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Abstract Background Sleep’s impact on the human immune system and inflammatory responses makes it a potential risk factor for lung function impairment. However, the relationship between sleep duration and lung function impairment in middle-aged and young adults has been rarely investigated. Methods A total of 9,284 aged 20–64 years were categorized into four groups according to sleep duration (≤ 6 h, 7 h, 8 h, and ≥ 9 h), with 7 h as the reference, by using the U.S. NHANES data, 2007–2012. Forced expiratory volume in the 1 s (FEV1), forced vital capacity (FVC), FEV1 to FVC (FEV1/FVC) ratio, peak expiratory flow (PEF), and forced expiratory flow at 25–75% (FEF25 − 75%) were measured by spirometry. Restrictive impairment was defined as baseline FVC

ABSTRACT: Clostridium perfringens (C. perfringens) causes avian necrotic enteritis, leading to huge economic losses to the poultry industry. This pathogen induces host immunosuppression; however, the molecular mechanism is still unclear. Thus, we established a laying hen infection model to explore this mechanism. We randomly divided 20 one-old-day laying hens into the control and infection groups. The infection group was infected intragastrically with 1 × 109 colony-forming units of C. perfringens in 1 mL of sterile phosphate-buffered saline (PBS) once a day from d 17 to 20; the control group received the same volume of PBS without the bacterium. Twenty-four hours after the last challenge, we sacrificed the laying hens and collected the jejunum for analysis. The infection group presented alterations in blood biochemical parameters and necrotic lesion scores as well as damage to the jejunum. Proteomics revealed 427 upregulated and 291 downregulated proteins in the infection group. In the infection group, CD3, CD4, and CD8 messenger RNA expression (mRNA) expression was decreased; LAMTOR1 and mTORC1 mRNA expression was increased; CD276 protein expression was enhanced; and the PI3K/Akt/MMP pathway was activated in jejunum of laying hens. This is the first study to report CD276 expression in the jejunum related to immunosuppression in a laying hen model of necrotic enteritis. It provides some new key targets to potentially control avian necrotic enteritis.

Abstract Background Patients with chronic conditions need multiple medications daily to manage their condition. However, most patients have poor compliance, which affects the effectiveness of treatment. To address these challenges, we establish a medication reminder system for the intelligent generation of universal medication schedule (UMS) to remind patients with chronic diseases to take medication accurately and to improve safety of home medication. Methods To design medication time constraint with one drug (MTCOD) for each drug and medication time constraint with multi-drug (MTCMD) for each two drugs in order to better regulate the interval and time of patients’ medication. Establishment of a medication reminder system consisting of a cloud database of drug information, an operator terminal for medical staff and a patient terminal. Results The cloud database has a total of 153,916 pharmaceutical products, 496,708 drug interaction data, and 153,390 pharmaceutical product-ingredient pairs. The MTCOD data was 153,916, and the MTCMD data was 8,552,712. An intelligent UMS medication reminder system was constructed. The system can read the prescription information of patients and provide personalized medication guidance with medication timeline for chronic patients. At the same time, patients can query medication information and get remote pharmacy guidance in real time. Conclusions Overall, the medication reminder system provides intelligent medication reminders, automatic drug interaction identification, and monitoring system, which is helpful to monitor the entire process of treatment in patients with chronic diseases.

Abstract Glaesserella parasuis (G. parasuis) induces vascular damage and systemic inflammation. However, the mechanism by which it causes vascular damage is currently unclear. Baicalin has important anti-inflammatory, antibacterial and immunomodulatory functions. In this study, we explored the ability of baicalin and probenecid to protect against G. parasuis challenge in a piglet model. Sixty piglets were randomly divided into a control group; an infection group; a probenecid group; and 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups. The probenecid group and the 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups were injected intramuscularly with 20 mg/kg body weight (BW) probenecid and 25 mg/kg BW, 50 mg/kg BW and 100 mg/kg BW baicalin, respectively. All piglets except those from the control group were injected intraperitoneally with 1 × 108 CFU of G. parasuis. The control group was injected intraperitoneally with TSB. The results showed baicalin and probenecid protected piglets against G. parasuis challenge, improved body weight and decreased temperature changes in piglets. Baicalin and probenecid attenuated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA levels in the blood for 48 h, inhibited the production of the nucleosides ATP, ADP, AMP and UMP from 24 to 72 h, reduced Panx-1/P2Y6/P2X7 expression, weakened NF-kB, AP-1, NLRP3/Caspase-1 and ROCK/MLCK/MLC signalling activation, and upregulated VE-cadherin expression in the blood vessels of piglets challenged with G. parasuis. Baicalin and probenecid alleviated pathological tissue damage in piglets induced by G. parasuis. Our results might provide a promising strategy to control and treat G. parasuis infection in the clinical setting.

Abstract Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.

Abstract Introduction Ixekizumab, an interleukin 17A (IL-17A) inhibitor, has demonstrated rapid and sustained improvement in the signs and symptoms in patients with active radiographic axial spondyloarthritis (r-axSpA) in global and Chinese populations. We studied the effect of ixekizumab on patient-reported outcomes (PROs) (including patient global, spinal pain, stiffness, and fatigue) and overall health-related quality of life (HRQoL) of ixekizumab in the phase 3 study in China. Methods In this Chinese phase 3, randomized, double-blind, placebo-controlled study, patients with r-axSpA were randomized (1:1) to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg) or placebo for 16 weeks. At week 16, patients receiving placebo were switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. Data for patient global, spinal pain, spinal pain at night, stiffness, and fatigue were collected through week 52. Minimally clinical important differences (MCIDs) were determined for spinal pain and spinal pain at night. The subgroup analyses by baseline disease duration since diagnosis and baseline C-reactive protein (CRP) level were conducted post hoc. Results Compared with placebo, patients treated with IXEQ4W reported significantly greater improvement with a rapid onset in changes from baseline of PROs (patient global, spinal pain, spinal pain at night, stiffness, and fatigue) through week 16. Improvements were maintained through week 52. A similar trend of improvement was also observed in MCID response in spinal pain and spinal pain at night. The improvement in overall HRQoL was supported by EQ-5D-5L assessment. Subgroup analyses demonstrated that IXEQ4W provided significantly greater efficacy at week 16 compared with placebo, irrespective of baseline disease duration or baseline CRP level. Conclusion IXEQ4W provided rapid and sustained improvement in clinically relevant PROs and overall HRQoL through 1-year treatment in Chinese patients with r-axSpA. Regardless of the baseline disease duration or baseline CRP level, consistent efficacy was observed. Trial Registration ClinicalTrials.gov identifier NCT04285229.

The purpose of this study is to investigate the intergranular corrosion resistance mechanism of 304 austenitic stainless steel treated by decreasing C contents and increasing the solid-solution treatment time. The findings indicate the effect of decreasing C contents and increasing the solid-solution treatment time effectively limits the intergranular corrosion behavior of the steel within an acceptable range (degree of sensitization, DOS values

BackgroundNowadays, social media plays a crucial role in disseminating information about cancer prevention and treatment. A growing body of research has focused on assessing access and communication effects of cancer information on social media. However, there remains a limited understanding of the comprehensive presentation of cancer prevention and treatment methods across social media platforms. Furthermore, research comparing the differences between medical social media (MSM) and common social media (CSM) is also lacking. ObjectiveUsing big data analytics, this study aims to comprehensively map the characteristics of cancer treatment and prevention information on MSM and CSM. This approach promises to enhance cancer coverage and assist patients in making informed treatment decisions. MethodsWe collected all posts (N=60,843) from 4 medical WeChat official accounts (accounts with professional medical backgrounds, classified as MSM in this paper) and 5 health and lifestyle WeChat official accounts (accounts with nonprofessional medical backgrounds, classified as CSM in this paper). We applied latent Dirichlet allocation topic modeling to extract cancer-related posts (N=8427) and identified 6 cancer themes separately in CSM and MSM. After manually labeling posts according to our codebook, we used a neural-based method for automated labeling. Specifically, we framed our task as a multilabel task and utilized different pretrained models, such as Bidirectional Encoder Representations from Transformers (BERT) and Global Vectors for Word Representation (GloVe), to learn document-level semantic representations for labeling. ResultsWe analyzed a total of 4479 articles from MSM and 3948 articles from CSM related to cancer. Among these, 35.52% (2993/8427) contained prevention information and 44.43% (3744/8427) contained treatment information. Themes in CSM were predominantly related to lifestyle, whereas MSM focused more on medical aspects. The most frequently mentioned prevention measures were early screening and testing, healthy diet, and physical exercise. MSM mentioned vaccinations for cancer prevention more frequently compared with CSM. Both types of media provided limited coverage of radiation prevention (including sun protection) and breastfeeding. The most mentioned treatment measures were surgery, chemotherapy, and radiotherapy. Compared with MSM (1137/8427, 13.49%), CSM (2993/8427, 35.52%) focused more on prevention. ConclusionsThe information about cancer prevention and treatment on social media revealed a lack of balance. The focus was primarily limited to a few aspects, indicating a need for broader coverage of prevention measures and treatments in social media. Additionally, the study’s findings underscored the potential of applying machine learning to content analysis as a promising research approach for mapping key dimensions of cancer information on social media. These findings hold methodological and practical significance for future studies and health promotion.

Abstract Glaesserella parasuis, an important respiratory bacterial pathogen, causes Glässer’s disease in piglets, with potential immunosuppression. We established a piglet infection model and explored the immunosuppression mechanism to improve our understanding of the host immune response to G. parasuis. Twenty piglets were randomly divided into two groups (n = 10). The infection group was intraperitoneally challenged with 2 × 108 CFU of G. parasuis in 2 mL TSB. The control group was intraperitoneally injected with equivalent TSB. After 72 h, the piglets were sacrificed, and spleen tissue was collected. PD-1/PD-L1 expression was determined. The splenocytes were isolated to detect CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3−CD21+cell differentiation. Via data-independent acquisition (DIA), we compared the proteomics of healthy and infected spleen tissues. Glaesserella parasuis modified CD3+ T, CD3+CD4+ T, CD3+CD8+ T and CD3−CD21+ cell differentiation and PD-1/PD-L1 expression in the spleen. The infection group had 596 proteins with significant differences in expression, of which 301 were significantly upregulated and 295 downregulated. Differentially expressed proteins (DEPs) were mainly related to immune responses. This is the first study on PD-1/PD-L1 expression in the spleen associated with immunosuppression in a piglet model to explore the protein changes related to immune responses via DIA.

The production of hybrid progeny through distant hybridization holds great significance in enriching germplasm resources for fish breeding. In this study, a hybridization experiment was conducted between female KOC (Cyprinus carpio haematopterus) and male GR (Gobiocypris rarus), resulting in the production of two distinct types of hybrid offspring. These progenies were classified as allodiploid and allotriploid based on their DNA content and chromosome numbers, hereafter referred to as CG and CCG. Subsequently, a comprehensive comparative analysis was performed between the CG and CCG hybrids and their parents, focusing on countable traits, measurable traits, erythrocyte morphology, as well as karyogene and mitochondrial gene composition. The majority of the examined countable and measurable traits in both CG and CCG exhibited similarities predominantly with GR, except for the ratios of body length (BL) to body height (BH) and head length (HL). Moreover, observing erythrocytes revealed the presence of dumbbell-shaped nuclei in CCG, a characteristic not observed in CG hybrids or the parents. Sequencing alignment revealed that the homeobox (Hox) genes and 5S RNA in CG and CCG were inherited from both KOC and GR, signifying their status as allodiploid and allotriploid organisms. The mitochondrial genes in CG and CCG showed substantial similarity to KOC, albeit with a few sites displaying paternal leakage inheritance from GR. In comparison to CG, the growth rate of CCG was found to be significantly faster, which could be attributed to the upregulation of growth hormone 1 (gh1) and the downregulation of myostatin b (mstn). This study successfully produced two hybrid offspring with distinct growth characteristics but similar genetic backgrounds, making them ideal subjects for future investigations into growth traits. The findings of this research established a fundamental basis for investigating the growth mechanism of fish and provided significant implications for the advancement of fish breeding through hybridization.

Abstract Background The cultivation of bananas encounters substantial obstacles, particularly due to the detrimental effects of cold stress on their growth and productivity. A potential remedy that has gained attention is the utilization of ethyl mesylate (EMS)-induced mutagenesis technology, which enables the creation of a genetically varied group of banana mutants. This complex procedure entails subjecting the mutants to further stress screening utilizing L-Hyp in order to identify those exhibiting improved resistance to cold. This study conducted a comprehensive optimization of the screening conditions for EMS mutagenesis and L-Hyp, resulting in the identification of the mutant cm784, which exhibited remarkable cold resistance. Subsequent investigations further elucidated the physiological and transcriptomic responses of cm784 to low-temperature stress. Results EMS mutagenesis had a substantial effect on banana seedlings, resulting in modifications in shoot and root traits, wherein a majority of seedlings exhibited delayed differentiation and limited elongation. Notably, mutant leaves displayed altered biomass composition, with starch content exhibiting the most pronounced variation. The application of L-Hyp pressure selection aided in the identification of cold-resistant mutants among seedling-lethal phenotypes. The mutant cm784 demonstrated enhanced cold resistance, as evidenced by improved survival rates and reduced symptoms of chilling injury. Physiological analyses demonstrated heightened activities of antioxidant enzymes and increased proline production in cm784 when subjected to cold stress. Transcriptome analysis unveiled 946 genes that were differentially expressed in cm784, with a notable enrichment in categories related to ‘Carbohydrate transport and metabolism’ and ‘Secondary metabolites biosynthesis, transport, and catabolism’. Conclusion The present findings provide insights into the molecular mechanisms that contribute to the heightened cold resistance observed in banana mutants. These mechanisms encompass enhanced carbohydrate metabolism and secondary metabolite biosynthesis, thereby emphasizing the adaptive strategies employed to mitigate the detrimental effects induced by cold stress.

Abstract Cytoplasmic projections (CPs) formed by the generative and sperm cells link the male gametes with the vegetative cell (VC) nucleus, which are required to build the male germ unit (MGU) assemblage in the angiosperm pollen grain. As molecular and genetic controls underlying CP development and formation of the MGU are unknown, it was hypothesized that physical association between germ cells and the VC nucleus might be lost in germ unit malformed (gum) mutants or in those which either block generative cell (GC) division or that additionally prevent gamete differentiation. In vivo, analysis of marked cellular components demonstrated a linkage of sperm cells (SCs) and the VC nucleus in gum mutant alleles despite their increased physical separation. Similarly, for several independent classes of bicellular pollen mutants, undivided GCs were associated with the VC nucleus like GCs in wild‐type pollen. We conclude that the early formation of GC CPs to establish the MGU is regulated independently of DUO1‐DAZ1 and DUO3 transcription factors as well as cyclin‐dependent kinase function (CDKA;1). As the absence of cytoplasmic protrusion was expected in the gum mutants in Arabidopsis, early histological studies reported temporal disappearance of cytoplasmic protrusion in several organisms. Our findings demonstrated the striking importance of live imaging to verify the broad conservation of the persistent MGU contact in all the angiosperms and its important role in successful double fertilization.

Poultry necrotic enteritis is an important enteric disease which might be controlled by antibiotics. However, with the excessive use of antibiotics, the phenomenon of drug resistance of Clostridium perfringens is becoming increasingly prominent. Anemoside B4 exhibits important anti-inflammatory, antioxidant and immunomodulatory effects. This study was performed to estimate the effect of Anemoside B4 on chicken necrotic enteritis induced by C. perfringens in vivo and in vitro. In the in vivo experiment we investigated the efficacy of Anemoside B4 on the growth curve, biofilm formation, haemolytic activity, virulence-related gene expression and NF-κB and PI3K/AKT/mTOR activation in Caco-2 cells induced by C. perfringens. The results showed that 12.5–50 μg/mL Anemoside B4 had no antibacterial activity but could inhibit biofilm formation, attenuate haemolytic activity and virulence-related gene expression of C. perfringens and weaken NF-κB and PI3K/Akt/mTOR activation triggered by C. perfringens in Caco-2 cells. In the in vivo experiment, 60 17-day-old healthy White Leghorns were randomly divided into six groups. The growing laying hens of the control group were fed a basic diet, and those of the five challenged groups were fed a basic diet (infection group), added 0.43 g/kg Anemoside B4 (0.43 g/kg Ane group), 0.86 g/kg Anemoside B4 (0.86 g/kg Ane group), 1.72 g/kg Anemoside B4 (1.72 g/kg Ane group) and 40 mg/kg lincomycin (lincomycin group), respectively. All challenged laying hens were infected with 1 × 109 CFU C. perfringens from day 17–20. Blood and intestinal samples were obtained, and the data demonstrated that Anemoside B4 improved the blood biochemical parameters, attenuated jejunum tissue injury, increased the spleen, thymus, bursa of fabricius index, and decreased lesion scores of the jejunum and the ileum. In the jejunum, Anemoside B4 and lincomycin downregulated the expression of IL-1β, IL-6, IL-10, TNF-α and IFN-γ at mRNA levels. Moreover, Anemoside B4 significantly enhanced both mRNA and protein levels of tight junctions ZO-1, Claudin-1 and MUC-2 in the jejunum. Anemoside B4 weakened p-P65, p-PI3K, p-Akt and p-mTOR protein expression in the jejunum infected by C. perfringens. Diets supplemented with Anemoside B4 alleviated C. perfringens-induced necrotic enteritis in laying hens by inhibiting NF-κB and PI3K/Akt/mTOR signalling pathways and improving intestinal barrier functions.

ABSTRACTAiming at achieving tunable reentrant structures with rigidity and uniformity, respectively, the C-shaped and S-shaped reentrant metamaterials were proposed by the bionic design of animal structures. Utilizing beam theory and energy methodology, the analytical expressions of the equivalent elastic modulus of the metamaterials were derived. Differences in deformation modes, mechanical properties, and energy absorption capacities were characterized by using experiments and the finite element analysis method. The effects of ligament angle and thickness on the mechanical characteristics of two novel metamaterials were investigated by using a parametric analysis. The results show that the stiffness, deformation mode, stress–strain curve, and energy absorption effects of three metamaterials are significantly different. This design philosophy can be extended from 2D to 3D and is applicable at multiple dimensions.

To improve the assimilation accuracy of satellite microwave observations, it is necessary to conduct precipitation detection before assimilation and exclude the data contaminated by the scattering of hydromorphic particles. The induction of microwave scattering is closely related to the effective radius of hydromorphic particles, and the motion state of hydromorphic particles at different scales can directly affect the internal dynamic structure of clouds, which will lead to precipitation. To further analyze and validate the impact of microwave scattering in a precipitation environment on the assimilation of satellite microwave soundings within the temperature-sensitive band, this article utilized the on-orbit observations of Microwave Temperature Sounder-III (MWTS-III) and Medium Resolution Spectral Imager onboard the Fengyun-3E (FY-3E) satellite to achieve multispectral fusion observation and precipitation detection over oceans, combined with the vertical dynamic characteristics of global numerical forecast in the cloud environment of China Meteorological Administration (CMA) Global Forecast System (CMA-GFS). By conducting the dynamic analysis of the hydrometeors in the cloud, the maximum possible effective particle radius of hydromorphic particles under the no-phase-transition condition and internal vertical motion is obtained. The consistency of the cloud liquid water path (CLWP) retrieved by MWTS-III and multispectral fusion precipitation detection is evaluated subsequently. The results show that the distribution of hydrometeors in the CMA-GFS forecast is broadly in line with the CLWP distribution obtained from the MWTS-III retrieval, regardless of Mie scattering or Rayleigh scattering. However, compared with Mie scattering, the weak convection of CMA-GFS shows better adaptability in the Rayleigh environment.

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is a prevalent pregnancy-specific complication that presents with maternal itching and elevated serum bile acid levels. ICP is associated with unfavorable pregnancy outcomes, severely decreasing the pregnant woman’s quality of life. Timely identification of ICP is crucial for effective management and improved outcomes. Methods We collected urine samples from 8 patients with ICP and 8 healthy individuals. We used Liquid Chromatography-Mass Spectrometry (LC-MS) to detect metabolite expression levels, then conducted a series of bioinformatic analyses to explore the potential biological meanings of differentially expressed metabolites, and preliminarily discovered several candidate biomarkers. To validate these candidate biomarkers, we performed Gas Chromatography-Mass Spectrometry (GC-MS) detection and analyzed their diagnostic values using receiver operating characteristic (ROC) curve. Results Untargeted metabolomics data showed that 6129 positive peaks and 6218 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory capability in discriminating ICP specimens from controls. Subsequent analysis extracted 64 significantly differentially expressed metabolites, which could be potential biomarkers for diagnosis of ICP. Based on the KEGG enrichment analyses, six candidate biomarkers were preliminarily identified. Two most promising biomarkers (3-hydroxypropionic acid and uracil) were validated by targeted metabolomics analyses with the area under the curve (AUC) of 0.920 and 0.850 respectively. Conclusion Based on preliminary screening from untargeted metabolomics and subsequent validation through targeted metabolomics, 3-hydroxypropionic acid and uracil were identified as promising diagnostic biomarkers for ICP.

The gut microbiota is engaged in multiple interactions affecting host health, and gut dysbiosis can lead to many diseases. However, the effects of acetylcysteine (NAC) on the gut microbiome composition in pigs using metagenomic sequencing have not been reported. In this study, we used metagenome sequencing to study the effects of NAC on the pig gut microbiome. Sequencing results showed that microbial diversity was changed after NAC treatment. Antibiotic Resistance Genes Database (ARDB) analysis demonstrated that the main genes modified were macb, tsnr, norm, bl2be-per, vansb and pbp1b in the NAC group. Our data showed that NAC could affect microbial distribution at the phylum, gene and species levels. At the species level, NAC significantly increased the abundances of Megasphaera, Lactobacillus reuteri and Megasphaeraelsdenii and reduced the abundances of Phascolarctobacterium succinatutens, Prevotellacopri and Selenomonasbovis compared with the control group. In addition, Gene Ontology (GO) analysis revealed that in the NAC group, cellular process, metabolic process and single-organism process were the dominant terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that RNA transport, MAPK signaling pathway, cell cycle, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and VEGF signaling pathway were the dominant signaling pathways in the NAC group. In conclusion, our results suggest that NAC may modify the piglet gut microbiome composition and these findings might provide a new strategy for maintaining animal and human health in the future.

Abstract Background At present, good results have been obtained in the treatment of hematogenous osteomyelitis(HO) in children by the use of drug-loaded calcium sulfate, but there are few clinical studies reported. The aim of this study was to investigate the clinical efficacy of radical debridement combined with drug-laden calcium sulphate antibiotics in paediatric haematogenous osteomyelitis. Methods In this study, we retrospectively analyzed the clinical data of 15 cases of pediatric hematogenous osteomyelitis admitted to our hospital in recent years. A total of 15 pediatric patients with HO treated in our hospital from January 2018 to February 2022 were included for evaluation. Results All 15 patients were treated with drug-laden calcium sulfate, and the antibiotic of choice was vancomycin in 14 cases and vancomycin combined with gentamicin in 1 case. The follow-up period ranged from 12 to 36 months, with a mean follow-up time of 24.73 months, and all children were treated with drug-laden calcium sulfate with satisfactory clinical outcomes. The results of serological examination showed that the preoperative white blood cell count level, C-reactive protein and erythrocyte sedimentation rate were higher than the postoperative ones, and the differences were statistically significant (P

Glaesserella parasuis (G. parasuis) can cause peritonitis in piglets. However, the pathogenesis of peritonitis remains unclear. Baicalin has been shown to possess anti-inflammatory and anti-oxidant functions. The aim of this study was to investigate the role of the PANX-1/P2X7 axis and the P2Y6 signaling pathway in peritonitis induced by G. parasuis and the effect of baicain on the PANX-1/P2X7 axis and P2Y6 pathway activation triggered by G. parasuis. A G. parasuis serovar 5 isolate SH0165 strain was obtained from the lungs of commercially produced pigs which had the typical symptoms of Glässer’s disease, namely arthritis, fibrinous polyserositis, hemorrhagic pneumonia, and meningitis. Then, 35 piglets were randomly divided into five groups, each group containing seven piglets. The groups consisted of a negative control group, an infection group, a 25 mg/kg baicalin group, a 50 mg/kg baicalin group, and a 100 mg/kg baicalin group. The results showed that G. parasuis could promote PANX-1/P2X7 axis and P2Y6 activation; induce NLRP3/caspase-1, IL-1β and IL-18 expression; trigger PLC/PKC and MLCK/MLC signaling activation; attenuate the expression of tight junction proteins ZO-1, E-cadherin, Occludins, and claudin 1; and stimulate CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum as measured via Western blot (p < 0.01; PLC, p < 0.05). Baicalin could significantly inhibit PANX-1/P2X7 axis, P2Y6, and NLRP3/caspase-1 activation; reduce IL-1β and IL-18 expression; attenuate PLC/PKC and MLCK/MLC activation; promote ZO-1, E-cadherin, occludins, and claudin 1 expression; and reduce CD14, CD24, CD36, CD47, and CD91 expression in the peritoneum induced by G. parasuis as measured via Western blot. Our results deepen the understanding of the mechanism of peritonitis triggered by G. parasuis and provide some novel potential methods of controlling G. parasuis infection.

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes.

This study aimed to compare the changes in physicochemical properties of the starch isolated from three banana cultivars (Musa AAA group, Cavendish subgroup; Musa ABB group, Pisang Awak subgroup; Musa AA group, Huangdijiao subgroup) at five different maturity stages. The results revealed both similarities and significant differences in micromorphology and physicochemical characteristics of the three banana varieties during different growth stages. Apparent amylose content and particle size of the three starches increased with the ripeness of banana. Light microscopy and scanning electron microscopy revealed that starch particles of the three starches had different microscopic characteristics, and that banana starch morphology was basically unchanged at various growth stages. Moreover, the pasting and thermal properties of the banana starches were significantly different at various growth stages. The resistant starch content of the three banana cultivars was about 80% at all growth stages. Musa AAA group, Cavendish subgroup had the highest resistant starch content at stage Ⅴ. This study provides insights into the starch changes of three banana cultivars during ripening.

Nutrient fertilizer application to agricultural land has led to greenhouse gas emissions and has altered soil nitrogen (N) deposition. In soil, N can be degraded in four ways: entering surface water through water flow, absorption by plants and microorganisms, decomposition into gas, and deposition as minerals. This study proposes the concept of N degradability and aims to clarify how farming activities affect N degradability in soil. Over 260 soil profiles were excavated, and the effective soil depth, coordinates, soil types, and vegetation were recorded at each measurement point. The following characteristics were determined in the soil samples: pH, organic matter, total N, total phosphorus, total potassium, total soluble N, available phosphorus, and available potassium. The sample characteristics were subjected to Pearson correlation analysis, principal component analysis, and one-way analysis of variance. The 260 samples included four soil types: dark brown soil, black soil, albic black soil, and meadow soil. Black soil exhibited more stable N levels compared with the other three soil types, showing a tendency towards N accumulation. Ground vegetation was categorized into seven types: forest, rice, maize, red adzuki bean, grassland, soybean, and others. Forests contributed the most to N deposition. Conversely, planting maize led to a tendency for N loss compared with forests. This study can provide a reference for the sustainable development of agriculture and the balance of ecological protection.

The rotary vector (RV) reducer, as a highly precise transmission mechanism, can lead to a series of consequential hazards when experiencing local faults. Conducting corresponding research on performance monitoring and fault diagnosis holds significant importance. In order to achieve higher diagnostic accuracy, better classification, prediction effect, and less use of sensors, this paper proposes a local fault diagnosis method of RV reducer based on Motor current signature analysis (MCSA). Firstly, the centre gear local fault electromechanical coupling model is created by combining the working principle of the servo motor, the working characteristics of the RV reducer, and the influencing factors of motor current. Then, according to the actual operating conditions of industrial robots (IRs), the corresponding experimental platform is designed and constructed, and current signals in four different modes are collected. Fast Fourier transform (FFT) is performed on the current signals to obtain frequency domain features, and the correctness of the local fault coupling model of the centre gear is experimentally verified. Finally, the time-domain statistical features, time–frequency domain features, and CNN features of servo-feedback current signals under different rotational speeds are extracted and used in the implementation of local fault diagnosis for the RV reducer, respectively. In this paper, it is confirmed that MCSA can be used for localized fault diagnosis of the RV reducer, and combined with a deep learning network, it can effectively predict the fault modes with an average accuracy of more than 96%.

Intrahepatic cholestasis of pregnancy (ICP) is one of the common pregnancy complications that may threaten the health of both pregnant women and their fetuses. Hence, it is of vital importance to identify key moleculars and the associated functional pathways of ICP, which will help us to better understand the pathological mechanisms as well as to develop precise clinical biomarkers. The emerging and developing of multiple omics approaches enable comprehensive studies of the genome, transcriptome, proteome and metabolome of clinical samples. The present review collected and summarized the omics based studies of ICP, aiming to provide an overview of the current progress, limitations and future directions. Briefly, these studies covered a broad range of research contents by the comparing of different experimental groups including ICP patients, ICP subtypes, ICP fetuses, ICP models and other complications. Correspondingly, the studied samples contain various types of clinical samples, in vitro cultured tissues, cell lines and the samples from animal models. According to the main research objectives, we further categorized these studies into two groups: pathogenesis and diagnosis analyses. The pathogenesis studies identified tens of functional pathways that may represent the key regulatory events for the occurrence, progression, treatment and fetal effects of ICP. On the other hand, the diagnosis studies tested more than 40 potential models for the early-prediction, diagnosis, grading, prognosis or differential diagnosis of ICP. Apart from these achievements, we also evaluated the limitations of current studies, and emphasized that many aspects of clinical characteristics, sample processing, and analytical method can greatly affect the reliability and repeatability of omics results. Finally, we also pointed out several new directions for the omics based analyses of ICP and other perinatal associated conditions in the future.

To investigate the effects of proactive safety control systems suitable for highway interchanges and improve road traffic safety. Simulated driving experiments were conducted to test the effects of the interchange warning system (IWS) on the ramp, merging section, diverging section, and accident section. Random forest (RF) and SHapley Additive exPlanations (SHAP) are used to analyze the effects between driving behavior and driving risk change in both situations without and with IWS. The results show that (1) as driving risk increases, drivers tend to increase the frequency of braking and engage in more comprehensive saccade behaviors. Concurrently, there is an increase in acceleration and speed variation, leading to a gradual decrease in speed. (2) Compared with the SVR and XGBoost, RF can better fit the nonlinear relationship between driving risk and driver behavior characteristics with the application of IWS. (3) The IWS mainly reduces driving risk by affecting operation behavior. When the mean speed, speed standard deviation (SD), acceleration SD, and maximum braking depth are at 40 to 70 km/h, 3 to 10 km/h, 0 to 0.6 m/s2, and 14 to 16, respectively, there is a significant reduction in driving risk. The application of the IWS expands the effective range of mean speed and speed SD for reducing driving risk to 40 to 100 km/h and 3 to 15 km/h, respectively.

The warming world greatly suffers the increase of frequency, severity and duration of heat wave events, which would cause the significant societal and environmental damages and implications from local to global scales. In order to eliminate the limitations of site observations in accurate spatial extent identification and large scale monitoring, this study tried to investigate global heat waves in 2018 using spatial datasets of land surface temperature (LST) derived from AQUA TIR sensors. A 15-year daily maximum LST dataset was used to identify the hot days and heat wave events using the relative threshold method based on the probability density function analysis of LST sequences, then they were adopted in analyzing spatial patterns of duration, frequency and intensity of heat wave events using heat wave numbers (HWN), the frequency of the appeared heat wave days (HWF) and the amplitude of heat wave impacts (HWA) indices, respectively. Our results indicated that more heat wave events and longer heat wave duration happened in low and middle latitudes under the warmer land surface in 2018 than last decade, especially many heat wave events occurred in the environmentally fragile regions and the dense population area. Urban regions achieved the largest HWA by 45.5 ± 6.9℃. Both annual HWF and HWN highlighted seven hot spot regions influenced by heat waves, and most of them distributed around the latitude 30°N and the latitude 30°S. Extreme heat wave of hot spot regions in the Southern Hemisphere mainly happened in winter and spring in contrast to that in North Hemisphere appeared in summer and autumn. Dry climate could contribute to the occurrence of heat waves, and heat wave indices variations also implied the compound consequences between heat waves and drought. Our findings demonstrate that remote sensing datasets are capable of providing the continuous whole-Earth coverage of heat wave changes, and they would play more important roles in preventing or mitigating the impacts of extreme heat events on people and natural environment.

Background Antineoplastic chemotherapies are dramatically efficient when they provoke immunogenic cell death (ICD), thus inducing an antitumor immune response and even tumor elimination. However, activated caspases, the hallmark of most cancer chemotherapeutic agents, render apoptosis immunologically silent. Whether they are dispensable for chemotherapy-induced cell death and the apoptotic clearance of cells in vivo is still elusive.Methods A rational cell-based anticancer drug library screening was performed to explore the immunogenic apoptosis pathway and therapeutic targets under apoptotic caspase inhibition. Based on this screening, the potential of caspase inhibition in enhancing chemotherapy-induced antitumor immunity and the mechanism of actions was investigated by various cells and mouse models.Results Heat shock protein 90 (Hsp90) inhibition activates caspases in tumor cells to produce abundant genomic and mitochondrial DNA fragments and results in cell apoptosis. Meanwhile, it hijacks Caspase-9 signaling to suppress intrinsic DNA sensing. Pharmacological blockade or genetic deletion of Caspase-9 causes tumor cells to secrete interferon (IFN)-β via tumor intrinsic mitochondrial DNA/the second messenger cyclic GMP–AMP (cGAS) /stimulator of interferon genes (STING) pathway without impairing Hsp90 inhibition-induced cell death. Importantly, both Caspase-9 and Hsp90 inhibition triggers an ICD, leading to the release of numerous damage-associated molecular patterns such as high-mobility group box protein 1, ATP and type I IFNs in vitro and remarkable antitumor effects in vivo. Moreover, the combination treatment also induces adaptive resistance by upregulating programmed death-ligand 1 (PD-L1). Additional PD-L1 blockade can further overcome this acquired immune resistance and achieve complete tumor regression.Conclusions Blockade of Caspase-9 signaling selectively provokes Hsp90-based chemotherapy-mediated tumor innate sensing, leading to CD8+ T cell-dependent tumor control. Our findings implicate that pharmacological modulation of caspase pathway increases the tumor-intrinsic innate sensing and immunogenicity of chemotherapy-induced apoptosis, and synergizes with immunotherapy to overcome adaptive resistance.

Background: Intrahepatic cholestasis of pregnancy (ICP) is likely to lead to unfavorable consequences. Total bile acid (TBA) is thought to be the sole ICP indicator available as of now, but it comes with some kind of restrictions in terms of sensitivity and specificity. We were endeavoring to find potential diagnostic biomarkers for ICP in this investigation. Methods: This case-control study with a prospective nature included 40 females in the stage of pregnancy who were diagnosed with ICP. It also included another 20 females who were also pregnant but with sound physical condition(control). Placental and plasma samples were collected from all females that were in the stage of pregnancy, except for 20 ICP patients, in which only plasma was collected. We used four-dimensional data-independent acquisition followed by enzyme-linked immunosorbent assay and immunohistochemistry to identify and validate plasma and placental profiles in ICP patients and controls. Bioinformatics was adopted in an effort to demonstrate the relevant biological processes and signalling pathways. Correlation analysis was used to analyse the consistency of tissue and plasma protein expression and the correlation between sequencing and experimental results. Results: The expression levels of nectin-1 (NECTIN1), Kunitz-type protease inhibitor 1 (SPINT1), and inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3) were remarkably higher in ICP patients than in controls. However, heparin cofactor 2 (SERPIND1) expression levels in female participants in the stage of pregnancy who were diagnosed with ICP were remarkably lower than those pregnant females with good physical fitness. In addition to the negative correlation between SERPIND1 and TBA, NECTIN1, SPINT1, and ITIH3 expression positively correlated with TBA. Area under the receiver operating characteristic curve (AUC) values of 0.7925, 0.8313, 0.8163, and 0.9025, respectively, were used to assess the diagnostic accuracies of NECTIN1, SPINT1, ITIH3, and SERPIND1. AUC (0.9438) was considerably greater when NECTIN1, SPINT1, and SERPIND1 were integrated, according to binary logistic regression. The AUC of the ROC curve for various combinations of SERPIND1 and other indicators was higher than itself, thus providing a more reliable ICP diagnosis. Furthermore, according to the bioinformatics analysis, the NECTIN1, SPINT1, ITIH3, and SERPIND1 were identified as secreted proteins because they were localized in the extracellular region. Conclusions: This research discovered new non-invasive ICP indicators. On top of this, it sheds new light on the crucial diagnostic function of secreted proteins in ICP.

Abstract Objectives The aim of this work is to verify the non-inferior efficacy and safety of CMAB008 compared with innovator infliximab in rheumatoid arthritis patients combined with methotrexate. Methods We conducted a randomized, double-blinded, parallel, positive control design, multicenter study, with a stable dose of methotrexate. Patients were enrolled randomly with a ratio of 1:1 to receive intravenously CMAB008 3 mg/kg or innovator infliximab 3 mg/kg at weeks 0, 2, 6, 14, 22 and 30. The primary efficacy endpoint was American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 30. The non-inferiority was established if the lower limit of the one-sided 97.5% confidence interval (CI) for the difference was more than − 15% and the equivalence was established if the two-sided 95% CI was within ± 15% in an exploratory equivalence analysis. The secondary endpoints included other efficacy assessment parameters, as well as immunogenicity, safety, and pharmacokinetics. Results In the full analysis population (FAS), 110 (57.6%) of 191 patients in the CMAB008 group and 120 (62.2%) of 193 patients in the innovator infliximab group reached the primary outcome of ACR20 at week 30. The differences of the rates were − 4.6% and the lower limit of one-sided 97.5% confidence interval was − 14.29%, not less than the lower limit of the non-inferiority margin (− 15%); so CMAB008 was non-inferior to innovator infliximab. Further, CMAB008 was equivalent to innovator infliximab both in FAS (difference − 4.6%, 95% CI − 14.29% to 5.12%) and PPS (difference – 3.3%, 95% CI – 13.18% to 6.62%). The efficacy, safety, immunogenicity, and pharmacokinetics are highly similar between CMAB008 and innovator infliximab. Conclusions Non-inferior efficacy of CMAB008 to innovator infliximab is illustrated with similar early and lasting therapeutic effects, and the equivalence is further demonstrated. CMAB008 is well tolerated and has semblable safety compared with the innovator infliximab. Trial registration number NCT03478111.

Abstract Polyether-etherketone (PEEK) is a corrosion-resistant material that has been widely used in aqueous lubrication. However, its anti-wear performance must be improved for its application in the industry. In this study, to improve the anti-wear performance of PEEK for aqueous boundary lubrication, PEEK/MoS2 composites were prepared by ball-milling and spark plasma sintering processes. A competitive MoS2 mechanism between the low shear strength property and the role of promoting wear debris generation influences the anti-wear performance of PEEK/MoS2 composites. Experiments demonstrated that the coefficients of friction (COF) and wear rate of PEEK composite with 0.25 wt% MoS2 were significantly reduced 68% and 94%, respectively. Furthermore, this was the first time that a PEEK composite could achieve a COF of less than 0.05 in aqueous boundary lubrication. Its anti-wear performance was verified to be better than that of PEEK/carbon fiber (CF) and Thordon composites. The PEEK/MoS2 composite may be a potential material for underwater equipment because of its outstanding anti-wear performance in aqueous boundary lubrication.

Additive manufacturing has significant advantages in complex parts of the vehicle manufacturing. As additive manufacturing is a kind of precise production activity, different components of manufacturing instruments need to be located in appropriate positions to ensure accuracy. The visual Simultaneous Localization and Mapping (SLAM) can be considered to be a practical means for this purpose. Considering dynamic characteristics of additive manufacturing scenarios, this paper constructs a deep learning-enhanced robust SLAM approach for production monitoring of additive manufacturing. The proposed method combines the semantic segmentation technique with the motion-consistency detection algorithm together. Firstly, the Transformer-based backbone network is used to segment the images to establish the a prior semantic information of dynamic objects. Next, the feature points of dynamic objects are projected by the motion-consistency detection algorithm. Then, the static feature points are adopted for feature matching and position estimation. In addition, we conducted a couple of experiments to test function of the proposed method. The obtained results show that the proposal can have excellent performance to promote realistic additive manufacturing process. As for numerical results, the proposal can improve image segmentation effect about 10% to 15% in terms of scenarios of visual SLAM-based additive manufacturing.

Terrestrial ecosystem respiration (Reco) in drylands (arid and semi-arid areas) contributes to the largest uncertainty of the global carbon cycle. Here, using the Reco data from 24 sites (98 site-years) in drylands from Fluxnet and corresponding MODIS remote sensing products, we develop a novel semi-empirical, yet physiologically-based remote sensing model: the ILEP_Reco model (a Reco model derived from ILEP, the acronym for “integrated LE and EVI proxy”). This model can simulate Reco observations across most biomes in drylands with a small margin of error (R2 = 0.56, RMSE = 1.12 gCm−2d−1, EF = 0.46, MBE = −0.06 gCm−2d−1) and performs significantly better than the previous model: Ensemble_all. The seasonal variation of Reco in drylands can be well simulated by the ILEP_Reco model. When we relate ILEP to the Q10 model, the corresponding ILEP_Q10 values in all 98 site-years distribute quite convergently, which greatly facilitates fixing the ILEP_Q10 value as a constant in different site-years. The spatial variation of Reco in drylands is then defined as reference respiration at the annual mean ILEP, which can be easily and powerfully simulated by the ILEP_Reco model. These results help us understand the spatial-temporal variations of Reco in drylands and thus will shed light on the carbon budget on a regional scale, or even a global one.

Considerable evidence suggests that the decline in physiological abilities prevalent in older drivers leads to a reduction in the visual and psychomotor functions required for safe driving. The purpose of this study is to further investigate the differences in driving behavior between older and younger drivers and to describe the change process of driving behavior. In this study, 19 younger and older drivers each were recruited for a driving simulation experiment that included five scenarios. Driving operation data, eye movement data, and physiological data of drivers in five conflict scenarios were collected. The differences in driving behaviors between the two groups were also compared and analyzed, on which the thresholds of different driving behavior nodes were determined and driving behavior graphs were established. The results show that the eye movement nodes of older drivers appear later in five scenarios, the operational nodes of older people appear later in two steering scenarios, and are closer to those of younger drivers in three straight ahead scenarios, indicating that older drivers were later in observing and collecting traffic information, and later in applying brakes and steering to avoid conflicts when steering. The study provides a reference for the analysis of driving behavior and driving safety of older people.

Objective: To examine whether joint management of cancer pain by physicians and pharmacists in clinics provides economic advantages from the perspective of the Chinese healthcare system.Methods: From February 2018 to March 2020, 100 patients who visited the joint cancer pain clinic at the Xiangya Hospital of Central South University were included. These patients were randomly assigned to either the control or intervention groups. The control group received regular outpatient services from a physician, while the intervention group received regular outpatient services from a physician and medication education provided by a pharmacist. The study considered various direct costs, including drug expenses, physician-pharmacist outpatient services, adverse event management, consultations, examinations, and readmissions. The outcome indicators considered were the cancer pain control rate and the reduction in pain scores. Decision tree modeling, single-factor sensitivity analysis, and probabilistic sensitivity analysis were performed to evaluate the cost-effectiveness of joint physician-pharmacist outpatient services compared to physician-alone outpatient services.Results: The intervention group showed a significantly higher cancer pain control rate than the control group (0.69 vs. 0.39, p = 0.03). In the decision tree model, the intervention group had a significantly lower pain score than the control group (0.23 vs. 0.14). The cost per person in the intervention group was $165.39, while it was $191.1 per person in the control group. The univariate sensitivity analysis showed that the cost of self-management for patients in the control group was identified as the primary sensitivity factor. Probabilistic sensitivity analysis indicated that the joint clinic group had a favorable incremental cost-effectiveness compared to the physician clinic group. In addition, the probabilistic sensitivity analysis demonstrated an absolute advantage in the incremental cost-effectiveness of the joint clinic group over the outpatient physician group.Conclusion: The participation of pharmacists in joint cancer pain clinic services led to improved pain management for patients, demonstrating a clear advantage in terms of cost-effectiveness.

Under water, on land, or in the air, creatures use a variety of grasping methods to hunt, avoid predators, or carry food. Numerous studies have been conducted to construct a bionic surface for grasping tasks. This paper reviews the typical biomimetic structures and surfaces (wedge-shaped surface, suction cup surface and thorn claw surface) for grasping scenarios. Initially, progress in gecko-inspired wedge-shaped adhesive surfaces is reviewed, encompassing the underlying mechanisms that involve tuning the contact area and peeling behavior. The applications of grippers utilizing this adhesive technology are also discussed. Subsequently, the suction force mechanisms and applications of surfaces inspired by octopus and remora suction cups are outlined. Moreover, this paper introduces the applications of robots incorporating the principles of beetle-inspired and bird-inspired thorn claw structures. Lastly, inspired by remoras’ adhesive discs, a composite biomimetic adhesive surface is proposed. It integrates features from wedge-shaped, suction cup, and claw thorn surfaces, potentially surpassing the adaptability of basic bioinspired surfaces. This surface construction method offers a potential avenue to enhance adhesion capabilities with superior adaptability to surface roughness and curvature.

BackgroundSince the end of 2019, Corona Virus Disease 2019, also known as COVID-19, has broken out in various countries. However, the change of China's COVID-19 prevention and control policy and the sharp increase in the number of infected people are making the teenagers have post-traumatic reactions. Negative post-traumatic reactions include: post-traumatic stress disorder (PTSD), depression, anxiety. Positive post-traumatic reaction mainly refers to post-traumatic growth (PTG). The purpose of this study is to explore the post-traumatic reaction, which refers to PTSD, depression, anxiety and the co-occurrence pattern of growth after trauma and to further explore the influence of family function on different categories of Post-traumatic Reactions.MethodsLatent profile analysis (LPA) was used to explore the co-occurrence of PTSD, depression, anxiety, and PTG. Multiple logistics regression was used to analyze the influence of family function on different categories of post-traumatic response.ResultsThere were three categories of post-traumatic reactions in adolescents infected with COVID-19 adolescents infected with COVID-19, namely: growth class, struggling class, and pain class. Multivariate Logistic regression showed that the growth class and struggling class were affected by problem solving and behavior control in family function, while the growth class and pain class were affected by problem solving, roles, behavior control, and general functioning. Multiple logistic regression showed that the growth class and struggling class were affected by problem solving and roles.ConclusionsThe findings of this study provide evidence for the identification of high-risk individuals and the provision of effective interventions in clinical practice, as well as the influence of family functioning on the different categories of PTSD among adolescents infected with COVID-19.

The high salt content in saline–alkaline land leads to insufficient nutrients, thereby reducing agricultural productivity. This has sparked widespread interest in improving saline–alkaline soil. In this investigation, 16S rRNA gene high-throughput sequencing was employed to examine the impacts of three cropping systems (monoculture, rotation, and mixture) on soil bacterial communities. It was found that cropping rotations and mixtures significantly increased soil bacterial α-diversity. Random forest analysis showed a significant linear relationship between AK and EC and bacterial α-diversity. In addition, principal coordinates analysis (PCoA) further confirmed the significant differences in β-diversity between different soil layers. Through co-occurrence network analysis, it was found that cropping rotations and mixtures increased the stability and complexity of co-occurrence networks. By calculating NST to analyze the assembly process of soil bacterial communities in different cropping systems, it was found that the assembly process of soil bacterial communities was dominated by a stochastic process. Functional prediction results showed that a large number of C, N, and S cycling microbes appeared in soil bacterial communities. Our study aims to establish a fresh perspective on the improvement and recovery of saline–alkaline soil.

The tension cable-supported power transmission structure (TC-PTS) is a new type of power transmission structure suitable for mountainous terrain, and is sensitive to wind load. In this regard, a nonlinear finite element analysis model of wind-induced vibration is proposed for the TC-PTS, and the wind-induced vibration response of the structure is analyzed. Firstly, the tangent stiffness matrix of the three-dimensional truss element for the supporting suspension cable and transmission line, considering the geometric nonlinearity of structures, is derived through the relationship between the element elastic energy and its displacement. Subsequently, the element mass matrix and damping matrix of the supporting suspension cable and transmission line, as well as the element nodal load vector obtained from wind load equivalence, are given. Then, based on the nonlinear finite element theory, the nonlinear dynamic equation of wind-induced vibration is established for the TC-PTS and solved using the Newmark-β method combined with the Newton–Raphson iterative method. Furthermore, the rain-flow counting method and Miner’s linear fatigue cumulative damage theory were used for wind-induced fatigue damage assessment. Finally, a two-span TC-PTS was selected as an example, and the wind-induced nonlinear vibration and fatigue damage assessment were analyzed through the proposed model. The results show that the proposed model has high computational accuracy and efficiency. The first three order vibration modes of the supporting-conductor part of the two-span TC-PTS were antisymmetric vertical bending, symmetric side bending, and antisymmetric side bending. With the increase in wind speed and wind direction angle, the maximum lateral displacement and tension of the supporting suspension cable and transmission line increased, and their degree of increase showed a nonlinear trend. In terms of the wind-induced fatigue analysis results of TC-PTS, the fatigue damage at the end of the supporting-conductor suspension cable was greater than the fatigue damage at its midpoint. Compared to the fatigue damage at the midpoint of the conductor, the fatigue damage at the end of the conductor was less affected by the wind direction angle, and both were more significantly affected by the wind speed.

Abstract Lung cancer is a leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) being the most common histological type. Owing to the limited therapeutic efficacy and side effects of currently available therapies for NSCLC, it is necessary to identify novel therapeutic targets for NSCLC. Long non-coding RNAs (lncRNAs) are non-protein-coding RNAs with a transcript length of more than 200 nucleotides, which play a vital role in the tumorigenesis and progression of multiple cancers, including NSCLC. Induction of programmed cell death (PCD) is the main mechanism leading to tumour cell death in most cancer treatments. Recent studies have demonstrated that lncRNAs are closely correlated with PCD including apoptosis, pyroptosis, autophagy and ferroptosis, which can regulate PCD and relevant death pathways to affect NSCLC progression and the efficacy of clinical therapy. Therefore, in this review, we focused on the function of lncRNAs in PCD of NSCLC and summarized the therapeutic role of targeting lncRNAs in PCD for NSCLC treatment, aiming to provide new sights into the underlying pathogenic mechanisms and propose a potential new strategy for NSCLC therapy so as to improve therapeutic outcomes with the ultimate goal to benefit the patients.

BackgroundSystemic lupus erythematosus (SLE) is a systemic autoimmune disease involving multiple organs throughout the body. The health care–seeking behaviors, disease progression of SLE, and patients' knowledge of and attitudes toward SLE have not been characterized in China. ObjectiveThe aim of this study was to depict the health care–seeking behaviors, disease progression, and medications in patients with SLE and to examine the factors associated with their disease flares, knowledge, and attitudes toward SLE in China. MethodsWe conducted a cross-sectional survey in 27 provinces in China. Descriptive statistical methods were used to depict the demographic characteristics, health care–seeking behaviors, medications, and health status. Multivariable logistic regression models were used to identify the factors associated with disease flares, medication changes, and attitudes toward SLE. An ordinal regression model was used to examine the factors associated with the knowledge of the treatment guidelines. ResultsWe recruited 1509 patients with SLE, and 715 had lupus nephritis (LN). Approximately 39.96% (603/1509) of the patients with SLE were primarily diagnosed with LN, and 12.4% (112/906) developed LN (mean time 5.2 years) from non-LN. Patients whose registered permanent residences or workplaces in other cities from the same province and adjacent provinces seeking health care accounted for 66.9% (569/850) and 48.8% (479/981) of the patients with SLE in the provincial capital cities, respectively. Mycophenolate mofetil was the most commonly used immunosuppressive drug in patients without LN (185/794, 23.3%) and patients with LN (307/715, 42.9%). Femoral head necrosis (71/228, 31.1%) and hypertension (99/229, 43.2%) were the most common adverse event (AE) and chronic disease during treatment, respectively. Change of hospitals for medical consultation (odds ratio [OR] 1.90, 95% CI 1.24-2.90) and development of 1 chronic disease (OR 3.60, 95% CI 2.04-6.24) and AE (OR 2.06, 95% CI 1.46-2.92) and more were associated with disease flares. A pregnancy plan (OR 1.58, 95% CI 1.18-2.13) was associated with changes in medication. Only 242 (16.03%) patients with SLE were familiar with the treatment guidelines, and patients with LN tended to be more familiar with the disease (OR 2.20, 95% CI 1.81-2.68). After receiving treatment, 891 (59.04%) patients changed their attitudes toward SLE from fear to acceptance, and patients with college education or higher (OR 2.09, 95% CI 1.10-4.04) were associated with a positive attitude toward SLE. ConclusionsA large proportion of patients seeking health care in the provincial capital cities of China migrated from other cities. Persistent monitoring of potential AEs and chronic diseases during SLE treatment and managing patients who changed hospitals for medical consultation are essential for controlling disease flares. Patients had insufficient knowledge about SLE treatment guidelines and would benefit from health education to maintain a positive attitude toward SLE.

Abstract Background As a major component of plant cell walls, cellulose provides the most abundant biomass resource convertible for biofuels. Since cellulose crystallinity and polymerization have been characterized as two major features accounting for lignocellulose recalcitrance against biomass enzymatic saccharification, genetic engineering of cellulose biosynthesis is increasingly considered as a promising solution in bioenergy crops. Although several transcription factors have been identified to regulate cellulose biosynthesis and plant cell wall formation, much remains unknown about its potential roles for genetic improvement of lignocellulose recalcitrance. Results In this study, we identified a novel rice mutant (Osfc9/myb103) encoded a R2R3-MYB transcription factor, and meanwhile generated OsMYB103L-RNAi-silenced transgenic lines. We determined significantly reduced cellulose levels with other major wall polymers (hemicellulose, lignin) slightly altered in mature rice straws of the myb103 mutant and RNAi line, compared to their wild type (NPB). Notably, the rice mutant and RNAi line were of significantly reduced cellulose features (crystalline index/CrI, degree of polymerization/DP) and distinct cellulose nanofibers assembly. These alterations consequently improved lignocellulose recalcitrance for significantly enhanced biomass enzymatic saccharification by 10–28% at p

Objectives Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, were evaluated in a 6-month, double-blind, phase 3 study in Chinese patients with active (polyarthritic) psoriatic arthritis (PsA) and inadequate response to ≥1 conventional synthetic disease-modifying antirheumatic drug.Methods Patients were randomised (2:1) to tofacitinib 5 mg twice daily (N=136) or placebo (N=68); switched to tofacitinib 5 mg twice daily after month (M)3 (blinded). Primary endpoint: American College of Rheumatology (ACR50) response at M3. Secondary endpoints (through M6) included: ACR20/50/70 response; change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI); ≥75% improvement in Psoriasis Area and Severity Index (PASI75) response, and enthesitis and dactylitis resolution. Safety was assessed throughout.Results The primary endpoint was met (tofacitinib 5 mg twice daily, 38.2%; placebo, 5.9%; p

BackgroundLung adenocarcinoma (LUAD) is a malignant tumor that seriously affects the prognosis of patients. Tumor-associated macrophages (TAMs) play a vital role in the tumor microenvironment and can be used as a potential target for tumor therapy, and phagocytosis regulators (PRs) are particularly important in this process. However, the PRs-related signature that can predict the potential prognostic and immunotherapeutic value in patients with LUAD has not been discovered.MethodsIn this study, we mainly analyzed the effect of phagocytosis regulators on the prognosis of LUAD, and based on multiple screening analyses including differential analysis, univariate Cox analysis, and Lasso analysis, we constructed a prognostic risk model consisting of five genes. To verify the stability of the model, survival analysis and ROC curve verification were carried out through multiple data sets. In addition, we also combined many factors, such as immune infiltrating cells, clinical grouping characteristics, immune examination sites, pro-inflammatory factors, and other factors as well as in vitro cell experiments and clinical tissue samples for further validation analysis.ResultsAfter identifying 29 differentially expressed PRs in LUAD samples, we further constructed a prognostic model consisting of five prognostic signatures (FURIN, KIF23, SASH3, GNPNAT1, and ITGAL). Further survival analysis tests, ROC verification, as well as univariate and multivariate Cox regression analysis showed that the risk score of the model could well predict the prognosis of LUAD patients and could be used as an independent prognostic factor. In addition, we further found that these phagocytic regulators-related signatures were closely related to the immune microenvironment and immunotherapy in LUAD patients, and could well predict the efficacy of immunotherapy in patients. In vitro cell experiments and Immunohistochemistry of clinical tissues showed that the expressions of FURIN, KIF23, SASH3, GNPNAT1 and ITGAL in normal lung cells/tissues and LUAD cells/tissues were consistent with bioinformatics results, and 3 of them had significant differences.ConclusionOur study identified a novel PRs-related signature that has potential application value in predicting the prognosis of LUAD patients and predicting the efficacy of immunotherapy. This provides a new basis for the prognosis assessment of LUAD patients and provides a novel target for immunotherapy of LUAD patients.

Excessive thermal stress can cause the failure of a solid oxide fuel cell (SOFC), and an inhomogeneous temperature field is one of the reasons for thermal stress in the cell. In the present work, the bi-dimensional thermo-mechanical coupling models of SOFCs with different interface morphologies including planar and corrugated cells are proposed. The temperature distribution of two types of cells under the action of heat conduction is analyzed. Further, the inhomogeneous temperature field caused by gas flow is used as the thermal load to compare the thermal stress distribution of planar and corrugated cells. The influence of interface morphology on the temperature distribution, stress distribution and the contribution of the temperature gradient to stress distribution are investigated. This research provides a reference for reducing thermal stress and improving the stability of SOFC.

Magnification endoscopy with narrow-band imaging (ME-NBI) technology is widely used in the early diagnosis of precancerous lesions and gastric cancer, which is critical to reducing the incidence of gastric cancer and improving the survival rate of gastric cancer patients. The diagnosis based on ME-NBI image is mostly in manual way in clinics. In order to improve its objectivity and efficiency, here we proposed a lightweight attention mechanism deep learning model to automatically classify ME-NBI images for artificial intelligence (AI) diagnosis of early gastric cancer, low-grade intraepithelial neoplasia, and non-neoplasm. We collected 4,098 images from 990 patients for model training and validation and evaluated the performance of our model by comparisons with that of other models, such as the benchmark model. An additional 587 images from 296 patients were collected as an independent test set to further evaluate our method’s performance. The validation set showed that the overall accuracy, recall, precision, F1 score, and the area under the curve of our method were higher than those of other methods. The independent test set showed that our method achieved state-of-the-art classification for low-grade intraepithelial neoplasia (accuracy = 93.9%, sensitivity = 92.6%). Our method displayed the advantages of lightweight and high effectiveness in classifying effectiveness, which is the potential for AI diagnosis of early gastric cancer, low-grade intraepithelial neoplasia, and non-neoplasm.

Abstract Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.