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Abstract Background Cognitive impairment is common in chronic schizophrenia patients. The purpose of this study was to explore the efficacy of Shen-based Qigong Exercise (SBQE) in improving the cognitive impairment of stable schizophrenia patients in rehabilitation wards. Methods SBQE is derived from the theory of “body-spirit syncretism (xin shen he yi)” in traditional Chinese medicine (TCM) and is extracted from the four traditional Qigong techniques. In this 12-week, randomized, single-blind, controlled study, a total of 40 schizophrenia patients were randomly assigned to either the SBQE group or the control group. The scores for the Scale for the Assessment of Negative Symptoms (SANS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were recorded at baseline and week 12, respectively. Results At week 12, the mean RBANS total score was 84.5 points in the SBQE group and 72.8 points in the control group. The estimated mean difference was − 11.60 points (2-sided 95% CI, -22.41 to -0.79; P = 0.04). This difference was statistically significant (time-by-group interaction effect estimates, F(1,38) = 5.07; P = 0.03). Conclusions Our preliminary findings indicated that SBQE led to an improvement in cognitive impairment in stable schizophrenia patients in rehabilitation wards. Further research with robust design and larger sample sizes is necessary to validate the effects of SBQE on cognitive function and psychiatric symptoms in schizophrenia, thus providing more substantial evidence for the clinical application of SBQE. Trial registration ClinicalTrials.gov Identifier: NCT05310955 on 22/02/2022; http://www.chictr.org.cn/ Identifier: ChiCTR2200057373 on 10/03/2022.

Abstract To let water jets land at the fire, pitch angle of the fire monitor has to be adjusted manually with successive rounds, which seriously affects the efficiency of fire extinguishing. To improve the efficiency, this paper proposes a technology for water jet trajectory modeling and landing point prediction to help with extinguishing automatically. Considering fragmentation and atomization of water jets, trajectories are analyzed and the predicted trajectory is closer to the real situation. Secondly, a compensation method for the prediction is proposed to further reduce the deviation between the predicted and the actual landing point, taking into account the combined effects of high altitude, initial jet velocity, and wind. On this basis, considering the difficulty of directly solving the analytical solution to the target initial pitch angle of the jets, a searching method is also proposed, which greatly improves the solving efficiency. Finally, through practical experiments and verification, the proposed model takes an average time of 0.00292 s, which is far less compared with other methods. The prediction error is improved by at least 45.3%, and the average deviation is less than 2 m.

Abstract The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD–ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.

Abstract Background Malnutrition is common in older patients with chronic heart failure (HF) and often accompanies a deterioration of their condition. The Controlling Nutritional Status (CONUT) score is used as an objective indicator to evaluate nutritional status, but relevant research in this area is limited. This study aimed to report the prevalence, clinical correlates, and outcomes of malnutrition in elder patients hospitalized with chronic HF. Methods A retrospective analysis was conducted on 165 eligible patients admitted to the Department of Cardiology at Huadong Hospital from January 2021 to December 2022. Patients were categorized based on their CONUT score into three groups: normal nutrition status, mild risk of malnutrition, and moderate to severe risk of malnutrition. The study examined the nutritional status of this population and its relationship with clinical outcomes. Results Findings revealed that malnutrition affected 82% of the older patients, with 28% experiencing moderate to severe risk. Poor nutritional scores were significantly associated with prolonged hospital stay, increased in-hospital mortality and all-cause mortality during readmissions within one year (P

Abstract Objective This study aimed to examine the correlation between preoperative body mass index (BMI) and adequate percentage of total weight loss (TWL%) outcome and present evidence of tiered treatment for patients with obesity in different preoperative BMI. Methods We included patients with complete follow-up data who underwent metabolic and bariatric surgery (BMS). We termed optimal clinical response as TWL% >20% at one year following MBS. To investigate dose-response association between preoperative BMI and optimal clinical response, preoperative BMI was analyzed in three ways: (1) as quartiles; (2) per 2.5 kg/m2 units (3) using RCS, with 3 knots as recommended. Results A total of 291 patients with obesity were included in our study. The corresponding quartile odds ratios associated with optimal clinical response and adjusted for potential confounders were 1.00 (reference), 1.434 [95% confidence interval (95%CI) = 0.589–3.495], 4.926 (95%CI = 1.538–15.772), and 2.084 (95%CI = 0.941–1.005), respectively. RCS analysis showed a non-linear inverted U-shaped association between preoperative BMI and optimal clinical response (Nonlinear P = 0.009). In spline analysis, when preoperative BMI was no less than 42.9 kg/m2, the possibility of optimal clinical response raised as preoperative BMI increased. When preoperative BMI was greater than 42.9 kg/m2, the possibility of optimal clinical response had a tendency to decline as preoperative BMI increased. Conclusion Our research indicated the non-linear inverted U-shaped correlation between preoperative BMI and adequate weight loss. Setting a preoperative BMI threshold of 42.9 is critical to predicting optimal clinical outcomes.

Objective: Characterized by its disabling nature, obsessive compulsive disorder (OCD) affects individuals profoundly, with nearly 40% of patients showing resistance to initial treatment methods. Despite being safe and easily accessible, transcranial direct current stimulation (tDCS) lacks extensive substantiation supporting its efficacy in treating OCD. The objective of this study was to evaluate how cathodal high-definition transcranial direct current stimulation (HD-tDCS) applied to the right orbitofrontal cortex affected patients with OCD in terms of efficacy. Method: 47 patients with OCD were enrolled. They were randomly allocated to active or sham stimulation groups, and underwent HD-tDCS stimulation treatment for 2 weeks. The central electrode located in the right orbitofrontal cortex region was cathodic. The severity of the patients' obsessive-compulsive symptoms, depression and anxiety were assessed before and after treatment. Result: Out of the total, 44 patients concluded the treatment, comprising 23 participants from the active stimulation group and 21 from the sham stimulation group. Notably, substantial reductions in symptoms related to OCD, depression, and anxiety were exhibited in both groups. With a response rate of 26.1% in the active stimulation group and 23.8% in the sham stimulation group, there was no significant difference in efficacy observed. Furthermore, the reduction in depression and anxiety symptoms at the conclusion of the treatment was not notably superior in the active stimulation group. Conclusion: This study provided evidence for the acceptability and safety of HD-tDCS. Nevertheless, the study did not reveal notable clinical effectiveness of tDCS in addressing moderate to severe OCD in comparison to the sham stimulation group.

Abstract Objective To investigate the effects of bracing on apical vertebral derotation and explore the factors that influence in-brace derotation effects in adolescent idiopathic scoliosis (AIS) patients. Summary of background data For patients with AIS, vertebral rotation causes cosmetic appearance abnormalities and acts as an indicator for curve progression. However, there have been few studies investigating the precise derotation effects of bracing for apical vertebra. The application of EOS imaging system enables quantitative evaluation of vertebral rotation in the axial plane in a standing position. Methods There were 82 eligible patients enrolled in current study, who underwent EOS imaging evaluation before and immediately after bracing. The clinical demographic data (age, gender, Risser sign and menstrual status) were recorded. The correlation analyses between derotation effects and key parameters (age, pre-brace Cobb angle, thoracic kyphosis, lumbar lordosis, vertebral rotation, pelvis axial rotation and apical vertebral level) were performed. The in-brace derotation effects stratified by gender, Risser sign, apical vertebral level, menarche status, coronal balance and sagittal balance were also analyzed. Results The rotation of apical vertebra was decreased from 8.8 ± 6.0 degrees before bracing to 3.8 ± 3.3 degrees immediately after bracing (p

ABSTRACT Neurotropic alphaherpesviruses, including herpes simplex virus type 1 and pseudorabies virus, establish a lifelong presence within the peripheral nervous system of their mammalian hosts. Upon entering cells, two conserved tegument proteins, pUL36 and pUL37, traffic DNA-containing capsids to nuclei. These proteins support long-distance retrograde axonal transport and invasion of the nervous system in vivo. To better understand how pUL36 and pUL37 function, recombinant viral particles carrying BioID2 fused to these proteins were produced to biotinylate cellular proteins in their proximity (

Objective: Chronic wounds are costly and difficult to treat, resulting in morbidity and even mortality in some cases due to a high methicillin-resistant Staphylococcus aureus (MRSA) burden contributing to chronicity. We aimed to observe the antimicrobial activity and healing-promoting effect of a novel photosensitizer Shengtaibufen (STBF)-mediated antibacterial photodynamic therapy (PDT) on MRSA-infected chronic leg ulcers. Patients and methods: This was a retrospective, comparative, single-center clinical study. A total of 32 patients with chronic lower limb wounds infected with MRSA from January 2022 to December 2023 were finally included in this study by searching the electronic medical records of the dermatology department of Huadong Hospital, including a group of red light combined with iodophor (control+iodophor, n=16, receiving red light once a week for 8 weeks and routine dressing change with iodophor once a day) and a group of STBF-mediated PDT (STBF-PDT) combined with iodophor (STBF-PDT+iodophor, n=16, receiving STBF-PDT and routine dressing change with iodophor once a day). STBF-PDT was performed once a week (1 mg/ml STBF, 1 h incubation, 630 nm red light, 80 J/cm2) for 8 weeks. The primary endpoints included wound clinical signs, wound size, wound-related pain, re-epithelialization score, MRSA load and wound-related quality of life (wound-QoL). Any adverse events were also recorded. Results: We found that STBF-PDT+iodophor could effectively alleviate clinical infection symptoms, accelerate wound closure, reduce average biological burden and improve wound-QoL without severe adverse events in comparison to the control+iodophor group. The STBF-PDT+iodophor group obtained a mean percentage reduction of 65.22% in wound size (from 18.96±11.18 cm2 to 6.59±7.94 cm2) and excellent re-epithelialization scores, as compared with a decrease of 30.17% (from 19.23±9.80 cm2 to 13.43±9.32 cm2) for the control+iodophor group. Significant differences in wound area were observed at week 6 (p=0.028*) and week 8 (p=0.002**). The bacterial load decreased by 99.86% (from 6.45 × 107±2.69 × 107 to 8.94 × 104±1.92 × 105 CFU/cm2, p

H5, H7, and H9 are pivotal avian influenza virus (AIV) subtypes that cause substantial economic losses and pose potential threats to public health worldwide. In this study, a novel triplex fluorescence reverse transcription-loop-mediated isothermal amplification (TLAMP) assay was developed in which traditional LAMP techniques were combined with probes for detection. Through this innovative approach, H5, H7, and H9 subtypes of AIV can be simultaneously identified and differentiated, thereby offering crucial technical support for prevention and control efforts. Three primer sets and composite probes were designed based on conserved regions of the haemagglutinin gene for each subtype. The probes were labelled with distinct fluorophores at their 3′ ends, which were detached to release the fluorescence signal during the amplification process. The detection results were interpreted based on the colour of the TLAMP products. Then, the reaction conditions were optimized, and three primer sets and probes were combined in the same reaction system, resulting in a TLAMP detection assay for the differential diagnosis of AIV subtypes. Sensitivity testing with in vitro-transcribed RNA revealed that the detection limit of the TLAMP assay was 205 copies per reaction for H5, 360 copies for H7, and 545 copies for H9. The TLAMP assay demonstrated excellent specificity, no cross-reactivity with related avian viruses, and 100% consistency with a previously published quantitative polymerase chain reaction (qPCR) assay. Therefore, due to its simplicity, rapidity, sensitivity, and specificity, this TLAMP assay is suitable for epidemiological investigations and is a valuable tool for detecting and distinguishing H5, H7, and H9 subtypes of AIV in clinical samples.

Starting in 2015, the widespread prevalence of hydropericardium-hepatitis syndrome (HHS) has led to considerable financial losses within China’s poultry farming industry. In this study, pathogenicity assessments, whole-genome sequencing, and analyses were conducted on 10 new isolates of the novel genotype FAdV-4 during a HHS outbreak in Guangxi Province, China, from 2019 to 2020. The results indicated that strains GX2019-010 to GX2019-013 and GX2019-015 to GX2019-018 were highly virulent, while strain GX2020-019 exhibited moderate virulence. Strain GX2019-014 was characterized as a wild-type strain with low virulence, displaying no pathogenic effects when 0.5 mL containing 106 TCID50 virus was inoculated into the muscle of specific pathogen-free (SPF) chickens at 4 weeks of age, while 107 TCID50 and 108 TCID50 resulted in mortality rates of 80 and 100%, respectively. The whole genomes of strains GX2019-010 to GX2019-013, GX2019-015 to GX2019-018, and GX2020-019 showed high homology with other Chinese newly emerging highly pathogenic FAdV-4 strains, whereas GX2019-014 was closer to nonmutant strains and shared the same residues with known nonpathogenic strains (B1-7, KR5, and ON1) at positions 219AA and 380AA of the Fiber-2 protein. Our work enriches the research on prevalent strains of FAdV-4 in China, expands the knowledge on the virulence diversity of the novel genotype FAdV-4, and provides valuable reference material for further investigations into the key virulence-associated genetic loci of FAdV-4.

Abstract An enzyme-free sandwich amperometric immunosensor based on bimetallic Pt/Ag nanoparticle (Pt/AgNPs)-functionalized chitosan (Chi)-modified multiwalled carbon nanotubes (MWCNTs) as dual signal amplifiers and Chi-modified MWCNTs (MWCNTs-Chi) as substrate materials was developed for ultrasensitive detection of fowl adenovirus group I (FAdV-I). MWCNTs have a large specific surface area, and many accessible active sites were formed after modification with Chi. Hence, MWCNTs-Chi, as a substrate material for modifying glassy carbon electrodes (GCEs), could immobilize more antibodies (fowl adenovirus group I-monoclonal antibody, FAdV-I/MAb). Multiple Pt/AgNPs were attached to the surface of MWCNTs-Chi to generate MWCNTs-Chi-Pt/AgNPs with high catalytic ability for the reaction of H2O2 and modified active sites for fowl adenovirus group I-polyclonal antibody (FAdV-I/PAb) binding. Amperometric i–t measurements were employed to characterize the recognizability of FAdV-I. Under optimal conditions, and the developed immunosensor exhibited a wide linear range (100.93 EID50 mL−1 to 103.43 EID50 mL−1), a low detection limit (100.67 EID50 mL−1) and good selectivity, reproducibility and stability. This immunosensor can be used in clinical sample detection.

Abstract Background In the past quite a long time, intraoperative cholangiography(IOC)was necessary during laparoscopic cholecystectomy (LC). Now magnetic resonance cholangiopancreatography (MRCP) is the main method for diagnosing common bile duct stones (CBDS). Whether MRCP can replace IOC as routine examination before LC is still inconclusive. The aim of this study was to analyze the clinical data of patients undergoing LC for cholecystolithiasis, and to explore the necessity and feasibility of preoperative routine MRCP in patients with cholecystolithiasis. Methods According to whether MRCP was performed before operation, 184 patients undergoing LC for cholecystolithiasis in the Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University from January 1, 2017 to December 31, 2018 were divided into non-MRCP group and MRCP group for this retrospective study. The results of preoperative laboratory test, abdominal ultrasound and MRCP, biliary related comorbidities, surgical complications, hospital stay and hospitalization expenses were compared between the two groups. Results Among the 184 patients, there were 83 patients in non-MRCP group and 101 patients in MRCP group. In MRCP group, the detection rates of cholecystolithiasis combined with CBDS and common bile duct dilatation by MRCP were higher than those by abdominal ultrasound (P 0.05), but there was significant difference in hospitalization expenses (P 0.05). Conclusions The preoperative MRCP can detect CBDS, cystic duct stones and anatomical variants of biliary tract that cannot be diagnosed by abdominal ultrasound, which is helpful to plan the surgical methods and reduce the surgical complications. From the perspective of health economics, routine MRCP in patients with cholecystolithiasis before LC does not increase hospitalization costs, and is necessary and feasible.

Mobile phone dependence (also known as internet dependence, MPD), defined as a problematic behavior characterized by excessive use or intermittent craving to use a mobile phone, results in various social, behavioral, and affective problems in daily life. In sports, MPD is directly related to the physical and mental health and sports performance of athletes. The individual and environmental factors, neurobiological mechanisms and theoretical models of MPD affecting athletic performance were analyzed by reviewing previous studies, aiming to construct effective training and development protocols to prevent and control the occurrence of MPD in athletes. At present, athletic performance can be affected by MPD through individual factors and environmental factors. The neurobiological mechanisms between the two are based on the brain reward system and microwave radiation from mobile phones, with athletic performance being restricted by alterations in the corresponding brain regions. Relevant theoretical models mainly include the social cognitive model of self-regulation and the integrative model of self-control, which explain the interrelationship between MPD and athletic performance from the perspectives of athletes’ self-regulation and self-control, respectively. As an emerging phenomenon, the influence pathways and mechanisms by which MPD affects athletic performance need to be further investigated. A longitudinal perspective should be adopted to trace the dynamic impact relationship between the two, and developing relevant theoretical frameworks from an interdisciplinary research perspective should be valuable for providing theoretical support for coaches and sports administrators to formulate scientific training protocols and thus improve the mental health of athletes.

Background: Mindfulness-based cognitive therapy (MBCT) has been documented to be effective in treating obsessive-compulsive disorder (OCD). However, the neurobiological basis of MBCT remains largely elusive, which makes it clinically challenging to predict which patients are more likely to respond poorly. Hence, identifying biomarkers for predicting treatment outcomes holds both scientific and clinical values. This prognostic study aims to investigate whether pre-treatment brain morphological metrics can predict the effectiveness of MBCT, compared with psycho-education (PE) as an active placebo, among patients with OCD. Methods: A total of 32 patients with OCD were included in this prognostic study. They received magnetic resonance imaging (MRI) brain scans before treatment. Subsequently, 16 patients received 10 weeks of MBCT, while the other 16 patients underwent a 10-week PE program. The effectiveness of the treatments was primarily assessed by the reduction rate of the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score before and after the treatment. We investigated whether several predefined OCD-associated brain morphological metrics, selected based on prior published studies by the ENIGMA Consortium, could predict the treatment effectiveness. Results: Both the MBCT and PE groups exhibited substantial reductions in Y-BOCS scores over 10 weeks of treatment, with the MBCT group showing a larger reduction. Notably, the pallidum total volume was associated with treatment effectiveness, irrespective of the intervention group. Specifically, a linear regression model utilizing the pre-treatment pallidum volume to predict the treatment effectiveness suggested that a one-cubic-centimeter increase in pallidum volume corresponded to a 22.3% decrease in the Y-BOCS total score reduction rate. Conclusions: Pallidum volume may serve as a promising predictor for the effectiveness of MBCT and PE, and perhaps, other treatments with the shared mechanisms by MBCT and PE, among patients with OCD.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

IntroductionThoracolumbosacral orthosis (TLSO) is the most commonly used type of brace for the conservative treatment of adolescent idiopathic scoliosis (AIS). Although lumbosacral orthosis (LSO) is designed to correct single thoracolumbar or lumbar (TL/L) curves, its effectiveness remains underexplored. This novel article aims to compare the effectiveness of LSO with TLSO in treating AIS with main TL/L curves.MethodsThis prospective controlled cohort study enrolled patients with AIS with main TL/L curves and minor thoracic curves who were treated with either TLSO or LSO. Demographic and radiographic data were compared between the two groups. Treatment outcomes were also assessed. Risk factors for minor curve progression were identified, and a cut-off value was determined within the LSO group.ResultsOverall, 82 patients were recruited, including 44 in the TLSO group and 38 in the LSO group. The initial TL/L curves showed no difference between both groups. However, the baseline thoracic curves were significantly larger in the TLSO group compared to the LSO group (25.98° ± 7.47° vs. 18.71° ± 5.95°, P

Traditional drug screening methods typically focus on a single protein target and exhibit limited efficiency due to the multifactorial nature of most diseases, which result from disturbances within complex networks of protein–protein interactions rather than single gene abnormalities. Addressing this limitation requires a comprehensive drug screening strategy. Network medicine is rooted in systems biology and provides a comprehensive framework for understanding disease mechanisms, prevention, and therapeutic innovations. This approach not only explores the associations between various diseases but also quantifies the relationships between disease genes and drug targets within interactome networks, thus facilitating the prediction of drug–disease relationships and enabling the screening of therapeutic drugs for specific complex diseases. An increasing body of research supports the efficiency and utility of network-based strategies in drug screening. This review highlights the transformative potential of network medicine in virtual therapeutic screening for complex diseases, offering novel insights and a robust foundation for future drug discovery endeavors.

Abstract Avian parvoviruses cause several enteric poultry diseases that have been increasingly diagnosed in Guangxi, China, since 2014. In this study, the whole-genome sequences of 32 strains of chicken parvovirus (ChPV) and 3 strains of turkey parvovirus (TuPV) were obtained by traditional PCR techniques. Phylogenetic analyses of 3 genes and full genome sequences were carried out, and 35 of the Guangxi ChPV/TuPV field strains were genetically different from 17 classic ChPV/TuPV reference strains. The nucleotide sequence alignment between ChPVs/TuPVs from Guangxi and other countries revealed 85.2–99.9% similarity, and the amino acid sequences showed 87.8–100% identity. The phylogenetic tree of these sequences could be divided into 6 distinct ChPV/TuPV groups. More importantly, 3 novel ChPV/TuPV groups were identified for the first time. Recombination analysis with RDP 5.0 revealed 15 recombinants in 35 ChPV/TuPV isolates. These recombination events were further confirmed by Simplot 3.5.1 analysis. Phylogenetic analysis based on full genomes showed that Guangxi ChPV/TuPV strains did not cluster according to their geographic origin, and the identified Guangxi ChPV/TuPV strains differed from the reference strains. Overall, whole-genome characterizations of emerging Guangxi ChPV and TuPV field strains will provide more detailed insights into ChPV/TuPV mutations and recombination and their relationships with molecular epidemiological features.

Abstract Background Ziziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement. Methods Mice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients. Results ZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model (P

The expansion and intensification of human activities have resulted in excessive nitrogen (N) in rivers, causing worldwide concern. To effectively manage agricultural non-point source pollution and ensure a safe drinking water supply in watersheds, it is crucial to trace and quantify the primary sources and spatial distribution patterns of N. In response to the challenge of unclear sources and agricultural non-point source pollution, this study utilised the Bayesian isotope mixing model and Soil and Water Assessment Toolmodel to identify the dominant nitrate sources and transformation processes. These models were employed to quantify N retention by the mainstream and tributaries in the Bai River Basin, which directly impacts the safety of drinking water in Beijing. Total N (TN) concentrations in the Yunzhou Reservoir (4.22 ± 0.04 mg.L˗1) and Miyun Reservoir (2.88 ± 0.62 mg.L˗1) inlets in autumn and winter were V class (2 mg.L˗1) category as per GB 3838–2002 standards. This implies higher risks of eutrophication and algal blooms exceeding the standards at individual points and seasons in the Bai River. Fertilisers were the main nitrate source in the Bai River Basin, contributing 44.6% during the dry season and 62.9% during the wet season, suggesting that nitrate is more susceptible to leaching and runoff during rainy periods. Rainfall was not a major contributor, with only 3.2% and 2.9% originating from the Hebei and Beijing areas of the Bai River, respectively. Annually, the Bai River Basin exports loads of approximately 629.3 t.a˗1 of TN and 433.7 t.a˗1 of organic N (Org-N) from the Bai River Basin land to the river. The TN and Org-N loads at the final destination in the Miyun Reservoir were 521.3 t.a˗1 and 100.3 t.a˗1, respectively. Of the exported TN and Org-N, 17.16% and 76.87%, respectively, were retained in the river network. Consequently, N transformation occurred in the Bai River, with nitrification–denitrification being particularly dominant. Nitrification was more evident in the nitrate-enriched river.

Nitrite has the potential risk of hypoxic poisoning or cancer in pickled food. In our previous study, Limosilactobacillus fermentum (L. fermentum) RC4 is effective in nitrite degradation by producing nitrite reductase B (NirB). To investigate the detailed mechanism from the genome, response, and regulation of NirB, the whole-genome sequence of L. fermentum RC4 was analyzed, the L. fermentum-EGFP-nirB with enhanced green fluorescent protein (EGFP) labeled the nitrite reductase large subunit nirB, and the recombined L. fermentum-NirB with overexpression NirB strain was conducted. The key genes within the dominant metabolism pathways may be involved in stress tolerance to regulate the degrading process. The green fluorescence density of EGFP indicated that NirB activity has a threshold and peaked under 300 mg/L nitrite concentration. NirB overexpressed in L. fermentum RC4 boosted the enzyme activity by 39.6% and the degradation rate by 10.5%, when fermented in 300 mg/L for 40 h, compared to the control group. RNA-seq detected 248 differential genes mainly enriched in carbohydrate, amino acid, and energy metabolism. The ackA gene for pyruvate metabolism and the mtnN gene for cysteine metabolism were up-regulated. NirB regulates these genes to produce acid and improve stress resistance for L. fermentum RC4 to accelerate nitrite degradation.

Background Music therapy is a promising complementary intervention for addressing various mental health conditions. Despite evidence of the beneficial effects of music, the acoustic features that make music effective in therapeutic contexts remain elusive.Aims This study aimed to identify and validate distinctive acoustic features of healing music.Methods We constructed a healing music dataset (HMD) based on nominations from related professionals and extracted 370 acoustic features. Healing-distinctive acoustic features were identified as those that were (1) independent from genre within the HMD, (2) significantly different from music pieces in a classical music dataset (CMD) and (3) similar to pieces in a five-element music dataset (FEMD). We validated the identified features by comparing jazz pieces in the HMD with a jazz music dataset (JMD). We also examined the emotional properties of the features in a Chinese affective music system (CAMS).Results The HMD comprised 165 pieces. Among all the acoustic features, 74.59% shared commonalities across genres, and 26.22% significantly differed between the HMD classical pieces and the CMD. The equivalence test showed that the HMD and FEMD did not differ significantly in 9.46% of the features. The potential healing-distinctive acoustic features were identified as the standard deviation of the roughness, mean and period entropy of the third coefficient of the mel-frequency cepstral coefficients. In a three-dimensional space defined by these features, HMD’s jazz pieces could be distinguished from those of the JMD. These three features could significantly predict both subjective valence and arousal ratings in the CAMS.Conclusions The distinctive acoustic features of healing music that have been identified and validated in this study have implications for the development of artificial intelligence models for identifying therapeutic music, particularly in contexts where access to professional expertise may be limited. This study contributes to the growing body of research exploring the potential of digital technologies for healthcare interventions.

Introduction: Negative symptoms and cognitive impairment are common residual symptoms of schizophrenia that seriously affect the quality of life and social function of patients. The intervention of residual symptoms is an important part of schizophrenia rehabilitation. Traditional Chinese exercise has been applied as a supplementary rehabilitation method for schizophrenia. However, research on its use and pertinence in the rehabilitation of residual symptoms remains lacking. In this study, we will verify the intervention effect of a new method, namely, shen-based qigong exercise, on the residual symptoms of schizophrenia, in the hopes of finding a safe and effective rehabilitation method for the residual symptoms of schizophrenia. Methods: This is a single-centre randomised controlled trial. A total of 60 schizophrenics who meet the criteria will be randomly divided into the control and intervention groups in accordance with the ratio of 1:1. Conventional drug treatment will remain unchanged in both groups. In this case, the control group will be given daily rehabilitation, whereas the intervention group will be given daily rehabilitation and shen-based qigong exercise intervention. The intervention period will be 12 weeks. The primary outcome will be negative symptoms assessed by the Scale for the Assessment of Negative Symptoms. The secondary outcome will be the global cognitive function assessed by the Repeatable Battery for the Assessment of Neuropsychological Status and event-related potential P300. Other outcomes will include specific cognitive domain (i.e. working memory), quality of life and social function. The results will be measured within 1 week before and after the intervention. Discussion: The results of this study will likely help find an economical and convenient rehabilitation method for the residual symptoms of schizophrenia and, at the same time, may promote the popularisation and application of traditional Chinese exercises and traditional Chinese medicine theories in the treatment of mental diseases. Trial registration: ClinicalTrials.gov registry number: NCT05310955.

ABSTRACTWith the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Chicken parvovirus (ChPV) infection can cause runting-stunting syndrome (RSS) in chickens. There is currently no commercially available vaccine for controlling ChPV, and ChPV infection in chickens is widespread globally. The rapid detection of ChPV is crucial for promptly capturing epidemiological data on ChPV. Two monoclonal antibodies (mAbs), 1B12 and 2B2, against the ChPV NS1 protein were generated. A double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was developed for detecting ChPV based on the mAb 1B12 and an anti-chicken polyclonal antibody against the ChPV NS1 protein. The detection limit for the ChPV recombinant pET32a-NS1 protein was approximately 31.2 ng/mL. A total of 192 throat and cloaca swab samples were analyzed for ChPV by the established DAS-ELISA and nested PCR methods. The concordance rate between the DAS-ELISA and the nested PCR method was 89.1%. The DAS-ELISA can detect the ChPV antigen without any cross-reaction with FAdV-4, FAdV-1, NDV, AIV, MS, CIAV, aMPV, EDSV, IBV, or AGV2. The method also has high repeatability, with a coefficient of variation (CV) of less than 5%. These findings indicate that the DAS-ELISA exhibits high accuracy, good sensitivity, and specificity, making it suitable for viral detection, field surveillance, and epidemiological studies.

Apocynum venetum leaf is commonly utilized for its beneficial effects in reducing blood pressure, inducing sedation, promoting diuresis, anti-aging, and cardioprotection, which also exhibit positive effects on the gut microbiota. The gut microbiota plays a role as an endocrine organ by producing bioactive metabolites that can directly or indirectly impact host physiology, specifically cardiovascular diseases. In this study, main chemical components of A. venetum leaf extract (AVLE) were identified by LC-MS, and an orally administered AVLE was employed to treat mice with doxorubicin (Dox)-induced cardiotoxicity. The results showed that AVLE contained hyperoside and oganic acids. The pharmacological findings revealed that AVLE regulated the gut microbiota, resulting in a significant increase in the levels of two organic acids, indole-3-propionic acid (IPA) and acetic acid (AA). Both IPA and AA exhibited the ability to reduce BNP, CK, and LDH levels in mice with Dox-induced cardiotoxicity. Moreover, IPA demonstrated an improvement in Dox-induced cardiac injury by inhibiting apoptosis, while AA promoted increased secretion of ghrelin through the parasympathetic nervous system, subsequently reducing cardiac fibrosis by decreasing collagen I, collagen III, and activin A. Hence, our study demonstrates that AVLE exerts a beneficial cardioprotective effect by modulating the gut microbiota, providing a potential novel target for the treatment and prevention of Dox-induced cardiotoxicity.

Interferon-alpha inducible protein 6 (IFI6) is an important interferon-stimulated gene. To date, research on IFI6 has mainly focused on human malignant tumors, virus-related diseases and autoimmune diseases. Previous studies have shown that IFI6 plays an important role in antiviral, antiapoptotic and tumor-promoting cellular functions, but few studies have focused on the structure or function of avian IFI6. Avian reovirus (ARV) is an important virus that can exert immunosuppressive effects on poultry. Preliminary studies have shown that IFI6 expression is upregulated in various tissues and organs of specific-pathogen-free chickens infected with ARV, suggesting that IFI6 plays an important role in ARV infection. To analyze the function of avian IFI6, particularly in ARV infection, the chicken IFI6 gene was cloned, a bioinformatics analysis was conducted, and the roles of IFI6 in ARV replication and the innate immune response were investigated after the overexpression or knockdown of IFI6 in vitro. The results indicated that the molecular weight of the chicken IFI6 protein was approximately 11 kDa and that its structure was similar to that of the human IFI27L1 protein. A phylogenetic tree analysis of the IFI6 amino acid sequence revealed that the evolution of mammals and birds was clearly divided into two branches. The evolutionary history and homology of chickens are similar to those of other birds. Avian IFI6 localized to the cytoplasm and was abundantly expressed in the chicken lung, intestine, pancreas, liver, spleen, glandular stomach, thymus, bursa of Fabricius and trachea. Further studies demonstrated that IFI6 overexpression in DF-1 cells inhibited ARV replication and that the inhibition of IFI6 expression promoted ARV replication. After ARV infection, IFI6 modulated the expression of various innate immunity-related factors. Notably, the expression patterns of MAVS and IFI6 were similar, and the expression patterns of IRF1 and IFN-β were opposite to those of IFI6. The results of this study further advance the research on avian IFI6 and provide a theoretical basis for further research on the role of IFI6 in avian virus infection and innate immunity.

Abstract Hepatocellular carcinoma (HCC), one of the most malignant tumors, is characterized by its stubborn immunosuppressive microenvironment. As one of the main members of the tumor microenvironment (TME) of HCC, tumor-associated macrophages (TAMs) play a critical role in its occurrence and development, including stimulating angiogenesis, enhancing immunosuppression, and promoting the drug resistance and cancer metastasis. This review describes the origin as well as phenotypic heterogeneity of TAMs and their potential effects on the occurrence and development of HCC and also discusses about various adjuvant therapy based strategies that can be used for targeting TAMs. In addition, we have highlighted different treatment modalities for TAMs based on immunotherapy, including small molecular inhibitors, immune checkpoint inhibitors, antibodies, tumor vaccines, adoptive cellular immunotherapy, and nanocarriers for drug delivery, to explore novel combination therapies and provide feasible therapeutic options for clinically improving the prognosis and quality of life of HCC patients.

Abstract Among the common methods used for antibody immobilization on electrode surfaces, which is the best available option for immunosensor fabrication? To answer this question, we first used graphene-chitosan-Au/Pt nanoparticle (G-Chi-Au/PtNP) nanocomposites to modify a gold electrode (GE). Second, avian reovirus monoclonal antibody (ARV/MAb) was immobilized on the GE surface by using four common methods, which included glutaraldehyde (Glu), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide/N-hydroxysuccinimide (EDC/NHS), direct incubation or cysteamine hydrochloride (CH). Third, the electrodes were incubated with bovine serum albumin, four different avian reovirus (ARV) immunosensors were obtained. Last, the four ARV immunosensors were used to detect ARV. The results showed that the ARV immunosensors immobilized via Glu, EDC/NHS, direct incubation or CH showed detection limits of 100.63 EID50 mL−1, 100.48 EID50 mL−1, 100.37 EID50 mL−1 and 100.46 EID50 mL−1 ARV (S/N = 3) and quantification limits of 101.15 EID50 mL−1, and 101.00 EID50 mL−1, 100.89 EID50 mL−1 and 100.98 EID50 mL−1 ARV (S/N = 10), respectively, while the linear range of the immunosensor immobilized via CH (0–105.82 EID50 mL−1 ARV) was 10 times broader than that of the immunosensor immobilized via direct incubation (0–104.82 EID50 mL−1 ARV) and 100 times broader than those of the immunosensors immobilized via Glu (0–103.82 EID50 mL−1 ARV) or EDC/NHS (0–103.82 EID50 mL−1 ARV). And the four immunosensors showed excellent selectivity, reproducibility and stability.

Oscillating water columns (OWCs) have been studied extensively as promising wave energy converters. Different factors can affect the pneumatic power of OWCs, such as model scaling, turbine damping, and air compressibility. In this study, the heave motion of the OWC was limited by adding friction, and the effect of orifice size on the pneumatic power of an OWC from an unconstrained to a fixed position was investigated using a numerical method combining the k-ε/laminar model, the VOF interface capturing method, the motion-based zonal mesh update method and the 6DOF solver. Two groups of validation experiments and a study of model scaling were carried out to verify the effectiveness of the numerical method. It is concluded that the orifice open area ratio has an optimal value of approximately 1% whether the model is stationary or heaving; however, the heave motion has a significant weakening effect on the pneumatic power. More power can be extracted by constraining the heave motion of the OWC.

Abstract Avian influenza virus H9 subtype (AIV H9) has contributed to enormous economic losses. Effective diagnosis is key to controlling the spread of AIV H9. In this study, a nonenzymatic highly electrocatalytic material was prepared using chitosan (Chi)-modified graphene sheet (GS)-functionalized Au/Pt nanoparticles (GS-Chi-Au/Pt), followed by the construction of a novel enzyme-free sandwich electrochemical immunosensor for the detection of AIV H9 using GS-Chi-Au/Pt and graphene–chitosan (GS-Chi) nanocomposites as a nonenzymatic highly electrocatalytic material and a substrate material to immobilize capture antibodies (avian influenza virus H9-monoclonal antibody, AIV H9/MAb), respectively. GS, which has a large specific surface area and many accessible active sites, permitted multiple Au/Pt nanoparticles to be attached to its surface, resulting in substantially improved conductivity and catalytic ability. Au/Pt nanoparticles can provide modified active sites for avian influenza virus H9-polyclonal antibody (AIV H9/PAb) immobilization as signal labels. Upon establishing the electrocatalytic activity of Au/Pt nanoparticles on graphene towards hydrogen peroxide (H2O2) reduction for signal amplification and optimizing the experimental parameters, we developed an AIV H9 electrochemical immunosensor, which showed a wide linear range from 101.37 EID50 mL−1 to 106.37 EID50 mL−1 and a detection limit of 100.82 EID50 mL−1. This sandwich electrochemical immunosensor also exhibited high selectivity, reproducibility and stability.

Updated vaccines based on Omicron subvariants have started to being rolled out. Analysis of antibody response in individuals with two or three vaccine doses suggests that BA.2 breakthrough infection barely increases cross-neutralization capacity against BA.4/5 or BA.2.75.

Abstract Background Currently, due to synergy enhancement of anti‐tumor effects and potent stimulation of abscopal effects, combination therapy with irradiation and programmed cell death protein 1/programmed death‐ligand 1 (PD‐1/PD‐L1) immune checkpoint inhibition (immuno‐radiotherapy, iRT) has revolutionized the therapeutic guidelines. It has been demonstrated that tumor‐draining lymph nodes (TDLN) are essential for effective antitumor immunity induced by radiotherapy, immunotherapy, or iRT. Given that the function of TDLN in iRT remains unclear, this study aimed to investigate the function and mechanism of TDLN in iRT‐induced abscopal effects. Methods The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN. The flow cytometry, multiple immunofluorescence analysis, and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment. Additionally, we tempted to interrogate the possible mechanisms via RNA‐sequencing of tumor‐infiltrating lymphocytes and TDLN. Results TDLN deficiency impaired the control of tumor growth by monotherapy. Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT‐stimulated anti‐tumor and abscopal effects. Furthermore, in the absence of TDLN, the infiltration of CD45+ and CD8+ T cells was substantially reduced in both primary and abscopal tumors, and the anti‐tumor function of CD8+ T cells was attenuated as well. Additionally, the polarization of tumor‐associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN. RNA‐sequencing data indicated that impaired infiltration and anti‐tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment. Conclusions TDLN play a critical role in iRT by promoting the infiltration of CD8+ T cells and maintaining the M1/M2 macrophage ratio.

Since July 16 2021, China’s national emissions trading scheme (ETS) has been officially launched. Comparing with the world’s major carbon markets, China’s carbon market is relatively immature and still needs further development and improvement. This paper lists global and local lessons to China’s national ETS, in terms of cap setting, permit allocation, MRV (Monitoring, Reporting, Verification), trading mechanism, implementation and so on. This article combines development experience with China’s national conditions to provide policy recommendations for the future construction of the national carbon market.

Summary: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants have seriously attacked the antibody barrier established by natural infection and/or vaccination, especially the recently emerged BQ.1.1 and XBB.1. However, crucial mechanisms underlying the virus escape and the broad neutralization remain elusive. Here, we present a panoramic analysis of broadly neutralizing activity and binding epitopes of 75 monoclonal antibodies isolated from prototype inactivated vaccinees. Nearly all neutralizing antibodies (nAbs) partly or totally lose their neutralization against BQ.1.1 and XBB.1. We report a broad nAb, VacBB-551, that effectively neutralizes all tested subvariants including BA.2.75, BQ.1.1, and XBB.1. We determine the cryoelectron microscopy (cryo-EM) structure of VacBB-551 complexed with the BA.2 spike and perform detailed functional verification to reveal the molecular basis of N460K and F486V/S mutations mediating the partial escape of BA.2.75, BQ.1.1, and XBB.1 from the neutralization of VacBB-551. Overall, BQ.1.1 and XBB.1 raised the alarm over SARS-CoV-2 evolution with unprecedented antibody evasion from broad nAbs elicited by prototype vaccination.

Clinical radiotherapy (RT) is severely limited by hypoxic tumor microenvironment and a lack of targeting precision. Therefore, it is crucial to develop highly efficient radiosensitizers to enhance RT efficacy. Herein, a novel kind of epidermal growth factor receptor (EGFR)-antagonistic affibody-functionalized Pt-based nanozyme for RT sensitization to EGFR-positive tumors was developed. In this study, porous platinum nanoparticles (pPt NPs) featuring catalase (CAT)-like activity and strong radiation energy absorption ability were first synthesized. Then, a thin biomimetic polydopamine (PDA) layer was coated on pPt NPs to optimize its biocompatibility as well as provide a reactive surface. Finally, a dimeric EGFR-antagonistic affibody called ZEGFR expressed by the Escherichia coli (E. coli), was conjugated to pPt@PDA NPs (termed pPt@PDA-ZEGFR NPs) to precisely recognize EGFR-positive A431 tumors. Under the navigation of ZEGFR, superior tumor homing was achieved with these Pt-based nanozymes, which was ascribed to EGFR receptor-mediated endocytosis. As high-Z metal NPs exhibit an inherently strong ability to absorb radiation energy and catalyze endogenous H2O2 in tumors, the pPt@PDA-ZEGFR NPs demonstrated superb therapeutic efficacy; specifically, the NPs significantly inhibited HIF-1α expression and increased RT-induced DNA damage. Furthermore, the biosafety of these Pt-based nanozymes was good during short-term treatment. In summary, EGFR-antagonistic affibody-functionalized Pt-based nanozymes are promising radiosensitizers for the precise therapy of EGFR-positive tumors.

Interferon-inducible transmembrane protein 3 (IFITM3) is an antiviral factor that plays an important role in the host innate immune response against viruses. Previous studies have shown that IFITM3 is upregulated in various tissues and organs after avian reovirus (ARV) infection, which suggests that IFITM3 may be involved in the antiviral response after ARV infection. In this study, the chicken IFITM3 gene was cloned and analyzed bioinformatically. Then, the role of chicken IFITM3 in ARV infection was further explored. The results showed that the molecular weight of the chicken IFITM3 protein was approximately 13 kDa. This protein was found to be localized mainly in the cytoplasm, and its protein structure contained the CD225 domain. The homology analysis and phylogenetic tree analysis showed that the IFITM3 genes of different species exhibited great variation during genetic evolution, and chicken IFITM3 shared the highest homology with that of Anas platyrhynchos and displayed relatively low homology with those of birds such as Anser cygnoides and Serinus canaria. An analysis of the distribution of chicken IFITM3 in tissues and organs revealed that the IFITM3 gene was expressed at its highest level in the intestine and in large quantities in immune organs, such as the bursa of Fabricius, thymus and spleen. Further studies showed that the overexpression of IFITM3 in chicken embryo fibroblasts (DF-1) could inhibit the replication of ARV, whereas the inhibition of IFITM3 expression in DF-1 cells promoted ARV replication. In addition, chicken IFITM3 may exert negative feedback regulatory effects on the expression of TBK1, IFN-γ and IRF1 during ARV infection, and it is speculated that IFITM3 may participate in the innate immune response after ARV infection by negatively regulating the expression of TBK1, IFN-γ and IRF1. The results of this study further enrich the understanding of the role and function of chicken IFITM3 in ARV infection and provide a theoretical basis for an in-depth understanding of the antiviral mechanism of host resistance to ARV infection.

H5, H7 and H9 are the most important subtypes of avian influenza viruses (AIVs), and nine neuraminidase (NA) subtypes (N1–N9) of AIVs have been identified in poultry. A method that can simultaneously detect H5, H7, H9 and the nine NA subtypes of AIVs would save time and effort. In this study, 13 pairs of primers, including 12 pairs of subtype-specific primers for detecting particular subtypes (H5, H7, H9 and N1–N9) and one pair of universal primers for detecting all subtypes of AIVs, were designed and screened. The 13 pairs of primers were mixed in the same reaction, and the 13 target genes were simultaneously detected. A GeXP assay using all 13 pairs of primers to simultaneously detect H5, H7, H9 and the nine NA subtypes of AIVs was developed. The GeXP assay showed specific binding to the corresponding target genes for singlet and multiplex templates, and no cross-reactivity was observed between AIV subtypes and other related avian pathogens. Detection was observed even when only 102 copies of the 13 target genes were present. This study provides a high-throughput, rapid and labor-saving GeXP assay for the simultaneous rapid identification of three HA subtypes (H5, H7 and N9) and nine NA subtypes (N1–N9) of AIVs.

Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease that has an increasing death rate but no effective treatment to now. Although biological and immunological hallmarks of PDAC have been frequently reported recently, early detection and the particularly aggressive biological features are the major challenges remaining unclear. In the current study, we retrieved multiple scRNA-seq datasets and illustrated the genetic programs of PDAC development in genetically modified mouse models. Notably, the transcription levels of Id1 were elevated specifically along with the PDAC development. Pseudotime trajectory analysis revealed that Id1 was closely correlated with the malignancy of PDAC. The gene expression patterns of human PDAC cells were determined by the comparative analysis of the scRNA-seq data on human PDAC and normal pancreas tissues. ID1 levels in human PDAC cancer cells were dramatically increased compared to normal epithelial cells. ID1 deficiency in vitro significantly blunt the invasive tumor-formation related phenotypes. IPA analysis on the differentially expressed genes suggested that EIF2 signaling was the core pathway regulating the development of PDAC. Blocking EFI2 signaling remarkably decreased the expression of ID1 and attenuated the tumor-formation related phenotypes. These observations confirmed that ID1 was regulated by EIF2 signaling and was the critical determinator of PDAC development and progression. This study suggests that ID1 is a potential malignant biomarker of PDAC in both mouse models and human and detecting and targeting ID1 may be a promising strategy to treat or even rescue PDAC.

Abstract Mesenchymal/stromal stem cells (MSCs) are a crucial component of the tumour microenvironment (TME). They can be recruited from normal tissues into the TME and educated by tumour cells to transform into tumour-associated MSCs, which are oncogenic cells that promote tumour development and progression by impacting or transforming into various kinds of cells, such as immune cells and endothelial cells. Targeting MSCs in the TME is a novel strategy to prevent malignant processes. Exosomes, as communicators, carry various RNAs and proteins and thus link MSCs and the TME, which provides options for improving outcomes and developing targeted treatment.

BackgroundObsessive-compulsive disorder (OCD) is a common and chronic mental illness with a high rate of disability. Internet-based cognitive behavioral therapy (ICBT) makes online treatment available to patients and has been shown to be effective. However, 3-arm trials on ICBT, face-to-face cognitive behavioral group therapy (CBGT), and only medication are still lacking. ObjectiveThis study is a randomized, controlled, assessor-blinded trial of 3 groups for OCD: ICBT combined with medication, CBGT combined with medication, and conventional medical treatment (ie, treatment as usual [TAU]). The study aims to investigate the efficacy and cost-effectiveness of ICBT related to CBGT and TAU for adults with OCD in China. MethodsIn total, 99 patients with OCD were selected and randomly assigned to the ICBT, CBGT, and TAU groups for treatment for 6 weeks. The primary outcomes were the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and the self-rating Florida Obsessive-Compulsive Inventory (FOCI), compared at baseline, during treatment (3 weeks), and after treatment (6 weeks), to analyze efficacy. The secondary outcome was the EuroQol Visual Analogue Scale (EQ-VAS) scores of the EuroQol 5D Questionnaire (EQ-5D). The cost questionnaires were recorded to analyze cost-effectiveness. ResultsRepeated-measures ANOVA was used for data analysis, and the final effective sample size was 93 (ICBT: n=32, 34.4%; CBGT: n=28, 30.1%; TAU: n=33, 35.5%). After 6-week treatment, the YBOCS scores of the 3 groups significantly decreased (P

The GX2020-019 strain of fowl adenovirus serotype 4 (FAdV-4) was isolated from the liver of chickens with hydropericardium hepatitis syndrome in Guangxi Province, China, and was purified by plaque assay three times. Pathogenicity studies showed that GX2020-019 can cause typical FAdV-4 pathology, such as hydropericardium syndrome and liver yellowing and swelling. Four-week-old specific pathogen-free (SPF) chickens inoculated with the virus at doses of 103 median tissue culture infectious dose (TCID50), 104 TCID50, 105 TCID50, 106 TCID50, and 107 TCID50 had mortality rates of 0, 20, 60, 100, and 100%, respectively, which were lower than those of chickens inoculated with other highly pathogenic Chinese isolates, indicating that GX2020-019 is a moderately virulent strain. Persistent shedding occurred through the oral and cloacal routes for up to 35 days postinfection. The viral infection caused severe pathological damage to the liver, kidney, lung, bursa of Fabricius, thymus, and spleen. The damage to the liver and immune organs could not be fully restored 21 days after infection, which continued to affect the immune function of chickens. Whole genome analysis indicated that the strain belonged to the FAdV-C group, serotype 4, and had 99.7–100% homology with recent FAdV-4 strains isolated from China. However, the amino acid sequences encoded by ORF30 and ORF49 are identical to the sequences found in nonpathogenic strains, and none of the 32 amino acid mutation sites that appeared in other Chinese isolates were found. Our research expands understanding of the pathogenicity of FAdV-4 and provides a reference for further studies.

Introduction: The tumor microenvironment (TME) is mainly characterized by abnormally elevated intracellular redox levels and excessive oxidative stress. However, the balance of the TME is also very fragile and susceptible to be disturbed by external factors. Therefore, several researchers are now focusing on intervening in redox processes as a therapeutic strategy to treat tumors. Here, we have developed a liposomal drug delivery platform that can load a Pt(IV) prodrug (DSCP) and cinnamaldehyde (CA) into a pH-responsive liposome to enrich more drugs in the tumor region for better therapeutic efficacy through enhanced permeability and retention effect.Methods: Using the glutathione-depleting properties of DSCP together with the ROS-generating properties of cisplatin and CA, we synergistically altered ROS levels in the tumor microenvironment to damage tumor cells and achieve anti-tumor effects in vitro.Results: A liposome loaded with DSCP and CA was successfully established, and this liposome effectively increased the level of ROS in the tumor microenvironment and achieved effective killing of tumor cells in vitro.Conclusion: In this study, novel liposomal nanodrugs loaded with DSCP and CA provided a synergistic strategy between conventional chemotherapy and disruption of TME redox homeostasis, leading to a significant increase in antitumor effects in vitro.

Summary: SARS-CoV-2 Omicron BA.2.75 subvariant has evolved to a series of progeny variants carrying several additional mutations in the receptor-binding domain (RBD). Here, we investigated whether and how these single mutations based on BA.2.75 affect the neutralization of currently available anti-RBD monoclonal antibodies (mAbs) with well-defined structural information. Approximately 34% of mAbs maintained effective neutralizing activities against BA.2.75, consistent with those against BA.2, BA.4/5, and BA.2.12.1. Single additional R346T, K356T, L452R, or F486S mutations further facilitated BA.2.75-related progeny variants to escape from broadly neutralizing antibodies (bnAbs) at different degree. Only LY-CoV1404 (bebtelovimab) displayed a first-class neutralization potency and breadth against all tested Omicron subvariants. Overall, these data make a clear connection between virus escape and antibody recognizing antigenic epitopes, which facilitate to develop next-generation universal bnAbs against emerging SARS-CoV-2 variants.

Abstract A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.

Avian reovirus (ARV) infection is prevalent in farmed poultry and causes viral arthritis and severe immunosuppression. The spleen plays a very important part in protecting hosts against infectious pathogens. In this research, transcriptome and translatome sequencing technology were combined to investigate the mechanisms of transcriptional and translational regulation in the spleen after ARV infection. On a genome-wide scale, ARV infection can significantly reduce the translation efficiency (TE) of splenic genes. Differentially expressed translational efficiency genes (DTEGs) were identified, including 15 upregulated DTEGs and 396 downregulated DTEGs. These DTEGs were mainly enriched in immune regulation signaling pathways, which indicates that ARV infection reduces the innate immune response in the spleen. In addition, combined analyses revealed that the innate immune response involves the effects of transcriptional and translational regulation. Moreover, we discovered the key gene IL4I1, the most significantly upregulated gene at both the transcriptional and translational levels. Further studies in DF1 cells showed that overexpression of IL4I1 could inhibit the replication of ARV, while inhibiting the expression of endogenous IL4I1 with siRNA promoted the replication of ARV. Overexpression of IL4I1 significantly downregulated the mRNA expression of IFN-β, LGP2, TBK1 and NF-κB; however, the expression of these genes was significantly upregulated after inhibition of IL4I1, suggesting that IL4I1 may be a negative feedback effect of innate immune signaling pathways. In addition, there may be an interaction between IL4I1 and ARV σA protein, and we speculate that the IL4I1 protein plays a regulatory role by interacting with the σA protein. This study not only provides a new perspective on the regulatory mechanisms of the innate immune response after ARV infection but also enriches the knowledge of the host defense mechanisms against ARV invasion and the outcome of ARV evasion of the host’s innate immune response.

Individuals with schizophrenia (SZ) show impairment in social functioning. The reward network and the emotional salience network are considered to play important roles in social interaction. The current study investigated alterations in the resting-state (rs-) amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo) and functional connectivity (fc) in the reward network and the emotional salience network in SZ patients. MRI scans were collected from 60 subjects, including 30 SZ patients and 30 matched healthy controls. SZ symptoms were measured using the Positive and Negative Syndrome Scale (PANSS). We analyzed the ALFF, fALFF and ReHo in key brain regions in the reward network and emotional salience network as well as rs-fc among the bilateral amygdala, lateral orbitofrontal cortex (OFC), medial OFC and insula between groups. The SZ patients demonstrated increased ALFF in the right caudate and right putamen, increased fALFF and ReHo in the bilateral caudate, putamen and pallidum, along with decreased fALFF in the bilateral insula. Additionally, reduced rs-fc was found between the right lateral OFC and the left amygdala, which simultaneously belong to the reward network and the emotional salience network. These findings highlight the association between impaired social functioning in SZ patients and aberrant resting-state ALFF, fALFF, ReHo and fc. Future studies are needed to conduct network-based statistical analysis and task-state fMRI, reflecting live social interaction to advance our understanding of the mechanism of social interaction deficits in SZ.

Abstract Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.

Abstract The current COVID-19 pandemic caused by constantly emerging SARS-CoV-2 variants still poses a threat to public health worldwide. Effective next-generation vaccines and optimized booster vaccination strategies are urgently needed. Here, we sequentially immunized mice with a SARS-CoV-2 wild-type inactivated vaccine and a heterologous mutant RBD vaccine, and then evaluated their neutralizing antibody responses against variants including Beta, Delta, Alpha, Iota, Kappa, and A.23.1. These data showed that a third booster dose of heterologous RBD vaccine especially after two doses of inactivated vaccines significantly enhanced the GMTs of nAbs against all SARS-CoV-2 variants we tested. In addition, the WT and variants all displayed good cross-immunogenicity and might be applied in the design of booster vaccines to induce broadly neutralizing antibodies.