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Abstract Background Clonorchiasis has significant socioeconomic importance in endemic areas; however, studies investigating the disease burden in specific sub-regions are lacking. This study aims to address the gap by quantifying the current disease burden caused by clonorchiasis in Guangdong province and assessing its distribution characteristics. Methods Comprehensive measures, including prevalence rates, disability-adjusted life years (DALYs), and direct medical costs, were used to assess the disease burden of clonorchiasis. To estimate the prevalence rate, the number of infections was divided by the examined population, based on the annual surveillance data on clonorchiasis cases during 2016–2021. The calculation of DALYs was based on the epidemiological parameters according to the definition issued by the World Health Organization. Cost data of clonorchiasis were utilized to quantify the direct medical costs. The distribution characteristics of disease burden were assessed through comparisons of groups of population defined by geographic area, time, and characteristics of people. Results In 2021, clonorchiasis posed a significant disease burden in Guangdong Province. The prevalence rate was found to be 4.25% [95% CI (4.02%, 4.49%)], with an associated burden of DALYs of 406,802.29 [95% CI (329,275.33, 49,215,163.78)] person-years. The per-case direct medical costs of patients with clonorchiasis were estimated to be CNY 7907.2 (SD = 5154.4). Notably, while the prevalence rate and DALYs showed a steady decrease from 2016 to 2020, there was a rising trend in 2021. Spatial clustering of clonorchiasis cases and DALYs was also observed, particularly along the Pearl River and Han River. This suggests a concentration of the disease in these regions. Furthermore, significant differences in prevalence rates were found among various demographic groups, including sex, age, occupation, and education level. Additionally, patients with longer hospital stays were more likely to incur higher direct medical costs. Conclusions The burden of clonorchiasis in Guangdong Province remains high, despite significant progress achieved through the implementation of the prevention and control programs. It is suggested that measures should be taken based on the distribution characteristics to maximize the effectiveness of prevention and control, with a primary focus on key populations and areas. Graphical Abstract

Heme, an iron-containing porphyrin derivative, holds great promise in fields like medicine, food production and chemicals. Here, we developed an engineered Corynebacterium glutamicum strain for efficient heme production by combining modular engineering and RBS engineering. The whole heme biosynthetic pathway was methodically divided into 5-ALA synthetic module, uroporphyrinogen III (UPG III) synthetic module and heme synthetic module for further construction and optimization. Three heme synthetic modules were compared and the siroheme-dependent (SHD) pathway was identified to be optimal in C. glutamicum for the first time. To further improve heme production, the expression of genes in UPG III synthetic module and heme synthetic module was coordinated optimized through RBS engineering, respectively. Subsequently, heme oxygenase was knocked out to reduce heme degradation. The engineered strain HS12 showed a maximum iron-containing porphyrin derivatives titer of 1592 mg/L with the extracellular secretion rate of 45.5% in fed-batch fermentation. Our study constructed a C. glutamicum chassis strain for efficient heme accumulation, which was beneficial for the advancement of efficient heme and other porphyrins production.

Abstract The immunoprotective components control COVID-19 disease severity, as well as long-term adaptive immunity maintenance and subsequent reinfection risk discrepancies across initial COVID-19 severity, remain unclarified. Here, we longitudinally analyzed SARS-CoV-2-specific immune effectors during the acute infection and convalescent phases of 165 patients with COVID-19 categorized by severity. We found that early and robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses ameliorate disease progression and shortened hospital stay, while delayed and attenuated virus-specific CD8+ T cell responses are prominent severe COVID-19 features. Delayed antiviral antibody generation rather than titer level associates with severe outcomes. Conversely, initial COVID-19 severity imprints the long-term maintenance of SARS-CoV-2-specific adaptive immunity, demonstrating that severe convalescents exhibited more sustained virus-specific antibodies and memory T cell responses compared to mild/moderate counterparts. Moreover, initial COVID-19 severity inversely correlates with SARS-CoV-2 reinfection risk. Overall, our study unravels the complicated interaction between temporal characteristics of virus-specific T cell responses and COVID-19 severity to guide future SARS-CoV-2 wave management.

As widely used energy-absorbing protective materials, the application of aluminum foam sandwich (AFS) panels remains constrained by the inherently low mechanical properties of the foam core. The incorporation of copper-coated carbon fibers (Cf) has proven to be effective in improving the mechanical properties of aluminum foam. Yet, the understanding of its foaming process and microstructure is still limited. In this work, AFS and Cf/AFS were fabricated by the packing rolling powder metallurgy method. The foaming behavior of AFS and Cf/AFS during elevated temperatures was in situ observed using synchrotron radiation X-ray imaging technology to investigate the effect of Cf on bubble nucleation, growth, and foam stability. Furthermore, the macroscopic pore size distribution, microscopic microstructure, and compressive mechanical properties of AFS and Cf/AFS were analyzed. The results showed that the existence of Cf greatly increases the nucleation rate, improves the foaming stability, and prevents the formation of localized abnormally large bubbles during the early nucleation and growth process. Meanwhile, Cf/AFS exhibited finer pore diameters and fewer pore defects than AFS. The distribution of Cf with excellent wettability along the pore wall prevented liquid film rupture and reduced coalescence. The compression experiment indicated that, in comparison to AFS, the compressive strength and energy absorption capacity of Cf/AFS have increased by approximately 40.6% and 84.8%, respectively.

RNA-binding motif protein 10 (RBM10) has a tumor suppressor role in multiple cancers. Combining Oncomine database results with tissue samples, Western blot analysis showed that RBM10 was significantly lower in lung adenocarcinoma (LUAD) than in adjacent normal tissues. Moreover, KM analysis revealed that the group with higher RBM10 expression in LUAD correlated with better overall survival (OS). Luciferase reporter assay revealed that an important tumor-promotive miRNA, miR-224-5p, was directly bound to the 3′UTR of RBM10, resulting in inhibition of RBM10 expression, and promoted LUAD progression both in vitro and in vivo. Mechanistically, we found that miR-224-5p directly targeted RBM10 to inhibit p53 expression during LUAD progression. Meanwhile, p53 affected RBM10 expression through p53/miR-224-5p axis. Our study identified RBM10 as a key tumor suppressor in the proliferation and metastasis of LUAD. The findings provide a novel mechanism involving a feedback loop of miR-224-5p/RBM10/p53 regulated tumor progression in LUAD, which may help with the design of more effective LUAD treatments.

Abstract Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate. Three-dimensional (3D) chromatin architecture takes part in disease processing by regulating transcriptional reprogramming. The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver (FLS) and reveal their effect on hepatic transcriptional reprogramming in laying hens. Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposition as well as higher total triglyceride and cholesterol in serum. A/B compartment switching, topologically associating domain (TAD) and chromatin loop changes are identified by high-throughput/resolution chromosome conformation capture (HiC) technology. Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage. H3K27ac differential peaks and differential expression genes (DEGs) identified through RNA-seq analysis are also enriched in these pathways. Notably, certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters. DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogramming. Furthermore, disturbed folate metabolism is observed, as evidenced by lower folate levels and altered enzyme expression. Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin structure variations during early FLS formation, which provides candidate transcription factors and folate as targets for FLS prevention or treatment.

Abstract The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy.

ABSTRACT: Oxidative stress is a frequent concern in the breeding of laying hens, and limit the healthy development of poultry. Dexamethasone (DXM) has been demonstrated to induce oxidative stress. Conversely, betaine is an alkaloid with a potent antioxidant activity. The study was designed to investigate the ameliorative effect of betaine on DXM-induced oxidative stress in laying hens. The results revealed that DXM treatment significantly decreased laying rate, shell strength, albumen height, Haugh unit, egg weight, folk weight and albumen weight, alongside increased malondialdehyde (MDA) and decreased total antioxidant capacity (T-AOC) in serum and liver (P < 0.05). In contrast, dietary betaine addition reversed those parameters mentioned above (P < 0.05). Hepatic RNA-seq analysis showed that there existed 110 up- and 88 down-regulated genes in DXM group when compared with the control. Meanwhile there were 117 upregulation and 169 downregulation genes in BT group when compared with DXM group. Besides, we found that dietary betaine addition significantly down-regulated cell adhesion molecules, glycerolipid metabolism and glycolysis gluconeogenesis pathways. In addition, a total of 44 and 94 differential metabolites were identified respectively from Con vs. DXM and DXM vs BT. More importantly, dietary betaine addition significantly increased the levels of pantothenic acid, gamma-Aminobutyric acid, equol and choline, all of which were related to antioxidant and anti-inflammatory properties. Furthermore, gut microbiota analysis indicated that the Chao and Observed_species indexes were remarkably higher in BT group (P

ABSTRACT: The hyperplasia and hypertrophy of preadipocytes were closely related to lipid deposition in animals. Butyric acid was reported to be involved in lipid metabolism. The aim of the current study was to investigate the effect of butyric acid on the proliferation and differentiation of the immortalized chicken preadipocyte 2 (ICP2). ICP2 were treated respectively with 12mM butyric acid for 48h in proliferation trial and 4mM butyric acid plus 200 μM oleic acid for 3 d in differentiation trial. For the proliferation trial, RNA-seq analysis revealed that 2039 genes were significantly up-regulated and 780 genes were significantly down-regulated with 12 mM butyric acid after 48 h treatment. Concurrently, Cell cycle, DNA replication and p53 signaling pathways were down-regulated in Butyric acid group. More importantly, 12 mM butyric acid restrained the expression of cell proliferation genes such as PCNA, CDK1 and CDK2 in Butyric acid group (P < 0.05), and the protein expression levels of PCNA and CDK1 were also significantly decreased (P < 0.05). The Oil red staining revealed a fewer presence of red fat droplets in ICP2 following treatment with 4 mM butyric acid, accompanied by decreased levels of total cholesterol (TC) and triglycerides (TG). RNA-seq analysis shown that the number of up and down-regulated genes were 2095 and 1042 respectively in OAB group (oleic acid+butyric acid) when compared with OA group (oleic acid). Meanwhile the AMPK signaling pathway, FOXO signaling pathway and focal adhesion were significantly enriched in OAB group. Additionally, 4 mM butyric acid inhibited the expression of lipid differentiation genes including FABP4, C/EBPα, PPARγ and LPL in OAB group (P < 0.05), as well as lipogenesis proteins such as FABP4, C/EBP-α and PPARγ (P < 0.05). In conclusion, 12 mM butyric acid effectively inhibited the proliferation of ICP2 by slowing down cell cycle progression, while 4 mM butyric acid alleviated lipid deposition by reducing the production of lipid droplets through inhibiting the expression of lipid differentiation marker genes and proteins.

Chronic graft-versus-host disease (cGVHD) is a potentially life-threatening complication after allogeneic hematopoietic stem cell transplantation. Standard steroid first-line treatment could not satisfy therapeutic needs due to limited efficacy. As a highly selective Janus kinase (JAK) 1 inhibitor, SHR0302 exhibits a reduced inhibition effect on JAK2 and might have less effect on hematopoiesis. This phase I clinical trial investigated the tolerability and safety of SHR0302 in combination with prednisone, and its early efficacy evidence as a potential first-line treatment to moderate/severe cGVHD. The standard 3 + 3 dose escalation was implemented to find the optimal dose of SHR0302. And prednisone was concurrently administrated with a dose of 1 mg/kg/d and then gradually tapered after 2 weeks. Eighteen patients were enrolled into the study. Grade ≥ 3 treatment-related adverse events were observed in 38.9% of patients. Only one patient developed DLT (grade ≥ 3 hypercholesterolemia) in the highest dose-level group who had pre-existing hypercholesterolemia. The maximum tolerated dose was not reached. No patient discontinued treatment due to AEs. Sixteen out of 18 patients were evaluable for responses, the ORR at week 4 and week 24 were 94.4 and 87.5%, respectively. Overall, the treatment of SHR0302 combined with prednisone was safe and well-tolerated, preliminary clinical results presented a high response for previously untreated cGVHD and a significant reduction in prednisone use in this study. A phase II trial will be conducted to further investigate its therapeutic effects clinically.

Background Interferons (IFNs) are essential for activating an effective immune response and play a central role in immunotherapy-mediated immune cell reactivation for tumor regression. Type III IFN (λ), related to type I IFN (α), plays a crucial role in infections, autoimmunity, and cancer. However, the direct effects of IFN-λ on the tumor immune microenvironment have not been thoroughly investigated.Methods We used mouse MB49 bladder tumor models, constructed a retroviral vector expressing mouse IFN-λ3, and transduced tumor cells to evaluate the antitumor action of IFN-λ3 in immune-proficient tumors and T cell-deficient tumors. Furthermore, human bladder cancer samples (cohort 1, n=15) were used for immunohistochemistry and multiplex immunoflurescence analysis to assess the expression pattern of IFN-λ3 in human bladder cancer and correlate it with immune cells’ infiltration. Immunohistochemistry analysis was performed in neoadjuvant immunotherapy cohort (cohort 2, n=20) to assess the correlation between IFN-λ3 expression and the pathological complete response rate.Results In immune-proficient tumors, ectopic Ifnl3 expression in tumor cells significantly increased the infiltration of cytotoxic CD8+ T cells, Th1 cells, natural killer cells, proinflammatory macrophages, and dendritic cells, but reduced neutrophil infiltration. Transcriptomic analyses revealed significant upregulation of many genes associated with effective immune response, including lymphocyte recruitment, activation, and phagocytosis, consistent with increased antitumor immune infiltrates and tumor inhibition. Furthermore, IFN-λ3 activity sensitized immune-proficient tumors to anti-PD-1/PD-L1 blockade. In T cell-deficient tumors, increased Ly6G–Ly6C+I-A/I-E+ macrophages still enhanced tumor cell phagocytosis in Ifnl3 overexpressing tumors. IFN-λ3 is expressed by tumor and stromal cells in human bladder cancer, and high IFN-λ3 expression was positively associated with effector immune infiltrates and the efficacy of immune checkpoint blockade therapy.Conclusions Our study indicated that IFN-λ3 enables macrophage-mediated phagocytosis and antitumor immune responses and suggests a rationale for using Type III IFN as a predictive biomarker and potential immunotherapeutic candidate for bladder cancer.

Abstract Background Studies on the gut microbiota of animals have largely focused on vertebrates. The transmission modes of commensal intestinal bacteria in mammals have been well studied. However, in gastropods, the relationship between gut microbiota and hosts is still poorly understood. To gain a better understanding of the composition of gut microbes and their transmission routes in gastropods, a large-scale and long-term experiment on the dynamics and transmission modes of gut microbiota was conducted on freshwater snails. Results We analyzed 244 microbial samples from the digestive tracts of freshwater gastropods and identified Proteobacteria and Bacteroidetes as dominant gut microbes. Aeromonas, Cloacibacterium, and Cetobacterium were identified as core microbes in the guts, accounting for over 50% of the total sequences. Furthermore, both core bacteria Aeromonas and Cloacibacterium, were shared among 7 gastropod species and played an important role in determining the gut microbial community types of both wild and cultured gastropods. Analysis of the gut microbiota at the population level, including wild gastropods and their offspring, indicated that a proportion of gut microbes could be consistently vertically transmitted inheritance, while the majority of the gut microbes resulted from horizontal transmission. Comparing cultured snails to their wild counterparts, we observed an increasing trend in the proportion of shared microbes and a decreasing trend in the number of unique microbes among wild gastropods and their offspring reared in a cultured environment. Core gut microbes, Aeromonas and Cloacibacterium, remained persistent and dispersed from wild snails to their offspring across multiple generations. Interestingly, under cultured environments, the gut microbiota in wild gastropods could only be maintained for up to 2 generations before converging with that of cultured snails. The difference observed in gut bacterial metabolism functions was associated with this transition. Our study also demonstrated that the gut microbial compositions in gastropods are influenced by developmental stages and revealed the presence of Aeromonas and Cloacibacterium throughout the life cycle in gastropods. Based on the dynamics of core gut microbes, it may be possible to predict the health status of gastropods during their adaptation to new environments. Additionally, gut microbial metabolic functions were found to be associated with the adaptive evolution of gastropods from wild to cultured environments. Conclusions Our findings provide novel insights into the dynamic processes of gut microbiota colonization in gastropod mollusks and unveil the modes of microbial transmission within their guts. Video Abstract

Abstract Background Gastropoda, the largest class within the phylum Mollusca, houses diverse gut microbiota, and some gastropods serve as intermediate hosts for parasites. Studies have revealed that gut bacteria in gastropods are associated with various biological aspects, such as growth, immunity and host–parasite interactions. Here, we summarize our current knowledge of gastropod gut microbiomes and highlight future research priorities and perspectives. Methods A literature search was undertaken using PubMed, Web of Science and CNKI for the articles on the gut microbiota of gastropods until December 31, 2022. We retrieved a total of 166 articles and identified 73 eligible articles for inclusion in this review based on the inclusion and exclusion criteria. Results Our analysis encompassed freshwater, seawater and land snails, with a specific focus on parasite-transmitting gastropods. We found that most studies on gastropod gut microbiota have primarily utilized 16S rRNA gene sequencing to analyze microbial composition, rather than employing metagenomic, metatranscriptomic, or metabolomic approaches. This comprehensive review provided an overview of the parasites carried by snail species in the context of gut microbiota studies. We presented the gut microbial trends, a comprehensive summary of the diversity and composition, influencing factors, and potential functions of gastropod gut microbiota. Additionally, we discussed the potential applications, research gaps and future perspectives of gut microbiomes in parasite-transmitting gastropods. Furthermore, several strategies for enhancing our comprehension of gut microbiomes in snails were also discussed. Conclusions This review comprehensively summarizes the current knowledge on the composition, potential function, influencing factors, potential applications, limitations, and challenges of gut microbiomes in gastropods, with a specific emphasis on parasite-transmitting gastropods. These findings provide important insights for future studies aiming to understand the potential role of gastropod gut microbiota in controlling snail populations and snail-borne diseases. Graphical abstract

Abstract Schistosoma parasites, causing schistosomiasis, exhibit typical host specificity in host preference. Many mammals, including humans, are susceptible to infection, while the widely distributed rodent, Microtus fortis, exhibits natural anti-schistosome characteristics. The mechanisms of host susceptibility remain poorly understood. Comparison of schistosome infection in M. fortis with the infection in laboratory mice (highly sensitive to infection) offers a good model system to investigate these mechanisms and to gain an insight into host specificity. In this study, we showed that large numbers of leukocytes attach to the surface of human schistosomes in M. fortis but not in mice. Single-cell RNA-sequencing analyses revealed that macrophages might be involved in the cell adhesion, and we further demonstrated that M. fortis macrophages could be mediated to attach and kill schistosomula with dependence on Complement component 3 (C3) and Complement receptor 3 (CR3). Importantly, we provided direct evidence that M. fortis macrophages could destroy schistosomula by trogocytosis, a previously undescribed mode for killing helminths. This process was regulated by Ca2+/NFAT signaling. These findings not only elucidate a novel anti-schistosome mechanism in M. fortis but also provide a better understanding of host parasite interactions, host specificity and the potential generation of novel strategies for schistosomiasis control.

ABSTRACT: Excess abdominal fat reduces carcass yield and feed conversion ratio, thereby resulting in significant economic losses in the poultry industry. Our previous study demonstrated that dietary addition of folic acid reduced fat deposition and changed gut microbiota and short-chain fatty acid. However, whether folic acid regulating abdominal fat deposition was mediated by gut microbiota was unclear. A total of 210 one-day-old broiler chickens were divided into 3 groups including the control (CON), folic acid (FA), and fecal microbiota transplantation (FMT) groups. From 14th day, broiler chickens in CON and FA groups were given perfusion administration with 1 mL diluent daily, while 1 mL fecal microbiota transplantation suspension from FA group prepared before was perfusion in FMT group receiving control diets. The result showed that abdominal fat percentage was significantly lower in FA and FMT groups when compared with CON group (P < 0.05). Morphology analysis revealed that the villus height of jejunum and ileum were significantly higher in FMT group (P < 0.05), and the villus height of jejunum was also significantly higher in FA group (P < 0.05), while the diameter and cross-sectional area (CSA) of adipocytes were significantly decreased in FA and FMT groups when compared with CON group (P < 0.05). Western blot results indicated that the expression levels of FOXO1 and PLIN1 in FMT group were significantly increased (P < 0.05), whereas the expression levels of PPARγ, C/EBPα, and FABP4 were significantly decreased (P < 0.05). Additionally, the Chao1, Observed-species, Shannon and Simpson indexes in FA and FMT groups were significantly higher (P < 0.05), but the microbiota were similar between FMT and FA groups (P < 0.05). LEfSe analysis determined that Lactobacillus, Clostridium and Dehalobacterium were found to be predominant in FA group, while Oscillospira, Shigella, and Streptococcus were the dominant microflora in FMT group. Furthermore, these cecal microbiota were mostly involved in infectious disease, cellular community prokaryotes, cell motility and signal transduction in FA group (P < 0.05), whereas functional capacities involved in signal transduction, cell motility, infectious disease and environment adaptation were enriched significantly of cecal microbiota in FMT group (P < 0.05). In summary, both fecal microbiota transplantation from the broiler chickens of dietary added folic acid and dietary folic acid addition effectively reduced abdominal fat deposition, indicating that the regulatory effect of folic acid on abdominal fat deposition was mediated partly by gut microbiota in broiler chickens.

Abstract Objectives Lymphatic metastasis, an early stage of the metastasis process, is associated with adverse clinical outcomes in urothelial carcinoma of the bladder (UCB). However, the role of inflammation in triggering lymphatic metastasis remains unclear. Methods We employed an RNA‐sequencing cohort (n = 50) from Sun Yat‐Sen Memorial Hospital (SYMH) to identify the most highly upregulated inflammatory gene associated with lymphatic metastasis. Using immunohistochemistry and immunofluorescence analyses, we validated the association of the identified molecule with clinical features and prognosis in an independent UCB cohort (n = 244) from SYMH. We also analysed TCGA‐BLCA cohort (n = 408) to identify its potential biological pathways and immune landscape. Results In our study, chitinase 3‐like 1 (CHI3L1) emerged as a significantly overexpressed proinflammatory mediator in UCB tissues with lymphatic metastasis compared to those without lymphatic metastasis (81.1% vs. 47.8%, P

Summary: Background: The impact of previous vaccination on protective immunity, duration, and immune imprinting in the context of BA.5-XBB.1.9.1 reinfection remains unknown. Methods: Based on a 2-year longitudinal cohort from vaccination, BA.5 infection and XBB reinfection, several immune effectors, including neutralizing antibodies (Nabs), antibody-dependent cellular cytotoxicity (ADCC), virus-specific T cell immunity were measured to investigate the impact of previous vaccination on host immunity induced by BA.5 breakthrough infection and BA.5-XBB.1.9.1 reinfection. Findings: In absence of BA.5 Nabs, plasma collected 3 months after receiving three doses of inactivated vaccine (I-I-I) showed high ADCC that protected hACE2-K18 mice from fatality and significantly reduced viral load in the lungs and brain upon BA.5 challenge, compared to plasma collected 12 months after I-I-I. Nabs against XBB.1.9.1 induced by BA.5 breakthrough infection were low at day 14 and decreased to a GMT of 10 at 4 months and 28% (9/32) had GMT ≤4, among whom 67% (6/9) were reinfected with XBB.1.9.1 within 1 month. However, 63% (20/32) were not reinfected with XBB.1.9.1 at 5 months post BA.5 infection. Interestingly, XBB.1.9.1 reinfection increased Nabs against XBB.1.9.1 by 24.5-fold at 14 days post-reinfection, which was much higher than that against BA.5 (7.3-fold) and WT (4.5-fold), indicating an immune imprinting shifting from WT to XBB antigenic side. Interpretation: Overall, I-I-I can provide protection against BA.5 infection and elicit rapid immune response upon BA.5 infection. Furthermore, BA.5 breakthrough infection effectively protects against XBB.1.9.1 lasting more than 5 months, and XBB.1.9.1 reinfection results in immune imprinting shifting from WT antigen induced by previous vaccination to the new XBB.1.9.1 antigen. These findings strongly suggest that future vaccines should target variant strain antigens, replacing prototype strain antigens. Funding: This study was supported by R&D Program of Guangzhou National Laboratory (SRPG23-005), National Key Research and Development Program of China (2022YFC2604104, 2019YFC0810900), S&T Program of Guangzhou Laboratory (SRPG22-006), and National Natural Science Foundation of China (81971485, 82271801, 81970038), Emergency Key Program of Guangzhou Laboratory (EKPG21-30-3), Zhongnanshan Medical Foundation of Guangdong Province (ZNSA-2020013), and State Key Laboratory of Respiratory Disease (J19112006202304).

Abstract Background Previous studies have frequently reported a high prevalence of co-occurring anxiety and depression among people who experienced stressful events in childhood. However, few have noted the symptomatic relationship of this comorbidity among childhood sexual abuse (CSA) survivors. Therefore, this study’s objectives were as follows: (1) to examine the relationship across symptoms between anxiety and depression among CSA survivors; (2) to compare differences between male and female network structures among CSA survivors. Methods A total of 63 Universities and Colleges in Jilin Province, China, covered 96,218 participants in this study, a sub-set data of which met the criteria of CSA was analyzed with the network analysis. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), measured CSA. Anxiety was measured by the seven-item Generalized Anxiety Disorder Scale (GAD-7), and depression was measured by the Patient Health Questionnaire (PHQ-9). The sex difference between anxiety and depression among CSA survivors was compared. Results 3,479 college students reported the experience of CSA (CTQ-SF total scores ≥ 8), with a prevalence of 3.62% (95% CI: 3.50–3.73%). Among CSA survivors, control worry, sad mood, and energy were central and bridge symptoms of the anxiety and depression network. Meanwhile, male CSA survivors appeared to have a stronger correlation between guilt and suicide, but female CSA survivors seemed to have a stronger correlation between control worry and suicide. Moreover, the edge of control worry-relax-afraid was stronger in the male network, while the edge of restless-relax was stronger in the female network. Conclusion Control worry, sad mood, and energy are crucial to offer targeted treatment and to relieve anxiety and depression symptoms for CSA survivors. Guilt needs more attention for male CSA survivors, while control worry remains more important for female CSA survivors to reduce suicidal ideation and suicide attempts.

Abstract Introduction Unbiased metagenomic next-generation sequencing (mNGS) has been used for infection diagnosis. In this study, we explored the clinical diagnosis value of mNGS for pulmonary complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods From August 2019 to June 2021, a prospective study was performed to comparatively analyze the pathogenic results of mNGS and conventional tests for bronchoalveolar lavage fluid (BALF) from 134 cases involving 101 patients with pulmonary complications after allo-HSCT. Results More pathogens were identified by mNGS than with conventional tests (226 vs 120). For bacteria, the diagnostic sensitivity (P = 0.144) and specificity (P = 0.687) were similar between the two methods. For fungus except Pneumocystis jirovecii (PJ), conventional tests had a significantly higher sensitivity (P = 0.013) with a similarly high specificity (P = 0.109). The sensitivities for bacteria and fungi could be increased with the combination of the two methods. As for PJ, both the sensitivity (100%) and specificity (99.12%) of mNGS were very high. For viruses, the sensitivity of mNGS was significantly higher (P = 0.021) and the negative predictive value (NPV) was 95.74% (84.27–99.26%). Pulmonary infection complications accounted for 90.30% and bacterium was the most common pathogen whether in single infection (63.43%) or mixed infection (81.08%). The 6-month overall survival (OS) of 88.89% in the early group (mNGS ≤ 7 days) was significantly higher than that of 65.52% (HR 0.287, 95% CI 0.101–0.819, P = 0.006) in the late group (mNGS > 7 days). Conclusions mNGS for BALF could facilitate accurate and fast diagnosis for pulmonary complications. Early mNGS could improve the prognosis of patients with pulmonary complications after allo-HSCT. Trial Registration ClinicalTrials.gov identifier, NCT 04051372.

The pore fusion behavior of the core layer interface in the welded aluminum foam sandwich was observed through synchrotron radiation. Meanwhile, the effect of the FSW in foaming is explored. The FSW leads to the early formation of cracks in the core layer of powder in the weld zone. The heterogeneous nucleation of bubbles occurs at the interface and forms small pores. The evolutionary processes of small pores promote interfacial fusion. In addition, the presence of the panel changes the state of the melt at the interface, which benefits the fusion of the melt at the interface.

BackgroundBullying victimization is highly prevalent among sexual minority youths, particularly in educational settings, negatively affecting their mental health. However, previous studies have scarcely explored the symptomatic relationships among anxiety, depression, and posttraumatic stress disorder (PTSD) among sexual minority youths who experienced bullying on college campuses. ObjectiveThe objectives of our study were to (1) characterize the anxiety-depression-PTSD network structures of gay or lesbian, bisexuals, and other sexual minority youths previously bullied on college campuses; and (2) compare symptomatic associations in the anxiety-depression-PTSD networks among bullied sexual minority youths and heterosexual youths’ groups. MethodsThis cross-sectional study recruited college participants from Jilin Province, China. Data were analyzed using a subset of the data extracted after screening for sexual orientation and history of bullying victimization. Sexual minority youths were then divided into 3 subgroups: gay or lesbian (homosexual), bisexual, and other. Mental health symptom severity was assessed using scales: the 7-item Generalized Anxiety Disorder Scale measuring anxiety, the 9-item Patient Health Questionnaire measuring depression, and the 10-item Trauma Screening Questionnaire measuring PTSD symptoms. Combining the undirected and Bayesian network analyses, the anxiety-depression-PTSD networks were compared among sexual minority youths subgroups, and the difference between heterosexual youths and sexual minority youths was investigated. Chi-square tests were used to compare the difference in categorical variables, while independent-sample t tests were run on continuous variables. ResultsIn this large-scale sample of 89,342 participants, 12,249 identified as sexual minority youths, of which 1603 (13.1%, 95% CI 12.5%-13.7%) reported being bullied on college campuses in the past year. According to the expected influence (EI) and bridge expected influence (bEI) index, in the global network structure of anxiety, depression, and PTSD, sad mood (EI=1.078, bEI=0.635) and irritability (EI=1.077, bEI=0.954) were identified as central and bridge symptoms; emotional cue reactivity (EI=1.015) was a central symptom of PTSD in this global network. In the anxiety-depression-PTSD Bayesian network, anhedonia had the highest prediction priority for activating other symptoms; and feeling afraid linked symptoms from anxiety to the PTSD community. Compared to their heterosexual counterparts, sexual minority youths exhibited a stronger association between difficulty concentrating and appetite. The “sad mood-appetite” edge was strongest in the gay or lesbian network; the “irritability-exaggerated startle response” edge was strongest in the bisexual network. ConclusionsFor the first time, this study identified the most central and bridge symptoms (sad mood and irritability) within the depression-anxiety-PTSD network of sexual minority youths with past bullying-victim experiences on college campuses. Emotional cue reactivity, anhedonia, and feeling afraid were other vital symptoms in the comorbid network. Symptomatic relationships existed showing heterogeneity in bullied heterosexual youths and sexual minority youth networks, which also was present within the sexual minority youth subgroups. Consequently, refined targeted interventions are required to relieve anxiety, depression, and PTSD symptoms.

Streets comprise a major area of urban land use and connect built areas to one another. However, the role of streetscapes for maintaining urban plant diversity remains poorly understood. In this study, urban street vegetation was investigated in Oulu, Finland, and Yokohama, Japan, to explore how species richness and composition of plant communities change among different street habitat types, including road-verge grass beds, asphalted surfaces, stone pavements, curbside gaps, wall bases, street shrubbery, and tree bases. All plant species were recorded separately for different street habitat types along a maximum of 500 m of street sections. The gamma diversity of each habitat type and the contributions of native and exotic species were evaluated based on species accumulation curves. Plant species composition was examined using non-metric multidimensional scaling and Venn diagrams. A total of 145 and 273 species were recorded in Oulu and Yokohama, respectively. In Oulu, native species contributed more to the total diversity across habitat types, whereas in Yokohama, we observed similar contributions of native and exotic species to the total diversity. There was a large overlap in species occurrence among different habitat types in Oulu, where the road-verge grass beds included over 90 % of the total diversity, and all species present in asphalted habitats. Road verge grass beds in Oulu and street shrubbery in Yokohama include a large number of unique species, implying that these species have adapted to the environment in each habitat. Thus, streetscape vegetation includes a mixture of common urban species and some unique species depending on habitat type, which is often overlooked as a part of the spontaneous plant diversity across streetscapes. We propose that diverse street habitats, including both gray and green surfaces, support diverse plant species and may thereby create biodiverse urban streetscapes.

Legume crops establish symbiosis with nitrogen-fixing rhizobia for biological nitrogen fixation (BNF), a process that provides a prominent natural nitrogen source in agroecosystems; and efficient nodulation and nitrogen fixation processes require a large amount of phosphorus (P). Here, a role of GmPAP4, a nodule-localized purple acid phosphatase, in BNF and seed yield was functionally characterized in whole transgenic soybean (Glycine max) plants under a P-limited condition. GmPAP4 was specifically expressed in the infection zones of soybean nodules and its expression was greatly induced in low P stress. Altered expression of GmPAP4 significantly affected soybean nodulation, BNF, and yield under the P-deficient condition. Nodule number, nodule fresh weight, nodule nitrogenase, APase activities, and nodule total P content were significantly increased in GmPAP4 overexpression (OE) lines. Structural characteristics revealed by toluidine blue staining showed that overexpression of GmPAP4 resulted in a larger infection area than wild-type (WT) control. Moreover, the plant biomass and N and P content of shoot and root in GmPAP4 OE lines were also greatly improved, resulting in increased soybean yield in the P-deficient condition. Taken together, our results demonstrated that GmPAP4, a purple acid phosphatase, increased P utilization efficiency in nodules under a P-deficient condition and, subsequently, enhanced symbiotic BNF and seed yield of soybean.

Traditional methods for synthesizing single-site catalysts are typically complicated and require special chemicals due to their tendency to agglomerate. In this study, we present a self-disperse copper-based catalyst synthesized via a dry mixing method for acetylene hydrochlorination. During the reaction, the copper precursor compounds, i.e., CuBr, and CuI, were converted to CuCl. Subsequently, the formed CuCl crystals underwent a significant structural transformation, leading to the formation of small clusters and Cu single sites. The catalytic activity of 5% CuCl + C prepared through the dry mixing method decreased from 93.7% to 92.9% after 100 h of reaction under the condition of GHSV (C2H2) = 60 mL·h−1·g−1. A comparison of the 5% CuCl + C with the 5% CuCl/C obtained by the impregnation method reveals that the catalytic stability of the former was higher than the one prepared by the conventional impregnation method. The exceptional catalytic performance can be attributed to the reaction-induced active sites being highly dispersed and the porous structure of activated carbon being maximally preserved, which was confirmed by HAADF-STEM, BET, TPR, and TG. The reaction-induced dispersion of CuCl on carbon provides a new strategy for preparing single-site catalysts for acetylene hydrochlorination.

Liver fibrosis can occur in many chronic liver diseases, and no effective treatments are available due to the poorly characterized molecular pathogenesis. Semaphorin 4D (Sema4D) has immune functions and serves important roles in T cell priming. Here, we found that Sema4D was highly expressed in fibrotic liver, and the expression of Sema4D increased with hepatic stellate cells (HSCs) activation. Knockout of Sema4D alleviated liver fibrosis. Mechanistically, knockout of Sema4D alleviated liver fibrosis by suppressing the expression of AOX1 in retinol metabolism. Further investigation demonstrated that retinoic acid receptor α (RARA), an important nuclear receptor of retinoic acid, was reduced by Sema4D knockout during liver fibrogenesis. Sema4D knockout-mediated suppression of liver fibrosis was partly mediated by regulating the balance of Th1, Th2, Th17, and T-bet+Treg cells via inhibiting AOX1/RARA. Thus, targeting Sema4D may hold promise as a potential therapeutic approach for treating liver fibrosis.

ABSTRACT: Excess abdominal fat is a common phenomenon in broiler chickens. Gut microbiota could regulate lipid metabolism through their effects on short-chain fatty acids (SCFAs) production. This study was conducted to investigate the potential relationship between abdominal fat development and cecal microorganism populations. Abdominal fat and cecum contents were collected at 3, 7, 14, 21, 28, 35, and 42 d of age. The results showed that abdominal fat weight increased with age. The abdominal fat percentage was higher between 7 and 21 d of age than at 3 d (P < 0.05), and it increased again at 28 to 42 d (P < 0.05). Morphological analysis showed that adipocyte diameter and cross-sectional area (CSA) increased significantly after 14 d of age (P < 0.05). Moreover, gut microbiota analysis indicated that the Chao1 and Shannon indices were higher between 14 and 28 d than at 3 d of age (P < 0.05). Furthermore, LEfse analysis revealed that Faecalibacterium, Anaerotruncus, Anaeroplasma, Subdoligranulum, and Clostridium emerged to become dominant at 14 d. A greater abundance of Bacteroides, Ruminococcus, Dehalobacterium, and Lactobacillus were determined at 28 d when compared with 14 d of age. Parabacteroides, Ochrobactrum, Lactobacillus, Blautia, Alistipes, Dehalobacterium, Odoribacter, and Suuterella were found to be predominant at 42 d. PICRUSt analysis revealed that amino acid metabolism, lipid metabolism, and terpenoids and polyketides metabolism were elevated at 14 d; the immune and digestive systems were significantly developed at 28 d. In addition, cecum propionic acid and butyric acid contents gradually increased (P < 0.05), while the isobutyric acid contents gradually decreased with advancing age (P < 0.05). Correlation analysis among SCFAs, differential genera and abdominal fat suggested that Coprobacillus, Shigella, and Butyricicoccus had negative correlations with propionic acid, butyric acid, and abdominal fat weight, but positive correlations with isobutyric acid. Isobutyric acid was identified as being negatively associated with abdominal fat weight, while the reverse was found for propionic acid and butyric acid. In conclusion, abdominal fat development is correlated with the emergence of specific microbes and d 14 may be a pivotal age for establishing this relationship.

Abstract Recently, the interest in extracellular vesicles released by bacteria has rapidly increased. Bacterial extracellular vesicles (BEVs) have been involved in bacteria‐bacteria and bacteria‐host interactions, which strengthen health or bring about various pathologies. However, BEV separation, characterization, and functional studies require the establishment of guidelines and further optimization in order to stimulate the development of science in BEV research and a following successful transformation into clinical applications. This position paper is authored by the Microbial Vesicles Task Force of the Chinese Society for Extracellular Vesicles (CSEV) composed of experienced medical laboratory specialists, microbiologists, virologists, biologists and material biologists who are actively engaged in BEV research. Herein, we present a concise description of BEV research and discover challenges and critical gaps in current BEV‐based analyses for clinical applications. Finally, we also offer suggestions and considerations to improve experimental reproducibility and interoperability in BEV research to promote progress in the field.

Abstract Background Neuroblastoma (NB) is the most common extracranial solid tumor occurring during childhood and high-risk NB patients have a poor prognosis. The amplified MYCN gene serves as an important determinant of a high risk of NB. Methods We performed an integrative screen using public NB tissue and cell line data, and identified that SMAD9 played an important role in high-risk NB. An investigation of the super-enhancers database (SEdb) and chromatin immunoprecipitation sequencing (ChIP-seq) dataset along with biological experiments of incorporating gene knockdown and CRISPR interference (CRISPRi) were performed to identify upstream regulatory mechanism of SMAD9. Gene knockdown and rescue, quantitative real-time PCR (Q-RT-PCR), cell titer Glo assays, colony formation assays, a subcutaneous xenograft model and immunohistochemistry were used to determine the functional role of SMAD9 in NB. An integrative analysis of ChIP-seq data with the validation of CRISPRi and dual-luciferase reporter assays and RNA sequencing (RNA-seq) data with Q-RT-PCR validation was conducted to analyze the downstream regulatory mechanism of SMAD9. Results High expression of SMAD9 was specifically induced by the transcription factors including MYCN, PHOX2B, GATA3 and HAND2 at the enhancer region. Genetic suppression of SMAD9 inhibited MYCN-amplified NB cell proliferation and tumorigenicity both in vitro and in vivo. Further studies revealed that SMAD9 bound to the MYCN promoter and transcriptionally regulate MYCN expression, with MYCN reciprocally binding to the SMAD9 enhancer and transactivating SMAD9, thus forming a positive feedback loop along with the MYCN-associated cancer cell cycle. Conclusion This study delineates that SMAD9 forms a positive transcriptional feedback loop with MYCN and represents a unique tumor-dependency for MYCN-amplified neuroblastoma.

Suzuki cross-coupling reaction was employed to easily obtain a triazine-based porous organic polymer (2,4,6-tris(5-bromothiophene-2-yl)-1,3,5-triazine [TBrTh]–1,3,5-benzene-triyltriboronic acid pinacol ester [BTBPE]–covalent triazine framework [CTF]) containing thiophene units. The chemical structure of TBrTh–BTBPE–CTF was revealed by solid-state 13C NMR, Fourier-transform infrared, and X-ray photoelectron spectroscopy. TBrTh–BTBPE–CTF with an amorphous structure exhibited excellent thermal stability and intrinsic porosity (373 m2·g−1 of Brunauer–Emmett–Teller surface area). Consequently, temozolomide (TMZ) was used as an oral alkylating agent in melanoma treatment to explore the drug loading and releasing behavior of TBrTh–BTBPE–CTF as a result of the low cytotoxicity of thiophene-based polymers. The successful loading of TMZ within the polymeric structure was suggested by thermogravimetric analysis and N2 sorption isotherms. The release experiments were performed in phosphate-buffered saline at pH values of 5.5 and 7.4, exhibiting good controlled-release properties. These results suggest that the current porous organic polymer is expected to be a drug carrier for the delivery and release of TMZ.

In order to investigate the effect of blanching temperature and air frying time on the quality of catfish skin, the cooking loss rate and thermal stability of fish skin were analyzed after blanching (50, 70, 90 ℃). On the basis of blanching, the moisture, fat, brittleness and transverse relaxation time (T2) of fish skin were measured after air frying for 2, 4, 6, 8, 10 and 12 min, respectively. The microstructure of fish skin at different blanching temperatures and air frying for 12 min were analyzed. The results showed that: The cooking loss rate of the fish skin was 2.15% blanched at 70 ℃, the thermal stability temperature was 121.97 ℃ and 146.88 ℃, the moisture content was 2.89%, the fat content was 10.85%, and the deformation distance was 0.13 mm after air frying for 12 min. Comparing with 50 ℃ and 90 ℃, 70 ℃ blanching fish skin, the cooking loss rate was moderate, the thermal stability was better, when air frying for 12 min, the moisture content was the lowest, the deformation distance was the smallest, the fat content was lower, and the structure was uniform and smooth. So blanching temperature 70 ℃ was the better temperature which was conducive to the development of products.

ABSTRACT: Fatty liver syndrome (FLS) is a kind of nutritional metabolic disease in laying hens. Revealing FLS pathogenesis during the early period is what really makes sense for the prevention or nutritional regulation strategies. In the study, 9 healthy or naturally occurring early FLS birds were screened based on visual inspection, liver index and morphologic analysis. Liver and fresh cecal content samples were collected. Then transcriptomic and 16S rRNA technologies are applied to investigate hepatic transcriptome and cecum microbiota composition. Unpaired Student t test and some omics methods were used for statistical analysis. Results showed higher liver weight and index were found in FLS group; morphologic analysis indicated that there existed more lipid droplets in the liver of birds with FLS. Based on DESeq2 analysis, there were 229 up- and 487 down-regulated genes in the FLS group, among which most genes related to de novo fatty acid synthesis were up-regulated such as acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase, and ELOVL fatty acid elongase 6 (ELOVL6). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that pathways associated with lipid metabolism and liver damage were affected. 16S rRNA sequencing analysis of cecum microbiota showed that there was a significant difference between the Con and FLS groups. LEfSe analysis revealed that the relative abundance of Coprococcus, Odoribacter, Collinsella, Turicibacter, YRC22, Enterococcus, Shigella, and Bifidobacterium were down-regulated in the FLS group, whereas the abundance of Bacteroides, Mucispirillum, Butyricicoccus, Campylobacter, Akkermansia, and Clostridium were up-regulated. The KEGG enrichment from differential microbiota suggested that some metabolism-related functions were altered to some extent. Taken together, during the developmental of early fatty liver of laying hens, lipogenesis was enhanced, whereas abnormal metabolism occurs not only in lipid transportation but also in hydrolysis, which caused structural damage to the liver organ. Moreover, the dysbiosis of the cecum microbiota occurred. All of these serve as targets or provide theoretical references for the development of probiotics for fatty liver prevention in laying hens.

ABSTRACT: The liver undergoes a slow process for lipid deposition during chick embryonic period. However, the underlying physiological and molecular mechanisms are still unclear. Therefore, the aim of the current study was to reveal the epigenetic mechanism of hepatic transcriptional reprogramming changes based on the integration analysis of RNA-seq and H3K27ac labeled CUT&Tag. Results showed that lipid contents increased gradually with the embryonic age (E) 11, E15, and E19 based on morphological analysis of Hematoxylin-eosin and Oil Red O staining as well as total triglyceride and cholesterol detection. The hepatic protein level of SREBP-1c was higher in E19 when compared with that in E11 and E15, while H3K27ac and H3K4me2 levels declined from E11 to E19. Differential expression genes (DEGs) among these 3 embryonic ages were determined by transcriptome analysis. A total of 107 and 46 genes were gradually upregulated and downregulated respectively with the embryonic age. Meanwhile, differential H3K27ac occupancy in chromatin was investigated. But the integration analysis of RNA-seq and CUT&Tag data showed that the overlap genes were less between DEGs and target genes of differential peaks in the promoter regions. Further, some KEGG pathways enriched from target genes of typical enhancer were overlapped with those from DEGs in transcriptome analysis such as insulin, FoxO, MAPK signaling pathways which were related to lipid metabolism. DNA motif analysis identify 8 and 10 transcription factors (TFs) based on up and down differential peaks individually among E11, E15, and E19 stages where 7 TFs were overlapped including COUP-TFII, FOXM1, FOXA1, HNF4A, RXR, ERRA, FOXA2. These results indicated that H3K27ac histone modification is involved in the transcriptional reprogramming regulation during embryonic development, which could recruit TFs binding to mediate differential enhancer activation. Differential activated enhancer impels dynamic transcriptional reprogramming towards lipid metabolism to promote the occurrence of special phenotype of hepatic lipid deposition.

Using the powder-metallurgy rolling method, aluminum foam sandwich (AFS) panels with a metallurgical bond between the foam core and the panel can be produced. In this study, by manipulating the foaming temperature and duration, AFS panels were fabricated with varying core densities and thicknesses, all maintaining a panel thickness close to 1 mm. Through the three-point bending test, this research deeply delved into how core density influences the mechanical behaviors of these AFS panels. It became evident that a rise in core density positively affects the bending strength and failure load of the panels but inversely impacts their total energy absorption efficiency. Differing core densities brought about distinct failure patterns: low-density samples primarily showed panel indentation and core shear failures, whereas those of high density demonstrated panel yield and fractures. Furthermore, the research offers predictions on the initial failure loads for different failure modes and introduces a comprehensively designed failure diagram, laying a foundational theory for the production of AFS panels.

Carboxylesterase (CarE) was considered as important phase-I detoxifying enzymes which participated in detoxification of different types of insecticides. Up-regulation of CarE genes has been proved playing a major role in insecticide resistance in many pest insects, but its involvement in resistance to insecticides in Plutella xylostella has been rarely reported. In this study, a CarE cDNA named PxαE8 was identified in P. xylostella, which has an open reading frame of 1 599 nucleotides and putatively encodes 532 amino acids. The investigation of spatial expression profiles of PxαE8 revealed that it was expressed in all developmental stages, especially in larvae and adults. The body part/tissue-specific expression profiles showed that the PxαE8 mainly expressed in fat body, malpighian tubule and hemolymph of larvae. Further, the relative expression of PxαE8 in two multi-resistant field populations, Hainan (HN) and Guangdong (GD) populations, was found 24.4- and 15.5-fold higher than that in susceptible population, respectively. Knockdown of PxαE8 by RNA interference dramatically increased the mortalities of larvae of HN population treated with LC50 of beta-cypermethrin and phoxim by 25.3 and 18.3%, respectively. These results suggested that up-regulation of PxαE8 was involved in resistance to both beta-cypermethrin and phoxim in P. xylostella, which shed light on further understanding of molecular mechanisms of multi-insecticide-resistance in P. xylostella and other pest insects.

Currently, there is still no effective curative treatment for the development of late-stage liver fibrosis. Here, we have illustrated that TB001, a dual glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) agonist with higher affinity towards GCGR, could retard the progression of liver fibrosis in various rodent models, with remarkable potency, selectivity, extended half-life and low toxicity. Four types of liver fibrosis animal models which were induced by CCl4, α-naphthyl-isothiocyanate (ANIT), bile duct ligation (BDL) and Schistosoma japonicum were used in our study. We found that TB001 treatment dose-dependently significantly attenuated liver injury and collagen accumulation in these animal models. In addition to decreased levels of extracellular matrix (ECM) accumulation during hepatic injury, activation of hepatic stellate cells was also inhibited via suppression of TGF-β expression as well as downstream Smad signaling pathways particularly in CCl4-and S. japonicum-induced liver fibrosis. Moreover, TB001 attenuated liver fibrosis through blocking downstream activation of pro-inflammatory nuclear factor kappa B/NF-kappa-B inhibitor alpha (NFκB/IKBα) pathways as well as c-Jun N-terminal kinase (JNK)-dependent induction of hepatocyte apoptosis. Furthermore, GLP-1R and/or GCGR knock-down results represented GCGR played an important role in ameliorating CCl4-induced hepatic fibrosis. Therefore, TB001 can be used as a promising therapeutic candidate for the treatment of multiple causes of hepatic fibrosis demonstrated by our extensive pre-clinical evaluation of TB001.

BackgroundPrevious studies have focused on the comorbidity of appearance anxiety and social anxiety, but few studies have focused on the protective role of self-compassion as underlying this mechanism, in young people like University students. With the increase of prevalence of appearance anxiety and social anxiety in this age group, it is necessary to explore factors that can buffer against the symptoms of these disorders. Therefore, the aims of this study were to research the effect of appearance anxiety and social anxiety, then to examine whether self-compassion has a protective effect on social anxiety.MethodThe study was cross-sectional and conducted online from October 2021 to November 2021 in Jilin Province, China. A total of 63 Universities in the province participated in this study, totaling 96,218 participants, of which 40,065 were males (41.64%) and 56,153 females (58.36%), the mean age of the sample was 19.59 (±1.74). The Appearance Anxiety Scale-Brief Version was used to measure appearance anxiety. The Social Anxiety subscale of the Self-Consciousness Scale was used to measure social anxiety. The Self-Compassion Scale-Short Form was used to measure self-compassion. A structural equation model (SEM) was run to examine the mediating effect of self-compassion on the relationship between appearance anxiety and social anxiety.ResultOverall, appearance anxiety was positively associated with social anxiety [β = 0.334, 95% CI = (0.328, 0.341), p < 0.001], and self-compassion could mediate the effect of appearance anxiety on social anxiety [β = 0.128, 95% CI = (0.124, 0.132), p < 0.001]. Self-compassion played a partial mediating role between appearance anxiety and social anxiety.ConclusionIndividuals with high appearance anxiety are also at higher risk of social anxiety, but self-compassion can buffer against this relationship. These findings begin to explore novel approaches to treat social anxiety and can provide valuable insights for self-compassion training.

BackgroundExposure to childhood trauma (CT) is associated with various deleterious mental health outcomes, increasing the risk of suicidal behaviors. The objective of this study is to investigate the different effects of three forms of CT, including emotional abuse (EA), physical abuse (PA), and sexual abuse (SA), on potential psychopathological symptoms among college students.MethodsA total of 117,769 students from 63 Chinese colleges participated in this study. There were 1,191 participants in the EA group (1.24%; 95% CI: 1.17–1.31%), 1,272 participants in the PA group (1.32%; 95% CI: 1.25–1.40%), and 3,479 participants in the SA group (3.62%; 95% CI: 3.50–3.73%). CT was measured by the Childhood Trauma Questionnaire-Short Form. Psychopathological symptoms (i.e., depression, anxiety, and PTSD) were measured by the PHQ-9, GAD-7, and Trauma Screening Questionnaire, respectively. Network analysis was applied to analyze psychopathological symptoms between three CT subgroups (EA, PA, and SA). The associations and centralities of the networks were calculated, and the network characteristics of the three subgroups were contrasted.ResultsThe main symptoms across all three groups are uncontrollable worry, sad mood, irritability, and fatigue, which indicates these core symptoms play essential roles in maintaining the whole psychological symptoms network. Furthermore, there are significant differences in symptom associations between the three groups. The comparison of network structures of the three groups shows that the SA group reports more PTSD symptoms, the EA group reports more suicide-related symptoms, and the PA group reports more anxiety symptoms.ConclusionSpecific symptoms were disclosed across each group by the distinctive core psychopathological symptoms found in the CT subgroup networks. The present study's findings show different associations between CT and psychopathology and may help classify potential diagnostic processes. Therefore, local governments and academic institutions are recommended for early intervention to promote the psychological well-being of CT survivors.

Pd membranes can play an important role in H2 separation and purification for the development of sustainable and renewable energies. By supporting on porous substrates, Pd layer thickness can be reduced to several micrometers, thus improving the H2 permeance by several orders of magnitude. However, the supported thin Pd membranes are concomitant with pinhole formation due to either fabrication (e.g., electroless-plating) or thermal treatment, which exist as a remarkable challenge for its widespread applications. This study presents a novel and facile approach for self-repair of Pd membrane defects by immersing the stainless-steel supported Pd membranes in PdCl2 solution. Three membranes were deliberately selected with a low selectivity of 152–1687 (400 ​°C, 0.1Mpa), for which disproportionation reactions between Pd2+ and Fe/Cr/Ni at the defect sites spontaneously occur leading to the formation of Pd particles at the exact point of defects. This self-repair process can be enhanced when applying a high pressure of 30–50 ​bar in the PdCl2 solution for 30 ​min, by overcoming the capillary resistance and penetrating through the pinholes. Interestingly, densely distributed hillocks were observed on the membrane surface probably due to reduction of PdCl2 under following H2 treatment, thus increasing the H2 permeance with a higher effective surface area. The H2/N2 selectivity can be improved by more than one order of magnitude (in the best case from 1687 to 8768) and a long-term stability test of 300 ​h was achieved for the repaired membranes, corroborating the application potential of this approach.

Biomphalaria snails play a crucial role in the transmission of the human blood fluke Schistosoma mansoni. The gut microbiota of intermediate hosts is known to influence their physiological functions, but little is known about its composition and role in Biomphalaria snails. To gain insights into the biological characteristics of these freshwater intermediate hosts, we conducted metagenomic sequencing on Biomphalaria straminea and B. glabrata to investigate variations in their gut microbiota. This study revealed that the dominant members of the gut microbiota in B. glabrata belong to the phyla Bacteroidetes and Proteobacteria, which were also found to be the top two most abundant gut bacteria in B. straminea. We identified Firmicutes, Acidovorax and Bosea as distinctive gut microbes in B. straminea, while Aeromonas, Cloacibacterium and Chryseobacterium were found to be dependent features of the B. glabrata gut microbiota. We observed significant differences in the community structures and bacterial functions of the gut microbiota between the two host species. Notably, we found a distinctive richness of antibiotic resistance genes (ARGs) associated with various classes of antibiotics, including bacitracin, chloramphenicol, tetracycline, sulfonamide, penicillin, cephalosporin_ii and cephalosporin_i, fluoroquinolone, aminoglycoside, beta-lactam, multidrug and trimethoprim, in the digestive tracts of the snails. Furthermore, this study revealed the potential correlations between snail gut microbiota and the infection rate of S. mansoni using Spearman correlation analysis. Through metagenomic analysis, our study provided new insights into the gut microbiota of Biomphalaria snails and how it is influenced by host species, thereby enhancing our understanding of variant patterns of gut microbial communities in intermediate hosts. Our findings may contribute to future studies on gastropod–microbe interactions and may provide valuable knowledge for developing snail control strategies to combat schistosomiasis in the future.

This paper employs an innovative investigation approach to study pore evolution in Al-Si-Mg-Cu alloy within aluminum foam sandwiches (AFS) by integrating data from heating–expansion ratio curves, in situ observation of synchronous radiation, and microscopic analysis of the matrix’s microstructure at different stages. Additionally, the cavity design and plate type control for large-scale AFS production are explored. Findings categorize the precursor heating into three stages: rapid heating, solid–liquid transition, and stable foaming. During solid–liquid transition, the expansion rate experiences a sudden drop, associated with pore nucleation and edge cracking of precursors. Pores nucleate as elongated crack-like structures along the rolling direction, guided by the Mg-enriched regions. In stable foaming, these pores evolve, become spherical, and the matrix rapidly expands. Using square tubes for sealing on the preform cavity sides creates a dense edge zone during rolling, halting crack propagation into the powder core. Adopting edge sealing during foaming mitigates boundary effects, thereby improving AFS panel flatness.

At present, the double-enzyme catalyzed method using maltooligosyltrehalose synthase (MTSase) and maltooligosyltrehalose trehalohydrolase (MTHase) is the mainstream technology for industrial trehalose production. However, MTSase and MTHase are prepared mainly using the heterologous expression in the engineered Escherichia coli strains so far. In this study, we first proved that the addition of 3 U/g neutral pullulanase PulA could enhance the trehalose conversion rate by 2.46 times in the double-enzyme catalyzed system. Then, a CBM68 domain was used to successfully assist the secretory expression of MTSase and MTHase from Arthrobacter ramosus S34 in Bacillus subtilis SCK6. At the basis, an engineered strain B. subtilis PSH02 (amyE::pulA/pHT43-C68-ARS/pMC68-ARH), which co-expressed MTSase, MTHase, and PulA, was constructed. After the 24 h fermentation of B. subtilis PSH02, the optimum ratio of the extracellular multi-enzymes was obtained to make the highest trehalose conversion rate of 80% from 100 g/L maltodextrin. The high passage stability and multi-enzyme preservation stability made B. subtilis PSH02 an excellent industrial production strain. Moreover, trehalose production using these extracellular enzymes produced via the one-step fermentation of B. subtilis PSH02 would greatly simplify the procedure for multi-enzyme preparation and be expected to reduce production costs.

Abstract Background Aedes aegypti and Aedes albopictus are invasive mosquito species and significantly impact human health in southern China. Microbiota are confirmed to affect the development and immunity of mosquitoes. However, scientists have focused more on midgut microbiota of female mosquitoes and bacterial differences between female and male Aedes mosquitoes. The relationship between the midgut and entire body microbiota of Aedes is unclear. In this study, we collected mosquito samples reared under the same laboratory conditions and compared the microbial composition of midgut and entire bodies of Aedes aegypti and Aedes albopictus using 16S rRNA gene sequencing. Methods In this study, we collected mosquito samples reared under the same laboratory conditions and compared the microbial composition of midgut and entire bodies of Aedes aegypti and Aedes albopictus using 16S rRNA gene sequencing. Results A total of 341 OTUs were identified, showing that Proteobacteria was the dominant phylum and Methylobacterium the dominant genus in both Aedes aegypti and Aedes albopictus. The bacterial diversity and community structures of the entire bodies were similar between males and females in both Aedes aegypti and Aedes albopictus. Conversely, the bacterial compositions of male and female Aedes aegypti and Aedes albopictus were significantly different. NMDS analysis, UPGMA analysis, diversity indices and OTU distribution demonstrated that compositions and structures in midgut microbiota were similar but significantly different in the entire bodies of Aedes aegypti and Aedes albopictus. Functional prediction analysis showed that metabolism and environmental information processing were the dominant KEGG pathways at level 1. Our study showed that there were significantly different level 2 and 3 KEGG pathways in the midgut microbiota (16 level 2 and 24 level 3) and the entire bodies (33 level 2 and 248 level 3) between female Aedes albopictus and Aedes Aegypti. Conclusions Our findings that Aedes aegypti and Aedes albopictus reared in the same laboratory harbor a similar gut bacterial microbiome but different entire body microbiota imply that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype, but the entire body microbiota is more genetically determined. Our findings improved the understanding of the microbiota in the entire and partial tissues of Aedes mosquitoes. Graphical abstract

Abstract Background Hepatic schistosomiasis, a chronic liver injury induced by long-term Schistosoma japonicum (S. japonicum) infection, is characterized by egg granulomas and fibrotic pathology. Hepatic progenitor cells (HPCs), which are nearly absent or quiescent in normal liver, play vital roles in chronic and severe liver injury. But their role in the progression of liver injury during infection remains unknown. Methods In this study, the hepatic egg granulomas, fibrosis and proliferation of HPCs were analyzed in the mice model of S. japonicum infection at different infectious stages. For validating the role of HPCs in hepatic injury, tumor necrosis factor-like-weak inducer of apoptosis (TWEAK) and TWEAK blocking antibody were used to manipulate the proliferation of HPCs in wild-type and IL-33−/− mice infected with S. japonicum. Results We found that the proliferation of HPCs was accompanied by inflammatory granulomas and fibrosis formation. HPCs expansion promoted liver regeneration and inhibited inflammatory egg granulomas, as well as the deposition of fibrotic collagen. Interestingly, the expression of IL-33 was negatively associated with HPCs’ expansion. There were no obvious differences of liver injury caused by infection between wild-type and IL-33−/− mice with HPCs’ expansion. However, liver injury was more attenuated in IL-33−/− mice than wild-type mice when the proliferation of HPCs was inhibited by anti-TWEAK. Conclusions Our data uncovered a protective role of HPCs in hepatic schistosomiasis in an IL-33-dependent manner, which might provide a promising progenitor cell therapy for hepatic schistosomiasis.

BackgroundIncidences of social anxiety disorder (SAD), appearance anxiety, and eating disorders (ED) show an increased prevalence among young people. However, symptoms' associations between these disorders have not been investigated in depth. Network analysis is an approach that can be used to explain the relationship(s) between symptoms of different psychological disorders. Using network analysis, this study aimed to explore the association and potential interacting mechanisms between SAD, appearance anxiety, and ED.MethodsThis study included 96,218 University students from Jilin Province, China. SAD, appearance anxiety and ED were assessed using the Social Anxiety Subscale of the Self-Consciousness Scale (SASS), the Appearance Anxiety Scale Brief Version (AASBV), and the Sick, Control, One, Fat, Food questionnaire (SCOFF), Chinese versions. Network analysis was employed to investigate the symptom associations, while the stability of the network model was analyzed using statistical measures.ResultsThe prevalence of ED among the total sample was 38% (95% CI: 38.1–38.8%), while this figure was 31.2% (95% CI: 30.7–31.6%) in males and 43.6% (95% CI: 43.2–44.0%) in females. Additionally, the total score of SAD was significantly higher in females (11.83 ± 5.37) than it in males (10.02 ± 5.46) (P < 0.001). While the total score of appearance anxiety was also different significantly in gender (39.21 ± 9.49 in females vs. 38 ± 9.42 in males) (P < 0.001). Results showed that ED was associated with all three aspects of appearance anxiety, including “appearance concern,” “appearance satisfaction,” and “wish for good looks.” Appearance anxiety and SAD were also associated; specifically, symptoms of “appearance satisfaction” were significantly associated with the symptoms “easily talk to strangers” and “appearance concern”, which was also significantly associated with “embarrassed”. Compared with males, females showed significantly stronger associations with appearance anxiety symptoms, while ED symptoms were associated with “troubled by being watched” and “appearance concern”.ConclusionAppearance anxiety was associated with both ED and SAD symptoms. ED may have a potential relationship with SAD, affecting appearance anxiety indirectly. Significant differences were found among males and females in symptom associations between appearance anxiety and SAD. This study therefore clarified that young people should have body-positive interventions and challenge the normative body image discourse, which may help alleviate symptoms of SAD and ED.

BackgroundStroke is one of the leading causes of mortality across the world. However, there is a paucity of information regarding mortality rates and associated risk factors in patients with acute ischemic stroke (AIS) undergoing endovascular thrombectomy (EVT). In this study, we aimed to clarify these issues and analyzed previous publications related to mortality in patients treated with EVT.MethodsWe analyzed the survival of 245 consecutive patients treated with mechanical thrombectomy for AIS for which mortality information was obtained. Early mortality was defined as death occurring during hospitalization after EVT or within 7 days following hospital discharge from the stroke event.ResultsEarly mortality occurred in 22.8% of cases in this cohort. Recanalization status (modified thrombolysis in cerebral infarction, mTICI) (p = 0.002), National Institute of Health Stroke Scale Score (NIHSS) score 24-h after EVT (p < 0.001) and symptomatic intracerebral hemorrhage (sICH) (p < 0.001) were independently associated with early mortality. Age, sex, cardiovascular risk factors, NIHSS score pre-treatment, Alberta Stroke Program Early CT Score (ASPECTS), stroke subtype, site of arterial occlusion and timing form onset to recanalization did not have an independent influence on survival. Non-survivors had a shorter hospitalization (p < 0.001) but higher costs related to their hospitalization and outpatient care.ConclusionThe recanalization status, NIHSS score 24-h after EVT and sICH were predictors of early mortality in AIS patients treated with EVT.

Background: Childhood sexual abuse (CSA) is one of the prevalent forms of trauma experienced during childhood and adolescence. Previous research underscores its associations with depression, anxiety, post-traumatic stress disorder (PTSD), and psychosis. Objective: This study examined symptom connections between depression, anxiety, PTSD, and psychosis while simultaneously investigating whether these connections differed by gender among CSA survivors. Methods: A large-scale, cross-sectional study among 96,218 college students was conducted in China. Participants’ CSA was measured by the Childhood Trauma Questionnaire-Short Form (CTQ-SF). Participants’ PTSD, psychosis, depression, and anxiety were measured by the Trauma Screening Questionnaire (TSQ), the Psychosis Screener (PS), the nine-item Patient Health Questionnaire (PHQ-9), and the 7-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Network analysis was used to explore the potential associations between these symptoms and to compare the sex differences in the symptoms model. Results: Among participants who suffered from CSA, females were more likely from left-behind households, while males were more likely from households with a high annual income (P

Abstract Co-infection of maize chlorotic mottle virus (MCMV) with a virus in the Potyviridae family, such as sugarcane mosaic virus, usually leads to maize lethal necrosis (MLN). Over the past decade, MCMV/MLN has emerged in many countries/regions of the world and resulted in serious yield loss in maize production. Although partial functions of some MCMV-encoded proteins have been identified, the host factors related to MCMV replication are poorly understood. Here, we show that maize peroxisomes can form aggregated bodies in MCMV-infected leaf cells. The dsRNA binding-dependent fluorescence complementation assay indicated that the aggregated peroxisomes in maize served as the major replication site of MCMV. In addition, our results revealed that all the three maize catalases were present mostly in peroxisomes in the presence or absence of MCMV. Furthermore, we determined that inhibition of catalase activity or induction of reactive oxygen species (ROS) in maize protoplasts significantly reduced the accumulation of MCMV RNA. In summary, this research reveals the replication site of MCMV and an important role of maize catalases in supporting virus replication. Our results are conducive to understanding the pathogenesis of MCMV and identifying targets for resistance breeding or gene regulation strategies.

Surface structure and composition play essential roles in the osseointegration of titanium implants. In the present study, a nanoscale surface structure incorporated with calcium ions was fabricated on a titanium surface by hydrothermal treatment. The characteristics of the surfaces were analysed, and the bioactivity of the samples was evaluated in vitro and in vivo. nm-Ti and nm/Ca-Ti surfaces were significantly more hydrophilic than control-Ti surfaces. nm/Ca-Ti samples showed much faster bone-like apatite precipitation in simulated body fluid than the other samples. The results of MC3T3-E1 cell tests demonstrated that both nm-Ti and nm/Ca-Ti surfaces accelerated cell adhesion and proliferation. The highest level of osteogenesis-related genes (Runx2, bone morphogenetic protein-2, osteopontin and osteocalcin) were observed in nm/Ca-Ti samples, followed by nm-Ti samples. Alizarin red staining experiment showed that the amount of extracellular matrix mineralized nodules in nm/Ca-Ti group was significantly higher than others. In animal experiments using SD rats, nm/Ca-Ti showed the highest value of new bone formation at two and four weeks. The present study suggested that the nanostructure and calcium ions showed synergetic effects on accelerating bone-like apatite precipitation and osteoblast cell growth and differentiation. Animal experiment further indicated that such surface could promote early osteogenesis.

BackgroundRupture of anterior communicating artery (ACoA) aneurysm often leads to cognitive impairment, especially memory complaints. The medial superior frontal gyrus (SFGmed), a node of the default mode network (DMN), has been extensively revealed to participate in various cognitive processes. However, the functional connectivity (FC) characteristics of SFGmed and its relationship with cognitive performance remain unknown after the rupture of the ACoA aneurysm.MethodsResting-state functional MRI (fMRI) and cognitive assessment were acquired in 27 eligible patients and 20 controls. Seed-based FC between unilateral SFGmed and the rest of the brain was calculated separately, and then compared their intensity differences between the two groups. Furthermore, we analyzed the correlation between abnormal FC and cognitive function in patients with ruptured ACoA aneurysm.ResultsCognitive impairment was confirmed in 51.9% of the patients. Compared with the controls, patients suffering from ruptured ACoA aneurysm exhibited a similar FC decline between each side of SFGmed and predominant nodes within DMN, including the precuneus, angular gyrus, cingulate cortex, left hippocampus, left amygdala, left temporal pole (TPO), and left medial orbitofrontal cortex (mOFC). Besides, significantly decreased FC of left SFGmed and left insula, right middle temporal gyrus (MTG), as well as right mOFC, were also found. In addition, only enhanced insular connectivity with right SFGmed was determined, whereas increased FC of the left SFGmed was not observed. Correlation analyses showed that lower total cognitive performance or stronger subjective memory complaints were related to reduced connectivity in the SFGmed and several cortical regions such as the angular gyrus and middle cingulate cortex (MCC).ConclusionOur results suggest that patients with ruptured ACoA aneurysm exist long-term cognitive impairment and intrinsic hypoconnectivity of cognition-related brain regions within DMN. Deactivation of DMN may be a potential neural mechanism leading to cognitive deficits in these patients.