Search

Given their dangerous effects on the nervous system, neurotoxins represent a significant threat to public health. Various therapeutic approaches, including chelating agents, receptor decoys, and toxin-neutralizing antibodies, have been explored. While prophylactic vaccines are desirable, it is oftentimes difficult to effectively balance their safety and efficacy given the highly dangerous nature of neurotoxins. To address this, we report here on a nanovaccine against neurotoxins that leverages the detoxifying properties of cell membrane-coated nanoparticles. A genetically modified cell line with constitutive overexpression of the α7 nicotinic acetylcholine receptor is developed as a membrane source to generate biomimetic nanoparticles that can effectively and irreversibly bind to α-bungarotoxin, a model neurotoxin. This abrogates the biological activity of the toxin, enabling the resulting nanotoxoid to be safely delivered into the body and processed by the immune system. When co-administered with an immunological adjuvant, a strong humoral response against α-bungarotoxin is generated that protects vaccinated mice against a lethal dose of the toxin. Overall, this work highlights the potential of using genetic modification strategies to develop nanotoxoid formulations against various biological threats.

Abstract The progression of colorectal cancer is closely associated with diet. Fasting-mimicking diet (FMD) is a promising type of dietary intervention that have beneficial effects in the prevention and treatment of various cancers. We investigated the therapeutic effect of 4-day FMD against colorectal cancer in mice through immune cell analysis, microbiota composition analysis and anti-PD-1 treatment. These FMD cycles effectively suppressed colorectal cancer growth, reduced cell proliferation and angiogenesis, increased tumor-infiltration lymphocytes especially CD8+T cells. FMD stimulated protective gut microbiota, especially Lactobacillus. Supplementation of Lactobacillus johnsonii induced similar results as FMD intervention, which also suppressed tumor growth and increased CD45+ and CD8+ T cells. Additionally, FMD synthesizing with anti-PD-1 therapy effectively inhibited CRC progression. These findings suggest that Lactobacillus. johnsonii is necessary for the anticancer process of FMD in CRC. FMD through its effects on both gut microbiota and immune system, effectively suppressed colorectal cancer progression in mouse model.

Abstract Background Zinc has been proven to be effective against periodontitis, and also reported to reduce the risk of cardiovascular diseases (CVD). This study aims to explore the regulatory effect of zinc intake on the association between periodontitis and atherosclerotic cardiovascular disease (ASCVD). Methods This was a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). Logistic regression model was used to explore the association between zinc-RDA or periodontitis and 10-year ASCVD risk ≥ 20%, and results were shown as odds ratio (OR) and 95% confidence interval (95% CI). The regulatory effect of zinc intake on the association between periodontitis and 10-year ASCVD risk ≥ 20% was also assessed using logistic regression model. Subgroup analysis was performed based on age, gender, obesity, education level, lipid-lowering therapy, and dental floss. Results 6,075 patients were finally included for analysis. Zinc intake reaching the recommended level (OR = 0.82, 95%CI: 0.69–0.98) and periodontitis (OR = 2.47, 95%CI: 2.04-3.00) were found to be associated with 0.82-fold and 2.47-fold odds of 10-year ASCVD risk ≥ 20%, respectively. In addition, we found that the odds of 10-year ASCVD risk ≥ 20% was lower in patients with zinc intake reaching the recommended level than those without [OR (95%CI): 2.25 (1.81–2.80) vs. 2.72 (2.05–3.62)]. The similar regulatory effect was found in patients with age ≥ 60 years and

Abstract Antitumor therapies based on adoptively transferred T cells or oncolytic viruses have made significant progress in recent years, but the limited efficiency of their infiltration into solid tumors makes it difficult to achieve desired antitumor effects when used alone. In this study, an oncolytic virus (rVSV-LCMVG) that is not prone to induce virus-neutralizing antibodies was designed and combined with adoptively transferred T cells. By transforming the immunosuppressive tumor microenvironment into an immunosensitive one, in B16 tumor-bearing mice, combination therapy showed superior antitumor effects than monotherapy. This occurred whether the OV was administered intratumorally or intravenously. Combination therapy significantly increased cytokine and chemokine levels within tumors and recruited CD8+ T cells to the TME to trigger antitumor immune responses. Pretreatment with adoptively transferred T cells and subsequent oncolytic virotherapy sensitizes refractory tumors by boosting T-cell recruitment, down-regulating the expression of PD-1, and restoring effector T-cell function. To offer a combination therapy with greater translational value, mRNA vaccines were introduced to induce tumor-specific T cells instead of adoptively transferred T cells. The combination of OVs and mRNA vaccine also displays a significant reduction in tumor burden and prolonged survival. This study proposed a rational combination therapy of OVs with adoptive T-cell transfer or mRNA vaccines encoding tumor-associated antigens, in terms of synergistic efficacy and mechanism.

To enhance the energy absorption properties of the energy-absorbing structure, carbon fiber-reinforced polymer (CFRPs) with higher specific energy absorption and porous material aluminum foam with better compressive characteristics were organically combined, and a lighter aluminum foam winding carbon fiber-reinforced polymer structure (CFRP-FA-FW) was designed. Through quasi-static compression testing, the deformation mode and energy absorption properties of CFRP-FA-FW under axial load were examined. The energy absorption and specific energy absorption of CFRP-FA-FW are both increased by 113.55 % and 60.73 %, respectively, compared to the simple composite structure CFRP-FA. Finite element simulation was used for the parametric analysis of the CFRP-FA-FW structure to assess the effects of the relative density of the aluminum foam, the fiber lay-up angle, and the thickness. The results reveal that the change in the relative density of aluminum foam has little impact on the failure deformation mode of CFRP-FA-FW under axial load; the structure has a higher energy absorption capacity and a smoother energy absorption process when the fiber lay-up angle is [0°/90°]ns and [45°]ns; the energy absorption capacity of CFRP-FA-FW is significantly improved by increasing the thickness of the carbon fiber lay-up, and the procedure is also more efficient.

Exposure to nicotine by cigarette smoking have shown strongly defectives on the physiological function of ovaries, which in turn leads to disorders of fertility in women. However, the potential molecular mechanisms remain to be elucidated. In this study, we notably found that nicotine was likely to specifically raise the expression of histone deacetylase 3 (HDAC3) to promote the apoptosis and autophagy of granulosa cells (GCs) and block follicular maturation. Moreover, prostaglandin E2 (PGE2) inhibited the apoptosis of GCs and facilitated follicular maturation, and nicotine appeared to inhibit PGE2 secretion by freezing the expression of cyclooxygenase 1 (COX1), which was the rate-limiting and essential enzyme for PGE2 synthesis. Epigenetically, the nicotine was observed to diminish the histone H3 lysine 9 acetylation (H3K9ac) level and compact the chromatin accessibility in −1776/-1499 bp region of COX1 by evoking the expression of HDAC3, with the deactivated Cas9-HDAC3/sgRNA system. Mechanistically, the COX1 protein was found to pick up and degrade the autophagy related protein beclin 1 (BECN1) to control the autophagy of GCs. These results provided a potential new molecular therapy to recover the damage of female fertility induced by nicotine from cigarette smoking.

Abstract The dermis and epidermis, crucial structural layers of the skin, encompass appendages, hair follicles (HFs), and intricate cellular heterogeneity. However, an integrated spatiotemporal transcriptomic atlas of embryonic skin has not yet been described and would be invaluable for studying skin‐related diseases in humans. Here, single‐cell and spatial transcriptomic analyses are performed on skin samples of normal and hairless fetal pigs across four developmental periods. The cross‐species comparison of skin cells illustrated that the pig epidermis is more representative of the human epidermis than mice epidermis. Moreover, Phenome‐wide association study analysis revealed that the conserved genes between pigs and humans are strongly associated with human skin‐related diseases. In the epidermis, two lineage differentiation trajectories describe hair follicle (HF) morphogenesis and epidermal development. By comparing normal and hairless fetal pigs, it is found that the hair placode (Pc), the most characteristic initial structure in HFs, arises from progenitor‐like OGN+/UCHL1+ cells. These progenitors appear earlier in development than the previously described early Pc cells and exhibit abnormal proliferation and migration during differentiation in hairless pigs. The study provides a valuable resource for in‐depth insights into HF development, which may serve as a key reference atlas for studying human skin disease etiology using porcine models.

Abstract In the quest to connect bulk topological quantum numbers to measurable parameters in real materials, current established approaches often necessitate specific conditions, limiting their applicability. Here we propose and demonstrate an approach to link the non-trivial hierarchical bulk topology to the multidimensional partition of local density of states (LDOS), denoted as the bulk-LDOS correspondence. In finite-size topologically nontrivial photonic crystals, we observe the LDOS partitioned into three distinct regions: a two-dimensional interior bulk area, a one-dimensional edge region, and zero-dimensional corner sites. Contrarily, topologically trivial cases exhibit uniform LDOS distribution across the entire two-dimensional bulk area. Our findings provide a general framework for distinguishing topological insulators and uncovering novel aspects of topological directional band-gap materials, even in the absence of in-gap states.

Salt stress is a critical abiotic factor that adversely affects plant growth and productivity by impairing photosynthesis. This study explores the impact of exogenous ascorbic acid (AsA) on the photosynthetic performance of tomato seedlings (Solanum lycopersicum L. cv. Ligeer 87-5) under salt stress. Hydroponic experiments were conducted in a solar greenhouse, where tomato seedlings were subjected to the following five treatments: Control, NaCl, NaCl + AsA, NaCl + lycorine (LYC), and NaCl + LYC + AsA. Our findings demonstrate that salt stress significantly reduced chlorophyll and carotenoid contents, levels of chlorophyll synthesis precursors (5-aminolevulinic acid (ALA), porphobilinogen (PBG), uroporphyrinogen III (Urogen III), protoporphyrin IX (Proto IX), magnesium protoporphyrin IX (Mg-Proto IX), protochlorophyllide (Pchl)), and essential elements (Mg, Fe, Mn, Zn, Mo, and P) in both roots and leaves. These reductions led to a substantial decline in net photosynthetic rate (Pn) and compromised photosystem II (PSII). In contrast, exogenous AsA application significantly enhanced the content of photosynthetic pigment precursors and essential elements, improved stomatal aperture and gas exchange efficiency, and boosted the photosynthetic performance of tomato seedlings under salt stress. Furthermore, AsA treatment mitigated the negative effects of salt stress by protecting PSII, increased light energy utilization efficiency, and alleviated both stomatal and non-stomatal limitations. The application of the AsA synthesis inhibitor LYC exacerbated the detrimental effects of salt stress, further reducing chlorophyll content and photosynthetic efficiency. In conclusion, exogenous AsA plays a vital role in enhancing the photosynthetic performance and stress tolerance of tomato seedlings under salt stress by stabilizing chlorophyll biosynthesis, facilitating essential element absorption, and optimizing stomatal function. This study provides a new approach and feasible measures for improving tomato resistance and yield, which is significant for enhancing crop productivity, managing saline soils, and promoting sustainable agricultural practices.

Escherichia coli (E. coli) is commonly utilized as a vehicle for anti-tumor therapy due to its unique tumor-targeting capabilities and ease of engineering modification. To further explore the role of E. coli in tumor treatment, we consider that E. coli outer membrane vesicles (E. coli-OMVs) play a crucial role in the therapeutic process. Firstly, E. coli-OMVs were isolated and partially purified by filtration and ultracentrifugation, and were characterized using techniques such as nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western Blot (WB). The obtained extracellular nanoparticles, containing OMVs, were found to inhibited the growth of CT26 tumor in mice, while the expression of Bax protein was increased and the expression of Bcl-2 protein decreased. In vitro experiments showed that E. coli-OMVs entered CT26 cells and inhibited cell proliferation, invasion and migration. In addition, in the presence of E. coli-OMVs, we observed an increase in apoptosis rate and a decrease in the ratio of Bcl-2/Bax. These data indicate that E. coli-OMVs inhibits the growth of CT26 colon cancer by inducing apoptosis of CT26 cells. These findings propose E. coli-OMVs as a promising therapeutic drug for colorectal cancer (CRC), providing robust support for further research in related fields.

ObjectiveAcute ischemic stroke (AIS) is a heterogeneous condition. To stratify the heterogeneity, identify novel phenotypes, and develop Clinlabomics models of phenotypes that can conduct more personalized treatments for AIS.MethodsIn a retrospective analysis, consecutive AIS and non-AIS inpatients were enrolled. An unsupervised k-means clustering algorithm was used to classify AIS patients into distinct novel phenotypes. Besides, the intergroup comparisons across the phenotypes were performed in clinical and laboratory data. Next, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select essential variables. In addition, Clinlabomics predictive models of phenotypes were established by a support vector machines (SVM) classifier. We used the area under curve (AUC), accuracy, sensitivity, and specificity to evaluate the performance of the models.ResultsOf the three derived phenotypes in 909 AIS patients [median age 64 (IQR: 17) years, 69% male], in phenotype 1 (N = 401), patients were relatively young and obese and had significantly elevated levels of lipids. Phenotype 2 (N = 463) was associated with abnormal ion levels. Phenotype 3 (N = 45) was characterized by the highest level of inflammation, accompanied by mild multiple-organ dysfunction. The external validation cohort prospectively collected 507 AIS patients [median age 60 (IQR: 18) years, 70% male]. Phenotype characteristics were similar in the validation cohort. After LASSO analysis, Clinlabomics models of phenotype 1 and 2 were constructed by the SVM algorithm, yielding high AUC (0.977, 95% CI: 0.961–0.993 and 0.984, 95% CI: 0.971–0.997), accuracy (0.936, 95% CI: 0.922–0.956 and 0.952, 95% CI: 0.938–0.972), sensitivity (0.984, 95% CI: 0.968–0.998 and 0.958, 95% CI: 0.939–0.984), and specificity (0.892, 95% CI: 0.874–0.926 and 0.945, 95% CI: 0.923–0.969).ConclusionIn this study, three novel phenotypes that reflected the abnormal variables of AIS patients were identified, and the Clinlabomics models of phenotypes were established, which are conducive to individualized treatments.

Purpose To introduce the cranial-dorsal-hip angle (∠CDH) as a novel quantitative tool for assessing fetal position in the first trimester and to validate its feasibility for future AI applications.

Abstract This study aimed to develop a physical-based approach for predicting the spatial likelihood of shallow landslides at the regional scale in a transition zone with extreme topography. Shallow landslide susceptibility study in an area with diverse vegetation types as well as distinctive geographic factors (such as steep terrain, fractured rocks, and joints) that dominate the occurrence of shallow landslides is challenging. This article presents a novel methodology for comprehensively assessing shallow landslide susceptibility, taking into account both the positive and negative impacts of plants. This includes considering the positive effects of vegetation canopy interception and plant root reinforcement, as well as the negative effects of plant gravity loading and preferential flow of root systems. This approach was applied to simulate the regional-scale shallow landslide susceptibility in the Dadu River Basin, a transition zone with rapidly changing terrain, uplifting from the Sichuan Plain to the Qinghai–Tibet Plateau. The research findings suggest that: (1) The proposed methodology is effective and capable of assessing shallow landslide susceptibility in the study area; (2) the proposed model performs better than the traditional pseudo-static analysis method (TPSA) model, with 9.93% higher accuracy and 5.59% higher area under the curve; and (3) when the ratio of vegetation weight loads to unstable soil mass weight is high, an increase in vegetation biomass tends to be advantageous for slope stability. The study also mapped the spatial distribution of shallow landslide susceptibility in the study area, which can be used in disaster prevention, mitigation, and risk management.

Abstract Cardiocerebrovascular diseases (CVDs) are the leading cause of death worldwide, consuming huge healthcare budget. For CVD patients, the prompt assessment and appropriate administration is the crux to save life and improve prognosis. Thrombolytic therapy, as a non-invasive approach to achieve recanalization, is the basic component of CVD treatment. Still, there are risks that limits its application. The objective of this review is to give an introduction on the utilization of thrombolytic therapy in cardiocerebrovascular blockage diseases, including coronary heart disease and ischemic stroke, and to review the development in risk assessment of thrombolytic therapy, comparing the performance of traditional scales and novel artificial intelligence-based risk assessment models.

Abstract Background Mental health is a vital part of an individual’s overall health and well-being, and the relationship between society and individuals has always been a focus of academic and public attention. However, the effect of social equity perceptions on individual mental health remains unclear. Methods Data were collected from 8,922 survey respondents with an average age of 47.533 years from the China Labor-force Dynamics Survey 2016 and 2018. The Center for Epidemiological Studies Depression scale was used to assess mental health. A two-way fixed effects regression model was used to determine the association between social equity perception and individual mental health. Results Individuals with higher perceptions of social equity were more likely to report better mental health ( $$\beta$$ β = -0.944, p < 0.01). Happiness, life satisfaction, and social trust partially play mediating roles in the relationship between social equity perception and individual mental health, while education and age play moderating roles. Conclusion Social equity perception is a vital factor that affects mental health. Public policies should focus on helping less educated and older people improve their social equity perception to improve their mental health.

Abstract Background The interplay between gut microbiota and tumor microenvironment (TME) in the pathogenesis of colorectal cancer (CRC) is largely unknown. Here, we elucidated the functional role of B. adolescentis and its possible mechanism on the manipulation of Decorin+ macrophages in colorectal cancer. Methods The relative abundance of B. adolescentis in tumor or para-tumor tissue of CRC patients was analyzed. The role of B. adolescentis was explored in the CRC animal models. The single cell-RNA sequencing (scRNA-seq) was used to investigate the myeloid cells subsets in TME. The expression level of TLR2/YAP axis and its downstream Decorin in macrophages were tested by Western blot and qRT-PCR. Knockdown of Decorin in Raw264.7 was performed to investigate the effect of Decorin+ macrophages on subcutaneous tumor formation. Multi-immunofluorescence assay examined the number of Decorin+ macrophages on the CRC tissue. Results We found that the abundance of B. adolescentis was significantly reduced in tumor tissue of CRC patients. Supplementation with B. adolescentis suppressed AOM/DSS-induced tumorigenesis in mice. ScRNA-seq and animal experiment revealed that B. adolescentis increased Decorin+ macrophages. Mechanically, Decorin was activated by TLR2/YAP axis in macrophages. The abundance of B. adolescentis was correlated with the number of Decorin+ macrophages and the expression level of TLR2 in tumor tissue of CRC patients. Conclusions These results highlight that B. adolescentis induced Decorin+ macrophages and provide a novel therapeutic target for probiotic-based modulation of immune microenvironment in CRC.

Abstract This study aimed to introduce a minimally invasive technique for maxillary sinus floor elevation using the lateral approach (lSFE) and to determine the factors that influence the stability of the grafted area in the sinus cavity. Thirty patients (30 implants) treated with lSFE using minimally invasive techniques from 2015 to 2019 were included in the study. Five aspects of the implant (central, mesial, distal, buccal, and palatal bone heights [BHs]) were measured using cone-beam computed tomography (CBCT) before implant surgery, immediately after surgery (T0), 6 months after surgery (T1), and at the last follow-up visit (T2). Patients’ characteristics were collected. A small bone window (height, (4.40 ± 0.74) mm; length, (6.26 ± 1.03) mm) was prepared. No implant failed during the follow-up period (3.67 ± 1.75) years. Three of the 30 implants exhibited perforations. Changes in BH of the five aspects of implants showed strong correlations with each other and BH decreased dramatically before second-stage surgery. Residual bone height (RBH) did not significantly influence BH changes, whereas smoking status and type of bone graft materials were the potentially influential factors. During the approximate three-year observation period, lSFE with a minimally invasive technique demonstrated high implant survival rate and limited bone reduction in grafted area. In conclusion, lSFE using minimally invasive techniques was a viable treatment option. Patients who were nonsmokers and whose sinus cavity was filled with deproteinized bovine bone mineral (DBBM) had significantly limited bone resorption in grafted area.

Abstract The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and “anatomical escape” characteristics threaten the effectiveness of current coronavirus disease 2019 (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. Here we investigate immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants in hamsters. Intranasal delivery of dNS1-RBD induces innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrains the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (Il6, Il1b, and Ifng) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.

Eucalyptus roots form symbiotic relationships with arbuscular mycorrhizal (AM) fungi in soil to enhance adaptation in challenging environments. However, the evolution of the AM fungal community along a chronosequence of eucalypt plantations and its relationship with soil properties remain unclear. In this study, we evaluated the tree growth, soil properties, and root AM fungal colonization of Eucalyptus grandis W. Hill ex Maiden plantations at different ages, identified the AM fungal community composition by high-throughput sequencing, and developed a structural equation model among trees, soil, and AM fungi. Key findings include the following: (1) The total phosphorus (P) and total potassium (K) in the soil underwent an initial reduction followed by a rise with different stand ages. (2) The rate of AM colonization decreased first and then increased. (3) The composition of the AM fungal community changed significantly with different stand ages, but there was no significant change in diversity. (4) Paraglomus and Glomus were the dominant genera, accounting for 70.1% and 21.8% of the relative abundance, respectively. (5) The dominant genera were mainly influenced by soil P, the N content, and bulk density, but the main factors were different with stand ages. The results can provide a reference for fertilizer management and microbial formulation manufacture for eucalyptus plantations.

Copy number variation (CNV) is an important structural variation used to elucidate complex economic traits. In this study, we sequenced 25 Wannan spotted pigs (WSPs) to detect their CNVs and identify their selection signatures compared with those of 10 Asian wild boars. A total of 14,161 CNVs were detected in the WSPs, accounting for 0.72% of the porcine genome. The fixation index (Fst) was used to identify the selection signatures, and 195 CNVs with the top 1% of the Fst value were selected. Eighty genes were identified in the selected CNV regions. Functional GO and KEGG analyses revealed that the genes within these selected CNVs are associated with key traits such as reproduction (GAL3ST1 and SETD2), fatty acid composition (PRKG1, ACACA, ACSL3, UGT8), immune system (LYZ), ear size (WIF1), and feed efficiency (VIPR2). The findings of this study contribute novel insights into the genetic CNVs underlying WSP characteristics and provide essential information for the protection and utilization of WSP populations.

AIM: To investigate the effect of repeated intravitreal injection of ranibizumab and aflibercept on corneal nerve of patients with macular edema.METHODS: A total of 64 patients(64 eyes)enrolled in our hospital from June 2021 to June 2022 were treated with intravitreal injection of anti-vascular endothelial growth factor(VEGF). There were 20 cases(20 eyes)of diabetic macular edema, 19 cases(19 eyes)of wet age-related macular degeneration and 25 cases(25 eyes)of retinal vein occlusion. Corneal confocal microscope was used to collect images of corneal subbasal nerve plexus before injections and at 1mo after each intravitreal injection based on 3+pro re nata(PRN)treatment regimen. Furthermore, the length and density of corneal nerve were measured.RESULTS: There was no significant difference in corneal nerve density of patients injected with aflibercept between pre-injection and post-injection(P>0.05), while the corneal nerve length after 2nd and 3rd injections was lower than that of pre-injection(all P0.05), and there was no significant differences in corneal nerve density and length after 3 injections of the two drugs(all P>0.05).CONCLUSION: Repeated intravitreal anti-VEGF drug may affect corneal nerve to some extent. For patients who need repeated intravitreal injections of anti-VEGF, attention should be paid to the changes of corneal nerves.

Abstract Background Accessing household toilets is vital for adolescent health during crucial stages of growth and development; however, some ethnic minority families in China lack toilets. The relationship between household toilet accessibility and the physical health of adolescents in China’s ethnic minority areas has been underexamined. Methods Using two waves of data from the China Education Panel Survey (2013 and 2014), this study explored the effect of household toilet accessibility on Chinese ethnic minority adolescents’ physical health. The sample consisted of 576 ethnic minority adolescents with an average age of approximately 13 years. To test the health effect of household toilet accessibility on ethnic minority adolescents, a fixed effects ordinary least squares model and difference-in-differences combined with propensity score matching method were used. Results The results of the fixed effects model and difference-in-differences combined with propensity score matching showed a significant and positive effect of household toilet accessibility on adolescents’ physical health. The heterogeneity analysis indicated that among the toilet types of soil cesspits, cement cesspits, squat toilets, and flush toilets, the flush toilets were proven to be the most efficient in improving adolescents’ physical health. Moreover, the family living arrangement was proven to play a moderating role in the effect of household toilet accessibility on the physical health of ethnic minority adolescents. The average marginal effects of household toilet accessibility on the physical health of ethnic minority adolescents who lived without parents were more evident and significant than those who lived with their parents. Conclusion Promoting household toilet accessibility in China’s ethnic minority areas is essential for improving adolescents’ health. Moreover, having a household toilet is not sufficient, the quality and dignity of household toilets are also important.

Abstract Background Immunotherapy has made significant progress in cancer treatment; however, the responsiveness to immunotherapy varies widely among patients. Growing evidence has demonstrated the role of the gut microbiota in the efficacy of immunotherapy. Main body Herein, we summarise the changes in the microbiota in different cancers under various immunotherapies. The microbial‐host signal transmission on immunotherapeutic responses and mechanisms associated with microbial translocation to tumours in the context of immunotherapy are also discussed. In addition, we have highlighted the clinical application value of methods for regulating the microbiota. Finally, we elaborate on the relationship between the microbiota, host and immunotherapy, and provide potential directions for future research. Conclusion Different microbiota cause changes in the tumour microenvironment through microbial signals thereby affecting immunotherapy efficacy. Translocation of gut microbiota and the role of extraintestinal microbiota in immunotherapy deserve attention. Microbiota regulation is a novel strategy for combination therapy with immunotherapy. Although there are several aspects that deserve further refinement and exploration with regard to administration and clinical translation. Nevertheless, it is foreseeable that the microbiota will become an integral part of cancer treatment.

AbstractIntroduction Blood bone metabolic biomarkers are noninvasive indices for evaluating metabolic bone diseases. We investigated the relationships between blood bone metabolic biomarkers and anemia in chronic kidney disease (CKD) patients and analyzed the effects of parathyroidectomy (PTX) on the above indices.Methods In this cross-sectional study, 100 healthy controls and 239 CKD patients, including 46 secondary hyperparathyroidism (SHPT) patients with PTX, were enrolled. Moreover, a prospective study was conducted in which 28 PTX patients were followed up. The degree of anemia was classified as mild, moderate, or severe based on the tertiles of hemoglobin (Hb) levels of the anemic CKD patients, with cutoff values of 83 g/L and 102 g/L. Bone metabolic biomarkers, including calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF23), and α-klotho, were tested.Results The mean estimated glomerular filtration rate (eGFR) in CKD patients was 25.7 ± 36.0 ml/min/1.73 m2, and 84.10% of CKD patients had anemia. The baseline Hb levels in the mild, moderate, and severe anemia subgroups were 110.86 ± 5.99 g/L, 92.71 ± 5.96 g/L, and 67.38 ± 10.56 g/L, respectively. CKD patients had higher adjusted Ca, P, alkaline phosphatase (ALP), iPTH, and FGF23 levels and lower α-klotho levels than controls. Baseline adjusted Ca, P, iPTH, and α-klotho levels were associated with Hb levels in CKD patients. Blood adjusted Ca, P, and iPTH levels were correlated with anemia severity. After PTX (median interval: 6.88 months), anemia and high blood adjusted Ca, P, iPTH, and FGF23 levels were ameliorated, while α-klotho levels were increased.Conclusions Blood adjusted Ca, P, iPTH, and α-klotho levels were correlated with Hb levels in CKD patients. Correction of bone metabolic disorders may be a therapeutic strategy for anemia treatment.

Under long-term agricultural water saving strategy implemented in the Yellow River basin (YRB), this study analyzed long-term regional groundwater responses and their ecological impacts in an arid irrigation district (Hetao) in the upper YRB. The Mann-Kendall trend test was adopted to examine the trends of the monitoring data of climatic-anthropogenic factors and groundwater depth-salinity, as well as the modeling and remote-sensing results of natural vegetation growth. Results indicated significant decreasing net water diversion while increasing drainage since agricultural water saving, which is a major cause of groundwater reduction instead of climatic factors. This reduction was further confirmed with significant increasing groundwater depth (GWD) trends found in about 90 out of the total 224 monitoring wells across Hetao during 1970–2015. An overall salt accumulation was recognized for Hetao, but groundwater salinity only significantly changed in a few areas with insignificant trends found for more than 70 out of the total 114 monitoring wells during 1995–2015. Meanwhile, significant large-scale decreasing trends were detected for both simulated natural vegetation biomass and remote-sensing derived vegetation index, and wetland loss problem was also found. Particularly, relatively strong similarities were found among the spatial distributions of significant increasing GWD, decreasing vegetation biomass and index, and losing wetlands. This further suggested that the reduction might have caused negative ecological impacts. Overall, the results provided important information regarding long-term regional groundwater responses and their ecological impacts under agricultural water saving, which is significant for agricultural water management for arid irrigation districts.

Abstract Background Revegetation is widely used in degraded grassland restoration. However, the responses of grassland plant and soil properties to fencing (FC) and grazing (GZ) remain poorly understood, especially the vegetation–soil coupling coordination (Cd) mechanism. This study explored single and interactive responses of vegetation and soil properties under FC and GZ after revegetation. Methods A field experiment with FC and GZ treatments was conducted in Loess Plateau reconstructed grassland, with degraded grassland as the control (CK). Plant and soil properties and Cd were analyzed using the analytic hierarchy process (AHP) and principal component analysis (PCA). Results The order of soil comprehensive evaluation (SCE) was GZ > FC > CK, while that of vegetation comprehensive evaluation (VCE) was FC > GZ > CK. The Cd of CK was 0.39 (mild imbalance), while the values of FC and GZ were 0.57 and 0.54, respectively (little coordination). The VCE/SCE of FC was 1.48 (soil lag type), and the values of GZ and CK were 0.69 and 0.35, respectively (vegetation lag and vegetation loss type, respectively). Conclusions Both GZ and FC improved Cd and facilitated recovery. However, degraded grasslands should be restored via moderate grazing for sustainable ecological and economic development.

Bone morphogenetic protein 2 (BMP2) has been reported to regulate adipogenesis, but its role in porcine beige adipocyte formation remains unclear. Our data reveal that BMP2 is significantly induced at the early stages of porcine beige adipocyte differentiation. Additionally, supplementing rhBMP2 during the early stages, but not the late stages of differentiation, significantly enhances porcine SVF adipogenesis, thermogenesis, and proliferation. Furthermore, compared to the empty plasmid-transfected-SVFs, BMP2-overexpressed SVFs had the enhanced lipid accumulation and thermogenesis, while knockdown of BMP2 in SVFs exhibited the opposite effect. The RNA-seq of the above three types of cells revealed the enrichment of the annotation of thermogenesis, brown cell differentiation, etc. In addition, the analysis also highlights the significant enrichment of cell adhesion, the MAPK cascade, and PPARγ signaling. Mechanistically, BMP2 positively regulates the adipogenic and thermogenic capacities of porcine beige adipocytes by activating PPARγ expression through AKT/mTOR and MAPK signaling pathways.

The cellular automata (CA) method has played an important role in the research and development of metallic materials. CA can interpret the microstructure changes of materials and obtain more abundant, accurate and intuitive information of microstructure evolution than conventional methods. CA can visually represent the process of grain formation, growth, development and change to us in a graphical way, which can assist us in analysis, thinking and solving problems. In the last five years, the application of CA in materials research has been rapidly developed, and CA has begun to occupy an increasingly important position in the simulation research of metallic materials. After introducing the advantages and limitations of CA compared to other widely used simulation methods, the purpose of this paper is to review the recent application progress on the microstructure simulation of metallic materials using CA, such as solidification, recrystallization, phase transformation and carbide precipitation occurring during forming and heat treatment. Specifically, recent research advances on microstructure simulation by CA in the fields of additive manufacturing, welding, asymmetrical rolling, corrosion prevention, etc., are also elaborated in this paper. Furthermore, this paper points out the future work direction of CA simulation in the research of metallic materials, especially in the simulation of the crystal structure, the prediction of mechanical properties, CA simulation software and rule systems, etc. These are expected to attract wide attention of researchers in the field of metallic materials and promote the development of CA in materials research.

At present, there is a research gap concerning the specific functions and mechanisms of the Notch gene family and its signaling pathway in jawless vertebrates. In this study, we identified a Notch1 homologue (Lr. Notch1) in the Lethenteron reissneri database. Through bioinformatics analysis, we identified Lr. Notch1 as the likely common ancestor gene of the Notch gene family in higher vertebrates, indicating a high degree of conservation in the Notch gene family and its signaling pathways. To validate the biological function of Lr. Notch1, we conducted targeted silencing of Lr. Notch1 in L. reissneri and analyzed the resultant gene expression profile before and after silencing using transcriptome analysis. Our findings revealed that the silencing of Lr. Notch1 resulted in differential expression of pathways and genes associated with signal transduction, immune regulation, and metabolic regulation, mirroring the biological function of the Notch signaling pathway in higher vertebrates. This article systematically elucidated the origin and evolution of the Notch gene family while also validating the biological function of Lr. Notch1. These insights offer valuable clues for understanding the evolution of the Notch signaling pathway and establish a foundation for future research on the origin of the Notch signaling pathway, as well as its implications in human diseases and immunomodulation.

The collimator is one of the high-heat-flux components used to avoid a series of vacuum and thermal problems. In this paper, the heat load distribution throughout the collimator is first calculated through experimental data, and a transient thermodynamic simulation analysis of the original model is carried out. The error of the pipe outlet temperature between the simulated and experimental values is 1.632%, indicating that the simulation result is reliable. Second, the model is optimized to improve the heat transfer performance of the collimator, including the contact mode between the pipe and the flange, the pipe material and the addition of a twisted tape in the pipe. It is concluded that the convective heat transfer coefficient of the optimized model is increased by 15.381% and the maximum wall temperature is reduced by 16.415%; thus, the heat transfer capacity of the optimized model is effectively improved. Third, to adapt the long-pulse steady-state operation of the experimental advanced superconducting Tokamak (EAST) in the future, steady-state simulations of the original and optimized collimators are carried out. The results show that the maximum temperature of the optimized model is reduced by 37.864% compared with that of the original model. The optimized model was changed as little as possible to obtain a better heat exchange structure on the premise of ensuring the consumption of the same mass flow rate of water so that the collimator can adapt to operational environments with higher heat fluxes and long pulses in the future. These research methods also provide a reference for the future design of components under high-energy and long-pulse operational conditions.

Abstract Background Long-term fasting for elective surgery has been proven unnecessary based on established guidelines. Instead, preoperative carbohydrate loading 2 h before surgery and recommencing oral nutrition intake as soon as possible after surgery is recommended. This study was performed to analyze the compliance with and effect of abbreviated perioperative fasting management in patients undergoing surgical repair of fresh fractures based on current guidelines. Methods Patients with fresh fractures were retrospectively analyzed from the prospectively collected database about perioperative managements based on enhanced recovery of surgery (ERAS) from May 2019 to July 2019 at our hospital. A carbohydrate-enriched beverage was recommended up to 2 h before surgery for all surgical patients except those with contraindications. Postoperatively, oral clear liquids were allowed once the patients had regained full consciousness, and solid food was allowed 1 to 2 h later according to the patients’ willingness. The perioperative fasting time was recorded and the patients’ subjective comfort with respect to thirst and hunger was assessed using an interview-assisted questionnaire. Results In total, 306 patients were enrolled in this study. The compliance rate of preoperative carbohydrate loading was 71.6%, and 93.5% of patients began ingestion of oral liquids within 2 h after surgery. The median (interquartile range) preoperative fasting time for liquids and solids was 8 (5.2–12.9) and 19 (15.7–22) hours, respectively. The median postoperative fasting time for liquids and solids was 1 (0.5–1.9) and 2.8 (2.2–3.5) hours, respectively. A total of 70.3% and 74.2% of patients reported no thirst and hunger during the perioperative period, respectively. Logistic regression analysis showed that the preoperative fasting time for liquids was an independent risk factor for perioperative hunger. No risk factor was identified for perioperative thirst. No adverse events such as aspiration pneumonia or gastroesophageal reflux were observed. Conclusions In this study of a real clinical practice setting, abbreviated perioperative fasting management was carried out with high compliance in patients with fresh fractures. The preoperative fasting time should be further shortened to further improve patients’ subjective comfort.

Immune evasion is essential for carcinogenesis and cancer progression. Programmed death-ligand 1 (PD-L1), a critical immune checkpoint molecule, interacts with programmed death receptor-1 (PD-1) on immune cells to suppress anti-tumor immune responses. In the past decade, antibodies targeting PD-1/PD-L1 have tremendously altered cancer treatment paradigms. Post-translational modifications have been reported as key regulators of PD-L1 expression. Among these modifications, ubiquitination and deubiquitination are reversible processes that dynamically control protein degradation and stabilization. Deubiquitinating enzymes (DUBs) are responsible for deubiquitination and have emerged as crucial players in tumor growth, progression, and immune evasion. Recently, studies have highlighted the participation of DUBs in deubiquitinating PD-L1 and modulating its expression. Here, we review the recent developments in deubiquitination modifications of PD-L1 and focus on the underlying mechanisms and effects on anti-tumor immunity.

Background and Purpose: The prevalence of elderly patients prompts anesthesiologists to determine the optimal dose of medication due to the altered pharmacokinetics and pharmacodynamics of this population. The present study aimed to determine the 95% effective dose (ED95) of remimazolam tosylate in anesthesia induction to inhibit endotracheal intubation-related cardiovascular reaction in frail and non-frail senile patients.Methods: A prospective sequential allocation dose-finding study of remimazolam tosylate was conducted on 80 elderly patients who received general anesthesia between May and June 2022 at the First Affiliated Hospital of Nanchang University. The initial dose was 0.3 mg/kg. The blood pressure and heart rate fluctuations during intubation were either

BackgroundAvoidant attachment poses a serious risk to intimate relationships and offspring. However, there are few studies on the face-processing characteristics and impairments of avoidant individuals based on basic emotion theory. Therefore, this study investigated the issues of emotional processing and deactivation strategies in individuals with avoidant attachment.MethodsAvoidant and secure individuals were recruited to participate in an eye-tracking experiment and a two-choice oddball task in which they had to distinguish facial expressions of basic emotions (sadness, anger, fear, disgust, and neutral). Eye fixation durations to various parts of the face, including the eyes, nose, and mouth, were measured, and three event-related potentials (ERP) components (P100, N170, and P300) were monitored.ResultsAvoidant individuals could not process facial expressions as easily as secure individuals. Avoidant individuals focused less on the eyes of angry faces when compared to secure individuals. They also exhibited a more positive P100 component and a less negative N170 component when processing faces and a larger amplitude of the P300 component than secure individuals when processing emotional expressions.ConclusionAvoidant individuals use deactivating strategies and exhibit specific characteristics at different stages, which are of great significance in social interaction.

Circular RNAs (circRNAs) are a class of non-coding RNAs with diverse functions, and previous studies have reported that circRNAs are involved in the growth and development of pigs. However, studies about porcine circRNAs over the past few years have focused on a limited number of tissues. Based on 215 publicly available RNA sequencing (RNA-seq) samples, we conducted a comprehensive analysis of circRNAs in nine pig tissues, namely, the gallbladder, heart, liver, longissimus dorsi, lung, ovary, pituitary, skeletal muscle, and spleen. Here, we identified a total of 82,528 circRNAs and discovered 3818 novel circRNAs that were not reported in the CircAtlas database. Moreover, we obtained 492 housekeeping circRNAs and 3489 tissue-specific circRNAs. The housekeeping circRNAs were enriched in signaling pathways regulating basic biological tissue activities, such as chromatin remodeling, nuclear-transcribed mRNA catabolic process, and protein methylation. The tissue-specific circRNAs were enriched in signaling pathways related to tissue-specific functions, such as muscle system process in skeletal muscle, cilium organization in pituitary, and cortical cytoskeleton in ovary. Through weighted gene co-expression network analysis, we identified 14 modules comprising 1377 hub circRNAs. Additionally, we explored circRNA–miRNA–mRNA networks to elucidate the interaction relationships between tissue-specific circRNAs and tissue-specific genes. Furthermore, our conservation analysis revealed that 19.29% of circRNAs in pigs shared homologous positions with their counterparts in humans. In summary, this extensive profiling of housekeeping, tissue-specific, and co-expressed circRNAs provides valuable insights into understanding the molecular mechanisms of pig transcriptional expression, ultimately deepening our understanding of genetic and biological processes.

Abstract Background The internet has become ubiquitous in contemporary human life. However, little is known about the association between internet use and older people’s aging process, especially that of older women. Methods Using the nationally representative dataset of the China Longitudinal Aging Social Survey 2016, we examined the relationship between internet usage and the successful aging of older Chinese women. The sample in this study consisted of 2713 respondents with an average age of 69.963 years. Successful aging was defined as no major diseases, no disability, high cognitive functioning, high physical functioning, and active engagement with life. Older women’s internet use behavior was represented by internet use frequency. Probit and instrumental variable models were employed to test the association between internet use frequency and successful aging of older women. The Karlson/Holm/Breen (KHB) mediation analysis was used to estimate the mediating effect of social capital on the relationship between internet use frequency and older women’s successful aging. Results Using a probit model (coefficient = 0.030, p

Abstract Despite tremendous success of molecular targeted therapy together with immunotherapy, only a small subset of patients can benefit from them. Chemotherapy remains the mainstay treatment for most of tumors including non-small cell lung cancer (NSCLC); however, non-selective adverse effects on healthy tissues and secondary resistance are the main obstacles. Meanwhile, the quiescent or dormant cancer stem-like cells (CSLCs) are resistant to antimitotic chemoradiotherapy. Complete remission can only be realized when both proliferative cancer cells and quiescent cancer stem cells are targeted. In the present research, we constructed a cooperatively combating conjugate (DTX-P7) composed of docetaxel (DTX) and a heptapeptide (P7), which specifically binds to cell surface Hsp90, and assessed the anti-tumor effects of DTX-P7 on non-small cell lung cancer. DTX-P7 preferentially suppressed tumor growth compared with DTX in vivo with a favorable distribution to tumor tissues and long circulation half-life. Furthermore, we revealed a distinctive mechanism whereby DTX-P7 induced unfolded protein response and eventually promoted apoptosis. More importantly, we found that DTX-P7 promoted cell cycle reentry of slow-proliferating CSLCs and subsequently killed them, exhibiting a “proliferate to kill” pattern. Collecitvely, by force of active targeting delivery of DTX via membrane-bound Hsp90, DTX-P7 induces unfolded protein response and subsequent apoptosis by degrading Hsp90, meanwhile awakens and kills the dormant cancer stem cells. Thus, DTX-P7 deserves further development as a promising anticancer therapeutic for treatment of various membrane-harboring Hsp90 cancer types. Graphical Abstract

Abstract Background Runs of homozygosity (ROH) are continuous homozygous regions typically located in the DNA sequence of diploid organisms. Identifications of ROH that lead to reduced performance can provide valuable insight into the genetic architecture of complex traits. Here, we systematically investigated the population genetic structure of five Anhui indigenous pig breeds (AHIPs), and compared them to those of five Western commercial pig breeds (WECPs). Furthermore, we examined the occurrence and distribution of ROHs in the five AHIPs and estimated the inbreeding coefficients based on the ROHs (FROH) and homozygosity (FHOM). Finally, we identified genomic regions with high frequencies of ROHs and annotated candidate genes contained therein. Results The WECPs and AHIPs were clearly differentiated into two separate clades consistent with their geographical origins, as revealed by the population structure and principal component analysis. We identified 13,530 ROHs across all individuals, of which 4,555 and 8,975 ROHs were unique to AHIPs and WECPs, respectively. Most ROHs identified in our study were short (

ObjectivesThis study examined how living without parents at different stages of childhood and adolescence affects physical and mental health in adulthood.MethodsThe data came from 3,464 survey respondents aged 18–36 in the 2018 China Labor-Force Dynamics Survey. Physical health was self-rated. Mental health was measured by the Center for Epidemiological Studies Depression scale. The ordered probit and ordinary least-squares regression analyses were employed to determine the associations between growing up without parents at different stages in pre-adulthood and individual physical and mental health in adulthood.ResultsIndividuals who did not live with their parents during their minor years were more likely to report worse physical and mental health in adulthood, compared to those who lived with their parents. This difference was heterogeneous among different age stages and genders.ConclusionsAbsence of parents in the household has long-term impacts on the physical and mental health of children in adulthood, especially for females. The government should make feasible institutional arrangements to avoid the separation of minor children from their parents.

Summary: Long-read sequencing (LRS) facilitates both the genome assembly and the discovery of structural variants (SVs). Here, we built a graph-based pig pangenome by incorporating 11 LRS genomes with an average of 94.01% BUSCO completeness score, revealing 206-Mb novel sequences. We discovered 183,352 nonredundant SVs (63% novel), representing 12.12% of the reference genome. By genotyping SVs in an additional 196 short-read sequencing samples, we identified thousands of population stratified SVs. Particularly, we detected 7,568 Tibetan specific SVs, some of which demonstrate significant population differentiation between Tibetan and low-altitude pigs, which might be associated with the high-altitude hypoxia adaptation in Tibetan pigs. Further integrating functional genomic data, the most promising candidate genes within the SVs that might contribute to the high-altitude hypoxia adaptation were discovered. Overall, our study generates a benchmark pangenome resource for illustrating the important roles of SVs in adaptive evolution, domestication, and genetic improvement of agronomic traits in pigs.

The magnesium alloy was made into orthopedic steel plates to repair tibial fractures of New Zealand white rabbits and to explore the biocompatibility, degradation behavior, and mechanical properties of the magnesium alloy plates in repairing fractures in vivo. Fifty-four rabbits were randomly divided into experimental, control, and sham-operated groups. Tibial fractures in the experimental and the control groups were fixed with magnesium alloy and titanium alloy plates, respectively, and only bone tunnels were established without any implants in the sham-operated group. The concentrations of serum alanine transaminase, creatinine (CREA), creatine kinase (CK), and magnesium ion were measured before and 1 day, 1, 2, 4, 8, and 16 weeks after operation, respectively, to evaluate the biocompatibility of magnesium alloy plates. The corrosion products and components were observed using a scanning electron microscope with an energy-dispersive spectroscopy system, and the corrosion rate was observed by weight loss testing. Then the degradation behavior of magnesium alloy plate was analyzed. Analysis of mechanical properties of magnesium alloy plates was done by four-point bending tests. There were no statistically significant differences in serum alanine transaminase, CREA, or CK at each time point among the three groups (P>0.05). The degradation behavior of the magnesium alloy plates increased with the longer implantation time. The four-point bending test results indicated that the mechanical properties of magnesium alloy plates decreased gradually during the degradation. The results showed that magnesium alloy plates implanted into rabbit tibias degrade gradually with the implantation time, and the mechanical properties of the magnesium alloy weaken gradually during the degradation. Meanwhile, the magnesium alloy plate had excellent biocompatibility and biosafety in the process of degradation in vivo.

Both inosine and guanosine are precursors of uric acid that may cause the diseases of hyperuricemia and gout in humans. Here, a promising bacterial strain for efficiently biodegrading both inosine and guanosine was successfully isolated from a healthy human intestine and identified as Bacillus paranthracis YD01 with 16S rRNA analysis. An initial amount of 49.6 mg·L−1 of inosine or 49.9 mg·L−1 of guanosine was completely removed by YD01 within 12 h, which showed that YD01 had a strong ability to biodegrade inosine and guanosine. Furthermore, the initial amount of 49.2 mg·L−1 of inosine or 49.5 mg·L−1 of guanosine was totally catalyzed by the intracellular crude enzymes of YD01 within 6 h, and the initial inosine amount of 49.6 mg·L−1 or guanosine of 49.7 mg·L−1 was biodegraded by the extracellular crude enzymes of YD01 within 9 h. Illumina Hiseq sequencing and database gene annotation were used to elucidate the genomic characteristics of B. paranthracis YD01. Purine nucleoside phosphorylase, encoded by gene 1785, gene 3933, and gene 4403, was found in the KEEG database, which played a crucial role in the biodegradation of inosine and guanosine. The results of this study provide valuable insights into the mechanisms for biodegrading inosine and guanosine using B. paranthracis YD01.

Gossypol, generally found in the roots, stems, leaves, and, especially, the seeds of cotton plants, is highly toxic to animals and humans, which inhibits the use of cotton stalks as a feed resource. Here, a promising fungal strain for biodegrading gossypol was successfully isolated from the soil of cotton stalk piles in Xinjiang Province, China, and identified as Aspergillus terreus-YJ01 with the analysis of ITS. Initial gossypol of 250 mg·L−1 could be removed by 97% within 96 h by YJ01, and initial gossypol of 150 mg·L−1 could also be catalyzed by 98% or 99% within 36 h by the intracellular or extracellular crude enzymes of YJ01. Sucrose and sodium nitrate were found to be the optimal carbon and nitrogen sources for the growth of YJ01, and the optimal initial pH and inoculum size for the growth of YJ01 were 6.0 and 1%, respectively. To further elucidate the mechanisms underlying gossypol biodegradation by YJ01, the draft genome of YJ01 was sequenced using Illumina HiSeq, which is 31,566,870 bp in length with a GC content of 52.27% and a total of 9737 genes. Eight genes and enzymes were predicted to be involved in gossypol biodegradation. Among them, phosphoglycerate kinase, citrate synthase, and other enzymes are related to the energy supply process. With sufficient energy, β-1, 4-endo-xylanase may achieve the purpose of biodegrading gossypol. The findings of this study provide valuable insights into both the basic research and the application of A. terreus-YJ01 in the biodegradation of gossypol in cotton stalks.

The synergy between human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB) could accelerate the deterioration of immunological functions. Previous studies have explored the pathogenic mechanisms of HIV mono-infection (HMI), MTB mono-infection (MMI) and MTB/HIV co-infection (MHCI), but their similarities and specificities remain to be profoundly investigated. We thus designed a computational framework named IDEN to identify gene pairs related to these states, which were then compared from different perspectives. MMI-related genes showed the highest enrichment level on a greater number of chromosomes. Genes shared by more states tended to be more evolutionarily conserved, posttranslationally modified and topologically important. At the expression level, HMI-specific gene pairs yielded higher correlations, while the overlapping pairs involved in MHCI had significantly lower correlations. The correlation changes of common gene pairs showed that MHCI shared more similarities with MMI. Moreover, MMI- and MHCI-related genes were enriched in more identical pathways and biological processes, further illustrating that MTB may play a dominant role in co-infection. Hub genes specific to each state could promote pathogen infections, while those shared by two states could enhance immune responses. Finally, we improved the network proximity measure for drug repurposing by considering the importance of gene pairs, and approximately ten drug candidates were identified for each disease state.

IntroductionProstate adenocarcinoma (PRAD) is a highly aggressive malignancy with high mortality and poor prognosis, and its potential mechanism remains unclear. Our study aimed to identify novel markers for the prognosis of PRAD using bioinformatics technology.MethodsThe GSE32571 dataset was downloaded from the GEO database, and analyzed via the limma R package to identify differentially expressed genes (DEGs) and differentially expressed immune score-related genes (DEISRGs). The immune-related genes (IRGs) were further obtained by overlapping DEISRGs and DEGs, and the core gene was identified via survival analysis. Furthermore, the expression level, prognostic value, and potential functions of the core gene were evaluated via multiple bioinformatics databases.ResultsA total of 301 IRGs were identified from the GSE32571 dataset, and IFITM1 was a down-regulated gene in several types of cancer, including PRAD. Besides, low expression of IFITM1 was associated with a poor prognosis in PRAD. GSEA indicated that the vital pathways of IFITM1-associated genes were mainly enriched in primary immunodeficiency, Th17 cell differentiation, Th1, and Th2 cell differentiation, natural killer cell-mediated cytotoxicity, myeloid dendritic cell activation, regulation of leukocyte activation, etc. Furthermore, IFITM1 was closely correlated with 22 types of tumor-infiltrating immune cells.DiscussionIFITM1 was a prognostic biomarker for PRAD patients, and it can be acted as a potential immune therapy target in PRAD.

Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. Lactobacillus johnsonii (L. johnsonii), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage L. johnsonii could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in Il10−/− mice. We identified this subset of immune cells activated by L. johnsonii as CD206+ macrophagesIL−10. Mechanistically, L. johnsonii supplementation enhanced the mobilization of CD206+ macrophagesIL−10 through the activation of STAT3 in vivo and in vitro. In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of L. johnsonii by macrophages. Clinically, there was positive correlation between the abundance of L. johnsonii and the expression level of MRC1, IL10 and TLR1/2 in UC tissues. L. johnsonii could activate native macrophages into CD206+ macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. L. johnsonii may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.

T cell receptor (TCR) repertoire as a biomarker for predicting immunotherapy efficiency has been widely studied. However, its dynamics during radiotherapy combined with PD-1 blockade is little known. Using paired tumor and blood samples from the phase Ib clinical study (NCT03222440), we investigate the time-spatial TCR repertoire in esophageal squamous cell carcinoma (ESCC) patients treated with first-line definitive radiotherapy concurrently with anti-PD-1 antibody camrelizumab, and also evaluate the association between TCR repertoire and clinical outcomes. TCR sequencing was performed on tumor biopsies (n = 34, 15 pairs) and peripheral CD8+ T cells (n = 36, 18 pairs) collected at baseline and during treatment (after 40 Gy radiation and 2 rounds of camrelizumab). Whole exome sequencing was applied to estimate genomic mutations and tumor mutation burden. We show that the intratumoral TCR repertoire at baseline was correlated with tumor microenvironment and presented heterogeneity inter-individually. T-cell clones inflowed mutually between tumors and peripheral blood under combination treatment, resulting in an elevation of intratumoral TCR diversity. The peripheral CD8+ TCR diversity at baseline, increased tumor-peripheral Morisita-Horn overlap during treatment, and expansion of persistent intratumoral T-cell clones during treatment predicted improved survival. While it is unclear whether radiation contributed to the TCR changes versus PD-1 therapy alone, our results firstly reveal radiotherapy combined with PD-1 blockade greatly promoted time-spatial alteration of TCR repertoire between tumor and peripheral blood, which demonstrate the peripheral CD8+ TCR diversity at baseline and dynamic alteration of intratumoral TCRs acted as potential effective biomarkers of radiotherapy combined with immunotherapy in ESCC.

The genetic resources among pigs in Anhui Province are diverse, but their value and potential have yet to be discovered. To illustrate the genetic diversity and population structure of the Anhui pigs population, we resequenced the genome of 150 pigs from six representative Anhui pigs populations and analyzed this data together with the sequencing data from 40 Asian wild boars and commercial pigs. Our results showed that Anhui pigs were divided into two distinct types based on ancestral descent: Wannan Spotted pig (WSP) and Wannan Black pig (WBP) origins from the same ancestor and the other four populations origins from another ancestor. We also identified several potential selective sweep regions associated with domestication characteristics among Anhui pigs, including reproduction-associated genes (CABS1, INSL6, MAP3K12, IGF1R, INSR, LIMK2, PATZ1, MAPK1), lipid- and meat-related genes (SNX19, MSTN, MC5R, PRKG1, CREBBP, ADCY9), and ear size genes (MSRB3 and SOX5). Therefore, these findings expand the catalogue and how these genetic differences among pigs and this newly generated data will be a valuable resource for future genetic studies and for improving genome-assisted breeding of pigs and other domesticated animals.