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Abstract Background Microbiological diagnosis of pulmonary tuberculosis (PTB) is hampered by a low pathogen burden, low compliance and unreliable sputum sampling. Although endobronchial ultrasound-guided transbronchoscopic lung biopsy (EBUS-TBLB) has been found to be useful for the assessment of intrapulmonary nodules in adults, few data are available for the clinical diagnosis of pulmonary tuberculosis. Here, we evaluated EBUS-TBLB as a diagnostic procedure in adult patients with radiologically suspected intrapulmonary tuberculous nodules. Methods This was a retrospective analysis of patients admitted with pulmonary nodules between January 2022 and January 2023 at Hangzhou Red Cross Hospital. All patients underwent EBUS-TBLB, and lung biopsy samples were obtained during hospitalization. All samples were tested for Mycobacterium tuberculosis using acid‒fast smears, Bactec MGIT 960, Xpert MTB/RIF, next-generation sequencing (NGS), and DNA (TB‒DNA) and RNA (TB‒RNA). The concordance between different diagnostic methods and clinical diagnosis was analysed via kappa concordance analysis. The diagnostic efficacy of different diagnostic methods for PTB was analysed via ROC curve. Results A total of 107 patients were included in this study. Among them, 86 patients were diagnosed by EBUS-TBLB, and the overall diagnostic rate was 80.37%. In addition, 102 enrolled patients had benign lesions, and only 5 were diagnosed with lung tumours. Univariate analysis revealed that the diagnostic rate of EBUS-TBLB in pulmonary nodules was related to the location of the probe. The consistency analysis and ROC curve analysis revealed that NGS had the highest concordance with the clinical diagnosis results (agreement = 78.50%, κ = 0.558) and had the highest diagnostic efficacy for PTB (AUC = 0.778). In addition, Xpert MTB/RIF + NGS had the highest concordance with the clinical diagnosis results (agreement = 84.11%, κ = 0.667) and had the highest efficacy in the diagnosis of PTB (AUC = 0.826). Conclusion EBUS-TBLB is a sensitive and safe method for the diagnosis of pathological pulmonary nodules. Xpert MTB/RIF combined with NGS had the highest diagnostic efficacy and can be used in the initial diagnosis of PTB.

Abstract Introduction This retrospective study aimed to investigate treatment patterns and outcomes in patients with NSCLC harboring EGFR20ins in China. EGFR20ins mutations are associated with poor responses to EGFR-TKIs, and limited real-world data exist regarding the efficacy of various treatment modalities. Methods In this retrospective, single-center study, treatment outcomes, including PFS and ORR, were evaluated for different treatment regimens based on imaging assessments. The impact of mutation heterogeneity on treatment efficacy was also explored. Results Data from 302 patients diagnosed with NSCLC with EGFR20ins were analyzed. EGFR-TKI monotherapy demonstrated suboptimal PFS compared to platinum-based chemotherapy in the first-line setting (3.00 m vs. 6.83 m, HR = 3.674, 95%CI = 2.48–5.44, p

Coumarins, derived from the phenylpropanoid pathway, represent one of the primary metabolites found in angiosperms. The alignment of the tetrahydropyran (THP) and tetrahydrofuran (THF) rings with the lactone structure results in the formation of at least four types of complex coumarins. However, the mechanisms underlying the structural diversity of coumarin remain poorly understood. Here, we report the chromosome-level genome assembly of Notopterygium incisum, spanning 1.64 Gb, with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding genes. Additionally, we identified the key enzymes responsible for shaping the structural diversity of coumarins, including two p-coumaroyl CoA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture, two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis, and five CYP736 cyclases involved in THP and THF ring formation. Notably, two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first time. Evolutionary analysis implies that tandem and ectopic duplications of the CYP736 subfamily, specifically arising in the Apiaceae, contributed to the structural diversity of coumarins in N. incisum. Conclusively, this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia (OIH), but the underlying mechanisms remain elusive. The presence of astrocyte-neuron lactate shuttle (ANLS) makes astrocytes necessary for some neural function and communication. The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH. After 7 days consecutive morphine injection, a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4 (PDK4), phosphorylated pyruvate dehydrogenase (p-PDH) and accumulation of L-lactate was elevated in the spinal dorsal horn. Intrathecally administration of inhibitors of PDK, lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns. The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro. In this study, we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS. In this process, PDK-p-PDH-lactate axis serves a pivotal role, which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

Abstract Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.

Abstract We investigate the geodesic motions of timelike particles around a static hairy black hole with conformally coupled scalar field. We mainly focus on the effects of the scalar charge and electric charge on the marginally bound orbits (MBO), innermost stable circular orbits (ISCO) and on the precessing orbits around this black hole. Our results show that both the scalar and electric charges suppress the energy as well as the angular momentum of the particles in the bound orbits. Then, we study the relativistic periastron precessions of the particles and constrain the charge parameters by employing the observational result of the S2 star’s precession in SgrA*. It is found that the constraints on the charge parameters from S2 star’s motion are tighter than those from black hole shadow. Finally, we analyze the periodic motions of the particles and figure out samples of periodic orbits’ configurations around the hairy black hole.

Abstract Background Triple-negative breast cancer (TNBC) is characterized by its high metastatic potential, which results in poor patient survival. Cancer-associated fibroblasts (CAFs) are crucial in facilitating TNBC metastasis via induction of mitochondrial biogenesis. However, how to inhibit CAF-conferred mitochondrial biogenesis is still needed to explore. Methods We investigated metastasis using wound healing and cell invasion assays, 3D-culture, anoikis detection, and NOD/SCID mice. Mitochondrial biogenesis was detected by MitoTracker green FM staining, quantification of mitochondrial DNA levels, and blue-native polyacrylamide gel electrophoresis. The expression, transcription, and phosphorylation of peroxisome-proliferator activated receptor coactivator 1α (PGC-1α) were detected by western blotting, chromatin immunoprecipitation, dual-luciferase reporter assay, quantitative polymerase chain reaction, immunoprecipitation, and liquid chromatography-tandem mass spectrometry. The prognostic role of PGC-1α in TNBC was evaluated using the Kaplan–Meier plotter database and clinical breast cancer tissue samples. Results We demonstrated that PGC-1α indicated lymph node metastasis, tumor thrombus formation, and poor survival in TNBC patients, and it was induced by CAFs, which functioned as an inducer of mitochondrial biogenesis and metastasis in TNBC. Shikonin impeded the CAF-induced PGC-1α expression, nuclear localization, and interaction with estrogen-related receptor alpha (ERRα), thereby inhibiting PGC-1α/ERRα-targeted mitochondrial genes. Mechanistically, the downregulation of PGC-1α was mediated by synthase kinase 3β-induced phosphorylation of PGC-1α at Thr295, which associated with neural precursor cell expressed developmentally downregulated 4e1 recognition and subsequent degradation by ubiquitin proteolysis. Mutation of PGC-1α at Thr295 negated the suppressive effects of shikonin on CAF-stimulated TNBC mitochondrial biogenesis and metastasis in vitro and in vivo. Conclusions Our findings indicate that PGC-1α is a viable target for blocking TNBC metastasis by disrupting mitochondrial biogenesis, and that shikonin merits potential for treatment of TNBC metastasis as an inhibitor of mitochondrial biogenesis through targeting PGC-1α.

Abstract Cnidium monnieri, a medicinal herb of the Cnidium genus and the Apiaceae family, is among the most important traditional Chinese medicines and is widely distributed in China. However, to date, no C. monnieri-related genomic information has been described. In this study, we assembled the C. monnieri genome of approximately 1210.23 Mb with a contig N50 of 83.14 Mb. Using PacBio HiFi and Hi-C sequencing data, we successfully anchored 93.86% of the assembled sequences to 10 pseudochromosomes (2n = 20). We predicted a total of 37,460 protein-coding genes, with 97.02% of them being functionally annotated in Non-Redundant, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and other databases. In addition, we identified 2,778 tRNAs, 4,180 rRNAs, 258 miRNAs, and 1,700 snRNAs in the genome. This is the first reported C. monnieri genome. Hopefully, the availability of this chromosome-level reference genome provides a significant basis for upcoming natural product-related biosynthetic pathway assessment in C. monnieri.

Abstract Background The association between the triglyceride glucose (TyG) index and the risk of early-onset atherosclerotic cardiovascular disease (ASCVD) events or all-cause mortality in young and middle-aged people is not fully elucidated. Methods The present study included 64,489 young and middle-aged people who participated in the 2006 Kailuan Study physical examination. Multivariate Cox proportional hazards models and restricted cubic spline curves were used to assess the association of TyG index with early-onset ASCVD events and all-cause mortality. Results During a median of 11-year follow-up, 1984 (3.08%) participants experienced at least one ASCVD event and 1,392 (2.16%) participants experienced all-cause death. A higher TyG index was significantly associated with a higher risk of early-onset ASCVD events (HR: 1.61, 95% CI 1.38–1.89) and all-cause mortality (HR: 1.39, 95% CI 1.17–1.65), respectively. For each unit increase in TyG index, the risk of early-onset ASCVD events increased by 20%. In addition, there was a non-linear association between the TyG index and early-onset ASCVD events (P for non-linear

BackgroundThe current lower limb robotic exoskeleton training (LRET) for treating and managing stroke patients remains a huge challenge. Comprehensive ICF analysis and informative treatment options are needed. This review aims to analyze LRET’ s efficacy for stroke patients, based on ICF, and explore the impact of intervention intensities, devices, and stroke phases.MethodsWe searched Web of Science, PubMed, and The Cochrane Library for RCTs on LRET for stroke patients. Two authors reviewed studies, extracted data, and assessed quality and bias. Standardized protocols were used. PEDro and ROB2 were employed for quality assessment. All analyses were done with RevMan 5.4.ResultsThirty-four randomized controlled trials (1,166 participants) were included. For function, LRET significantly improved motor control (MD = 1.15, 95%CI = 0.29–2.01, p = 0.009, FMA-LE), and gait parameters (MD = 0.09, 95%CI = 0.03–0.16, p = 0.004, Instrumented Gait Velocity; MD = 0.06, 95%CI = 0.02–0.09, p = 0.002, Step length; MD = 4.48, 95%CI = 0.32–8.65, p = 0.04, Cadence) compared with conventional rehabilitation. For activity, LRET significantly improved walking independence (MD = 0.25, 95%CI = 0.02–0.48, p = 0.03, FAC), Gait Velocity (MD = 0.07, 95%CI = 0.03–0.11, p = 0.001) and balance (MD = 2.34, 95%CI = 0.21–4.47, p = 0.03, BBS). For participation, social participation (MD = 0.12, 95%CI = 0.03–0.21, p = 0.01, EQ-5D) was superior to conventional rehabilitation. Based on subgroup analyses, LRET improved motor control (MD = 1.37, 95%CI = 0.47–2.27, p = 0.003, FMA-LE), gait parameters (MD = 0.08, 95%CI = 0.02–0.14, p = 0.006, Step length), Gait Velocity (MD = 0.11, 95%CI = 0.03–0.19, p = 0.005) and activities of daily living (MD = 2.77, 95%CI = 1.37–4.16, p = 0.0001, BI) for the subacute patients, while no significant improvement for the chronic patients. For exoskeleton devices, treadmill-based exoskeletons showed significant superiority for balance (MD = 4.81, 95%CI = 3.10–6.52, p

Abstract Background Disorders of the gut microbiome could be responsible for the progression of multiple organ dysfunction syndrome. In this study, we examined the effect of esmolol on the gut microbiome in a rat model of sepsis induced by cecal ligation and puncture (CLP). Methods The animals (n = 32) were randomly divided into 3 groups: Sham group (sham operation + normal saline treatment, n = 8), CLP group (cecal ligation and puncture + normal saline treatment, n = 12), and CLP + ESM group (cecal ligation and puncture + esmolol treatment, n = 12). After 24 h, feces in the colon were collected for 16S rRNA gene sequencing and nitric oxide analysis. In addition, colon was removed for immunohistochemical staining of inducible nitric oxide synthase (iNOS). Results Four rats in the CLP group and two rats in the CLP + ESM group died. The abundance of Lactobacillus in the CLP + ESM group was higher than CLP group (P = 0.048). In the linear discriminant analysis effect size analysis, Norank f Muribaculaceae, Escherichia–Shigella and Lactobacillus were the predominant bacteria in the Sham group, CLP group and CLP + ESM group, respectively. The iNOS expression in colonocytes stained by brown in the CLP group were much more than Sham group (P = 0.001). Compared to CLP group, the iNOS expression in colonocytes reduced after esmolol treatment (P = 0.013). The concentration of nitric oxide in colon feces was different in Sham group, CLP group and CLP + ESM group (1.31 ± 0.15μmmol/l vs. 1.98 ± 0.27μmmol/l vs. 1.51 ± 0.14μmmol/l, P = 0.001). In addition, the concentration of nitric oxide in CLP group was higher than Sham group (P = 0.001) or CLP + ESM group (P = 0.001). Conclusions Esmolol increased the fecal abundance of Lactobacillus in a rat model of sepsis. Moreover, esmolol reduced the iNOS expression of colonocytes and the nitric oxide concentration of colon feces.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial–mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Abstract Background The excretory/secretory (ES) antigen of Trichinella spiralis muscle larvae (ML) is currently the most widely used diagnostic antigen to detect T. spiralis infection. However, this antigen has certain drawbacks, such as a complicated ES antigen preparation process and lower sensitivity during the early phase of infection. The aim of this study was to investigate the features of a novel T. spiralis trypsin (TsTryp) and evaluate its potential diagnostic value for trichinellosis. Methods The TsTryp gene was cloned and recombinant TsTryp (rTsTryp) expressed. Western blotting and an enzyme-linked immunosorbent assay (ELISA) were performed to confirm the antigenicity of rTsTryp. The expression pattern and distribution signature of TsTryp at various life-cycle stages of T. spiralis were analyzed by quantitative PCR, western blotting and the immunofluorescence test. An ELISA with rTsTryp and ML ES antigens was used to detect immunoglobulins G and M (IgG, IgM) in serum samples of infected mice, swine and humans. The seropositive results were further confirmed by western blot with rTsTryp and ML ES antigens. Results TsTryp expression was observed in diverse T. spiralis life-cycle phases, with particularly high expression in the early developmental phase (intestinal infectious larvae and adults), with distribution observed mainly at the nematode outer cuticle and stichosome. rTsTryp was identified by T. spiralis-infected mouse sera and anti-rTsTryp sera. Natural TsTryp protease was detected in somatic soluble and ES antigens of the nematode. In mice infected with 200 T. spiralis ML, serum-specific IgG was first detected by rTsTryp-ELISA at 8 days post-infection (dpi), reaching 100% positivity at 12 dpi, and first detected by ES-ELISA at 10 dpi, reaching 100% positivity at 14 dpi. Specific IgG was detected by rTsTryp 2 days earlier than by ES antigens. When specific IgG was determined in serum samples from trichinellosis patients, the sensitivity of rTsTryp-ELISA and ES antigens-ELISA was 98.1% (51/52 samples) and 94.2% (49/52 samples), respectively (P = 0.308), but the specificity of rTsTryp was significantly higher than that of ES antigens (98.7% vs. 95.4%; P = 0.030). Additionally, rTsTryp conferred a lower cross-reaction, with only three serum samples in total testing positive from 11 clonorchiasis, 20 cysticercosis and 24 echinococcosis patients (1 sample from each patient group). Conclusions TsTryp was shown to be an early and highly expressed antigen at intestinal T. spiralis stages, indicating that rTsTryp represents a valuable diagnostic antigen for the serodiagnosis of early Trichinella infection. Graphical Abstract

Echocardiography is essential for the diagnosis and treatment of cardiovascular diseases, especially congenital heart disease. However, the interpretation of echocardiography requires the accumulation of abundant professional experience for cardiologists, which may lead to missed diagnoses and misdiagnoses due to differences between operators. The development of artificial intelligence and its subset, deep learning, has altered this potential crisis in recent years with their rapid, accurate, and consistent nature. While the application of deep learning in echocardiography is still in its infancy, recent studies demonstrate that deep learning models can quickly obtain information by extracting samples from large databases. Moreover, growing evidence suggests that deep learning can be used for standard section recognition in echocardiography and auxiliary diagnosis of heart disease. In this review, we begin by outlining the principles of deep learning. Then, we investigate the current application of deep learning in echocardiography, underscoring its significance. Furthermore, we discuss its limitations and finally highlight future development prospects.

Abstract Background Indoor air pollution causes severe psychological stress and promotes depression. A better understanding of the impact of solid fuel consumption and socioeconomic indicators on mental health is critical to promote successful aging. In this study, we analyzed the relationship of depression with socioeconomic status (SES) and solid fuel use, and illustrated the mediating role of solid fuel use in the relationship between SES and depression. Methods 9250 participants from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey were included in this study. A logistic regression analysis was used to calculate odds ratio (OR) and 95% confidence interval (CI) of depression for different types of fuel consumption. The stepwise approach and the Sobel test were used to test the mediation effect. Results Older people who reported the consumption of solid fuels showed higher odds of having depressive symptoms (OR = 1.16, 95% CI:1.03, 1.31). In model with depression as the outcome variable, the ORs of low education level and low annual household income level were 1.30 (95% CI: 1.15, 1.47) and 1.43 (95% CI: 1.28, 1.59) respectively. Solid fuel consumption accounted for 38.40% of the effect of a low education level and 54.73% of the effect of low income on depression. Conclusions Solid fuel use and SES are associated with depression, and solid fuel use may act as a potential mediator connecting socioeconomic indicators and depression.

Leveraging the dispatchability of 5G base station energy storage (BSES) not only enables the mobile network operator (MNO) to gain additional revenue, but also facilitates the integration of renewable energy sources in distribution network (DN). However, since BSES and DN are owned by different stakeholders, integrating BSES into DN operations poses significant challenges. In this regard, this paper proposes a DN optimal dispatch model that incorporates the adaptive aggregation of 5G base stations (BSs) through a cooperative game framework. Firstly, the dispatchability of BSESs is analyzed and modelled. Considering it is difficult to dispatch every single unit optimally, an adaptive aggregation model of 5G BSs is established, where the electrical coupling degree and the communication service similarity are taken as comprehensive metrics. On this basis, an optimal dispatch model of DN based on cooperative game is constructed, where the total operational costs of 5G BSs and DN are considered as the characteristic function. The number of 5G BS clusters and the aggregating results are adjusted adaptively during optimization. The optimal aggregation of 5G BSs is achieved using the Affinity Propagation (AP) clustering algorithm. Furthermore, to solve the optimal dispatch model of the DN with enhanced computational efficiency, the particle swarm optimization algorithm integrated with second-order cone programming (PSO-SOCP) is employed. After dispatching, the benefit allocation between MNO and distribution system operator (DSO) is conducted using the Shapley value method and the Equal Profit Method to obtain an entire range of allocation results. Finally, simulations are carried out with results proving the effectiveness of the proposed method.

IntroductionNutritional literacy (NL) has a critical influence on food choices. The objective of the present study was to examine the association of NL with nutrition label use.MethodsA cross-sectional study was conducted in Bengbu, China. In total, 955 adults were interviewed using a questionnaire designed for the present study to collect information on demographics, lifestyle, nutrition label use, and NL. Binary logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for nutrition label use and its predictive variables.ResultsIn total, 40.4% of the participants reported looking at nutrition label when purchasing prepackaged foods. NL was significantly positively associated with nutrition label use and specifically with checking nutrition facts table, purported nutrition benefits and purported health benefits. In terms of specific facets of NL, nutrition knowledge, applying skills, and critical skills were associated with nutrition label use. After stratification by monthly income and education, the association between NL and nutrition label use was discovered only in individuals with low monthly income. Additionally, nutrition knowledge was associated with nutrition label use only in adults with high education level, whereas applying skills were associated with nutrition label use only in those with low education level.ConclusionThe use of nutrition label remains low among Chinese community residents, especially the purported nutritional benefits and purported health benefits. NL is positively associated with nutrition label use, especially with respect to functional and critical NL, with differences based on socioeconomic status. The findings highlight the need for NL interventions targeting individuals with different levels of education and income to encourage use of nutrition label in China.

Wildlife conservation and management in human-dominated landscapes are major concerns for wildlife ecologists and managers. The dynamics of human disturbance, combined with seasonal limitations in the availability of nutritious foods, may restrict wildlife population growth and recovery. However, understanding how large mammal species adjust their population distribution in forest habitats with seasonal changes in food and disturbances requires a deeper and more extensive analysis. In this study, we found that three ungulate species, roe deer (Capreolus pygargus), sika deer (Cervus nippon), and wild boar (Sus scrofa), employ robust, conservative, and flexible distribution strategies, respectively, to adapt to the effects of seasonal changes and human disturbances. Moreover, croplands, villages, and grazing have some negative effects on the distribution of roe deer and sika deer, while wild boar can be highly abundant near human land use. Additionally, roe deer, sika deer, and wild boar are also affected by the abundance of shrub species they consume. During the cold season, the populations of the Amur tiger (Panthera tigris altaica) and Amur leopard (P. pardus orientalis) were primarily located near roads and dense forests, respectively. In the warm season, the distribution of both big cats was influenced by prey abundance, and Amur tigers also avoided grazing livestock. Nevertheless, the negative effects of human land use on Amur tigers and wild boars increased during the warm season, which was attributed to more frequent human activities during that time. Consequently, it is crucial to implement season-specific habitat management, particularly by regulating human disturbances during the warm season, in order to promote the recovery and expansion of populations of big cats and ungulates.

The hematopoietically-expressed homeobox gene (HHEX) played a critical role in regulating the immune system that the abnormality of which was involved in the psychopathology and cognitive deficits of psychiatric disorders. The aim of this study was to investigate the effect of HHEX rs1111875 polymorphism on the susceptibility and cognitive deficits of first-episode schizophrenic patients (FSP). We assessed cognitive function in 239 first-episode patients meeting DSM-IV for schizophrenia, and 368 healthy controls using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The HHEX rs1111875 polymorphism was genotyped. Our results showed that the allelic and genotypic frequencies of HHEX rs1111875 polymorphism didn't differ between FSP and healthy controls (both p > 0.05) after adjusting for sex and age. Cognitive test scores in FSP were significantly lower than those in healthy controls on all scales (all p 0.05) after adjusting for covariates. There was a significant genotype (p 0.05) effect on the delayed memory score after adjusting for covariates. The HHEX rs1111875 polymorphism was significantly associated with the delayed memory score in FSP (p 0.05) after adjusting for covariates. Our findings supported that the HHEX rs1111875 polymorphism did not contribute to the susceptibility to FSP. However, this polymorphism might influence the delayed memory in FSP. Moreover, FSP had poorer cognitive function than healthy controls except for the visuospatial/constructional domain.

Background: As the second most common gynecological cancer, cervical cancer (CC) seriously threatens women's health. The poor prognosis of CC is closely related to the post-infection microenvironment (PIM). This study investigated how lipid metabolism-related genes (LMRGs) affect CC PIM and their role in diagnosing CC. Methods: We analyzed lipid metabolism scores in the CC single-cell landscape by AUCell. The differentiation trajectory of epithelial cells to cancer cells was revealed using LMRGs and Monocle2. Consensus clustering was used to identify novel subgroups using the LMRGs. Multiple immune assessment methods were used to evaluate the immune landscape of the subgroups. Prognostic genes were determined by the LASSO and multivariate Cox regression analysis. Finally, we perform molecular docking of prognostic genes to explore potential therapeutic agents. Results: We revealed the differentiation trajectory of epithelial cells to cancer cells in CC by LMRGs. The higher LMRGs expression cluster had higher survival rates and immune infiltration expression. Functional enrichment showed that two clusters were mainly involved in immune response regulation. A novel LMR signature (LMR.sig) was constructed to predict clinical outcomes in CC. The expression of prognostic genes was correlated with the PIM immune landscape. Small molecular compounds with the best binding effect to prognostic genes were obtained by molecular docking, which may be used as new targeted therapeutic drugs. Conclusion: We found that the subtype with better prognosis could regulate the expression of some critical genes through more frequent lipid metabolic reprogramming, thus affecting the maturation and migration of dendritic cells (DCs) and the expression of M1 macrophages, reshaping the immunosuppressive environment of PIM in CC patients. LMRGs are closely related to the PIM immune landscape and can accurately predict tumor prognosis. These results further our understanding of the underlying mechanisms of LMRGs in CC.

Abstract Background Allergic diseases typically refer to a heterogeneous group of conditions primarily caused by the activation of mast cells or eosinophils, including atopic dermatitis (AD), allergic rhinitis (AR), and asthma. Asthma, AR, and AD collectively affect approximately one‐fifth of the global population, imposing a significant economic burden on society. Despite the availability of drugs to treat allergic diseases, they have been shown to be insufficient in controlling relapses and halting disease progression. Therefore, new drug targets are needed to prevent the onset of allergic diseases. Method We employed a Mendelian randomization approach to identify potential drug targets for the treatment of allergic diseases. Leveraging 1798 genetic instruments for 1537 plasma proteins from the latest reported Genome‐Wide Association Studies (GWAS), we analyzed the GWAS summary statistics of Ferreira MA et al. (nCase = 180,129, nControl = 180,709) using the Mendelian randomization method. Furthermore, we validated our findings in the GWAS data from the FinnGen and UK Biobank cohorts. Subsequently, we conducted sensitivity tests through reverse causal analysis, Bayesian colocalization analysis, and phenotype scanning. Additionally, we performed protein‐protein interaction analysis to determine the interaction between causal proteins. Finally, based on the potential protein targets, we conducted molecular docking to identify potential drugs for the treatment of allergic diseases. Results At Bonferroni significance (p

Antimicrobial peptides could inhibit the growth of harmful bacteria and promote the growth performance in weaned piglets. Here, we investigated the effects of dietary supplementation with cecropin antimicrobial peptides (CAP) on growth performance, diarrhea rate, intestinal health in nursery Hainan piglets. For this, 120 healthy nursery Hainan male piglets (13.29 ± 0.29 kg, 44 days old) were randomly divided into 5 groups—a control (CON) group (fed a basal diet), an antibiotic control (AC) group (fed a basal diet supplemented with 250 mg/kg colistin sulfate); and 3 experimental groups (provided the basal diet supplemented with 250, 500, or 1,000 mg/kg CAP). Pre-feeding lasted 7 days and the official period lasted 40 days. The results showed that compared with the CON group, dietary supplementation of 500 mg/kg CAP had significantly increased the average daily gain (ADG, p

Abstract Background Maternal and neonatal health services are life-saving interventions for neonatal health outcomes. As Rwanda endeavors to accomplish sustainable development goals, adequate ANC is essential to lessen of neonatal mortality. The utilization of ANC continues to be inadequate and high neonatal mortality rate persevere in Rwanda. Understanding the direct and indirect factors that affect newborn health outcomes is necessary for well-targeted interventions. However, few studies had been conducted in Rwanda to evaluate the importance of ANC in improving neonatal health. This study therefore assessed the association between ANC and neonatal outcomes. Methods The Demographic and Health Surveys (DHS) are household surveys that are cross-sectional, nationally representative, and used to collect data on population, health, and nutrition. Data from the 2010,2015 and 2020 Rwanda Demographic and Health Surveys (RDHS) were used. The study involved 17,747 women between the ages of 15 and 49 who had a single live birth and at least one ANC visit in five years prior to each survey. Bivariate and multivariable logistic regression, a survey adjusted for clusters at multiple level, and the estimation of adjusted odds ratios (aOR) and 95% confidence intervals were used to evaluate the relationship between the outcome and independent variables. Results Out of 17,747 women ;7638(42.91%) of the mothers had adequate ANC visits and low birth weight (LBW) was found among 833(4.63%) neonates. The birth of a LBW baby (aOR:4.64;95%CI:3.19,6.74) was directly related to increased odds of neonatal death. Mothers aged 20–34 years (aOR:0.40; 95%CI:0.20,0.81), a preceding birth interval of 24months or greater (aOR:0.41:95%CI:0.28,0.60), baby being female (aOR:0.72; 95%CI:0.54,0.96), having adequate ANC visits (aOR:0.64;95% CI:0.46,0.89) and the birth order of the newborn being ranked second or third (aOR:0.60; 95%CI:0.38,0.95) were negatively associated with neonatal death. Conclusion Health education programs targeting teen and primigravida mothers should be encouraged. Among the newborn survival interventions, addressing short birth intervals and the effective management of LBW cases should be explored. The findings confirm the fundamental importance of adequate ANC in the neonatal survival.

Abstract In this paper, we investigate the gravitational lensing effects in the weak and strong field limits of a static black hole with conformally coupled scalar field. In the weak field limit, with the use of Gauss–Bonnet theorem we calculate the deflection angle of the light. It is found that comparing to Schwarzschild and Reissner–Nordstr $$\ddot{\text {o}}$$ o ¨ m (RN) black holes in general relativity, the weak deflection angle can be enhanced/suppressed by the scalar hair. In the strong field limit, we first compute the light deflection angle via calculating the lensing coefficients, all of which increase as the values of electric and scalar charges increase. Then we evaluate the lensing observables in strong field regime by supposing the hairy black hole as the candidate of M87* and SgrA* supermassive black holes, respectively. We find that the scalar hair has significant influences on various observables. In particular, the lensing observables of the charged black hole with positive scalar hair and RN black hole have degeneracy, which will be broken by the case with negative scalar hair. Our theoretical findings imply that it is feasible to employ the gravitational lensing effects as a probe of Einstein–Maxwell theory with negative scalar field differentiating from general relativity, once the future astrophysical observation is precise enough.

Abstract C-type lectin (CTL) is a protein that binds to saccharides and plays an important role in parasite adhesion, host cell invasion and immune evasion. Previous studies showed that recombinant T. spiralis C-type lectin (rTsCTL) promotes larval invasion of intestinal epithelium cells (IEC), whereas anti-rTsCTL antibodies inhibits larval invasion. Syndecan-1 (SDC-1) is a member of the heparan sulfate proteoglycan family which is mainly expressed on the surface of IEC and in extracellular matrices where they interact with a plethora of ligands. SDC-1 has a principal role in maintaining cell morphogenesis, establishing cell–cell adhesions, and regulating the gut mucosal barrier. The aim of this study was to investigate whether rTsCTL binds to SDC-1 on IEC, and the binding of rTsCTL with SDC-1 promotes larval invasion and its mechanism. IFA results show that rTsCTL and SDC-1 co-localized on Caco-2 cell membrane. GST pull-down and Co-IP verified the direct interaction between rTsCTL and SDC-1 on Caco-2 cells. qPCR and Western blotting revealed that rTsCTL binding to SDC-1 increased the expression of SDC-1 and claudin-2, and reduced the expression of occludin and claudin-1 in Caco-2 cells incubated with rTsCTL via the STAT3 pathway. β-Xyloside (a syndecan-1 synthesis inhibitor) and Stattic (a STAT3 inhibitor) significantly inhibited rTsCTL binding to syndecan-1 in Caco-2 cells and activation of the STAT3 pathway, abrogated the effects of rTsCTL on the expression of gut tight junctions, and impeded larval invasion. The results demonstrate that binding of rTsCTL to SDC-1 on Caco-2 cells activated the STAT3 pathway, decreased gut tight junction expression, damaged the integrity of the gut epithelial barrier, and mediated T. spiralis invasion of the gut mucosa. TsCTL might be regarded as a candidate vaccine target against T. spiralis invasion and infection.

Abstract The behaviour analysis of farmers is very important to gradually improve the sustainable production capacity of the land and promote the economics reasonable increasement. How to effectively extract video features and identify human behaviour is a current research hotspot. In this paper, the authors propose a convolutional neural network model based on the deformable convolution including a residual module and an attention module. The model fuses and encodes video spatial features on the time axis and extracts semantic information. The authors combine the attention mechanism to extract local and global features in the video, which are used to calculate spatial features and micro‐motion features, respectively. Temporal attention mechanism fuses each micro‐motion feature of video to extract higher‐level semantic features of motion. Next, the authors describe their proposed model based on deep learning. First, the authors introduce a video frame sampling method based on the TRN algorithm. Second, they design a feature extraction and fusion model based on the ResNet model and the attention mechanism that extract local and global features in videos. Finally, the authors classify and identify the extracted video features through the classifier. The authors’ approach shows comparable performance on publicly available datasets.

In order to enhance the stability of the power grid and increase the ability of the power grid to absorb photovoltaic energy, while enriching the prediction model of photovoltaic power generation, improve the precision reading of the prediction model. This paper proposes a short-term forecasting model of photovoltaic power generation based on K-means++clustering- Snake Optimizer algorithm (SO) - Gate Recurrent Unit(GRU). First, Pearson correlation coefficient analysis is used to screen out variables that are not related to the actual output of power generation.Then, select historical data with similar weather fluctuation degree as the training sample through K-means++clustering, use SO algorithm to optimize the parameters of GRU network, and use the optimized GRU network to predict photovoltaic power generation, Finally, through the simulation of a photovoltaic power station in Beijing, the results show that the prediction model proposed in this paper has improved the prediction accuracy compared with other traditional prediction models when the weather is almost no fluctuation, the weather has some fluctuations and the weather fluctuation is very severe. This research can provide reference for energy storage research of integrated energy system.

This study aimed to explore the relationship between life events and non-suicidal self-injury (NSSI) in college students, as well as the mediating effect of sleep disturbances and psychotic-like experiences (PLEs). After excluding invalid questionnaires, 5,754 were retained, and the valid efficiency was 75.94%. The subjects were aged 16 to 29 years (M = 19.166; SD = 1.392), with 1,969 males (34.22%) and 3,785 females (65.78%). Life events, sleep disturbances, PLEs, and NSSI were assessed using standard scales. Data were analyzed by Pearson Correlation Analysis and bias-correction percentile Bootstrap method. The results show that (1) life events were significant positive predictors of NSSI, sleep disturbances, and PLEs; (2) sleep disturbances, PLEs, and the chain mediation between the two, were mediators between life events and NSSI. Life events are thus shown to be an important external factor influencing NSSI in university students, and this process is mediated through sleep disturbances, PLEs, and the chain between the two. Interventions for NSSI can therefore be made by improving college students’ sleep quality and reducing PLEs.

Transglutaminase (TGase) was added to soy protein isolate (SPI) dispersion after the combination treatment of high intensity ultrasound (HIU) and high hydrostatic pressure (HHP) to catalyze the formation of cold gel, which was used to encapsulate riboflavin. The structure, physicochemical properties and in vitro digestion characteristics of riboflavin-loaded SPI cold gel were investigated. HIU-HHP combined treatment enhanced the strength, water retention, elastic property, thermal stability and protein denaturation degree of riboflavin-loaded SPI cold gels, and improved the gel network structure, resulting in a higher encapsulation efficiency of riboflavin and its chemical stability under heat and light treatment. HIU-HHP combined treatment reduced the erosion and swelling of SPI cold gel in simulated gastrointestinal fluid, and improved the sustained release effect of SPI gel on riboflavin by changing the digestion mode and rate of gel. In addition, HIU-HHP combined treated gels promoted the directional release of riboflavin in the simulated intestinal fluid, thereby improving its bioaccessibility, which was related to the secondary structure orderliness, tertiary conformation tightness and aggregation degree of protein during the gastrointestinal digestion. Therefore, HIU-HHP combined treatment technology had potential application value in improving the protection, sustained/controlled release and delivery of SPI cold gels for sensitive bioactive compounds.

The posttranslational N-glycosylation of food proteins is important to their structure and function. However, the N-glycoproteomics of yellow preserved egg white were rarely reported. This study explored the changes of N-glycoproteome in yellow preserved eggs white after salt and alkali treatment. A total of 213 N-glycosites were identified on 102 glycoproteins, revealing prevalent glycosylation motifs and multiple N-glycosites within proteins. Salt and alkali treatment significantly altered the glycosylation patterns, impacting major proteins differently. GO analysis indicated the roles of differentially expressed glycoproteins in responding to stimuli and biological regulation. KEGG analysis emphasized the importance of salivary secretion pathway in enzyme secretion and peptide generation. Protein domain analysis highlighted the downregulation of Serpin. Protein-protein interaction networks revealed Apolipoprotein B as central players. This study provides essential structural information on the glycosylation modifications of egg white proteins, contributing to our understanding of the mechanisms behind the functional properties of preserved eggs.

BackgroundCross-sectional evidence suggests that persistently short or long sleep duration is associated with sensory impairment. Thus, this study was conducted to investigate the associations between sleep duration and altered sleep duration with sensory impairment in Chinese older adults.MethodsLongitudinal data (2008–2014) obtained through the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were analyzed. Sleep duration was classified as normal (7–8 h), short (

We investigated the effect of melatonin on bisphenol A (BPA)-induced oxidative stress damage in testicular tissue and Leydig cells. Mice were gavaged with 50 mg/kg BPA for 30 days, and concurrently, were injected with melatonin (10 mg/kg and 20 mg/kg). Leydig cells were treated with 10 μmol/L of BPA and melatonin. The morphology and organ index of the testis and epididymis were observed and calculated. The sperm viability and density were determined. The expressions of melatonin receptor 1A and luteinizing hormone receptor, and the levels of malonaldehyde, antioxidant enzymes, glutathione, steroid hormone synthases, aromatase, luteinizing hormone, testosterone, and estradiol were measured. TUNEL assay was utilized to detect testicular cell apoptosis. The administration of melatonin at 20 mg/kg significantly improved the testicular index and epididymis index in mice treated with BPA. Additionally, melatonin promoted the development of seminiferous tubules in the testes. Furthermore, the treatment with 20 mg/kg melatonin significantly increased sperm viability and sperm density in mice, while also promoting the expressions of melatonin receptor 1A and luteinizing hormone receptor in Leydig cells of BPA-treated mice. Significantly, melatonin reduced the level of malonaldehyde in testicular tissue and increased the expression of antioxidant enzymes (superoxide dismutase 1, superoxide dismutase 2, and catalase) as well as the content of glutathione. Moreover, melatonin also reduced the number of apoptotic Leydig cells and spermatogonia, aromatase expression, and estradiol level, while increasing the expression of steroid hormone synthases (steroidogenic acute regulatory protein, cytochrome P450 family 17a1, cytochrome P450 17α-hydroxylase/20-lyase, and, 17β-hydroxysteroid dehydrogenase) and the level of testosterone. Melatonin exhibited significant potential in alleviating testicular oxidative stress damage caused by BPA. These beneficial effects may be attributed to melatonin’s ability to enhance the antioxidant capacity of testicular tissue, promote testosterone synthesis, and reduce testicular cell apoptosis.

Canine parvovirus (CPV) is one of the most common lethal viruses in canines. The virus disease is prevalent throughout the year, with high morbidity and mortality rate, causing serious harm to dogs and the dog industry. Previously, yeast two hybrid method was used to screen the protein chaperonin containing TCP-1 (CCT7) that interacts with VP2. However, the mechanism of interactions between CCT7 and VP2 on CPV replication remains unclear. In this study, we first verified the interaction between CCT7 and viral VP2 proteins using yeast one-to-one experiment and co-immunoprecipitation (CoIP) experiment. Laser confocal microscopy observation showed that CCT7 and VP2 were able to co-localize and were mostly localized in the cytoplasm. In addition, the study of VP2 truncated mutant found that the interaction region of VP2 with CCT7 was located between amino acids 231 and 320. Cycloheximide (CHX) chase experiments showed that CCT7 can improve the stability of VP2 protein. After further regulation of CCT7 expression in F81 cells, it was found that the expression level of VP2 protein was significantly reduced after knocking down CCT7 expression by RNA interference (RNAi) or HSF1A inhibitor, and increased after overexpressing host CCT7. The study reveals the role of VP2 interacting protein CCT7 in the replication process of CPV, which could provide a potential target for the prevention and control of CPV.

Abstract Background Motor learning is essential for performing specific tasks and progresses through distinct stages, including the rapid learning phase (initial skill acquisition), the consolidation phase (skill refinement), and the stable performance phase (skill mastery and maintenance). Understanding the cortical activation dynamics during these stages can guide targeted rehabilitation interventions. Methods In this longitudinal randomized controlled trial, functional near‐infrared spectroscopy was used to explore the temporal dynamics of cortical activation in hand‐related motor learning. Thirty‐one healthy right‐handed individuals were randomly assigned to perform either easy or intricate motor tasks with their non‐dominant hand over 10 days. We conducted 10 monitoring sessions to track cortical activation in the right hemisphere (according to lateralization principles, the primary hemisphere for motor control) and evaluated motor proficiency concurrently. Results The study delineated three stages of nondominant hand motor learning: rapid learning (days 1 and 2), consolidation (days 3–7), and stable performance (days 8–10). There was a power‐law enhancement of motor skills correlated with learning progression. Sustained activation was observed in the supplementary motor area (SMA) and parietal lobe (PL), whereas activation in the right primary motor cortex (M1R) and dorsolateral prefrontal cortex (PFCR) decreased. These cortical activation patterns exhibited a high correlation with the augmentation of motor proficiency. Conclusions The findings suggest that early rehabilitation interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation (tDCS), could be optimally directed at M1 and PFC in the initial stages. In contrast, SMA and PL can be targeted throughout the motor learning process. This research illuminates the path for developing tailored motor rehabilitation interventions based on specific stages of motor learning. NEW and NOTEWORTHY In an innovative approach, our study uniquely combines a longitudinal design with the robustness of generalized estimating equations (GEEs). With the synergy of functional near‐infrared spectroscopy (fNIRS) and the Minnesota Manual Dexterity Test (MMDT) paradigm, we precisely trace the evolution of neural resources during complex, real‐world fine‐motor task learning. Centering on right‐handed participants using their nondominant hand magnifies the intricacies of right hemisphere spatial motor processing. We unravel the brain's dynamic response throughout motor learning stages and its potent link to motor skill enhancement. Significantly, our data point toward the early‐phase rehabilitation potential of TMS and transcranial direct current stimulation on the M1 and PFC regions. Concurrently, SMA and PL appear poised to benefit from ongoing interventions during the entire learning curve. Our findings carve a path for refined motor rehabilitation strategies, underscoring the importance of timely noninvasive brain stimulation treatments.

IntroductionWith an incidence rate as high as 46%-58%, hypoglycemia is a common complication of glycemic management among those suffering from type 2 diabetes mellitus(T2DM). According to preclinical research, hypoglycemia episodes may impair cognition by harming neurons. However, there is still controversy regarding the clinical evidence for the relationship between hypoglycemic events and the likelihood of cognitive impairment. Furthermore, little research has been done on the dose-response association between hypoglycemia incidents and the possibility of cognitive impairment. To address these knowledge gaps, the present research intends to update the comprehension of the association among hypoglycemic events and the risk of cognitive impairment and to clarify the correlation between dose and response by incorporating the most recent investigations.Method and analysisThis work has developed a protocol for a systematic review and meta-analysis that will examine, via a well-organized assessment of several databases, the relationship between the incidence of hypoglycemia and the probability of cognitive impairment. Observational studies investigating the connection between hypoglycemia episodes and cognitive impairment will be included. The databases that will be searched are PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), Cochrane Library, Embase, the China National Knowledge (CNKI), Wan Fang, the Chinese Science and Technology Periodical Database (VIP), and Du Xiu. Literature from the establishment of each database to December 2023 will be included in the search. Two researchers will independently screen the studies that satisfy the requirements for both inclusion and exclusion. A third researcher will be asked to mediate any disputes. The methodological caliber of the studies included will be assessed utilizing the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal method. With regard to GRADE, which stands for Grading of Recommendations, Assessment, Development, and Evaluation, the quality of the evidence will be evaluated. ROBIS Tool will be used to evaluate the risk of bias in the development of the systematic review. If the data is accessible, meta-analysis and dose-response curve analysis will be employed by Stata software. However, if the data does not allow for such analysis, a descriptive review will be performed.Discussion and conclusionHypoglycemic episodes may raise the likelihood of cognitive impairment, according to earlier investigations. This study will update the relevant evidence and explore the dose-response connection between hypoglycemic episodes and cognitive impairment. The results of this review will have significant effects on decision-making by individuals with diabetes, healthcare providers, and government policy institutions.Trial registrationProspero registration number: CRD42023432352.

BackgroundProteases secreted by Trichinella spiralis intestinal infective larvae (IIL) play an important role in larval invasion and pathogenesis. However, the mechanism through which proteases mediate larval invasion of intestinal epithelial cells (IECs) remains unclear. A novel T. spiralis trypsin (TsTryp) was identified in IIL excretory/secretory (ES) proteins. It was an early and highly expressed protease at IIL stage, and had the potential as an early diagnostic antigen. The aim of this study was to investigate the biological characteristics of this novel TsTryp, its role in larval invasion of gut epithelium, and the mechanisms involved.Methodology/principal findingTsTryp with C-terminal domain was cloned and expressed in Escherichia coli BL21 (DE3), and the rTsTryp had the enzymatic activity of natural trypsin, but it could not directly degrade gut tight junctions (TJs) proteins. qPCR and western blotting showed that TsTryp was highly expressed at the invasive IIL stage. Immunofluorescence assay (IFA), ELISA and Far Western blotting revealed that rTsTryp specifically bound to IECs, and confocal microscopy showed that the binding of rTsTryp with IECs was mainly localized in the cytomembrane. Co-immunoprecipitation (Co-IP) confirmed that rTsTryp bound to protease activated receptors 2 (PAR2) in Caco-2 cells. rTsTryp binding to PAR2 resulted in decreased expression levels of ZO-1 and occludin and increased paracellular permeability in Caco-2 monolayers by activating the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. rTsTryp decreased TJs expression and increased epithelial permeability, which could be abrogated by the PAR2 antagonist AZ3451 and ERK1/2 inhibitor PD98059. rTsTryp facilitated larval invasion of IECs, and anti-rTsTryp antibodies inhibited invasion. Both inhibitors impeded larval invasion and alleviated intestinal inflammation in vitro and in vivo.ConclusionsTsTryp binding to PAR2 activated the ERK1/2 pathway, decreased the expression of gut TJs proteins, disrupted epithelial integrity and barrier function, and consequently mediated larval invasion of the gut mucosa. Therefore, rTsTryp could be regarded as a potential vaccine target for blocking T. spiralis invasion and infection.

Several gestational weight gain (GWG) guidelines have been established based on monocenter or multicenter researches. We aimed to examine the associations between categories of GWG under the Institute of Medicine (IOM) recommendation guideline, the Chinese National Health Commission (NHC) guideline, and weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project and adverse birth outcomes. We used data from an antenatal micronutrient supplementation trial in rural western China between 2002 and 2006. Maternal weekly average GWG during the second and third trimesters was calculated and classified into inadequate, adequate and excessive GWG according to the IOM and NHC, respectively. Weight-gain-for-gestational-age z-scores derived from the INTERGROWTH-21st Project were grouped into three subgroups using two approaches: z-score percentile75th and z-score 1 SD. Infant birth weight and gestational age were measured using standard approaches. Generalized linear model with binomial family and logit link was applied to estimate the odds ratio (OR) and 95% confidential intervals (CI) for GWG categories and adverse birth outcomes. Among 1,239 women with normal weight (18.5 kg/m2 to 23.9 kg/m2) during early pregnancy, 18.0% and 34.2% were classified as adequate GWG according to IOM and NHC, respectively. Less than half of Chinese women reached optimal GWG by any recommendation guideline. According to NHC, excessive GWG showed a significant association with macrosomia (OR 3.75, 95% CI 1.03, 13.74), large-for-gestation-age (LGA) (OR 2.12, 95% CI 1.01, 4.45), and inadequate GWG was associated with post-term birth (OR 2.25, 95% CI 1.21, 4.16), compared with adequate GWG. Inappropriate GWG was associated with adverse birth outcomes even among women with normal weight during early pregnancy. The monitoring and interventions of weight status during pregnancy, especially for the second and third trimesters, are of great public health importance for optimal birth outcomes. Additionally, developing guideline of appropriate GWG ranges should account for the traits of regional population.

Abstract Snow cover over the Tibetan Plateau (TP)–the Third Pole of the earth has been recognized as a reliable signal of summer floods or droughts in East Asia (EA). The distribution of snow cover can be influenced by vegetation, however, the impacts of changes in cover of non-growing season vegetation–withered grass stem over TP on the climatic effects of snow cover remains poorly understood. Here, we showed that the relationship between TP winter snow cover (TPWSC) and EA summer precipitation (EASP) strengthened starting in the early 1990s but weakened after the early 2000s. The weakening of the TPWSC–EASP relationship was linked to the effects of vegetation cover increment (VCI) on winter and spring snow cover over the TP. A possible mechanism behind this linkage is that VCI leads to a shortened persistence of TPWSC anomalies and weakened surface diabatic heating anomalies in spring. Consequently, the influences of TP thermal forcing on the downstream atmospheric circulation in summer were altered, resulting in a different pattern of EASP anomalies. These findings highlight the importance of snow—vegetation feedback and its potential to alter the effectiveness of snow cover in seasonal climate prediction.

Abstract Background When prepubertal lambs are superovulated, the ovarian response to gonadotropin stimulation has great individual difference and the collected oocytes have lower developmental ability than that of adult ewes. Over the years, growth hormone (GH) has been used in assisted reproduction because it can improve the reproductive performance in humans and animals. However, the effect of GH on ovaries and oocytes of prepubertal lambs remains unclear. Methods Before and during follicle-stimulating hormone (FSH) superovulation of prepubertal lambs (4‒6-week-old), the lambs were treated with high (50 mg) or low dose (25 mg) of ovine GH in a long (5 days) or short (2 days) period. The recovered oocytes were used for in vitro maturation and fertilization, and several parameters of oocyte quality and development capacity were evaluated. The possible underlying mechanisms of GH action were explored by analysis of granulosa cell (GC) transcriptome, ovarian proteome and follicular fluid metabolome. Results Treatment of lambs with 50 mg GH over 5 days (long treatment) potentially promoted the response of lambs to superovulation and improved the development capacity of retrieved oocytes, consequently increasing the high quality embryo yield from lambs. A number of differently expressed genes or proteins were found in ovaries between GH-treated and untreated lambs. Cellular experiments revealed that GH reduced the oxidative stress of GCs and promoted the GC proliferation probably through activation of the PI3K/Akt signaling pathway. Finally, analysis of follicular fluid metabolome indicated that GH treatment altered the abundance of many metabolites in follicular fluid, such as antioxidants and fatty acids. Conclusions GH treatment has a beneficial role on function of lamb ovaries, which supports the development of follicles and oocytes and improves the efficiency of embryo production from prepubertal lambs.

We aimed to examine the effects of antibiotic and probiotic usage on the gut microbiota structure and the presence of antibiotic-resistance genes (ARGs) in infants during the first six months of life. Questionnaires and fecal samples were collected within three days of birth, two months, and six months to assess antibiotic and probiotic exposure. Gut microbiotas were sequenced via 16S rRNA, and ARGs were conducted by qPCR, including beta-lactam (mecA, blaTEM), tetracycline (tetM), fluoroquinolone (qnrS), aminoglycoside (aac(6′)-Ib), and macrolide (ermB). Infants were categorized by antibiotic and probiotic usage and stratified by delivery mode, microbial composition, and ARG abundances were compared, and potential correlations were explored. A total of 189 fecal samples were analyzed in this study. The gut microbiota diversity (Chao1 index) was significantly lower in the “only probiotics” (PRO) group compared to the “neither antibiotics nor probiotics” (CON) group at six months for the CS stratification (p = 0.029). Compositionally, the abundance of core genus Bifidobacterium_pseudocatenulatum was less abundant for the antibiotic during delivery (IAP) group than that in the CON group within the first three days (p = 0.009), while core genus Enterococcus_faecium was more abundant in the PRO than that in the CON group (p = 0.021) at two months. ARGs were highly detected, with Enterococcus hosting tetM and Escherichia associated with blaTEM within three days of birth, though no correlation was found between Bifidobacterium and ARGs. These findings emphasized the critical importance of carefully managing antibiotic and probiotic exposures in early life, with implications for promoting lifelong health through preserving a healthy infant gut ecosystem.

B355252 is a small molecular compound known for potentiating neural growth factor and protecting against neuronal cell death induced by glutamate in vitro and cerebral ischemia in vivo. However, its other biological functions remain unclear. This study aims to investigate whether B355252 suppresses neuroinflammatory responses and cell death in the brain. C57BL/6j mice were intraperitoneally injected with a single dosage of lipopolysaccharide (LPS, 1 mg/kg) to induce inflammation. B355252 (1 mg/kg) intervention was started two days prior to the LPS injection. The animal behavioral changes were assessed pre- and post-LPS injections. The animal brains were harvested at 4 and 24 h post-LPS injection, and histological, biochemical, and cytokine array outcomes were examined. Results showed that B355252 improved LPS-induced behavioral deterioration, mitigated brain tissue damage, and suppressed the activation of microglial and astrocytes. Furthermore, B355252 reduced the protein levels of key pyroptotic markers TLR4, NLRP3, and caspase-1 and inhibited the LPS-induced increases in IL-1β, IL-18, and cytokines. In conclusion, B355252 demonstrates a potent anti-neuroinflammatory effect in vivo, suggesting that its potential therapeutic value warrants further investigation.

Abstract Background The excessive consumption of take-out food has increased the risk of nutrition-related chronic diseases. Nutrition literacy (NL) is an important influencing factor of food choice. This study aimed to explore the relationship between nutrition literacy and take-out food consumption. Methods A cross-sectional study was conducted on 2130 college students in Bengbu, China. A self-reported questionnaire that included demographic information, lifestyle behavior, take-out food consumption, and nutrition literacy scale was used. Ordinal logistic regression models were used to analyze the association between nutrition literacy and take-out food consumption. Results Of the students surveyed, 61.5% consumed take-out food at least once a week. NL was significantly associated with the frequency of take-out food consumption ≥ 4 times/week (OR = 0.995, 95% CI = 0.990-1.000); the difference specifically was discovered for applying skills, interactive skills, and critical skills. Moreover, students with high level NL ate less (Spicy) hot pot (OR = 0.996, 95% CI = 0.992-1.000), but more vegetable and fruit salad (OR = 1.009, 95% CI = 1.002–1.015). Conclusions NL, especially in applying skills, interactive skills, and critical skills, is not only associated with consumption frequency of take-out food among college students, but also links with types of take-out food consumption. Our findings emphasize that targeted interventions on nutritional skills literacy should be needed to improve dietary behaviors for student’s good health.

Abstract The damage of wind turbines suffered from lightning strikes has been a key issue for the safe and reliable operation of wind farms. Accurate determination of the annual lightning flash number to a wind turbine is essential for designing proper lightning protection measures. The interaction of downward and multiple upward leaders (MULs) is studied in this paper, which also considers the stochastic nature and branched behaviour of the lightning attachment phenomenon. Firstly, with an improved stochastic lightning model, the relationship among the striking distance, the height of wind turbines and the return stroke current is established. Moreover, a modified method for predicting the annual lightning flash number strikes to a wind turbine is proposed. The simulation results show that the striking distance and the collection area not only depend on the return stroke current, but also on the height and blade angle. Besides, the comparations between the calculation results and field statistics indicate that the conventional electric geometry model is not satisfied with the need of lightning protection for wind turbines. Note that there is only a difference of 4% between the modified method and the observation value. These quantitative researches provide the guidance of calculation results for the optimization of the blade lightning protection system (LPS) design.

METRNL is a recently identified secreted protein with emerging functions. This study is to find major cellular source of circulating METRNL and to determine METRNL novel function. Here, we show METRNL is abundant in human and mouse vascular endothelium and released by endothelial cells using endoplasmic reticulum-Golgi apparatus pathway. By creating endothelial cell-specific Metrnl knockout mice, combined with bone marrow transplantation to produce bone marrow-specific deletion of Metrnl, we demonstrate that most of circulating METRNL (approximately 75%) originates from the endothelial cells. Both endothelial and circulating METRNL decrease in atherosclerosis mice and patients. By generating endothelial cell-specific Metrnl knockout in apolipoprotein E-deficient mice, combined with bone marrow-specific deletion of Metrnl in apolipoprotein E-deficient mice, we further demonstrate that endothelial METRNL deficiency accelerates atherosclerosis. Mechanically, endothelial METRNL deficiency causes vascular endothelial dysfunction including vasodilation impairment via reducing eNOS phosphorylation at Ser1177 and inflammation activation via enhancing NFκB pathway, which promotes the susceptibility of atherosclerosis. Exogenous METRNL rescues METRNL deficiency induced endothelial dysfunction. These findings reveal that METRNL is a new endothelial substance not only determining the circulating METRNL level but also regulating endothelial function for vascular health and disease. METRNL is a therapeutic target against endothelial dysfunction and atherosclerosis.

Summary: KRAS mutations are frequently detected in non-small cell lung cancers (NSCLCs). Although covalent KRASG12C inhibitors have been developed to treat KRASG12C-mutant cancers, effective treatments are still lacking for other KRAS-mutant NSCLCs. Thus, identifying a KRAS effector that confers poor prognosis would provide an alternative strategy for the treatment of KRAS-driven cancers. Here, we show that KRAS drives expression of deubiquitinase USP13 through Ras-responsive element-binding protein 1 (RREB1). Elevated USP13 promotes KRAS-mutant NSCLC metastasis, which is associated with poor prognosis in NSCLC patients. Mechanistically, USP13 interacts with and removes the K63-linked polyubiquitination of β-catenin at lysine 508, which enhances the binding between β-catenin and transcription factor TCF4. Importantly, we identify 2-methoxyestradiol as an effective inhibitor for USP13 from a natural compound library, and it could potently suppress the metastasis of KRAS-mutant NSCLC cells in vitro and in vivo. These findings identify USP13 as a therapeutic target for metastatic NSCLC with KRAS mutations.

IntroductionFindings based on the use of transcranial magnetic stimulation and electromyography (TMS-EMG) to determine the effects of motor lateralization and aging on intracortical excitation and inhibition in the primary motor cortex (M1) are inconsistent in the literature. TMS and electroencephalography (TMS-EEG) measures the excitability of excitatory and inhibitory circuits in the brain cortex without contamination from the spine and muscles. This study aimed to investigate the effects of motor lateralization (dominant and non-dominant hemispheres) and aging (young and older) and their interaction effects on intracortical excitation and inhibition within the M1 in healthy adults, measured using TMS-EMG and TMS-EEG.MethodsThis study included 21 young (mean age = 28.1 ± 3.2 years) and 21 older healthy adults (mean age = 62.8 ± 4.2 years). A battery of TMS-EMG measurements and single-pulse TMS-EEG were recorded for the bilateral M1.ResultsTwo-way repeated-measures analysis of variance was used to investigate lateralization and aging and the lateralization-by-aging interaction effect on neurophysiological outcomes. The non-dominant M1 presented a longer cortical silent period and larger amplitudes of P60, N100, and P180. Corticospinal excitability in older participants was significantly reduced, as supported by a larger resting motor threshold and lower motor-evoked potential amplitudes. N100 amplitudes were significantly reduced in older participants, and the N100 and P180 latencies were significantly later than those in young participants. There was no significant lateralization-by-aging interaction effect in any outcome.ConclusionLateralization and aging have independent and significant effects on intracortical excitation and inhibition in healthy adults. The functional decline of excitatory and inhibitory circuits in the M1 is associated with aging.