficiency, security, and practical value in secure communications.

A reliable constitutive model is a prerequisite to simulate a new complex forming technique, which is represented by the near-net shape forging process of aluminum wheels in this study. The aim of the present work was to identify the physical-based constitutive model parameters of Al-Zn-Mg alloy via the inverse analysis method based on experimental data and numerical analysis: the stress–strain curves at different temperatures and strain rates were obtained based on hot compression tests. On the basis of the shape of the compressed specimens and experimental force–displacement data, the friction coefficients and the optimized physical-based constitutive model were determined by using two-times inverse analysis techniques. Results showed that the global average error between the predicted and experimental force–displacement curves was only 3.8%. Then, thermo-mechanical finite element models were built in the Deform-3D software to simulate the two-stage forging processes of the near-net shape forging of aluminum alloy wheels, and the results showed that the predicted load–stroke curves were in good agreement with the experimental ones in all forging stages, which verified the prediction accuracy of the optimized physical-based constitutive model. In addition, the identification of the physical-based constitutive model parameters by the inverse analysis method provides a theoretical basis for formulating and optimizing the near-net shape forging process parameters of aluminum alloy wheels.

2A12 aluminum alloy is a high-strength aerospace alloy. During its extrusion process, the extrusion process parameters have a great impact on the microstructure evolution of the extruded products. There are three extrusion process parameters controlled in the actual project, which are the initial temperature of billet, the initial temperature of die and the extrusion speed. Combined with a back propagation (BP) neural network and finite element method (FEM) simulation, based on the constitutive equation and recrystallization evolution process of 2A12 aluminum alloy, this paper establishes a prediction model for the grain size of extruded pipe by these three extrusion process parameters. This paper used a 35MN extruding machine for a production verification of 2A12 pipe. The results show that the predicted grain size is 3% smaller than the actual size.

Abstract Although soil microbial communities are central in ecosystem functioning, we know little of their characterization for those associated with grazing‐tolerant host plant species in grassland ecosystems in response to grazing. In this study, we used a high‐throughput sequencing approach to characterize soil microbes from the rhizosphere and bulk soil of grazing‐tolerant grass species, Stipa breviflora, in the Inner Mongolian desert steppe. We found that response mechanisms of soil bacteria distinct from fungal communities, and variance also occur between the rhizosphere and bulk soil communities under long‐term grazing. Soil fungal communities and the co‐occurrence networks in S. breviflora rhizosphere were more sensitive to long‐term grazing than bacteria. We reveal that rhizosphere effects and soil water content were the main drivers of the changes in fungal communities and their co‐occurrence networks. Moreover, the dominant bacterial phyla Bacteroidetes and Proteobacteria and fungal phyla Ascomycota and Glomeromycota might participate in regulating processes of S. breviflora's response to grazing. Overall, these findings give new snapshots of mechanisms of how grazing affects soil microbial communities, in an attempt to contribute to a clearer understanding of grazing‐tolerant mechanism of S. breviflora.

Abstract Background It is of utmost importance to investigate novel therapies for cancer, as it is a major cause of death. In recent years, immunotherapies, especially those against immune checkpoints, have been developed and brought significant improvement in cancer management. However, on the other hand, immune checkpoints blockade (ICB) by monoclonal antiboties may cause common and severe adverse reactions (ADRs), the cause of which remains largely undetermined. We hypothesize that ICB-agents may induce adverse reactions through off-target protein interactions, similar to the ADR-causing off-target effects of small molecules. In this study, we propose a hybrid phenotype mining approach which integrates molecular level information and provides new mechanistic insights for ICB-associated ADRs. Methods We trained a conditional random fields model on the TAC 2017 benchmark training data, then used it to extract all drug-centric phenotypes for the five anti-PD-1/PD-L1 drugs from the drug labels of the DailyMed database. Proteins with structure similar to the drugs were obtained by using BlastP, and the gene targets of drugs were obtained from the STRING database. The target-centric phenotypes were extracted from the human phenotype ontology database. Finally, a screening module was designed to investigate off-target proteins, by making use of gene ontology analysis and pathway analysis. Results Eventually, through the cross-analysis of the drug and target gene phenotypes, the off-target effect caused by the mutation of gene BTK was found, and the candidate side-effect off-target site was analyzed. Conclusions This research provided a hybrid method of biomedical natural language processing and bioinformatics to investigate the off-target-based mechanism of ICB treatment. The method can also be applied for the investigation of ADRs related to other large molecule drugs.

Abstract Multilayer ceramic capacitors (MLCCs) for energy storage applications require a large discharge energy density and high discharge/charge efficiency under high electric fields. Here, 0.87BaTiO3-0.13Bi(Zn2/3(Nb0.85Ta0.15)1/3)O3 (BTBZNT) MLCCs with double active dielectric layers were fabricated, and the effects of inner electrode and sintering method on the energy storage properties of BTBZNT MLCCs were investigated. By using the pure Pt as inner electrode instead of Ag0.6Pd0.4 alloys, an alternating current (AC) breakdown strength (BDS) enhancement from 1047 to 1500 kV/cm was achieved. By investigating the leakage current behavior of BTBZNT MLCCs, the Pt inner electrode and two-step sintering method (TSS) were confirmed to enhance the Schottky barrier and minimize the leakage current density. With relatively high permittivity, dielectric sublinearity, and ultra-high BDS, the Pt TSS BTBZNT MLCCs exhibited a surprisingly discharge energy density (U dis) of 14.08 J/cm3. Moreover, under an operating electric field of 400 kV/cm, the MLCCs also exhibited thermal stability with U dis variation < ±8% over a wide temperature (t) range from -50 to 175 °C and cycling reliability with U dis reduction < 0.3% after 3000 charge-discharge cycles. These remarkable performances make Pt TSS BTBZNT MLCCs promising for energy storage applications.

Abstract Background Loss of vigor caused by seed aging adversely affects agricultural production under natural conditions. However, priming is an economical and effective method for improving the vigor of aged seeds. The objective of this study was to test the effectiveness of exogenous ascorbic acid (ASC) and glutathione (GSH) priming in the repairing of aged oat (Avena sativa) seeds, and to test the hypothesis that structural and functional systems in mitochondria were involved in this process. Results Oat seeds were artificially aged for 20 days at 45 °C, and were primed with solutions (1 mmol L− 1) of ASC, GSH, or ASC + GSH at 20 °C for 0.5 h before or after their aging. Seed germination, antioxidant enzymes in the ASC-GSH cycle, cytochrome c oxidase (COX) and mitochondrial malate dehydrogenase (MDH) activities, and the mitochondrial ultrastructures of the embryonic root cells were markedly improved in aged oat seeds through post-priming with ASC, GSH, or ASC + GSH, while their malondialdehyde and H2O2 contents decreased significantly (P

Abstract The level of difficulty involved in separating marker genotypes greatly determines the utilization of such marker-aided selection (MAS) by breeders. Genotyping by use of agarose gel electrophoresis is easily accepted by breeders due to its simple requirements and easy operation in the lab. Here, we extracted 19,937 large fragment insertions/deletions (LInDels) that were 30–55 bp based on two indica rice and one japonica rice reference genome sequences. Thousands of primer pairs were designed by the Primer 3 program to amplify the corresponding LInDels, and 6582 LInDel markers with unique genome loci were reserved after being tested by e-PCR; 346 of these markers were validated in a panel of 22 cultivars by running on a 1.5% agarose gel. Most LInDel markers had a considerable number of polymorphisms. The LInDel markers have an equivalent efficiency to that of the SSR and SNP markers in identifying hybrids, estimating genetic distance and developing genetic linkage maps. The hybrid genotypes of the LInDel markers exhibited three bands, which were the result of heteroduplex formation between the insertion allele and the deletion allele. Fifty-five breeding markers, including 9 intragenic markers and 46 closely linked LInDel markers, were developed for 55 known genes that are related to yield, biotic and abiotic stress tolerance. These agarose-resolvable LInDel markers will be welcomed by breeders and will play an important role in MAS.

The main joints of lower limb are hip, knee, ankle, and toe. Because of accidents or diseases, some people have to amputate. Wearing prosthesis can help them return to normal life. In the past, Active Knee joint and Active Knee-Ankle transfemoral prosthesis are studied. While in the stance phase, toe joint play an important role. In this article, the dynamic model and control method of Knee-Ankle-Toe Active Transfemoral Prosthesis are studied. The main contents are as follows: Firstly, according to the ground reaction force, the gait cycle is divided into three phases, Early and Middle Stance Phase (E&MSP), Late Stance Phase (LSP) and Swing Phase (SP), and the mechanical model of Knee-Ankle-Toe Active Transfemoral Prosthesis (KATATP) is established. Secondly, consider the cooperative movement of amputee and prosthesis, the kinematics model of prosthesis is established by Lie Groups and Lie Algebras, and the dynamic model of prosthesis is established by Lagrange equation. Thirdly, the whole gait cycle is a complete system and each phase is a different subsystem, switching rules and controllers of different subsystems are designed. Finally, experiments show that KATAP with the switching control enables amputee to have a biomechanically appropriate walking gait and achieve smooth transition between different gait phases.

ObjectivesTo investigate bone mineral density (BMD) differences between assisted reproductive technology (ART)-conceived children and naturally conceived (NC) children.Study DesignThis retrospective cohort study included ART-conceived children and controls aged 1 to 12 years assessed with a follow-up protocol. Maternal and paternal background, birth condition, and growth and development indicators were analyzed.ResultsThe ART and NC groups exhibited differences in maternal and paternal childbearing age; maternal weight; maternal body mass index (BMI); maternal alcohol consumption; paternal smoking; delivery method; and serum zinc, iron, and lead levels. Multifactor analysis adjusted for relevant factors showed that paternal childbearing age and group significantly affected the BMD Z score. In the subgroup analysis, in vitro fertilization (IVF) (p=0.026) or intracytoplasmic sperm injection (ICSI) (p=0.008) had a positive impact on the BMD Z score. Male infertility only (p=0.010) or male infertility combined with polycystic ovary syndrome (PCOS) (p=0.026) may affect the BMD Z score. In the embryo transfer cycle subgroup analysis, compared with natural conception, both stimulation cycle fresh embryo transfer (p=0.019) and natural cycle frozen embryo transfer (p=0.006) had a positive effect on the BMD Z score.ConclusionsThe BMD levels of the ART and control groups were generally in the normal range. Paternal childbearing age and the use of ART independently affected the BMD Z score of the offspring.

Background. The results of epidemiological studies on the association between dietary protein intake and gestational diabetes mellitus (GDM) are controversial. Thus, this systematic review and meta-analysis of cohort studies were established to attain comprehensive findings regarding the association between dietary protein and the risk of GDM. Methods. Bibliographic databases including PubMed, Scopus, Web of Science, and Google Scholar were searched to discover papers related to dietary protein and the risk of GDM. The summary relative risks with 95% confidence intervals (CIs) were estimated through a random effect model for the analysis of the highest versus the lowest categories of dietary proteins. Results. A significantly increased risk of GDM among women who consumed the highest amount of animal protein was observed (summarized risk estimate: 1.52; 95% CI: 1.07, 2.17; I2 = 50.8%). No significant associations were identified regarding vegetable protein (summarized risk estimate:0.99, 95% CI: 0.80 to 1.23, I2 = 63.8%) and total protein (summarized risk estimate: 1.12; 95% CI: 0.88, 1.41; I2 = 35.4%). Conclusion. This review revealed that total protein intake had no relationship with the risk of GDM, while animal protein increases this risk. Further larger prospective cohort studies are required to confirm our results.

Current studies regarding the effects of grassland management strategies on the soil nutrient cycle have mostly focused on soil organic carbon (SOC). Less is known about the responses of SOC, total nitrogen (TN), and total phosphorous (TP) stocks to grassland management strategies at different soil depths. We therefore quantified vertical variations in SOC, TN, and TP stocks as well as controlling factors under three grassland management strategies (i.e., enclosure control, grazing twice a year, grazing combined with mowing) in 2014 and 2017 in a semi-arid grassland of northern China. We found that grazing twice a year and grazing combined with mowing led to an increase in plant production as well as soil C and N sequestration during 2014 to 2017. Changes in plant aboveground biomass (AGB), belowground biomass (BGB), and root-to-shoot ratio (R:S) all exerted significant positive effects on changes in soil C and N sequestration in the surface soil layer (0–30 cm), while changes in AGB and plant community composition played a more important role in mediating soil C, N, and P sequestration in response to grassland management strategies in the subsoil layer (30–100 cm). Specifically, grassland management strategies influence soil C, N, and P sequestration capacity by altering plant community composition. The results of this study provide new insights into the response mechanisms of plants and soils to grassland management practices and offer a range of new possible strategies that might be applied to the effective management of semi-arid grasslands.

With the acceleration of urbanization and the development of the automobile industry, the contradiction between the traffic capacity of existing urban roads and the growing traffic demand has become increasingly acute. Traffic congestion is becoming increasingly prominent. The purpose of this article is to consider the characteristics of traffic risk factors and to study the method of establishing a flexible traffic system. It can relieve traffic congestion and provide a smooth and orderly traffic environment using intelligent transportation systems to control and direct traffic flow. Based on the large urban road network, this research uses the theory of coordinated control and learning mechanism, fuzzy control, dynamic reprogramming, and other theories to study phase sequence, balance peripheral load, and overall traffic flow. It also uses on-board sensors to optimize the collection and processing of network information, decompose traffic guidance work, select the optimal route, and autonomously guide the intelligent transportation system. Under the flexible demand scheme, the average load of the trunk road is reduced by a larger degree, which is 4% lower than that of the fixed demand scheme. At the same time, the average load of the branch has increased more, which is 4% higher than that of the fixed demand scheme. It can be seen that under the elastic demand scheme, the distribution of traffic flow in the road network is more balanced and the optimization effect of relieving traffic pressure on trunk roads and improving the utilization rate of branch roads is more significant.

Ni–Co–P alloy coatings were successfully fabricated by jet electrodeposition with varying pulse frequencies and duty cycles in order to prolong the longevity of steel C1045 substrates. The results showed that the microstructures and properties of samples were significantly affected by pulse frequencies and duty cycles. All the samples with varying pulse frequencies and duty cycles exhibited a face-centered cubic (FCC) structure. Additionally, the average grain size of the samples reached 20.6 nm. The microhardness of the coatings was observed to first increase, and then decrease, with a rise in pulse frequencies and duty cycles. The microhardness reached 656.2 HV0.1, and the wear scar width of the coatings reached 414.4 µm at 4 kHz pulse frequency and 80% duty cycle. Additionally, the corrosion current densities (Icorr) of samples reached a minimum value of 0.74 µA·cm−2, the corrosion rates (Rcorr) reached a minimum value of 8.9 µm·year−1, and the charge transfer resistance (Rct) reached a maximum value of 8.36 × 104 Ω·cm−2, which indicated the optimal seawater corrosion resistance of the deposited coatings.

The parametric representation and aerodynamic shape optimization of a three-dimensional circular-to-rectangular transition nozzle designed and built using control lines distributed along the circumferential direction were investigated in this study. A surrogate model based on class/shape transformation, principal component analysis and radial basis neural network was proposed with fewer design parameters for parametric representation and performance parameter prediction of the three-dimensional circular-to-rectangular transition nozzle. The surrogate model was combined with Non-dominated Sorting Genetic Algorithm-II to optimize the aerodynamic shape of the nozzle. The results showed that the surrogate model effectively achieved the parametric representation and aerodynamic shape optimization of the three-dimensional circular-to-rectangular transition nozzle. The geometric dimensions and performance parameters of the parametric reconstructed model were comparable to that of the initial model, implying that they can meet the needs of optimal design. The axial thrust coefficient and lift of the optimized nozzle were increased by approximately 0.742% and 15.707%, respectively.

Piceatannol (PIC) is a natural stilbene extracted from grape skins that exhibits biological activities such as antibacterial, antitumor, and antioxidant activities. The present study was carried out to further investigate the effect of PIC on the antibacterial activity of different antibiotics and to reveal the antibacterial mechanism of PIC. We found that PIC had an inhibitory effect against Staphylococcus aureus (S. aureus); its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 128 μg/mL and 256 μg/ mL, respectively. Additionally, we measured the fractional inhibitory concentration (FIC) of PIC combined with antibiotics via the checkerboard method. The results showed that when PIC and ciprofloxacin (CIP) were combined, they displayed a synergistic effect against S. aureus. Moreover, this synergistic effect was verified by time–kill assays. Further, the results of the membrane permeability assay and proton motive force assay revealed that PIC could enhance the sensitivity of S. aureus to CIP by dissipating the bacterial proton motive force (PMF), particularly the ∆ψ component, rather than increasing membrane permeability. PIC also inhibited bacterial adenosine triphosphate (ATP) synthesis and was less likely to induce bacterial resistance but exhibited slight hemolytic activity on mammalian erythrocytes. In summary, the combination of PIC and CIP is expected to become a new drug combination to combat S. aureus.

Human pose estimation is a basic and critical task in the field of computer vision that involves determining the position(or spatial coordinates)of the joints of thehumanbody inagivenimageor video. It iswidelyused inmotion analysis, medical evaluation, and behavior monitoring. In this paper, the authors propose a method for multi-view human pose estimation. Two image sensors were placed orthogonally with respect to each other to capture the pose of the subject as theymoved, and this yielded accurate and comprehensive results of three-dimensional (3D)motion reconstruction that helped capture theirmulti-directional poses. Following this, we propose amethod based on 3D pose estimation to assess the similarity of the features of motion of patients with motor dysfunction by comparing differences between their range of motion and that of normal subjects. We converted these differences into Fugl-Meyer assessment (FMA) scores in order to quantify them. Finally, we implemented the proposed method in the Unity framework, and built a Virtual Reality platform that provides users with human-computer interaction to make the task more enjoyable for them and ensure their active participation in the assessment process. The goal is to provide a suitable means of assessing movement disorders without requiring the immediate supervision of a physician. [ABSTRACT FROM AUTHOR]

Background: The cycle of feeding and fasting is fundamental to life and closely coordinated with changes of metabolic programs. During extended starvation, ketogenesis coupled with fatty acid oxidation in the liver supplies ketone bodies to extrahepatic tissues as the major form of fuel. In this study, we demonstrated that PAQR9, a member of the progesterone and adipoQ receptor family, has a regulatory role on hepatic ketogenesis. Methods: We analyzed the phenotype of Paqr9-deleted mice. We also used biochemical methods to investigate the interaction of PAQR9 with PPARα and HUWE1, an E3 ubiquitin ligase. Results: The expression of Paqr9 was decreased during fasting partly depending on PPARγ. The overall phenotype of the mice was not altered by Paqr9 deletion under normal chow feeding. However, fasting-induced ketogenesis and fatty acid oxidation were attenuated by Paqr9 deletion. Mechanistically, Paqr9 deletion decreased protein stability of PPARα via enhancing its poly-ubiquitination. PAQR9 competed with HUWE1 for interaction with PPARα, thus preventing ubiquitin-mediated degradation of PPARα. Conclusion: Our study reveals that PAQR9 impacts starvation-mediated metabolic changes in the liver via post-translational regulation of PPARα.

In this study, we developed a fluorescent aptasensor based on Fe3O4/Au/g-C3N4 and a FAM-labeled aptamer (FAM-SMZ1S) against sulfamethazine (SMZ) for the specific and sensitive detection of SMZ in food matrix. The FAM-SMZ1S was adsorbed by the Fe3O4/Au/g-C3N4 via π–π stacking and electrostatic adsorption, serving as a basis for the ultrasensitive detection of SMZ. Molecular dynamics was used to explain the reasons why SMZ1S and SMZ were combined. This aptasensor presented sensitive recognition performance, with a limit of detection of 0.16 ng/mL and a linear range of 1–100 ng/mL. The recovery rate ranged from 91.6% to 106.8%, and the coefficient of variation (CV) ranged from 2.8% to 13.4%. In addition, we tested the aptasensor for the monitoring of SMZ in various matrix samples, and the results were well-correlated (R2 ≥ 0.9153) with those obtained for HPLC detection. According to these results, the aptasensor was sensitive and accurate, representing a potentially useful tool for the detection of SMZ in food matrix.

Z-conformation nucleic acid binding protein 1 (ZBP1), a powerful innate immune sensor, has been identified as the important signaling initiation factor in innate immune response and the multiple inflammatory cell death known as PANoptosis. The initiation of ZBP1 signaling requires recognition of left-handed double-helix Z-nucleic acid (includes Z-DNA and Z-RNA) and subsequent signaling transduction depends on the interaction between ZBP1 and its adapter proteins, such as TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), receptor-interacting serine/threonine-protein kinase 1 (RIPK1), and RIPK3. ZBP1 activated innate immunity, including type-I interferon (IFN-I) response and NF-κB signaling, constitutes an important line of defense against pathogenic infection. In addition, ZBP1-mediated PANoptosis is a double-edged sword in anti-infection, auto-inflammatory diseases, and tumor immunity. ZBP1-mediated PANoptosis is beneficial for eliminating infected cells and tumor cells, but abnormal or excessive PANoptosis can lead to a strong inflammatory response that is harmful to the host. Thus, pathogens and host have each developed multiplex tactics targeting ZBP1 signaling to maintain strong virulence or immune homeostasis. In this paper, we reviewed the mechanisms of ZBP1 signaling, the effects of ZBP1 signaling on host immunity and pathogen infection, and various antagonistic strategies of host and pathogen against ZBP1. We also discuss existent gaps regarding ZBP1 signaling and forecast potential directions for future research.

Block of proliferation 1 (BOP1) is a key protein that helps in the maturation of ribosomes and promotes the progression of the cell cycle. However, its role in the leaf morphogenesis of cotton remains unknown. Herein, we report and study the function of GhBOP1 isolated from Gossypium hirsutum. The sequence alignment revealed that BOP1 protein was highly conserved among different species. The yeast two-hybrid experiments, bimolecular fluorescence complementation, and luciferase complementation techniques revealed that GhBOP1 interact with GhPES and GhWDR12. Subcellular localization experiments revealed that GhBOP1, GhPES and GhWDR12 were localized at the nucleolus. Suppression of GhBOP1 transcripts resulted in the uneven bending of leaf margins and the presence of young wrinkled leaves by virus-induced gene silencing assay. Abnormal palisade arrangements and the presence of large upper epidermal cells were observed in the paraffin sections of the wrinkled leaves. Meanwhile, a jasmonic acid-related gene, GhOPR3, expression was increased. In addition, a negative effect was exerted on the cell cycle and the downregulation of the auxin-related genes was also observed. These results suggest that GhBOP1 plays a critical role in the development of wrinkled cotton leaves, and the process is potentially modulated through phytohormone signaling.

Undifferentiated pleomorphic sarcoma (UPS), an aggressive soft-tissue sarcoma of adults, has been characterized by low tumor mutational burden (TMB) and high copy number alterations. Clinical trials of programmed death-1 (PD-1) blockade in UPS have reported widely varying efficacy. We describe two patients with recurrent scalp UPS that experienced clinical benefit from PD-1 blockade. These tumors had high TMB with a UV-induced mutational pattern. Analysis of additional head and neck UPS cases identified five out of seven tumors with high TMB and an ultraviolet (UV) mutational signature. Head and neck UPS tumors also had increased programmed death-ligand 1 (PD-L1) expression and CD8+ T cell infiltration as compared with UPS tumors arising from other sites. In summary, we found that UPS tumors of the head and neck, but not elsewhere, have a PD-L1+, T-cell-inflamed tumor microenvironment and high TMB, suggesting that these tumors represent a distinct genetic subgroup of UPS for which immune checkpoint inhibitor therapy might be effective.

Introduction: The avascular necrosis of the femoral head represents the death of bone tissue due to the lack of blood supply. The disease has a progressive evolution; it leads to femoral head collapse and severe arthritis when left untreated. The application of a pedicled bone flap graft is an effective treatment for femoral head necrosis. A pure Mg screw is a kind of degradable screw that can fix the grafted bone flap and prevent long-term stress occlusion and secondary dissection. Case presentation: The report shows the results of the treatment of traumatic femoral head necrosis with a pedicled bone flap with pure Mg screw. A patient had avascular necrosis of the femoral head after 2 years of internal fixation of the femoral neck fracture. We removed the patient's internal fixation hollow nail, cleaned the necrotic bone tissue and took part of the same ipsilateral pedicle iliac bone graft in the femoral head defect with biodegradable pure Mg screw fixation. Within 2 years after the surgery, the patients had no significant progressive necrosis of the femoral head. Postoperative Harris scores showed that the patient's left hip function was significantly improved compared with his preoperative state. The pure Mg screw in the body had gradually degraded. After 2 years, the screw's diameter had been significantly reduced compared with 3 days after the surgery. The postoperative Harris score showed that the patient's left hip function was significantly improved compared with the second preoperative examination. Discussion: The discussion includes the reasons for the choices of surgical approaches, the mode of pure Mg screw degradation and the postoperative functional assessment of the patient's left hip. Conclusion: Pure Mg screw fixation pedicled bone flap transplantation is an effective surgical treatment for femoral head necrosis in young patients. Pure Mg screw is a biodegradable internal fixation device with good biocompatibility, which has a good clinical application prospects. The translational potential of this article: Degradable pure Mg screw has the potential to preserve hip joint therapy for the treatment of femoral head necrosis.

In this paper, a finite-time control strategy composed of disturbance observer and sliding mode controller is investigated for five-degree of freedom (5-DOF) upper-limb exoskeleton subject to system uncertainties and external disturbances. First, a new finite-time disturbance observer (FTDO) is constructed to handle unknown disturbances and modeling uncertainties. Second, a nonsingular fast terminal sliding mode (TSM) approach is presented to follow the desired joint angles. By combining the novel FTDO and the nonsingular fast TSM technology, the exoskeleton angle tracking errors can be forced to zero within a finite time. Furthermore, the stability of the exoskeleton system is illustrated via Lyapunov. Finally, the tracking performance of the proposed control scheme is verified by simulations.

In the existing research of power quality disturbance (PQD) identification, the efficiency of signal processing is low and cannot meet the needs of practical application analysis. Furthermore, due to the lack of effective analysis of features, the complexity of classifiers is increased, and the efficiency of classification reduced by the redundant features. In this paper, in order to overcome these shortcomings, a PQD recognition method based on image enhancement techniques and feature importance analysis is proposed. First, PQD signals are converted into gray images, and three image enhancement techniques include gamma correction, edge detection, and peaks and valley detection are used to enhance the disturbance features. Then, the disturbance features are extracted from the binary images, and the original feature set is constructed, the classification ability of each feature is measured by Gini importance. Based on the descending order of the Gini importance, the sequence forward search (SFS) method is used for feature selection to determine the optimal feature subset. Finally, random forest (RF) classifier is constructed by the optimal feature subset to identify the PQD signals. The results of the simulation and contrast experiments show that the new method can determine the optimal classification subset, which recognizes the PQD signals effectively in different noise environments. Furthermore, the new method has higher signal processing efficiency compared with the EMD and ST methods.

In recent years, sensor-based human activity recognition (HAR) has gained tremendous attention around the world with a range of applications. Instead of using body sensor network-based recognition systems which are intrusive and increase equipment cost, we focus on the development of efficient HAR approach based on a single triaxial accelerometer. In order to improve the recognition accuracy of the system, a novel recognition approach based on kernel discriminant analysis (KDA) and quantum-behaved particle swarm optimization-based kernel extreme learning machine (QPSO-KELM) is proposed. KDA is utilized to extract more meaningful features and enhance the discrimination between different activities. To verify the effectiveness of KDA, three kinds of features including original features, linear discriminant analysis (LDA) features and KDA features are extracted and compared for activity recognition. In addition, QPSO-KELM is compared with two existing classification methods: support vector machine (SVM) and extreme learning machine (ELM), which are commonly utilized in activity recognition. Meanwhile, two comparative optimization methods for KELM are also discussed in the experiment. The experimental results demonstrate the superiority of the proposed approach.

The Tibetan Plateau is among the region’s most sensitive areas to global climate change. The observation data from 113 meteorological stations on the Tibetan Plateau and surrounding regions in China for 1971–2017 were used to analyze the periodic oscillations and trends in precipitation and extreme precipitation on multiple time scales to ensemble empirical mode decomposition. The relationship between extreme precipitation and sea-surface temperature (SST) anomalies was also explored. The results were as follows. (1) The timing of extreme-precipitation events in the highlands is consistent, with increased total precipitation and increased frequency, intensity, and extreme values of extreme precipitation. (2) Changes in temperature and precipitation are not completely synchronized. The total extreme precipitation, number of extreme-precipitation days, maximum single-day precipitation, and extreme single-day precipitation intensity all showed increases with fluctuations; the quasi-3-year oscillation contributes the most to the extreme precipitation. PRCPTOT is most strongly correlated with R10 and R95p. (3) The spatiotemporal patterns of the first and second empirical orthogonal function modes of the indices differed significantly and were not spatiotemporally uniform, but exhibited local clustering. (4) The Indian Ocean Warm Pool Strength and Western Pacific Warm Pool Strength indices were most highly correlated with each extreme-precipitation index, and the timings of the extreme-precipitation events lagged behind those of the SST anomalies. This study improves our understanding of extreme precipitation events in the context of climate warming and provides a basic analysis for the further assessment and prediction of extreme precipitation on the Tibetan Plateau and the surrounding ecologically fragile areas.

Herein, we developed a novel truncation technique for aptamer sequences to fabricate highly sensitive aptasensors based on molecular docking and molecular dynamics simulations. The binding mechanism and energy composition of the aptamer/sulfaquinoxaline (SQX) complexes were investigated. We successfully obtained a new SQX-specific aptamer (SBA28-1: CCCTAGGGG) with high affinity (Kd = 27.36 nM) and high specificity determined using graphene oxide. This aptamer has a unique stem-loop structure that can bind to SQX. Then, we fabricated a fluorescence aptasensor based on SBA28-1, gold nanoparticles (AuNPs), and rhodamine B (RhoB) that presented a good linear range of 1.25–160 ng/mL and a limit of detection of 1.04 ng/mL. When used to analyze water samples, the aptasensor presented acceptable recovery rates of 93.1–100.1% and coefficients of variation (CVs) of 2.2–10.2%. In conclusion, the fluorescence aptasensor can accurately and sensitively detect SQX in water samples and has good application prospects.

Ovate family proteins (OFPs) are valued as a family of transcription factors that are unique to plants, and they play a pluripotent regulatory role in plant growth and development, including secondary-cell-wall synthesis, DNA repair, gibberellin synthesis, and other biological processes, via their interaction with TALE family proteins. In this study, CHIP-SEQ was used to detect the potential target genes of AtOFP1 and its signal-regulation pathways. On the other hand, Y2H and BIFC were employed to prove that AtOFP1 can participate in ABA signal transduction by interacting with one of the TALE family protein called AtKNAT3. ABA response genes are not only significantly upregulated in the 35S::HAOFP1 OE line, but they also show hypersensitivity to ABA in terms of seed germination and early seedling root elongation. In addition, the AtOFP1-regulated target genes are mainly mitochondrial membranes that are involved in the oxidative–phosphorylation pathway. Further qRT-PCR results showed that the inefficient splicing of the respiratory complex I subunit genes NAD4 and NAD7 may lead to ROS accumulation in 35S::HA-AtOFP1 OE lines. In conclusion, we speculated that the overexpression of AtOFP1 may cause the ABA hypersensitivity response by increasing the intracellular ROS content generated from damage to the intima systems of mitochondria.