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Abstract Background This study investigated the role of Galectin-3 in the degeneration of intervertebral disc cartilage. Methods The patients who underwent lumbar spine surgery due to degenerative disc disease were recruited and divided into Modic I, Modic II, and Modic III; groups. HE staining was used to detect the pathological changes in endplates. The changes of Galectin-3, MMP3, Aggrecan, CCL3, and Col II were detected by immunohistochemistry, RT-PCR, and Western blot. MTT and flow cytometry were used to detect cartilage endplate cell proliferation, cell cycle, and apoptosis. Results With the progression of degeneration (from Modic I to III), the chondrocytes and density of the cartilage endplate of the intervertebral disc decreased, and the collagen arrangement of the cartilage endplate of the intervertebral disc was broken and calcified. Meanwhile, the expressions of Aggrecan, Col II, Galectin-3, Aggrecan, and CCL3 gradually decreased. After treatment with Galectin-3 inhibitor GB1107, the proliferation of rat cartilage end plate cells was significantly reduced (P

Abstract Background Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are increasingly recognized for their role in reducing the risk and improving the prognosis of heart failure (HF). However, the precise mechanisms involved remain to be fully delineated. Evidence points to their potential anti-inflammatory pathway in mitigating the risk of HF. Methods A two-sample, two-step Mendelian Randomization (MR) approach was employed to assess the correlation between SGLT-2 inhibition and HF, along with the mediating effects of inflammatory biomarkers in this relationship. MR is an analytical methodology that leverages single nucleotide polymorphisms as instrumental variables to infer potential causal inferences between exposures and outcomes within observational data frameworks. Genetic variants correlated with the expression of the SLC5A2 gene and glycated hemoglobin levels (HbA1c) were selected using datasets from the Genotype-Tissue Expression project and the eQTLGen consortium. The Genome-wide association study (GWAS) data for 92 inflammatory biomarkers were obtained from two datasets, which included 14,824 and 575,531 individuals of European ancestry, respectively. GWAS data for HF was derived from a meta-analysis that combined 26 cohorts, including 47,309 HF cases and 930,014 controls. Odds ratios (ORs) and 95% confidence interval (CI) for HF were calculated per 1 unit change of HbA1c. Results Genetically predicted SGLT-2 inhibition was associated with a reduced risk of HF (OR 0.42 [95% CI 0.30–0.59], P

Abstract Artificial electronic kagome lattices may emerge from electronic potential landscapes using customized structures with exotic supersymmetries, benefiting from the confinement of Shockley surface-state electrons on coinage metals, which offers a flexible approach to realizing intriguing quantum phases of matter that are highly desired but scarce in available kagome materials. Here, we devise a general strategy to construct varieties of electronic kagome lattices by utilizing the on-surface synthesis of halogen hydrogen-bonded organic frameworks (XHOFs). As a proof of concept, we demonstrate three XHOFs on Ag(111) and Au(111) surfaces, which correspondingly deliver regular, breathing, and chiral breathing diatomic-kagome lattices with patterned potential landscapes, showing evident topological edge states at the interfaces. The combination of scanning tunnelling microscopy and noncontact atomic force microscopy, complemented by density functional theory and tight-binding calculations, directly substantiates our method as a reliable and effective way to achieve electronic kagome lattices for engineering quantum states.

Abstract Background Clearance of apoptotic cells by efferocytosis is crucial for prevention of atherosclerosis progress, and impaired efferocytosis contributes to the aggravated atherosclerosis. Results In this study, we found that diabetic ApoE–/– mice showed aggravated atherosclerosis as hyperglycemia damaged the efferocytosis capacity at least partially due to decreased expression of Mer tyrosine kinase (MerTK) on macrophages. To locally restore MerTK in the macrophages in the plaque, hybrid membrane nanovesicles (HMNVs) were thus developed. Briefly, cell membrane from MerTK overexpressing RAW264.7 cell and transferrin receptor (TfR) overexpressing HEK293T cell were mixed with DOPE polymers to produce nanovesicles designated as HMNVs. HMNVs could fuse with the recipient cell membrane and thus increased MerTK in diabetic macrophages, which in turn restored the efferocytosis capacity. Upon intravenous administration into diabetic ApoE–/– mice, superparamagnetic iron oxide nanoparticles (SMN) decorated HMNVs accumulated at the aorta site significantly under magnetic navigation, where the recipient macrophages cleared the apoptotic cells efficiently and thus decreased the inflammation. Conclusions Our study indicates that MerTK decrease in macrophages contributes to the aggravated atherosclerosis in diabetic ApoE–/– mice and regional restoration of MerTK in macrophages of the plaque via HMNVs could be a promising therapeutic approach. Graphic Abstract

Abstract Background Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. Methods This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank. Lung function was assessed through the forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1). Cox proportional hazard models were applied to estimate the associations between lung function and incident depression. Mediation analyses were fitted to investigate the potential mediating role of biomarkers and metabolites in the association. Results A total of 9514 participants (3.4%) developed depression during a median follow-up of 13.91 years. Individuals in the highest quartile had a lower risk of depression (FVC % predicted: HR = 0.880, 95% CI = 0.830–0.933; FEV1% predicted: HR = 0.854, 95% CI = 0.805–0.905) compared with those in the lowest quartile of the lung function indices. Additionally, the restricted cubic splines suggested lung function indices had reversed J-shaped associations with incident depression (nonlinear P

Abstract Background Implant choice for the fixation of femoral neck fracture is one of the most important management controversies. This study aims to evaluate and compare the short-term outcomes associated with the use of the Femoral Neck System (FNS), Multiple Cancellous Screws (MCS), and Dynamic Hip Screws (DHS) in treating femoral neck fractures in a young patient population. Methods From June 2018 to June 2021, a total of 120 surgeries for a primary femoral neck fracture were retrospectively analyzed. This review encompassed demographic details of the patients and the mechanisms behind the injuries. Key surgical parameters such as operation duration, intraoperative blood loss, fluoroscopy duration, and hospital stay were meticulously documented. The employed surgical technique was described. All patients were followed up at 6 weeks, 3 months, 6 months, and 12 months postoperatively. Avascular necrosis of the femoral head (AVN), nonunion, malreduction, implant failure or other complications were noted. The functional status at the last follow-up was assessed using the Harris functional scoring criteria. Results There were 90 males and 30 females, with a mean age of 40.4 years. As to patient characteristics, there were no significant differences between the three groups. DHS group showed longer operation time(52.15 ± 4.80 min), more blood loss(59.05 ± 5.87 ml) and longer time of hospitalization(7.6 ± 0.90 d) than FNS group (39.65 ± 2.84 min, 45.33 ± 9.63 ml and 4.87 ± 0.48 d) and MCS group (39.45 ± 3.10 min, 48.15 ± 7.88 ml and 5.04 ± 0.49 d) (p

Abstract Nicotinamide phosphoribosyltransferase (NAMPT) plays an important role in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) via the nicotinamide (NAM) salvage pathway. While the structural biochemistry of eukaryote NAMPT has been well studied, the catalysis mechanism of prokaryote NAMPT at the molecular level remains largely unclear. Here, we demonstrated the NAMPT-mediated salvage pathway is functional in the Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris (Xcc) for the synthesis of NAD+, and the enzyme activity of NAMPT in this bacterium is significantly higher than that of human NAMPT in vitro. Our structural analyses of Xcc NAMPT, both in isolation and in complex with either the substrate NAM or the product nicotinamide mononucleotide (NMN), uncovered significant details of substrate recognition. Specifically, we revealed the presence of a NAM binding tunnel that connects the active site, and this tunnel is essential for both catalysis and inhibitor binding. We further demonstrated that NAM binding in the tunnel has a positive cooperative effect with NAM binding in the catalytic site. Additionally, we discovered that phosphorylation of the His residue at position 229 enhances the substrate binding affinity of Xcc NAMPT and is important for its catalytic activity. This work reveals the importance of NAMPT in bacterial NAD+ synthesis and provides insights into the substrate recognition and the catalytic mechanism of bacterial type II phosphoribosyltransferases.

Abstract Background The acquisition of a rich vocabulary is foundational to language proficiency. In the pedagogical pursuit of effective vocabulary teaching, educators explore diverse methodologies. Researchers investigated the impact of different neurocognitive, metacognitive, and socio-cultural strategies on enhancing vocabulary learning, particularly among Chinese English Language Learners. Objectives The study aims to determine the effectiveness of techniques derived from these theories compared to traditional teaching methods in enhancing vocabulary recall and recognition among English language learners. Methodology A quasi-experimental pre-test/post-test design was employed for the experimental and control groups, comprising 90 Chinese EFL learners selected from educational institutions in 2022–2023. The experimental group (n = 45) received instruction involving visual imagery, multisensory rotation, circle rotation, and mind mapping over eight sessions, while the control group (n = 45) received traditional teaching methods. Findings Statistical analysis, utilizing covariance and analysis of variance with SPSS software version 22, revealed significant improvements in recall and vocabulary recognition within and between the experimental and control groups. Conclusions The results indicate that incorporating techniques based on Neuro-Cognitive, Multimedia, Socio-Cultural, and Metacognitive theories positively influences vocabulary recall and recognition. This suggests the efficacy of these innovative methods in enhancing English language learning, highlighting their potential for broader integration into EFL instruction.

Abstract Background Schistosomiasis is a disease primarily caused by eggs laid by pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses the largest fecundity; each adult female produces an average of 3500 eggs per day. The lack of proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation of mechanisms regulating sexual maturation and egg production in Schistosoma japonicum. Methods We optimized in vitro culture conditions by replacing reagents that are part of the classical ABC169 medium. Fast Blue BB staining and 4′,6-diamidino-2-phenylindole (DAPI) labeling were applied to observe the sexual development status of the females. In vitro RNA interference (RNAi) technology was used to validate the capability of the modified medium. The detection of male β-alanyl-tryptamine (BATT) was conducted using liquid chromatography–mass spectrometry (LC–MS). Results Both m-AB169 (1640) and AB169 (1640) media are capable of facilitating the sexual development of paired virgin female S. japonicum, as well as sustaining the mature reproductive organs and egg production of adult S. japonicum for at least 22 days in vitro. M-AB169 (1640) provided a more stable condition for supporting the sexual maturity of female S. japonicum, as evidenced by the consistent initiation of egg production compared with AB169 (1640). Through a comparative analysis of S. japonicum and S. mansoni in diverse media, we demonstrated that these closely related species display distinct demands for their sexual development and egg production, suggesting a potential influence of nutritional factors on the observed variations in host ranges among different schistosome species. Importantly, we successfully identified the presence of the pheromone β-alanyl-tryptamine (BATT) in S. japonicum, previously identified in S. mansoni, highlighting its conserved role in schistosome reproductive development. Through the employment of double-stranded RNA (dsRNA) treatment to silence two genes that are involved in either the male (gli1, glioma-associated oncogene homolog 1) or female (vf1, vitellogenic factor 1) side in male-induced female reproductive development of S. mansoni, we confirmed that the combination of m-AB169 (1640) and RNAi technology has the capacity to facilitate in vitro studies of S. japonicum’s reproductive and oviposition processes. Conclusions We developed a novel medium, m-AB169 (1640), that not only maintains the mature reproductive organs and continuous oviposition of adult female Schistosoma japonicum for up to 22 days but also supports the reproductive development and subsequent egg-laying of virgin females after pairing with male worms. This study provides a valuable in vitro platform for functional studies of the mechanisms underlying the fascinating biology of the female sexual development and egg production of S. japonicum, which may accelerate the development of new strategies targeting schistosome egg production. Graphical Abstract

Abstract Temporal transcriptional variation is a major contributor to functional evolution and the developmental process. Parthenogenetic water fleas of the genus Daphnia (Cladocera) provide an ideal model to characterize gene expression patterns across distinct developmental stages. Herein, we report RNA-seq data for female Daphnia mitsukuri at three developmental stages: the embryo, juvenile (three timepoints) and adult. Comparisons of gene expression patterns among these three developmental stages and weighted gene co-expression network analysis based on expression data across developmental stages identified sets of genes underpinning each of the developmental stages of D. mitsukuri. Specifically, highly expressed genes (HEGs) at the embryonic developmental stage were associated with cell proliferation, ensuring the necessary foundation for subsequent development; HEGs at the juvenile stages were associated with chemosensory perception, visual perception and neurotransmission, allowing individuals to enhance detection of potential environmental risks; HEGs at the adult stage were associated with antioxidative defensive systems, enabling adults to mount an efficient response to perceived environmental risks. Additionally, we found a significant overlap between expanded gene families of Daphnia species and HEGs at the juvenile stages, and these genes were associated with visual perception and neurotransmission. Our work provides a resource of developmental transcriptomes, and comparative analyses that characterize gene expression dynamics throughout development of Daphnia.

Abstract Due to a wide variety and similar physicochemical properties of monohydroxy saturated fatty acids (OH-FAs) isomers as biomarkers, previously reported OH-FAs in environmental samples were mainly restricted to the α-, β-, (ω-1)- and ω-OH-FA isomers. Here, N,N-dimethylethylenediamine (DMED) labeling coupled with ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) analysis with multiple reaction monitoring mode (MRM) was developed to screen, identify and quantify position-specific isomers of OH-FAs (C8-C18). An identification strategy of positional isomers of OH-FAs, including α-, β-, 4 to (ω-2)-, (ω-1)- and ω-OH-FAs, was established by integrating the characteristics of peak intensity ratios of product ions based on the library of OH-FAs. Meanwhile, d4-DMED-labeled OH-FA standards as internal standards were adopted for the relative quantification of positional isomers. The extraction processes were optimized for different interface-environmental samples. Our method offers a promising tool to investigate position-specific isomers of OH-FAs in the land-atmosphere interface.

Abstract This study intended to evaluate the diagnostic accuracy of the prostate imaging reporting and data system (PI-RADS) and prostate-specific antigen density (PSAD) for clinically significant prostate cancer (csPCa) with PSA levels of 4–10 ng/ml. Between July 2018 and June 2022, a total of 453 patients with PSA levels of 4–10 ng/ml were retrospectively included, which were randomly assigned to the training group (323 patients) and validation group (130 patients). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with their 95% CI were calculated. The overall diagnostic performance was determined with area under the receiver operating characteristic curve (AUC), and an integrated nomogram combining PI-RADS score and PSAD was constructed and tested in a validation cohort. In the training group, the AUC for PI-RADS 2.1 and PSAD alone were 0.875 (95% CI 0.834–0.916) and 0.712 (95% CI 0.648–0.775). At the cutoff PI-RADS score ≥ 4, the sensitivity and specificity were 86.2% (95% CI 77.4–1.9%) and 84.7% (95% CI 79.6–88.8%), respectively. For PSAD, the sensitivity and specificity were 73.3% (95% CI 63.0–82.4%) and 62.1% (95% CI 55.8–68.5%) at the cutoff 0.162 ng/ml/ml. While combining PI-RADS with PSAD, the diagnostic performance was improved significantly, with AUC of 0.893 (95% CI 0.853–0.933). In the validation group, the nomogram yielded a AUC of 0.871 (95% CI 0.807–0.934), which is significantly higher than PI-RADS alone (0.829, 95% CI 0.759–0.899, P = 0.02). For patients with PSA levels of 4–10 ng/ml, PSAD demonstrated moderate diagnostic accuracy whereas PI-RADS showed high performance. By combination of PSAD and PI-RADS together, the diagnostic performance could be improved significantly.

Abstract Background Drought is considered the main environmental factor restricting apple production and thus the development of the apple industry. Rootstocks play an important role in enhancing the drought tolerance of apple plants. Studies of the physiology have demonstrated that ‘ZC9-3’ is a strong drought-resistant rootstock, whereas ‘Jizhen-2’ is a weak drought-resistant rootstock. However, the metabolites in these two apple rootstock varieties that respond to drought stress have not yet been characterized, and the molecular mechanisms underlying their responses to drought stress remain unclear. Results In this study, the physiological and molecular mechanisms underlying differences in the drought resistance of ‘Jizhen-2’ (drought-sensitive) and ‘ZC9-3’ (drought-resistant) apple rootstocks were explored. Under drought stress, the relative water content of the leaves was maintained at higher levels in ‘ZC9-3’ than in ‘Jizhen-2’, and the photosynthetic, antioxidant, and osmoregulatory capacities of ‘ZC9-3’ were stronger than those of ‘Jizhen-2’. Metabolome analysis revealed a total of 95 and 156 differentially accumulated metabolites in ‘Jizhen-2’ and ‘ZC9-3’ under drought stress, respectively. The up-regulated metabolites in the two cultivars were mainly amino acids and derivatives. Transcriptome analysis revealed that there were more differentially expressed genes and transcription factors in ‘ZC9-3’ than in ‘Jizhen-2’ throughout the drought treatment. Metabolomic and transcriptomic analysis revealed that amino acid biosynthesis pathways play key roles in mediating drought resistance in apple rootstocks. A total of 13 metabolites, including L-α-aminoadipate, L-homoserine, L-threonine, L-isoleucine, L-valine, L-leucine, (2S)-2-isopropylmalate, anthranilate, L-tryptophan, L-phenylalanine, L-tyrosine, L-glutamate, and L-proline, play an important role in the difference in drought resistance between ‘ZC9-3’ and ‘Jizhen-2’. In addition, 13 genes encoding O-acetylserine-(thiol)-lyase, S-adenosylmethionine synthetase, ketol-acid isomeroreductase, dihydroxyacid dehydratase, isopropylmalate isomerase, branched-chain aminotransferase, pyruvate kinase, 3-dehydroquinate dehydratase/shikimate 5-dehydrogenase, N-acetylglutamate-5-P-reductase, and pyrroline-5-carboxylate synthetase positively regulate the response of ‘ZC9-3’ to drought stress. Conclusions This study enhances our understanding of the response of apple rootstocks to drought stress at the physiological, metabolic, and transcriptional levels and provides key insights that will aid the cultivation of drought-resistant apple rootstock cultivars. Especially, it identifies key metabolites and genes underlying the drought resistance of apple rootstocks.

Abstract Objective Benign prostatic hyperplasia (BPH) is common in elder men. The current study aims to identify differentially expressed genes (DEGs) in hyperplastic prostate and to explore the role of Nik related kinase (NRK) in BPH. Methods Four datasets including three bulk and one single cell RNA-seq (scRNA-seq) were obtained to perform integrated bioinformatics. Cell clusters and specific metabolism pathways were analyzed. The localization, expression and functional activity of NRK was investigated via RT-PCR, western-blot, immunohistochemical staining, flow cytometry, wound healing assay, transwell assay and CCK-8 assay. Results A total of 17 DEGs were identified by merging three bulk RNA-seq datasets. The findings of integrated single-cell analysis showed that NRK remarkably upregulated in fibroblasts and SM cells of hyperplasia prostate. Meanwhile, NRK was upregulated in BPH samples and localized almost in stroma. The expression level of NRK was significantly correlated with IPSS and Qmax of BPH patients. Silencing of NRK inhibited stromal cell proliferation, migration, fibrosis and EMT process, promoted apoptosis and induced cell cycle arrest, while overexpression of NRK in prostate epithelial cells showed opposite results. Meanwhile, induced fibrosis and EMT process were rescued by knockdown of NRK. Furthermore, expression level of NRK was positively correlated with that of α-SMA, collagen-I and N-cadherin, negatively correlated with that of E-cadherin. Conclusion Our novel data identified NRK was upregulated in hyperplastic prostate and associated with prostatic stromal cell proliferation, apoptosis, cell cycle, migration, fibrosis and EMT process. NRK may play important roles in the development of BPH and may be a promising therapeutic target for BPH/LUTS.

Ticks are important vectors for many pathogens affecting humans and animals. This study was aimed at investigating the species composition, genetic diversity, and potential transmission risks of tick-borne pathogens in the Guangxi Zhuang Autonomous Region, China. A total of 980 ticks were collected from 14 prefecture-level cities in Guangxi between March and July 2021. Ticks were identified morphologically and genetically, and the population diversity of Rhipicephalus microplus was analyzed according to 16S rDNA, COXI , and ITS-2 gene sequences. Population genetics was assessed through F ST , AMOVA, and phylogenetic analyses. PCR was used to detect five common tick-borne pathogens: Rickettsia , Babesia , Theileria , Borrelia burgdorferi , and Anaplasma phagocytophilum . Rhipicephalus microplus was the dominant tick species, and was observed in 92.04% of all samples. Genetic diversity analysis revealed higher haplotype diversity for the 16S rDNA and COXI genes than the ITS-2 gene; these findings suggested a faster evolutionary rate for the first two markers. Population genetic differentiation was observed between Rhipicephalus microplus populations in Guilin, Hechi, and other regions, probably because of geographic isolation. Pathogen analysis revealed a 13.27% overall infection rate, and identified three Rickettsia , two Babesia , and three Theileria species. Co-infection with Theileria and Rickettsia was also detected. Notably, neither Borrelia nor Anaplasma was found in the tick samples. Phylogenetic analyses confirmed the distinctiveness of the Rickettsia and Piroplasma groups. This study provides a comprehensive assessment of tick species diversity and tick-borne pathogens in Guangxi, highlighting the potential health risks posed by Rhipicephalus microplus . The findings emphasize the need for expanded tick surveillance, enhanced pathogen detection methods, and integrated management strategies to mitigate the spread of tick-borne diseases. Future research should include the collection of free questing ticks and metagenomic approaches to provide a more comprehensive understanding of pathogen risk in the region.

Asian citrus psyllid (ACP), Diaphorina citri (Hemiptera: Liviidae), is one of the most devastating pests in citrus orchards due to its role in transmitting Huanglongbing (HLB). Currently, chemical control remains the most effective strategy for ACP management. Mineral oils are commonly used as insecticides or adjuvants in integrated pest management (IPM) practices. To extend the product life of synthetic pesticides, we evaluated the toxicity of chlorpyrifos (CPF), thiamethoxam (THX), or pyriproxyfen (PPF) mixed with mineral oil Lvying (LY) against ACP nymphs under different weather conditions. Individual application of CPF, THX, and PPF effectively controlled against ACP nymphs under no rain conditions, with mortality rates varying from 20 to 100% during 1–5 d after treatment. The addition of LY at 1.0% or 0.5% rates to CPF, THX, and PPF significantly enhanced their control efficacy, achieving sustained mortality rates from 60 to 100% during the same period. Light rain had less impact on the control efficacy of these insecticide mixtures compared to individual insecticides. However, cumulative rainfall above 20 mm significantly reduced the control efficacy of individual insecticides and their mixtures. The addition of LY decreased both surface tension and contact angle of THX solution on citrus leaves, thereby enhancing the solution’s wetting and increasing THX deposition. Moreover, the rainfastness of THX was improved after adding LY, leading to a greater retention on the leaves. LY at a rate of 1.0% exhibited excellent efficacy against ACP nymphs, and observations using scanning electron microscopy (SEM) showed that LY altered ACP mouthpart morphology and blocked spiracles, likely contributing to its insecticidal effects. This study revealed that mineral oils can serve as both insecticides to combine with synthetic pesticides for enhancing toxicity against ACP and as adjuvants to facilitate the deposition and rainfastness of synthetic pesticides on leaves, which could be recommended for sustainable ACP management in citrus orchards.

Brown planthoppers (BPHs, Nilaparvata lugens Stål) are a major threat to rice cultivation in Asia, necessitating the development of pest-resistant varieties for effective management. However, the adaptability of BPHs has resulted in the development of virulent populations, such as biotype Y BPHs, which exhibit significant virulence against the rice variety YHY15 that harbors the resistance gene Bph15. The various response mechanisms of BPH populations to resistant rice varieties are critical yet underexplored. Via RNA sequencing, the present study identified distinct transcriptional profiles in avirulent (biotype 1) and virulent (biotype Y) BPH nymphs both before and after feeding on YHY15 rice. Our findings revealed differential expression patterns of gene clusters involved in protein synthesis, hydrolysis, fatty acid biosynthesis, metabolism, cuticle composition, and translocation. Further analysis elucidated changes in the expression of genes associated with longevity and structural components of cuticles, highlighting specific disruptions in both biotype 1 and biotype Y BPHs. Moreover, the two biotypes showed differences in the expression level of genes involved in ATP-binding cassette (ABC) transporters. A functional assessment of ABC transporter genes revealed a role of NlABCG14 in the honeydew production of biotype Y BPHs to YHY15 rice, without impacting their survival and developmental dynamics. These insights deepen our understanding of the mechanisms of virulent BPHs response to resistant rice varieties and highlight potential targets for improving pest management strategies.

ObjectiveThis study aims to assess the effectiveness of the National Early Warning Score 2 (NEWS2) versus Glasgow Coma Scale (GCS) in predicting hospital mortality among patients with stroke and traumatic brain injury (TBI).LocationThis multicenter study was conducted at two anonymized tertiary care hospitals in distinct climatic regions of China, with a combined annual emergency admission exceeding 10,000 patients.PatientsThe study included 2,276 adult emergency admissions diagnosed with stroke (n = 1,088) or TBI (n = 1,188) from January 2021 to December 2023, excluding those with chronic pulmonary disease, severe cardiac conditions, or a history of brain surgery.Measuring and main outcomesThe receiver operating characteristic (ROC) curve and the area under the curve (AUC) were utilized to analyze the predictive accuracy of NEWS2 and GCS for hospital mortality at 24, 48, and 72 h post-admission and at discharge.ResultsOut of 2,276 patients (mean age 61.4, 65.6% male), 1855 survived while 421 succumbed. NEWS2 demonstrated superior predictive accuracy (AUC = 0.962) over GCS (AUC = 0.854) for overall hospital mortality. Specifically, NEWS2 outperformed GCS in predicting mortality at 24 h (0.917 vs. 0.843), 48 h (0.893 vs. 0.803), and 72 h (0.902 vs. 0.763). Notably, despite a higher AUC for NEWS2 at predicting 24-h hospital mortality, the sensitivity and specificity of GCS were considerably lower (12 and 31%, respectively) compared to NEWS2 (sensitivity of 95% and specificity of 81%). Subgroup analysis showed NEWS2 outperforming GCS in predicting in-hospital mortality for TBI and stroke patients. For TBI patients (n = 260), NEWS2 had an AUC of 0.960 (95% CI: 0.948–0.973) vs. GCS’s AUC of 0.811 (95% CI: 0.781–0.840). For stroke patients (n = 161), NEWS2 had an AUC of 0.930 (95% CI: 0.908–0.952) vs. GCS’s AUC of 0.858 (95% CI, 0.823–0.892). NEWS2 showed greater sensitivity in both groups, highlighting its effectiveness in identifying high-risk neurological patients.ConclusionNEWS2 scores are more precise and effective in predicting hospital mortality in stroke and TBI patients compared to GCS scores, although slightly less so within the first 24 h. Combining NEWS2 with GCS and clinical findings within the initial 24 h is recommended for a comprehensive prognosis evaluation.

Abstract Serological detection of syphilis‐specific antibodies is the most widely used clinical method for diagnosing syphilis. However, the current methods in clinical practice are too diverse, complicating result interpretation and wasting medical resources. To meet the resultant demand for a simple fast naked‐eye detection method, we employed the bacterial cell‐binding domain (CBD) of bacteriophage lysin to functionalize bio‐microparticles (engineered non‐culturable red‐colored Staphylococcus aureus bacteria), forming a bioprobe that can detect the syphilis‐specific antibodies from human serum in 5 min with naked eyes. Specifically, CBD is bioengineered by fusion with one of three antigens of the syphilis‐causing bacteria Treponema pallidum separately. The three resulting fusion proteins bind to the bacteria surface through the CBD motif, generating a bioprobe with the antigens exposed. When the bioprobe is added to the serum samples collected from the syphilis patients, the syphilis‐specific antibodies bind the antigens on the bioprobes and cross‐link them, forming eye‐visible red aggregates for the naked‐eye antibody detection. The bioprobe was validated on 209 clinical samples, revealing its high clinical sensitivity and specificity. Exploiting the natural biorecognition between the bacteria‐specific phage‐derived species and the phage host bacteria represents a promising strategy for producing facile probes for rapid point‐of‐care testing of infectious diseases.

Non-ST-segment elevation acute myocardial infarction (NSTEMI) is a life-threatening clinical emergency with a poor prognosis. However, there are no individualized nomogram models to identify patients at high risk of NSTEMI who may undergo death. The aim of this study was to develop a nomogram for in-hospital mortality in patients with NSTEMI to facilitate rapid risk stratification of patients. A total of 774 non-diabetic patients with NSTEMI were included in this study. Least Absolute Shrinkage and Selection Operator regression was used to initially screen potential predictors. Univariate and multivariate logistic regression (backward stepwise selection) analyses were performed to identify the optimal predictors for the prediction model. The corresponding nomogram was constructed based on those predictors. The receiver operating characteristic curve, GiViTI calibration plot, and decision curve analysis (DCA) were used to evaluate the performance of the nomogram. The nomogram model consisting of six predictors: age (OR = 1.10; 95% CI: 1.05-1.15), blood urea nitrogen (OR = 1.06; 95% CI: 1.00-1.12), albumin (OR = 0.93; 95% CI: 0.87-1.00), triglyceride (OR = 1.41; 95% CI: 1.09-2.00), D-dimer (OR = 1.39; 95% CI: 1.06-1.80), and aspirin (OR = 0.16; 95% CI: 0.06-0.42). The nomogram had good discrimination (area under the curve (AUC) = 0.89, 95% CI: 0.84-0.94), calibration, and clinical usefulness. In this study, we developed a nomogram model to predict in-hospital mortality in patients with NSTEMI based on common clinical indicators. The proposed nomogram has good performance, allowing rapid risk stratification of patients with NSTEMI.

Summary: Background: Mapping gut microecological features to serum metabolites (SMs) will help identify functional links between gut microbiome and cardiometabolic health. Methods: This study encompassed 836-1021 adults over 9.7 year in a cohort, assessing metabolic syndrome (MS), carotid atherosclerotic plaque (CAP), and other metadata triennially. We analyzed mid-term microbial metagenomics, targeted fecal and serum metabolomics, host genetics, and serum proteomics. Findings: Gut microbiota and metabolites (GMM) accounted for 15.1% overall variance in 168 SMs, with individual GMM factors explaining 5.65%–10.1%, host genetics 3.23%, and sociodemographic factors 5.95%. Specifically, GMM elucidated 5.5%–49.6% variance in the top 32 GMM-explained SMs. Each 20% increase in the 32 metabolite score (derived from the 32 SMs) correlated with 73% (95% confidence interval [CI]: 53%–95%) and 19% (95% CI: 11%–27%) increases in MS and CAP incidences, respectively. Among the 32 GMM-explained SMs, sebacic acid, indoleacetic acid, and eicosapentaenoic acid were linked to MS or CAP incidence. Serum proteomics revealed certain proteins, particularly the apolipoprotein family, mediated the relationship between GMM-SMs and cardiometabolic risks. Interpretation: This study reveals the significant influence of GMM on SM profiles and illustrates the intricate connections between GMM-explained SMs, serum proteins, and the incidence of MS and CAP, providing insights into the roles of gut dysbiosis in cardiometabolic health via regulating blood metabolites. Funding: This study was jointly supported by the National Natural Science Foundation of China, Key Research and Development Program of Guangzhou, 5010 Program for Clinical Research of Sun Yat-sen University, and the ‘Pioneer' and ‘Leading goose' R&D Program of Zhejiang.

In recent years, there has been explosive development in artificial intelligence (AI), which has been widely applied in the health care field. As a typical AI technology, machine learning models have emerged with great potential in predicting cardiovascular diseases by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of cardiovascular diseases. Although the field has become a research hot spot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, and reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of a comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, data set characteristics, model design, and statistical methods, as well as clinical implications, and provide possible solutions to these problems, such as gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, using specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, and enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.

BackgroundThe Chinese ethnic medicine Jie-Du-Huo-Xue Decoction (JDHXD) is used to alleviate neuroinflammation in cerebral ischemia (CI). Our previous studies have confirmed that JDHXD can inhibit microglial pyroptosis in CI. However, the pharmacological mechanism of JDHXD in alleviating neuroinflammation and pyroptosis needs to be further elucidated. New research points out that there is an interaction between autophagy and inflammasome NLRP3, and autophagy can help clear NLRP3. The NLRP3 is a key initiator of pyroptosis and autophagy. The effect of JDHXD promoting autophagy to clear NLRP3 to inhibit pyroptosis on cerebral ischemia-reperfusion inflammatory injury is currently unknown. We speculate that JDHXD can inhibit pyroptosis in CI by promoting autophagy to clear NLRP3.MethodsChemical characterization of JDHXD was performed using LC-MS. Model of middle cerebral artery occlusion/reperfusion (MCAO/R) was established in SD rats. Neurological deficits, neuron damage, and cerebral infarct volume were evaluated. Western Blot and immunofluorescence were used to detect neuronal pyroptosis and autophagy.Results30 possible substance metabolites in JDHXD medicated serum were analyzed by LC-MS (Composite Score > 0.98). Furthermore, JDHXD protects rat neurological function and cerebral infarct size after CI. JDHXD inhibited the expression of pyroptosis and autophagy after CI. Our western blot and immunofluorescence results showed that JDHXD treatment can reduce the expression of autophagy-related factors ULK1, beclin1, and LC3-Ⅱ. The expression of NLRP3 protein was lower in the JDHXD group than in the I/R group. Compared with the I/R group, the expressions of pyroptosis-related factors caspase-1 P 10, GSDMD-NT, IL-18, and IL-1β decreased in the JDHXD group. Furthermore, we observed an unexpected result: immunofluorescence demonstrated that Gasdermin D (GSDMD) was significantly absent in the infarct core, and highly expressed in the peri-infarct and contralateral cerebral hemispheres. This finding challenges the prevailing view that GSDMD is elevated in the ischemic cerebral hemisphere.ConclusionJDHXD inhibited pyroptosis and autophagy after MCAO/R. JDHXD suppressed pyroptosis and autophagy by inhibiting NLRP3, thereby alleviating CI. In addition, we present a different observation from previous studies that the expression of GSDMD in the infarct core was lower than that in the peri-infarct and contralateral non-ischemic hemispheres on day 3 of CI.

Introduction Lung-protective ventilation strategies (LPVS) for one-lung ventilation (OLV) in paediatric patients pose greater challenges than in adults. Optimising LPVS for paediatric OLV to mitigate postoperative pulmonary complications (PPCs) has emerged as a current research focal point. However, there remains a divergence of opinions concerning the individualised setting and application of positive end-expiratory pressure (PEEP). Lung dynamic compliance (Cdyn) can serve as a reflection of the lung’s physiological state in children during OLV and is a readily obtainable parameter. This study protocol is formulated to assess the effectiveness of Cdyn-guided PEEP titration on PPCs during paediatric OLV.Methods and analysis This study constitutes a single-centre, prospective, double-blind, randomised controlled trial. The trial aims to recruit 60 paediatric patients scheduled for video-assisted thoracoscopic surgery. These eligible patients will be randomly assigned to either the Cdyn-guided PEEP group or the conventional PEEP group during general anaesthesia for OLV. The primary outcome will involve assessing the incidence of PPCs at 7 days after surgery. Secondary outcomes will encompass the evaluation of the modified lung ultrasound score following surgery, as well as monitoring the oxygenation index, driving pressure and Cdyn during mechanical ventilation. Data collection will be performed by investigators who are kept blinded to the interventions.Ethics and dissemination The Clinical Trial Ethics Committee at Shenzhen Children’s Hospital has conferred ethical approvals for this trial (approval number: 2022076). Results from this trial will be disseminated in peer-reviewed journals and presented at professional symposiums.Trail registration number NCT05386901.

Nephrostomy catheter misplacement into the inferior vena cava after percutaneous nephrolithotomy is an extremely rare complication, and subsequent catheter-related thrombosis has been more rarely reported. Here, we report a rare case of nephrostomy catheter misplacement after percutaneous nephrolithotomy. During the procedure, due to bleeding upon establishing the puncture channel, a renal fistula catheter with a balloon was inserted to facilitate hemostasis. However, the catheter inadvertently migrated into the inferior vena cava, with the inflated balloon obstructing venous return, resulting in thrombosis formation within the inferior vena cava. The patient was urgently transferred to our hospital for intervention. Upon administering anticoagulation and antimicrobial therapy, we first placed a filter in the patient's inferior vena cava to prevent thrombus embolism to the pulmonary arteries during catheter removal. Under fluoroscopy, the catheter was withdrawn into the renal vein, followed by catheter-directed thrombolysis and thrombus aspiration. Eventually, the renal fistula catheter was gradually removed in stages without any bleeding and pulmonary embolism occurring throughout the treatment process. Through a review of relevant literatures, we analyzed the reasons for catheter misplacement and summarized the associated treatment experience.

Abstract Granular flows, such as rockslide debris flows, can reach high velocities and travel vast distances, but mechanisms behind this high mobility remain elusive. Using the Discrete Element Method, we implement confined shear flow with fractal particle size distribution to study the physical mechanisms inside the highly localized basal zones. Our results show that the shear strength of confined flow decreases at large fractal dimensions, and a notable transition in shear behavior also occurs with increasing fractal dimension: large particles exhibit low granular temperature and act as solid phase within a semi‐diluted suspension, and small particles enter the rolling regime. The small particles behave as interstitial fluids and reduce the shear strength of confined flow. We suggest that the reduction of shear strength stemming from the fractal particle size distribution may provide insights into the mechanisms within the highly localized basal zones, ultimately contributing to the high mobility of granular flows.

Fish intestinal health under intensive aquaculture mode plays an important role in growth, development, and immune function. The present study was aimed to systematically investigate the differences of intestinal health between wild and cultured Monopterus albus by biochemical parameters, histomorphology, and molecular biology. A total of 15 healthy M. albus per group, with an average body weight of 45 g, were sampled to analyze intestinal health parameters. Compared with wild fish, the cultured M. albus in the foregut had lower trypsin, lipase, SOD, CAT, T-AOC, and GSH-Px activities (P < 0.05) and higher amylase activity and MDA content (P < 0.05). The villus circumference and goblet cells in the cultured group were significantly lower than those in the wild group (P < 0.05). In addition, the cultured fish showed lower relative expression levels of occludin, zo-1, zo-2, claudin-12, claudin-15, mucin5, mucin15, lysozyme, complement 3, il-10, tgf-β1, tgf-β2, and tgf-β3 (P < 0.05) and higher il-1β, il-6, il-8, tnf-a, and ifnγ mRNA expressions than those of wild fish (P < 0.05). In terms of gut microbiota, the cultured group at the phylum level displayed higher percentages of Chlamydiae and Spirochaetes and lower percentages of Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, and Verrucomicrobia compared to the wild group (P < 0.05). At the genus level, higher abundances of Pseudomonadaceae_Pseudomonas and Spironema and lower abundances of Lactococcus and Cetobacterium were observed in the cultured group than in the wild group (P < 0.05). To our knowledge, this is the first investigation of the intestinal health status between wild and cultured M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, the present study showed significant differences in intestinal health between wild and cultured M. albus and the main manifestations that wild M. albus had higher intestinal digestion, antioxidant capacity, and intestinal barrier functions than cultured M. albus. These results would provide theoretical basis for the subsequent upgrading of healthy aquaculture technology and nutrient regulation of intestinal health of cultured M. albus.

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites, increased therapeutic efficacy, and reduced adverse effects. Over the past few years, sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential. These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature. Inspired by their unique properties, thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine. In this review, the state-of-the-art developments in thermosensitive hydrogels for precision therapy are investigated, which covers from the thermo-gelling mechanisms and main components to biomedical applications, including wound healing, anti-tumor activity, osteogenesis, and periodontal, sinonasal and ophthalmic diseases. The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.

This study investigates the effects of soybean lecithin (SL) on the growth, fatty acid composition, lipid metabolism, and gonadal development of rice field eels. Fourteen-month-old eels were fed either fish oil diets or varying levels of dietary soybean lecithin (0 %, 1.4 %, and 2.8 %) for 10 weeks. Dietary SL had no significant impact on growth, whereas 1.4 % SL led to a significant decrease in moisture content and an increase in crude protein content in eels. The content of both saturated and polyunsaturated fatty acids increased in muscles fed the higher SL diet, with a concurrent decline in saturated fatty acids and an increase in polyunsaturated fatty acids detected in the liver. The expression levels of genes related to lipid synthesis, including accα and PPARγ, and genes related to polyunsaturated fatty acid synthesis, such as pla2g4a, fad2 and scd, were significantly increased in the liver of eels fed with 1.4 % SL diet. SL supplementation enhances lipid transport and antioxidant capacity in the liver, reduces fat deposition, and protects the liver from damage. Hepatosomatic index of fish in the SL1.4 % and SL2.8 % groups decreased. Supplementation of the diet with 1.4 % SL led to a significant decrease in the content of saturated fatty acids and an increase in the content of polyunsaturated fatty acids in the gonads, with a significant increase in arachidonic acid levels. The gonadosomatic index also increased with increasing dietary SL content. Rice field eels fed diets containing SL exhibited elevated serum levels of E2, delayed ovary-to-testis transition, and a preference for retaining the female state. In conclusion, dietary supplementation with SL increased the proportion of highly unsaturated fatty acids in the tissues, enhanced lipid metabolism in the liver, and improved antioxidant capacity. Furthermore, SL supplementation has been demonstrated to promote ovarian development and delay sex reversal in rice field eels.

Straw return is a promising strategy for managing soil organic carbon (SOC) and improving yield stability. However, the optimal straw return strategy for sustainable crop production in the wheat (Triticum aestivum L.)–cotton (Gossypium hirsutum L.) cropping system remains uncertain. The objective of this study was to quantify the long-term (10 years) impact of carbon (C) input on SOC sequestration, soil aggregation and crop yields in a wheat–cotton cropping system in the Yangtze River Valley, China. Five treatments were arranged with a single-factor randomized design as follows: no straw return (Control), return of wheat straw only (Wt), return of cotton straw only (Ct), return of 50% wheat and 50% cotton straw (Wh-Ch) and return of 100% wheat and 100% cotton straw (Wt-Ct). In comparison to the Control, the SOC content increased by 8.4 to 20.2% under straw return. A significant linear positive correlation between SOC sequestration and C input (1.42–7.19 Mg ha−1 yr−1) (P2 and 1–2 mm at the 0–20 cm soil depth were also significantly elevated under straw return, with the greatest increase of the aggregate stability in the Wt-Ct treatment (28.1%). The average wheat yields increased by 12.4–36.0% and cotton yields increased by 29.4–73.7%, and significantly linear positive correlations were also detected between C input and the yields of wheat and cotton. The average sustainable yield index (SYI) reached a maximum value of 0.69 when the C input was 7.08 Mg ha−1 yr−1, which was close to the maximum value (SYI of 0.69, C input of 7.19 Mg ha−1 yr–1) in the Wt-Ct treatment. Overall, the return of both wheat and cotton straw was the best strategy for improving SOC sequestration, soil aggregation, yields and their sustainability in the wheat–cotton rotation system.

Abstract Background Clinically, hormone replacement therapy (HRT) is the main treatment for primary ovarian insufficiency (POI). However, HRT may increase the risk of both breast cancer and cardiovascular disease. Exosomes derived from human umbilical cord mesenchymal stem cell (hUC-MSC) have been gradually applied to the therapy of a variety of diseases through inflammation inhibition, immune regulation, and tissue repair functions. However, the application and study of hUC-MSC exosomes in POI remain limited. Methods Here, we first constructed four rat animal models: the POI-C model (the “cyclophosphamide-induced” POI model via intraperitoneal injection), the POI-B model (the “busulfan-induced” POI model), the POI-U model (the “cyclophosphamide-induced” POI model under ultrasonic guidance), and MS model (the “maternal separation model”). Second, we compared the body weight, ovarian index, status, Rat Grimace Scale, complications, and mortality rate of different POI rat models. Finally, a transabdominal ultrasound-guided injection of hUC-MSC exosomes was performed, and its therapeuticy effects on the POI animal models were evaluated, including changes in hormone levels, oestrous cycles, ovarian apoptosis levels, and fertility. In addition, we performed RNA-seq to explore the possible mechanism of hUC-MSC exosomes function. Results Compared with the POI-C, POI-B, and MS animal models, the POI-U model showed less fluctuation in weight, a lower ovarian index, fewer complications, a lower mortality rate, and a higher model success rate. Second, we successfully identified hUC-MSCs and their exosomes, and performed ultrasound-guided intraovarian hUC-MSCs exosomes injection. Finally, we confirmed that the ultrasound-guided exosome injection (termed POI-e) effectively improved ovarian hormone levels, the oestrous cycle, ovarian function, and fertility. Mechanically, hUC-MSCs may play a therapeutic role by regulating ovarian immune and metabolic functions. Conclusions In our study, we innovatively constructed an ultrasound-guided ovarian drug injection method to construct POI-U animal models and hUC-MSC exosomes injection. And we confirmed the therapeutic efficacy of hUC-MSC exosomes on the POI-U animal models. Our study will offer a better choice for new animal models of POI in the future and provides certain guidance for the hUC-MSCs exosome therapy in POI patients. Graphical abstract The schema of construction of different animal models, extraction and identifying hUC-MSCs and exosomes, therapy of ultrasound-guided hUC-MSCs exosome injection. Note: POI: premature ovarian insufficiency; hUC-MSCs: Human umbilical cord mesenchymal stem cells; POI-C: POI-cyclophosphamide; POI-B: POI-cyclophosphamide + Busulfan; POI-U: POI-Ultrasonic guidance cyclophosphamide injection; MS: POI-Maternal separation. POI-e: ultrasound-guided hUC-MSCs exosome injection; AMH: Anti-müllerian hormone; LH: Luteinizing hormone; FSH: Follicle-stimulating hormone; DA: dopamine; T: Testosterone; PRL: prolactin; GnRH: Gonadotropin-releasing hormone.

Abstract Background A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. Methods PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). Results In 20,887 screened references, 79 articles (82.5% in 2017–2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5–52,000, median 21) and large-span sample size (range 80–3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as “recommended”; however, 281 and 187 were “not recommended” and “warning,” respectively. Conclusion AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

Abstract Protein-modifying enzymes regulate the dynamics of myriad post-translational modification (PTM) substrates. Precise characterization of enzyme-substrate associations is essential for the molecular basis of cellular function and phenotype. Methods for direct capturing global substrates of protein-modifying enzymes in living cells are with many challenges, and yet largely unexplored. Here, we report a strategy to directly capture substrates of lysine-modifying enzymes via PTM-acceptor residue crosslinking in living cells, enabling global profiling of substrates of PTM-enzymes and validation of PTM-sites in a straightforward manner. By integrating enzymatic PTM-mechanisms, and genetically encoding residue-selective photo-crosslinker into PTM-enzymes, our strategy expands the substrate profiles of both bacterial and mammalian lysine acylation enzymes, including bacterial lysine acylases PatZ, YiaC, LplA, TmcA, and YjaB, as well as mammalian acyltransferases GCN5 and Tip60, leading to discovery of distinct yet functionally important substrates and acylation sites. The concept of direct capturing substrates of PTM-enzymes via residue crosslinking may extend to the other types of amino acid residues beyond lysine, which has the potential to facilitate the investigation of diverse types of PTMs and substrate-enzyme interactive proteomics.

Abstract Background Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, which is a significant cause of morbidity in China, the Philippines and Indonesia. Oncomelania hupensis (Gastropoda: Pomatiopsidae) is the unique intermediate host of S. japonicum. A complete genome sequence of O. hupensis will enable the fundamental understanding of snail biology as well as its co-evolution with the S. japonicum parasite. Assembling a high-quality reference genome of O. hupehensis will provide data for further research on the snail biology and controlling the spread of S. japonicum. Methods The draft genome was de novo assembly using the long-read sequencing technology (PacBio Sequel II) and corrected with Illumina sequencing data. Then, using Hi-C sequencing data, the genome was assembled at the chromosomal level. CAFE was used to do analysis of contraction and expansion of the gene family and CodeML module in PAML was used for positive selection analysis in protein coding sequences. Results A total length of 1.46 Gb high-quality O. hupensis genome with 17 unique full-length chromosomes (2n = 34) of the individual including a contig N50 of 1.35 Mb and a scaffold N50 of 75.08 Mb. Additionally, 95.03% of these contig sequences were anchored in 17 chromosomes. After scanning the assembled genome, a total of 30,604 protein-coding genes were predicted. Among them, 86.67% were functionally annotated. Further phylogenetic analysis revealed that O. hupensis was separated from a common ancestor of Pomacea canaliculata and Bellamya purificata approximately 170 million years ago. Comparing the genome of O. hupensis with its most recent common ancestor, it showed 266 significantly expanded and 58 significantly contracted gene families (P

Abstract Branched flows occur ubiquitously in various wave systems, when the propagating waves encounter weak correlated scattering potentials. Here we report the experimental realization of electrical tuning of the branched flow of light using a nematic liquid crystal (NLC) system. We create the physical realization of the weakly correlated disordered potentials of light via the inhomogeneous orientations of the NLC. We demonstrate that the branched flow of light can be switched on and off as well as tuned continuously through the electro-optical properties of NLC film. We further show that the branched flow can be manipulated by the polarization of the incident light due to the optical anisotropy of the NLC film. The nature of the branched flow of light is revealed via the unconventional intensity statistics and the rapid fidelity decay along the light propagation. Our study unveils an excellent platform for the tuning of the branched flow of light which creates a testbed for fundamental physics and offers a new way for steering light.

Abstract Retinoblastoma (RB) is the most prevalent ocular tumor of childhood, and its extraocular invasion significantly increases the risk of metastasis. Nevertheless, a single-cell characterization of RB local extension has been lacking. Here, we perform single-cell RNA sequencing on four RB samples (two from intraocular and two from extraocular RB patients), and integrate public datasets of five normal retina samples, four intraocular samples, and three extraocular RB samples to characterize RB local extension at the single-cell level. A total of 128,454 qualified cells are obtained in nine major cell types. Copy number variation inference reveals chromosome 6p amplification in cells derived from extraocular RB samples. In cellular heterogeneity analysis, we identified 10, 8, and 7 cell subpopulations in cone precursor like cells, retinoma like cells, and MKI67+ photoreceptorness decreased (MKI67+ PhrD) cells, respectively. A high expression level of SOX4 was detected in cells from extraocular samples, especially in MKI67+ PhrD cells, which was verified in additional clinical RB samples. These results suggest that SOX4 might drive RB local extension. Our study presents a single-cell transcriptomic landscape of intraocular and extraocular RB samples, improving our understanding of RB local extension at the single-cell resolution and providing potential therapeutic targets for RB patients.

Abstract Background Brucellosis is a zoonotic affliction instigated by bacteria belonging to the genus Brucella and is characterized by a diverse range of pervasiveness, multiple transmission routes, and serious hazards. It is imperative to amalgamate the current knowledge and identify gaps pertaining to the role of ticks in brucellosis transmission. Methods We systematically searched China National Knowledge Infrastructure (CNKI), WanFang, Google Scholar, and PubMed on the topic published until April 23, 2022. The procedure was performed in accordance with the Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The selected articles were categorized across three major topic areas, and the potential data was extracted to describe evidence-practice gaps by two reviewers. Results The search identified 83 eligible studies for the final analyses. The results highlighted the potential capacity of ticks in brucellosis transmission as evidenced by the detection of Brucella in 16 different tick species. The pooled overall prevalence of Brucella in ticks was 33.87% (range: 0.00–87.80%). The review also revealed the capability of Brucella to circulate in parasitic ticks' different developmental stages, thus posing a potential threat to animal and human health. Empirical evidence from in vitro rodent infection experiments has revealed that ticks possess the capability to transmit Brucella to uninfected animals (range: 45.00–80.00%). Moreover, significant epidemiological associations have been found between the occurrence of brucellosis in animals and tick control in rangelands, which further suggests that ticks may serve as potential vectors for brucellosis transmission in ruminants. Notably, a mere three cases of human brucellosis resulting from potential tick bites were identified in search of global clinical case reports from 1963 to 2019. Conclusions It is imperative to improve the techniques used to identify Brucella in ticks, particularly by developing a novel, efficient, precise approach that can be applied in a field setting. Furthermore, due to the lack of adequate evidence of tick-borne brucellosis, it is essential to integrate various disciplines, including experimental animal science, epidemiology, molecular genetics, and others, to better understand the efficacy of tick-borne brucellosis. By amalgamating multiple disciplines, we can enhance our comprehension and proficiency in tackling tick-borne brucellosis.

Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p

Cloud computing environments increasingly provision field-programmable gate arrays (FPGAs) for their programmability and hardware-level parallelism. While FPGAs are typically used by one tenant at a time, multitenant schemes supporting spatial sharing of cloud FPGA resources have been proposed in the literature. However, the spatial multitenancy of FPGAs opens up new attack surfaces. Investigating potential security threats to multitenant FPGAs is thus essential for better understanding and eventually mitigating the security risks. This work makes a notable step forward by systematically analyzing the combined threat of FPGA power wasters and satisfiability don’t-care hardware Trojans in shared cloud FPGAs. We demonstrate a successful remote undervolting attack that activates a hardware Trojan concealed within a victim FPGA design and exploits the payload. The attack is carried out entirely remotely, assuming two spatially colocated FPGA users isolated from one another. The victim user’s circuit is infected with a Trojan, triggered by a pair of don’t-care signals that never reach the combined trigger condition during regular operation. The adversary, targeting the exploitation of the Trojan, deploys power waster circuits to lower the supply voltage of the FPGA. The assumption is that, under the effect of the lowered voltage, don’t-care signals may reach the particular state that triggers the Trojan. We name this exploit X-Attack and demonstrate its feasibility on an embedded FPGA and real-world cloud FPGA instances. Additionally, we study the effects of various attack tuning parameters on the exploit’s success. Finally, we discuss potential countermeasures against this security threat and present a lightweight self-calibrating countermeasure. To the best of our knowledge, this is the first work on undervolting-based fault-injection attacks in multitenant FPGAs to demonstrate the attack on commercially available cloud FPGA instances.

This work studied the effect of solution heat treatment on the microstructure and properties of the Al–Cu alloy fabricated by wire arc additive manufacturing (WAAM), and focused on the influence of porosity and second phase evolution on the tensile properties and fatigue resistance of the alloy. The results show that with solution heat treatment at 530 °C for 1h, Al–Cu alloy fabricated by WAAM with low porosity (2.4 %) and high peak hardness (148.2 HV) can be obtained. Higher solution temperatures significantly increased the porosity, and extending the solution time caused the problems of increased porosity, micropore growth, microcracks as well as cavity. Influence of porosity on fatigue resistance is more significant than that on tensile properties. The results of tensile tests suggest that the effect of porosity on the strength of T6-treated alloy is limited and much smaller than that of the precipitation strengthening induced by precipitates, while the results of the fatigue crack propagation tests imply that porosity plays the dominant role in the fatigue crack propagation behaviors of the T6-treated alloy.

In this paper, a novel ultrawideband phased array is presented based on exponential curve modified dipoles. A tightly-coupled exponential curve modified dipole arm is used to extend the operating bandwidth with a simple coplanar strip structure, which avoids the use of additional complex impedance conversion networks and reduces the processing difficulty and cost. The problematic common-mode resonance is moved out of the required operating bandwidth by the shorting pin. A wide angle impedance matching layer is used to improve beam scanning ability of the array. The proposed antenna array achieves 8.5:1 (2.06-17.6 GHz) bandwidth at broadside, with a scanning range of ±45° from 2.06-17.6 GHz (8.5:1 bandwidth) in the E-plane and ±45° from 2.2-17.6 GHz (8:1 bandwidth) in the H-plane, subject to active VSWR < 3. A $6\times6$ prototype was fabricated and measured with good agreement in measured and simulated results, which verify the ultrawideband performance of proposed array.

Abstract The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.

Abstract Liquid crystals are a vital component of modern photonics, and recent studies have demonstrated the exceptional sensing properties of stimuli-responsive cholesteric liquid crystals. However, existing cholesteric liquid crystal-based sensors often rely on the naked eye perceptibility of structural color or the measurement of wavelength changes by spectrometric tools, which limits their practical applications. Therefore, developing a platform that produces recognizable sensing signals is critical. In this study, we present a visual sensing platform based on geometric phase encoding of stimuli-responsive cholesteric liquid crystal polymers that generates real-time visual patterns, rather than frequency changes. To demonstrate this platform’s effectiveness, we used a humidity-responsive cholesteric liquid crystal polymer film encoded with a q-plate pattern, which revealed that humidity causes a shape change in the vortex beam reflected from the encoded cholesteric liquid crystal polymers. Moreover, we developed a prototype platform towards remote humidity monitoring benefiting from the high directionality and long-range transmission properties of laser beams carrying orbital angular momentum. Our approach provides a novel sensing platform for cholesteric liquid crystals-based sensors that offers promising practical applications. The ability to generate recognizable sensing signals through visual patterns offers a new level of practicality in the sensing field with stimuli-responsive cholesteric liquid crystals. This platform might have significant implications for a broad readership and will be of interest to researchers working in the field of photonics and sensing technology.

The immune microenvironment plays a vital role in bone defect repair. To create an immune microenvironment that promotes osteogenesis, researchers are exploring ways to enhance the differentiation of M2-type macrophages. Functional peptides have been discovered to effectively improve this process, but they are limited by low efficiency and rapid degradation in vivo. To overcome these issues, peptide with both M2 regulatory and self-assembly modules was designed as a building block to construct an ultrasound-responsive nanofiber hydrogel. These nanofibers can be released from hydrogel in a time-dependent manner upon ultrasound stimulation, activating mitochondrial glycolytic metabolism and the tricarboxylic acid cycle, inhibiting reactive oxygen species production and enhancing M2 macrophage polarization. The hydrogel exhibits advanced therapeutic potential for bone regeneration by triggering M2 macrophages to secrete BMP-2 and IGF-I, accelerating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts. Thus, modularly designed biomimetic ultrashort peptide nanofiber hydrogels provide a novel strategy to rebuild osteogenic immune microenvironments for bone repair.

Human Action Recognition (HAR) based on skeleton sequences has attracted much attention due to the robustness and background insensitivity of skeletal data. The convolutional neural network (CNN) for spatio-temporal representation learning has been widely utilized for skeleton-based HAR. However, the long-term spatio-temporal modeling and action category-specific feature attention have not been fully exploited. In order to explore the current potential of CNNs for skeleton-based HAR, a novel CNN architecture with temporal-channel attention and convolution fusion is proposed. Specially, the network architecture is composed of two novel modules, the Temporal-Channels Attention Module (TCA) and Multiscale Temporal Convolution Fusion module (MTCF). TCA module is designed to generate a temporal-channel attention matrix for different visual channels and temporal features, motivating the CNN to focus on the critical category-associated feature representation learning. Along the channels, MTCF module adapts the grouped residual connections to flexibly extend the convolutional temporal receptive field, without introducing additional parameters. By reverse stacking, MTCF module creates a bidirectional information interaction among inter-channels, compensating for the receptive field and information imbalance between subgroups from different branches. The proposed method was evaluated on three benchmark datasets, including NTU RGB-D, NTU RGB-D120 and FineGYM. The results show that the proposed TCA-MTCF method improves the CNNs’ ability to model long-term temporal features of skeleton sequences, achieving the state-of-the-art performance for HAR.

Abstract Latent fingerprints (LFPs) at the crime scene are served as important clues to locate the trajectory of criminal behavior and portray the characteristics of the suspect. Therefore, visualizing LFPs is of considerable significance. In this work, the europium metal-organic framework (Eu-MOF) sensor was successfully constructed for sensitive detection of gallic acid (3,4,5-trihydroxybenzoic acid, GA) and visualization of the sweat LFPs. The boric-acid-modified Eu-MOF was prepared by using the simple one-pot solvothermal method using Eu as the metal ion center and 3,5-dicarboxybenzeneboronic acid (BBDC) as the organic ligand. The sensor showed desirable photoluminescent performance through the chelating of BBDC with Eu3+. The sensor exhibited the satisfactory linear relationship to GA in the range of 1 nM to 20 nM with a low detection limit of 0.34 nM under the optimized conditions. The prepared sensor with ideal selectivity to GA was successfully applied for visualizing LFPs on porous substrates with the high contrast and superior stability. Given the good performance of the sensor, all fingerprint images obtained from 1 200 samples presented clear friction ridges and met the identification criteria. Notably, the sensor had less impact on the subsequent deoxyribonucleic acid (DNA) detection, displaying a promising perspective for applications in extracting physical evidence of site investigation.