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Objectives: Colistin is known as the last resort antibiotic to treat the infections caused by multidrug resistant foodborne pathogens. The emergence and widespread dissemination of plasmid-mediated colistin resistance gene mcr-1 in the Escherichia coli (E. coli) incurs potential threat to public health. Here, we investigated the epidemiology, transmission dynamics, and genetic characterization of mcr-1 harbouring E. coli isolates from poultry originated in Hebei Province, China. Methods: A total of 297 faecal samples were collected from the two large poultry farms in Hebei Province, China. The samples were processed for E. coli identification by matrix-assisted laser desorption ionization-time of flight mass spectrometry and 16S rDNA sequencing. Then, the mcr-1 gene harbouring E. coli strains were identified by polymerase chain reaction and subjected to antimicrobial susceptibility testing by broth microdilution assay. The genomic characterization of the isolates was done by whole genome sequencing using the various bioinformatics tools, and multi-locus sequence typing was done by sequence analysis of the seven housekeeping genes. The conjugation experiment was done to check the transferability of mcr-1 along with the plasmid stability testing. Results: A total of six mcr-1 E. coli isolates with minimum inhibitory concentration of 4 μg/mL were identified from 297 samples (2.02%). The mcr-1 harbouring E. coli were identified as multidrug resistant and belonged to ST101 (n = 4) and ST410 (n = 2). The genetic environment of mcr-1 presented its position on IncHI2 plasmid in 4 isolates and p0111 in 2 isolates, which is a rarely reported plasmid type for mcr-1. Moreover, both type of plasmids was transferable to recipient J53, and mcr-1 was flanked by 3 mobile elements ISApl1, Tn3, and IS26 forming a novel backbone Tn3–IS26-mcr-1– pap2-ISApl1 on the p0111 plasmid. The phylogenetic analysis shared a common lineage with mcr-1 harbouring isolates from the environment, humans, and animals, which indicate its horizontal spread among the diverse sources, species, and hosts. Conclusion: This study recommends the one health approach for future surveillance across multiple sources and bacterial species to adopt relevant measures and reduce global resistance crises.

This article proposes an adaptive sliding mode control (SMC) strategy based on stochastic configuring networks (SCNs) to improve the stability of synchronous generator (SG) and virtual synchronous generator (VSG) paralleled microgrid and enhance the dynamic performance. First, derives an equivalent swing equation what coupling of inherent inertia/damping of SG and virtual inertia/damping of VSG, the parameters design problem is established to a stabilization problem of second-order uncertain nonlinear system with bounded uncertainties. Second, an adaptive sliding mode control based on variable-speed reaching law is designed to maintain the second-order nonlinear system stable, and the switch function of adaptive reaching law is improved to reduce system chattering. Then, the stochastic configuring networks is introduced to approximate the nonlinear term, and the approximation ability of SCNs is improved by designing the configuration range of input parameters of hidden layer nodes. The stability of proposed control strategy is proved by Lyapunov theory. Finally, the feasibility and effectiveness of the proposed control strategy are verified by the designed simulations and experiments.

Tied-arch bridges, a vital component of modern infrastructure, are susceptible to various forms of damage, particularly hangers. The detection and identification of such damages are crucial for maintaining structural integrity and safety. However, traditional methods face challenges in terms of accuracy and efficiency. This study aims to develop a refined method for hanger damage identification in tied-arch bridges, to address the limitations of existing techniques. By focusing on deflection changes at the anchoring points between the hangers and tie beams, we sought to enhance the precision of damage detection. We propose an innovative approach based on the concept of influence lines, introducing the ‘generalized deflection difference influence line'and the ‘deflection difference influence matrix’. Then proposed a new identification index for identifying the damaged hanger after matrix. An actual tied-arch bridge was used to validate the proposed approach. A detailed three-dimensional finite element model of the bridge was developed and calibrated using dynamic and static response data. Thirty different hanger-damage conditions were simulated to evaluate the effectiveness of the proposed method. Our findings reveal that the deflection difference influence matrix offers more detailed and comprehensive information on bridge distribution points than traditional methods. Our method proved effective in identifying hanger damage, irrespective of its location on the bridge. In additionally, the identification efficiency of the method can be improved by adjusting the magnitude of the applied load, with larger loads amplifying the detectability of damage. This study highlights the potential of the deflection difference influence matrix to revolutionize hanger damage identification for tied-arch bridges. Its adaptability, accuracy, and efficiency are significant advancements over existing methods. This study successfully demonstrates an innovative and reliable method for hanger damage identification.

Background: Using Mendelian randomization (MR) analysis, this study sought to determine the causal relationship between genetically predicted cheese intake, probiotics and breast cancer. Methods: A MR analysis including univariable and multivariable MR approaches using the public genome-wide association studies summary statistics was conducted to assess the causal effects. Results: Genetically predicted cheese intake per standard-deviation increase was associated with decreased risks of luminal A-like breast cancer (odds ratio [OR] = 0.80, 95 % confidence interval [CI]: 0.66–0.97, P = 0.03). No causal effect was detected between probiotics and breast cancer. Multivariable MR analysis showed that the causal effect between cheese intake and luminal A-like breast cancer might be driven by several major ingredients in cheese, including calcium, vitamin D and IGF-1 levels. Conclusions: Cheese intake is causally associated with luminal A-like breast cancer.

Purpose: To investigate the safety and efficacy of intensity modulated carbon ion radiation therapy (IM-CIRT) using pencil beam scanning technology for patients with unresectable sacrococcygeal chordoma (SC). Methods and Materials: A total of 35 patients with unresectable SC were retrospectively analyzed, including 54.3% (19/35) recurrent cases. In 68.6% (24/35) cases, tumor was located in S2 or above, and all cases were treated with hypofractionated IM-CIRT. The median dose was 70.4 Gy (range, 69-80 Gy) (relative biologic effectiveness) in 16 fractions (range, 16-23 fractions), typically delivered over 5 fractions per week. Results: The 3-year overall survival, cause-specific survival, progression-free survival, locoregional progression–free survival, and distant metastasis–free survival rates with a median follow-up time of 42 months (range, 12-91 months) for the entire cohort were 93.2%, 96.3%, 61.8%, 80%, and 77.3%, respectively. Multivariate analysis revealed that gross tumor volume (hazard ratio, 3.807; 95% CI, 1.044-13.887; P = .043) was the only significant prognostic factor for progression-free survival and the dose for the gross tumor volume ≥70.4 Gy (relative biologic effectiveness) was relevant with significantly better locoregional progression–free survival (hazard ratio, 0.190; 95% CI, 0.038-0.940; P = .042). No significant prognostic factor for overall survival, cause-specific survival, and distant metastasis–free survival and no severe (ie, grade ≥3) acute toxicity were identified. Severe late toxicities occurred in 3 patients (8.57%): pain (1 patient), motor neuropathy (1 patient), and skin ulcer (1 patient). Furthermore, no severe toxicity related to urinary function or defecation was observed following IM-CIRT. Pain grades improved or remained unchanged in 85.7% of patients. Conclusions: IM-CIRT produced acceptable 3-year outcomes without substantial late adverse effects, especially urinary and anorectal complications for SC, and did not appear to increase pain. IM-CIRT at high doses using hypofractionated radiation therapy may improve outcomes for local control and seems to be feasible even for postoperative recurrent SC.

Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494–3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494–3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.

Dynamic monitoring of reservoir water storage in arid areas is important for water resources assessment, hydroelectric power generation and agricultural irrigation. However, existing reservoir water calculation methods often rely on in-situ measurements, which limits their application in data scarce regionals and for regional scale analyses. Hence, we propose a novel method to estimate the water storage of channel-type reservoirs in arid areas with unknown underwater topography, with the Bosten Lake watershed serving as a case study site. The method first divides reservoirs into three types based on their upstream and downstream topography: V-shape, U-shape, and flat-shape reservoirs. For the V-shape and U-shape reservoirs, the underwater topography was produced by fitting a linear fit and a polynomial based on the observed elevation above the water surface, respectively. Meanwhile, extrapolation or splining techniques were used to derive the underwater topography for the flat-shape reservoir. The proposed methods are able to measure the underwater topography of the Bosten Lake watershed accurately, with the coefficient of determination (R2) values of 0.83, 0.75 and 0.61 for the V-shape, U-shape, and flat-shape reservoirs, respectively. In addition, the fit of the in-situ water depths of unmanned ships was matched to the simulated water depths for the Xiaoshankou and Bayi reservoirs, yielding R2 values of 0.91 and 0.83 as well as root mean square error (RMSE) of 1.27 m and 1.18 m, respectively. Our approach may be applied in other areas where river underwater topography data is lacking or sparse, and provide important basis for rational water resources management in these areas.

Polycyclic aromatic hydrocarbons (PAHs) and carbon dioxide primarily originate from the combustion of fossil fuels and biomass. The implementation of the Chinese “double carbon strategy” is expected to impact the distribution of PAH emissions, consequently influencing the spatial distribution trend of PAHs in surface soil. Therefore, it is crucial to quantitatively evaluate the effectiveness of the Chinese “double carbon strategy” on soil PAH pollution for the purpose of “the reduction of pollution and carbon emissions”. This study utilized 15,088 individual PAH concentration data from 943 soil samples collected between 2003 and 2020 in China, in conjunction with PAH emissions at a 10 km resolution, for meta-analysis. The calculated PAH emissions in this study are in line with the global PAH emission inventory (PKU-PAH-2007), with a relative standard deviation at the provincial level of less than 25 %. Subsequently, a novel method was developed using emission density and Kow of PAHs to predict PAH concentrations in surface soil based on a least-squares regression model. Compared to other environmental models, the method established in this study significantly reduced the percent sample deviation to less than 70 %. Furthermore, energy consumption data for China were simulated based on the implementation plan of the “double carbon strategy” to project PAH emissions and soil PAH levels for the years 2030 and 2060. The predicted PAH emissions in China were estimated to decrease to 41,300 t in 2030 and 10,406.5 t in 2060 from 78,815 t in 2020. Moreover, the heavily contaminated areas of soil PAHs (i.e., total PAH concentrations in soil exceeding 1000 μg kg−1) were projected to decrease by 45 % and 82 % in 2030 and 2060, respectively, compared to levels in 2020. These findings suggest that the implementation of the “double carbon strategy” can fundamentally reduce the pollution of PAHs in surface soil of China.

Background: Rheumatic valvular disease (RVD) represents a significant health concern in developing countries, yet a scarcity of detailed data exists. This study conducts a comprehensive examination of RVD patients in China, exploring aspects of the disease's spectrum, characteristics, investigation, management, and outcomes. Methods: The China Valvular Heart Disease (China-VHD) study, a nationwide, multicenter, prospective observational study, enrolled 13,917 adults with moderate-to-severe valvular heart disease from April to June 2018. Among these, 2402 patients with native RVD (19.7% of native VHD patients) were analyzed. Results: Among the RVD patients, the median age was 57 years (interquartile range 50–65), with 82.5% falling within the 40–70 age range; females were notably predominant (63.9%). Rheumatic etiology prevailed, particularly in southern regions (48.8%). Multivalvular involvement was observed in 47.4% of RVD cases, and atrial fibrillation emerged as the most common comorbidity (43.2%). Severe RVD affected 64.2% of patients. Valvular interventions were undertaken by 66.9% of RVD patients, predominantly involving surgical valve replacement (90.8%). Adverse events, encompassing all-cause mortality and heart failure hospitalization, occurred in 7.3% of patients during the 2-year follow-up. Multivariable analysis identified factors such as age, geographical region, low body mass index, renal insufficiency, left atrial diameter, and left ventricular ejection fraction

The present study focuses on investigating the microstructure, hardness, wear, and corrosion resistance of Al1.2CoCrFeNiScx high entropy alloys, where the Sc content (x) varies between 0, 0.1, 0.2, and 0.3. The results indicate that the addition of Sc promotes the formation of the FCC phase and improves the hardness and wear resistance, but reduces the corrosion resistance of the alloy. The alloy's evolution can be observed as a transition from a single BCC phase to a combination of Fe, Cr-rich BCC phase, Al, Co, Ni-rich BCC phase, and Ni, Sc-rich FCC phase. As the Sc content increases from 0 to 0.3, the hardness increases from 438 HV to 581 HV, representing a 32.6 % increment. This increase can be mainly attributed to grain size strengthening and solid solution strengthening. Additionally, the average friction coefficient experiences a notable reduction from 0.999 to 0.574, indicating a 42.5 % decrease. With respect to wear resistance, the Al1.2CoCrFeNiSc0.3 alloy exhibits superior performance, demonstrated by its lower friction coefficient, reduced wear rate, and smaller volume, width and depth of wear marks. Furthermore, the addition of Sc to the Al1.2CoCrFeNiScx alloys leads to an overall decrease in corrosion potential, accompanied by an increase in corrosion current density, suggesting that Sc has a detrimental effect on the corrosion resistance of the alloy. Moreover, the Al1.2CoCrFeNi alloy displays pitting corrosion, while the Al1.2CoCrFeNiScx alloys demonstrate intercrystalline corrosion, which preferentially occurs on the Ni, Sc-rich phase due to the high electrochemical activity and low equivalent chemical potential.

Objectives: The aim of this study was to investigate the association between physical activities combined with dietary habits and cardiovascular risk factors in adults from Nanjing, China. Methods: The cross-sectional survey conducted in 2017 involved a sample of 60 283 individuals aged ≥18 years in Nanjing municipality, China. The sampling method used was multistage stratified cluster sampling. The primary outcomes from multivariate logistic regression analysis with adjusted potential confounders were the relationships between physical activities combined with dietary habits and cardiovascular risk variables. Relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were used to assess an additive interaction between dietary habits and physical activities. Results: After adjusting potential confounders, cardiovascular risk factors were significantly associated with the association of physical inactivity and unhealthy diet, with the highest odds ratios (ORs) for low density lipoprotein-cholesterol (HLDL-c) (1.64, 95% CI [1.47, 1.84]) and hypertension (1.55, 95% CI [1.46, 1.64]). Additive interactions between physical inactivity and unhealthy diet were found in on cardiovascular risk factors of higher low-density lipoprotein-cholesterol (HLDL-c) (S, 2.57; 95% CI [1.27, 5.21]), type 2 diabetes (T2D) (S, 1.96; 95% CI [1.23, 3.13]), dyslipidemia (S, 1.69; 95% CI [1.08, 2.66]) and hypertension (S, 1.46; 95% CI [1.12, 1.89]). Their RERI was 0.39 (95% CI [0.18, 0.60]), 0.22 (95% CI [0.09, 0.35]), 0.11 (95% CI [0.03, 0.19]) and 0.17 (95% CI [0.06, 0.28]), respectively. OR of being HLDL-c, T2D, hypertension and dyslipidemia in participants of physical inactivity and unhealthy diet was 24%, 15%, 11% and 8.3%, respectively. Multiplicative interaction was detected in obesity, hypertension, T2D and HLDL-c. Conclusion: An unhealthy diet and physical inactivity were strongly linked to cardiovascular risk factors. This study also showed that an unhealthy diet and physical inactivity combined to produce an additive effect on T2D, hypertension, HLDL-c, and dyslipidemia, suggesting a higher risk than the total of these factors, especially HLDL-c. Preventive strategies aimed at reducing cardiometabolic risks such as hypertension, T2D, HLDL-c, and dyslipidemia are necessary for targeting physical inactivity and unhealthy diet.

Summary: This study aimed to investigate the prevalence of diabetes in valvular heart disease (VHD), as well as the relationship of diabetes with severity of valvular lesions and clinical outcome. A total of 11,862 patients with significant (≥moderate) VHD from the China Valvular Heart Disease study were included in the analysis. The primary outcome was the composite of all-cause death, hospitalization for heart failure, and myocardial infarction during two-year follow-up. The prevalence of diabetes was 14.5% (1,721/11,862) in VHD. After adjusting for patients’ demographics, diabetes was associated with a significantly lower risk of severe valvular lesion in aortic regurgitation and mitral regurgitation (MR). In multivariable analysis, diabetes was identified as an independent predictor of two-year outcome in patients with MR (hazard ratio: 1.345, 95% confidence interval: 1.069–1.692, p = 0.011). More efforts should be made to enhance our understanding and improve outcomes of concomitant VHD and diabetes.

Organic UV filters, which are often found in the environment, have been the focus of much public health concern. 2-ethylhexyl-4-methoxycinnamate (EHMC) is one of the most common organic UV filters present in the environment. However, few studies have investigated its developmental neurotoxic (DNT) effects and the underlying molecular mechanisms. In the present study, zebrafish embryos were exposed to low concentration of EHMC (0, 0.01, 0.1, 1 mg/L) in static water starting from 6 h post-fertilization (hpf). Results showed that EHMC exposure caused a reduction in somite count at 13 hpf, a diminishment in head-trunk angle at 30 hpf, a delay in hatching at 48 hpf, and a decrease in head depth and head length at both 30 and 48 hpf. Additionally, EHMC led to abnormal motor behaviors at various developmental stages including altered spontaneous movement at both 23 and 24 hpf, and decreased touch response at 30 hpf. Consistent with these morphological changes and motor behavior deficits, EHMC inhibited axonal growth of primary motor neurons at 30 and 48 hpf, and yielded subtle changes in muscle fiber length at 48 hpf, suggesting the functional relevance of structural changes. Moreover, EHMC exposure induced excessive cell apoptosis in the head and spinal cord regions, increased the production of reactive oxygen species (ROS) and malondialdehyde (MDA), and reduced the level of glutathione (GSH). Defects of lateral line system neuromasts were also observed, but no structural deformity of blood vessels was seen in developing zebrafish. Abnormal expression of axonal growth-related genes (gap43, mbp, shha, and α1-tubulin) and apoptosis-related genes (bax/bcl-2 and caspase-3) revealed potential molecular mechanisms regarding the defective motor behaviors and aberrant phenotype. In summary, our findings indicate that EHMC induced developmental neurotoxicity in zebrafish, making it essential to assess its risks and provide warnings regarding EHMC exposure.

Study region: Kaidu River Basin, an arid region of China Study focus: Water resources are scarce and unstable. Adverse changes in blue-green water resources can disrupt water balance and availability in arid regions. Therefore, it is crucial to effectively assess and predict future blue-green water resources in arid areas. This study utilizes the Soil and Water Assessment Tool (SWAT), Patch-generating Land Use Simulation (PLUS), and Global Circulation Models (GCMs) to analyze the interactive impacts of climate and land use/cover changes (LUCC) on blue-green water in arid basin from 1990 to 2050. New hydrological insights for the region: This work identified key factors influencing blue-green water changes, including forests, grasslands, and snowmelt. In the historical scenarios, the Kaidu River basin exhibited significant interannual variations in blue water and precipitation. In the future scenarios, blue water increases (+3.6%), and green water decreases (−1.8%) under SSP245 (medium emissions). Under SSP585 (high emissions), blue water decreases (−2.4%), and green water increases (+1.8%). Under SSP126 (low emissions), both blue water (+8.5%) and green water (+0.73%) show an increasing trend. The change in snowmelt is the main reason for the first peak of blue water in April May. Under historical and future snowmelt conditions, blue water shows a significant upward or downward trend with the amount of snowmelt. The findings provided practical hints for the enhancement of the management and allocation of precious water resources.

Background: Aphasia affects approximately one-third of stroke patients and yet its rehabilitation outcomes are often unsatisfactory. More effective strategies are needed to promote recovery. Objective: We aimed to examine the efficacy and safety of the theta-burst stimulation (TBS) on the language area in the superior frontal gyrus (SFG) localized by personalized functional imaging, in facilitating post-stroke aphasia recovery. Methods: This randomized sham-controlled trial uses a parallel design (intermittent TBS [iTBS] in ipsilesional hemisphere vs. continuous TBS [cTBS] in contralesional hemisphere vs. sham group). Participants had aphasia symptoms resulting from their first stroke in the left hemisphere at least one month prior. Participants received three-week speech-language therapy coupled with either active or sham stimulation applied to the left or right SFG. The primary outcome was the change in Western Aphasia Battery-Revised (WAB-R) aphasia quotient after the three-week treatment. The secondary outcome was WAB-R aphasia quotient improvement after one week of treatment. Results: Ninety-seven patients were screened between January 2021 and January 2022, 45 of whom were randomized and 44 received intervention (15 in each active group, 14 in sham). Both iTBS (estimated difference = 14.75, p

Tolerogenic dendritic cells (tolDCs) facilitate the suppression of autoimmune responses by differentiating regulatory T cells (Treg). The dysfunction of immunotolerance results in the development of autoimmune diseases, such as rheumatoid arthritis (RA). As multipotent progenitor cells, mesenchymal stem cells (MSCs), can regulate dendritic cells (DCs) to restore their immunosuppressive function and prevent disease development. However, the underlying mechanisms of MSCs in regulating DCs still need to be better defined. Simultaneously, the delivery system for MSCs also influences their function. Herein, MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ, maximizing efficacy in vivo. The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines. In the collagen-induced arthritis (CIA) mice model, alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39+CD73+ on MSCs. These enzymes hydrolyze ATP to adenosine and activate A2A/2B receptors on immature DCs, further promoting the phenotypic transformation of DCs to tolDCs and regulating naïve T cells to Tregs. Therefore, encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression. This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.

Background: Homologous recombination deficiency (HRD) phenotype will sensitize tumors to poly (ADP-ribose) polymerases inhibitors and platinum. However, previous studies did not focus on the prevalence of HRD among Chinese breast cancer (BC) patients. Methods: One hundred and forty-seven BC patients were included in this study. Their HRD status was assessed by Genomic Scar Score (GSS), which was determined according to the length, site, and type of copy number. HRD was defined as positive when a harmful BRCA1/2 mutation was detected or GSS ≥50. Results: Our data revealed that 9.5% of the 147 patients tested positive for BRCA1/2 mutation, while approximately 34.7% were HRD-positive. For triple negative BC (TNBC), HRD positivity rate (60.5%) was higher than Luminal A (5.3%), Luminal B (HER2-) (28.8%), and Luminal B (HER2+) (31.6%) subgroups. HRD-positive tumors were more likely to be ER/PR-negative and exhibited higher Ki-67 expression. 50.0% of the HRD-positive patients achieved pathologic complete remission (pCR) after neoadjuvant therapy. HRD-positive patients tended to have a higher risk for cancer recurrence or metastasis compared to HRD-negative patients (29.4% vs. 13.5%). Conclusion: We investigated the HRD status among Chinese BC patients using an HRD detection tool developed based on the Chinese population. The clinical characteristics, pathological profile, family history pattern, neoadjuvant efficacy, and disease progression events of HRD-positive and negative patients were described and compared. Thus, our data provided an evidence-based basis for applying the original HRD assay in Chinese BC.

ABSTRACT: Xylooligosaccharide (XOS) is known as a prebiotic, however, it is unknown whether XOS can directly protect against bacterial infection. This study aimed to investigate the direct inhibitory effects of XOS on Salmonella Typhimurium colonization and the inductive impairments in gut health and growth performance in broilers. We first probed the inhibitory effects of XOS on S. Typhimurium adhesion and its induction of intestinal epithelial cell (IPEC-J2) injuries. Afterward, 168 one-day-old yellow-feathered broilers were randomly divided into 3 groups (7 replicates/group): negative control (NC, received a basal diet), positive control (PC, received a basal diet with S. Typhimurium challenge) and XOS group (PC birds + 1,500 mg/kg XOS). All birds except those in NC were orally challenged with S. Typhimurium from 8 to 10 d of age. Parameters were analyzed on d 11. The results showed that XOS inhibited S. Typhimurium adhesion and the inductive injuries of IPEC-J2 cells by lowering (P < 0.05) certain adhesion-related genes expression of this bacterium. It also alleviated S. Typhimurium-induced increase (P < 0.05) in the expression of certain inflammatory cytokines and tight junction (TJ) proteins of IPEC-J2 cells. Supplementing XOS to S. Typhimurium-challenged broilers attenuated the elevations (P < 0.05) in S. Typhimurium colonization of ileal mucosa and its translocation to the liver and spleen, as well as increased (P < 0.05) certain TJ proteins expression of ileum. Besides, XOS addition normalized S. Typhimurium-induced impairments (P < 0.05) in ileal morphology, final body weight and average daily gain in broilers. Collectively, supplemental XOS directly suppressed intestinal colonization of S. Typhimurium by diminishing its adhesiveness and subsequently mitigated destructions in intestinal barriers, thus contributing to weaken growth retardation in challenged broilers. Our findings provide a new insight into the mechanisms of XOS limiting Salmonella infection in chickens.

Long-term waterproofing and water leakage treatment of existing underground structures have become prominent issues in the operation and maintenance of underground structures. The use of single organic or inorganic materials for water leakage treatment is not effective for solving practical engineering problems. Considering the properties of organic and inorganic materials, a novel composite material mixing the waterborne epoxy resin and superfine ordinary Portland cement-sulphoaluminate cement was presented, which was studied as a polymer-modified cementitious composite for waterproofing and plugging. This study investigated the primary physical properties of the raw materials of the polymer-modified cementitious composite. Experimental tests were performed to investigate the effects of waterborne epoxy resin on the impermeability, interface adhesion, and tensile deformation performances of the superfine cementitious waterproof material. The results showed that the average water penetration height of the waterborne epoxy resin-modified material was only 52.2% that of the cementitious materials, indicating better impermeability performance. When 3% waterborne epoxy resin was mixed, the bending bond strength of the polymer-modified composite material was 10.6% higher than that of the cementitious material. The direct tensile bond strength of the polymer-modified composite material with various waterborne epoxy resin content significantly improved, demonstrating a maximum increase of 72.6%. Compared with the original cementitious material, the toughness, tensile deformation capacity, and tensile strength of the polymer-modified superfine cementitious composite material were improved. The maximum tensile amount increased by 48.3% when an appropriate amount of waterborne epoxy resin was mixed, which is the primary performance in long-term waterproofing. Moreover, the bearing capacity increased by 335.2% compared with the cementitious materials when 7% waterborne epoxy resin was mixed. The key contribution of this research is to propose a high performance and effective polymer-modified composite material for the treatment of waterproofing and plugging. The findings from the study also provide industry practitioners with a comprehensive guide regarding the mechanical and impermeability performances of the polymer-modified superfine cementitious composite material.

Bisphenol S (BPS) is a raw material that is used extensively in various manufacturing processes but possesses a high detection rate in human red blood cells (RBCs). Accordingly, BPS is a potential toxicant in disturbing the function of RBCs and causing RBC-related diseases. To date, the effects and mechanisms of BPS-induced RBC-related diseases have not been elucidated. Here, using different models, including rats, zebrafish embryos and RBCs, the underlying mechanism of RBC-related diseases induced by BPS was explored. The accumulation of BPS in tissue was colon > kidney > liver > plasma > testicle > heart > brain in SD rats orally administered BPS (10 and 50 mg/kg bw/day) for 32 days, which was similar in both 10 mg/kg bw/day and 50 mg/kg bw/day group. Rats given BPS orally developed hyperlipidemia and increased RBC membrane cholesterol, as well as changes in RBC morphology and function. Moreover, BPS at the concentrations measured in rats plasma caused oxidative stress and phosphatidylserine exposure in vitro RBCs. These combined factors led to RBC aggregation in blood and an increasing in the number of RBCs in the blood vessels of the liver in rats. The dynamic visual observation of RBCs in vein vessels of zebrafish embryos exposed to BPS at 0, 1, 10 and 100 μg/L further found that the flow of RBCs in the tail vein is slow or even immobile, posing the risk of venous thrombosis. The present study provides new insight into the links between environmental pollutants and venous thrombosis.

Biomaterials with exceptional biocompatibility and bioactivity are now pushing the boundaries of bone tissue engineering. In this study, natural Arabic gum biopolymer incorporating titanium dioxide nanoparticles (NAG + TiO2NP) nanocomposite film was fabricated. The FTIR and XRD analysis show the presence of functional groups assigned to NAG biopolymers and highly crystalline anatase TiO2NP. Well dispersed TiO2NP can be seen from SEM micrograph suggesting good interaction between TiO2NP filler and NAG biopolymer matrix to enhance the mechanical characteristics of nanocomposite film. The NAG + TiO2NP nanocomposite film exhibited strong bioactivity to form bone-like apatite and promoted the proliferation of MG-63 cells attributed to their excellent biocompatibility and non-toxicity. The NAG + TiO2NP nanocomposite film also displays high antibacterial activity with (36.33 ± 1.53) mm and (27.00 ± 2.00) mm inhibition zone were recorded against Staphylococcus aureus and Escherichia coli. The findings indicate that the NAG + TiO2NP nanocomposite film, with its improved mechanical properties, high swelling capacity, biodegradability, and non-toxicity, shows promise as a viable option for bone tissue regeneration materials.

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common nasal diseases in children. Studies have shown that heavy metals are environmental risk factors for nasal diseases, and the pathogenic mechanisms may be related to dysregulation of nasal mucosal microbiota. However, it is unclear how heavy metal exposure relates to the nasal mucosal microbiota in nasal diseases. Therefore, we explored serum metal exposure levels and nasal mucosal microbiota composition in children with different nasal disease, and further studied the potential correlation between metal exposure and disease-related taxa. There were 64 children recruited for this study. The 23 metals concentrations in serum were measured by inductively coupled plasma mass spectrometry, and nasal mucosal bacteria was identified by 16S rRNA sequencing. Nasal diseases (AR and AH) in children were associated with alterations in the abundance and diversity of the nasal mucosal microbiota. The nasal microbiota of children with AR showed lower diversity, while the microbiota of children with AH showed higher diversity. Linear discriminant analysis Effect Size showed 108 differentially abundant taxa between AR and control groups, 35 differentially abundant taxa among large adenoid, moderate adenoid and small adenoid groups. The serum zinc concentration was negatively correlated with Pielou's eveness index and Simpson's Index in children classified by adenoid size. The spearman correlation analysis showed that multiple disease-related taxa were closely associated with metal concentrations in serum. Our findings may support a link between metal exposure and the diversity and composition of nasal bacteria in children with nasal disease, which present new evidence for the effects of metals on children health.

Tiliroside, as a dietary flavonoid, has great potential in preventing or treating non-alcoholic fatty liver disease (NAFLD). However, research on tiliroside metabolism remains unclear, limiting its further utilization in healthcare. Herein, we explored the hepatoprotective effect of tiliroside and performed an UHPLC-Q-Exactive Orbitrap/MS-based set of experiments to identify metabolites and metabolic pathways of tiliroside in human hepatocytes. Results showed that tiliroside can exert antioxidant activity to protect against palmitic acid (PA)-induced oxidative injury in hepatocytes. Moreover, tiliroside was found to be considerably transformed through metabolism in human hepatocytes based on full MS and MS/MS analysis. Fifteen metabolites derived from the glucuronidation, sulfation, hydrolysis, and oxidation of tiliroside were identified. Glucuronidation and sulfation played key roles in tiliroside metabolism, accounting for approximately 32% and 20% of metabolism after 240 min incubation, respectively. The findings could provide a scientific basis for a more rational and effective application of tiliroside in healthcare.

Hafnium nitride (HfN) possesses excellent mechanical properties such as high hardness and wear resistance, and is usually used as a protective coating on high-end equipment and precision instruments. Nevertheless, the high coefficient of friction of HfN coating poses a serious threat to equipment and instruments, so doping modifications are imperative. Here, HfN coatings doping with different Ag contents were prepared by magnetron sputtering. It was found in the experiments that the introduction of a trace amount of Ag atoms (∼1.85 at.%) could replace the Hf atoms in the HfN sublattice, resulting in a solid solution Hf-Ag-N. As compared with the pure HfN coating (20.3 GPa), the solid solution Hf-Ag-N coating has higher hardness (25.5 GPa), lower coefficient of friction (μ = 0.28) and lower wear rate (3.03 × 10−8 mm3/(N·mm). With increasing Ag content, solid solution structure disappears and a nanocomposite structure forms, leading to a sharp decrease in hardness of Hf-Ag-N coating due to the precipitation of soft Ag phase. Additionally, X-ray photoelectron spectroscopy and Raman spectrum analysis revealed that the reason for the low coefficient of friction of Hf-Ag-N solid solution coating is mainly due to the large number of tribo-oxidation products (HfO2, Ag2O) and self-lubricating phase (Ag) on the worn surface. The density functional theory further confirms that Ag atoms in solutes promote spontaneous oxidation of Hf-Ag-N which is important for causing tribo-oxidation. The results of this study expect to provide new idea as well as certain theoretical basis for designing new protective coatings.

The aim of this study was to characterize the riebeckite type rare earth ore found in the Bayan Obo deposit, in order to identify the distribution and occurrence of both rare earths and gangue species within the ore. Several analytical techniques were utilized to accomplish this, such as chemical analysis, quantitative XRD, a single polarizing microscope, and a mineral automatic analysis system. The analysis revealed that the primary rare earth minerals (REMs) in the ore were bastnaesite and monazite, with huanghoite, parisite, aeschynite, and fergusonite identified as secondary rare earth minerals. The main gangue species was magnetite, accompanied by smaller quantities of riebeckite and dolomite. The ore was rich in rare earth oxides, with a 3.81 wt% grade. The screen analysis of the pulverized ore indicates that the 43–100 μm fraction is the dominant size, while the finer size fractions below 43 μm contain the bastnaesite and monazite, as well as huanghoite, parisite, aeschynite, and fergusonite. Microstructural characterization showed that the REMs were both coarse-grained and fine-grained, occurring as granular aggregates and fine disseminations within the gangue. Bastnaesite and monazite were the major REMs, with dominant amounts of cerium, lanthanum, praseodymium, and neodymium, while parasite was identified as an impurity. Huanghoite and parisite contained barium and calcium as impurities, respectively. Aeschynite and fergusonite were REMs that included niobium in their composition. Bastnaesite and monazite were found to contain a much higher rare earth content than huanghoite, parisite, aeschynite, and fergusonite. Potential methods for recovering rare earths from this ore, such as magnetic separation and froth flotation, have been identified and may be applicable to similar ferruginous rare earth-bearing ores.

One of the key elements impacting the productivity of wheat production is soil salinity. Here, we characterize the metabolomic and transcriptome responses to salt stress in two distinct wheat cultivars with varying levels of salt tolerance. Cangmai 6005 (CM6005) is a new wheat variety bred in the Cangzhou Academy of Agriculture and Forestry Sciences. After salt treatment, the germination and seedling stage of CM6005 maintains green leaves and produces a longer bud length than the cultivar Kenong9204 (KN9204). In this study, we investigated genes/metabolite activity changes in both types subjected to salt and control treatments using integrated transcriptomics and metabolomics analyses. By comparing data from the salt-treated plants with the control, 5161 (3235 upregulated and 1926 downregulated) and 211 (29 up and 182 downregulated) DEGs(Differentially Expressed Genes) were identified in the germination and seedling stage of CM6005. A total of 2061 (898 upregulated and 1163 downregulated) and 99 (84 upregulated and 15 downregulated) DEGs were identified in the germination and seedling stage of KN9204. CM6005's germination and seedling stage saw the identification of 792 (492 upregulated and 300 downregulated) and 2217 (1195 upregulated and 1032 downregulated) DAMs(Differentially Accumulated Metabolites), while KN9204's germination and seedling stage saw the identification of 1999 (997 upregulated and 1002 downregulated) and 1702 (860 upregulated and 842 downregulated) DAMs. The effects of salt stress on glycerolipid metabolism, phenylalanine metabolism, and glycerophospholipid metabolism were significantly modulated under salt treatments in the germination and seedling stages of CM6005 and KN9204, respectively, according to an integrated analysis of gene expression and metabolite profiles, assessment of metabolic pathways, and KEGG enrichment. Our findings showed that salt treatments caused stress-induced significant alterations in both transcriptomes and metabolomes. Wheat salt tolerance was regulated by key pathways linked to glycerolipid and phenylalanine metabolism, and these pathways serve as a crucial guide for growing wheat in saline soil. GRAS and MYB transcription factors might also regulate Glycerolipid metabolism and Phenylalanine metabolism.

Global biodiversity is in rapid decline, yet the key threats to wildlife in many regions remain uncertain. Bats are one of the most diverse mammalian groups, playing vital roles in the ecosystems. There are at least 140 bat species in China, with 30 % of being regionally threatened or data deficient. Here, we used expert elicitation to assess the key threats and conservation strategies of bats in China. We designed an online questionnaire concerning the conservation of Chinese bats, and then distributed the questionnaire to bat experts worldwide via email. All participants were asked to rank each threat and conservation strategy according to the urgency and significance. After excluding participants without some knowledge of Chinese bats and conservation biology, we gathered the opinions of 119 bat experts from China and abroad. The results showed that the scores of different threats and conservation strategies were predicted by their categories. Loss of habitat, killing and hunting, and roost disturbance were regarded as the three top threats faced by Chinese bats. Most experts recognized that banning hunting and improving the legislation were two priority strategies for bat conservation, although monitoring of bat diversity, scientific publicity, and education were also important. Nearly 98 % of the experts supported the suggestion that threatened bats should be under special state protection because of their ecological services, economic value, population decline, scientific value, and other features. These results provide valuable implications for guiding the protection and management of bats in China.

Summary: A variety of anthropogenic organohalide contaminants generated from industry are released into the environment and thus cause serious pollution that endangers human health. In the present study, we investigated the microbial community composition of industrial saponification wastewater using 16S rRNA sequencing, providing genomic insights of potential organohalide dehalogenation bacteria (OHDBs) by metagenomic sequencing. We also explored yet-to-culture OHDBs involved in the microbial community. Microbial diversity analysis reveals that Proteobacteria and Patescibacteria phyla dominate microbiome abundance of the wastewater. In addition, a total of six bacterial groups (Rhizobiales, Rhodobacteraceae, Rhodospirillales, Flavobacteriales, Micrococcales, and Saccharimonadales) were found as biomarkers in the key organohalide removal module. Ninety-four metagenome-assembled genomes were reconstructed from the microbial community, and 105 hydrolytic dehalogenase genes within 42 metagenome-assembled genomes were identified, suggesting that the potential for organohalide hydrolytic dehalogenation is present in the microbial community. Subsequently, we characterized the organohalide dehalogenation of an isolated OHDB, Microbacterium sp. J1-1, which shows the dehalogenation activities of chloropropanol, dichloropropanol, and epichlorohydrin. This study provides a community-integrated multi-omics approach to gain functional OHDBs for industrial organohalide dehalogenation.

Understanding of the buffer scale effect on water quality changes analysis in arid and humid regions is of great significance for exploring the best scale for water quality pollution and scientific planning of land use. The objective of this study is to determine the optimal buffer scales (500, 1000, 1500, 2000, 2500 and 3000 m) of land use that affect ammonia nitrogen (NH3-N) and total phosphorus (TP) in the Jing-Bortala River Watershed (JBRW) (arid region) and the Liyang Region (LR) (humid region) under a site buffer. PLS-SEM was used to fit the pathway relationships between the influencing factors and water quality to investigate the driving factors of NH3-N and TP in different seasons. The results showed that: (1) seasonal fluctuations in NH3-N and TP concentrations were found in both the arid and humid regions, with the arid region having higher values than humid region; the coefficient of variation (CV) of NH3-N and TP was higher in arid and humid region, and the CV of NH3-N and TP were higher in spring and autumn in arid region than that in spring and autumn in humid region; (2) the 2500 m (0.262 ≤ R2 ≤ 0.633) buffer is the optimal scale for studying NH3-N and TP in arid region, whereas the 2000 m (0.262 ≤ R2 ≤ 0.686) scale works well in humid region; and (3) farmland (NDVI) was the largest influencing factor for NH3-N and TP changes in arid region, accounting for 28.95 % of the average percent total impacts. Furthermore, water area (NDWI) was the predominant influencing factor in humid region, occupying 33.93 % of the average percent total impacts. The influence of land use type (indices) on surface water quality is greater than that of environmental factors. Thus, these new insights into an appropriate buffer scale can be used as a guide for water pollution management in arid and humid environments.

This paper investigates the effect of Ø 0.11 mm Z-pinning on the structural properties of the composite T-joints via the ultrasound-guided insertion process. The structural properties of the joints are determined by the stiffener web pull-off testing. The experimental results show that carbon Z-pins exhibit a better improvement effect than steel Z-pins due to the interface between carbon Z-pins and laminate owning higher pullout strength. When the skin-flange area of the joints is inserted with 0.2 vol% of Ø 0.11 mm carbon Z-pins, the peak load and total energy absorption capacity can be improved by 72.4% and 436.5%, respectively. With the Ø 0.11 mm Z-pinning, the tensile strength decreased by only 2% when the volume content reached 0.2%. The improvements to the T-joint structural properties are explained by the enhancement mechanism of Ø 0.11 mm Z-pinning on mixed mode I/II interlaminar fracture toughness of laminates. Finally, the Ø 0.11 mm Z-pinned T-joint model is established to verify the experimental results.

Both reticuloendotheliosis and Marek's disease are neoplastic diseases of chickens caused by reticuloendotheliosis virus (REV) and Marek's disease virus (MDV), respectively. The infection of REV or MDV may lead to clinical tumors and also result in immunosuppression and easily allow secondary infection by other pathogens. Here, we investigated a breeder flock of three-yellow chickens in southern China that had been vaccinated with CVI988/Rispens at hatching and had experienced depression, weakness, reduction in weight gain, and an increased death rate after 120 d of age. The morbidity and mortality were 20% and 10%, respectively, at 140 d of age when this infection was diagnosed. The necropsy of the birds revealed significant tumor-like lesions in the heart, liver, spleen, and ceca. Peripheral blood lymphocytes and tumor-like tissues were sampled for PCR detection and for histopathological observation, for virus isolation and the subsequent immunofluorescent assay on the cell cultures and for gene sequencing of the isolated viruses. A REV isolate GX18NNR1 and a MDV isolate GX18NNM5 were both recovered from the sampled bird. Further phylogenetic analysis based on the env gene of REV and the meq gene of MDV demonstrated that GX18NNR1 was closely related to the reference REV strain MD-2, which was isolated from a contaminated commercial turkey herpesvirus vaccine. In addition, the GX18NNM5 was found to belong to the Chinese very virulent MDV strains' cluster. The coinfection of REV and MDV may contribute to tumor outbreaks with high morbidity and mortality in three-yellow chicken flocks.

The accurate annotation of protein localization is crucial in understanding protein function in tandem with a broad range of applications such as pathological analysis and drug design. Since most proteins do not have experimentally-determined localization information, the computational prediction of protein localization has been an active research area for more than two decades. In particular, recent machine-learning advancements have fueled the development of new methods in protein localization prediction. In this review paper, we first categorize the main features and algorithms used for protein localization prediction. Then, we summarize a list of protein localization prediction tools in terms of their coverage, characteristics, and accessibility to help users find suitable tools based on their needs. Next, we evaluate some of these tools on a benchmark dataset. Finally, we provide an outlook on the future exploration of protein localization methods.

The overuse of in-feed antibiotics has been associated with serious issues, including the developing of antibiotic-resistant pathogens and causing drug residues in poultry products. To date, many countries have restricted the use of growth-promoting antibiotics in food animals, resulting in the increased need for effective alternatives to in-feed antibiotic. Synbiotics, which are composed of probiotics and prebiotics, have been shown to act synergistically when applied simultaneously. Thus, this study investigated the effects of a synbiotic, composed of microencapsulated Lactobacillus plantarum (MLP) and fructooligosaccharide (FOS), on growth, immune and antioxidant parameters, and digestibility of calcium and phosphorus in broilers. A total of 168 newly hatched male broilers were randomly allotted to three dietary groups (n = 7): (1) a corn-soybean meal basal diet (CON); (2) basal diet + synbiotic (SYN); and (3) basal diet + aureomycin (ANT). Compared with the CON, chickens had greater average daily gain and digestibility of calcium and phosphorus in the SYN group (P

It has been indicated that amyloid β (Aβ) plaques can be accumulated within the basement membranes of cerebrovascular smooth muscle cells (CVSMCs) and stimulate the induction of cerebral amyloid angiopathy (CAA). However, the exact mechanism(s) of which small molecules including callistephin mitigate the formation of Aβ aggregation and associated CAA is not well-understood. Therefore, in the present study, Aβ1–42 samples in the aggregation buffer were co-incubated for 36 h without or with of callistephin and the protein aggregation features along with the associated cytotoxicity against CVSMCs as the core components of cerebral arterial wall were explored by different biochemical and cellular methods. Fluorescence (ThT, Nile red) and CD techniques indicated the inhibition of Aβ1–42 fibrillization in the presence of callistephin. Cellular assays revealed that cytotoxicity of Aβ1–42 samples aged in the aggregation buffer with callistephin was much less against CVSMCs than Aβ1–42 amyloid alone through regulation of membrane leakage and downregulation of TNF-α and IL-6 at protein level. In conclusion, these data may provide useful information about the possible mechanisms by which callistephin can show its protective effect against CAA.

P2Y14 nucleotide receptor is a Gi protein-coupled receptor, which is widely involved in physiological and pathologic events. Although several P2Y14R antagonists have been developed thus far, few have successfully been developed into a therapeutic drug. In this study, on the basis of two P2Y14R homology models, Glide docking-based virtual screening (VS) strategy was employed for finding potent P2Y14R antagonists with novel chemical architectures. A total of 19 structurally diverse compounds identified by VS and drug-like properties testing were set to experimental testing. 10 of them showed good inhibitory effects against the P2Y14R (IC50

SUMMARY: In this study, the metabolizable energy (ME) requirements were determined for Chinese yellow-feathered chickens aged from 29 to 56 d. In total, 1,200 29-d-old male yellow-feathered broilers were randomly assigned to 5 dietary treatments with 6 replicates each of 40 birds. Birds were fed 5 levels of dietary ME (2,799, 2,897, 2,997, 3,098, and 3,198 kcal ME/kg diet). Broilers that received high-energy diets had a higher (P < 0.05) final body weight, average daily gain (ADG), and average daily ME intake, and a lower (P < 0.05) feed conversion ratio (FCR) compared with those fed reduced energy diets. Increasing the dietary energy level had no significant influence on the carcass traits (P > 0.05), whereas the abdominal fat percentage and thigh intramuscular fat percentage increased significantly. The retention of energy and protein increased (P < 0.05) as the dietary energy concentration increased. Increasing the dietary energy level had no significant effect (P > 0.05) on the energy, protein, and fat contents in the whole body. The plasma concentrations of total cholesterol and total triglyceride were not (P > 0.05) affected by the dietary energy concentration but the plasma concentration of uric acid increased significantly. According to broken-line regression analysis, the recommended dietary ME levels that maximized ADG, optimized FCR, and minimized the deposition of abdominal fat (%) in yellow-feathered broiler chickens aged from 29 to 56 d were 3,198 kcal, 3,213 kcal, and 2,920 kcal ME/kg, respectively.

Summary: Pathological examination is the gold standard for cancer diagnosis, and breast tumor cells are often found in clusters. We report a case study on one triple-negative breast cancer (TNBC) patient, analyzing tumor development, metastasis, and prognosis with simultaneous DNA and RNA sequencing of pathologist-defined cell clusters from multiregional frozen sections. The cell clusters are isolated by laser capture microdissection (LCM) from primary tumor tissue, lymphatic vessels, and axillary lymph nodes. Data are reported for a total of 97 cell clusters. A combination of tumor cell-cluster clonality and phylogeny reveals 3 evolutionarily distinct pathways for this patient, each associated with a unique mRNA signature, and each correlated with disparate survival outcomes. Hub gene analysis indicates that extensive downregulation of ribosomal protein mRNA is a potential marker of poor prognosis in breast cancer.

Background: To develop and validate a deep learning signature (DLS) from diffusion tensor imaging (DTI) for predicting overall survival in patients with infiltrative gliomas, and to investigate the biological pathways underlying the developed DLS. Methods: The DLS was developed based on a deep learning cohort (n = 688). The key pathways underlying the DLS were identified on a radiogenomics cohort with paired DTI and RNA-seq data (n=78), where the prognostic value of the pathway genes was validated in public databases (TCGA, n = 663; CGGA, n = 657). Findings: The DLS was associated with survival (log-rank P < 0.001) and was an independent predictor (P < 0.001). Incorporating the DLS into existing risk system resulted in a deep learning nomogram predicting survival better than either the DLS or the clinicomolecular nomogram alone, with a better calibration and classification accuracy (net reclassification improvement 0.646, P < 0.001). Five kinds of pathways (synaptic transmission, calcium signaling, glutamate secretion, axon guidance, and glioma pathways) were significantly correlated with the DLS. Average expression value of pathway genes showed prognostic significance in our radiogenomics cohort and TCGA/CGGA cohorts (log-rank P < 0.05). Interpretation: DTI-derived DLS can improve glioma stratification by identifying risk groups with dysregulated biological pathways that contributed to survival outcomes. Therapies inhibiting neuron-to-brain tumor synaptic communication may be more effective in high-risk glioma defined by DTI-derived DLS. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

This paper presents a new method for generating the random fiber distributions of carbon fiber reinforced plastic with high volume fraction. The novelty is that an adaptive fiber shaking module is developed on the basis of Delaunay triangulation and combined with the proposed algorithm. The adaptability is to realize coordination between the parameters of fiber volume fraction and fiber spacing, in order to overcome the jamming limit and eliminate the unreasonable resin-rich zone that may appear at the boundary of the microstructures. The maximum fiber volume fraction reached is 67.43%. Statistical analysis is conducted on the generated microstructures, and there is a good agreement by comparing it with the statistical results of random sequential expansion algorithm and completely spatial random pattern. Finite element analysis is also performed to predict the elastic properties of the generated microstructures. It shows that a maximum absolute error is only 7.354% in elastic property by comparing with the experimental and simulation results in literatures. The proposed algorithm contributes to the further researches on the strength and micro-damage evolution of carbon fiber reinforced plastic.

Background: Gut microbiota could modulate brain functions and consequent behavior through gut-brain axis. We evaluated the impact of intestinal flora using probiotics in patients with Crohn’s disease (CD) on cognitive reactivity to sad mood. Method: Patients in Group 1 received multiple probiotics followed by Chamomile capsules. Patients in Group 2 received Chamomile capsules followed by multiple probiotics. Patients accomplished the Leiden Index of Depression Sensitivity (LEIDS-r), Beck Depression Inventory (BDI) questionnaires after each cycle of cross-over treatment. Results: The baseline LEIDS-r in two groups did not have significant difference. After 3 weeks of treatment, patients in Group 1 had better LEIDS-r scores compared with patients in Group 2 (36.6 vs. 40.9, P = 0.012). After crossover, patients in Group 1 had worse LEIDS-r scores compared with patients in Group 2 (39.2 vs. 35.2, P = 0. 0.016). Conclusion: Probiotics have the tendency to improve cognitive reactivity to sad mood in CD patients.

miR-101–3p may play a therapeutic role in various tumours. However, its anti-tumour mechanism remains unclear, and a definitive strategy to treat tumour cells in vivo is lacking. The objective of this study was to investigate the inhibitory mechanism of miR-101–3p on tumour cells and to develop relevant nanomedicines for in vivo therapy. The expression levels of miR-101–3p and its target protein TBLR1 in tumour tissues and cells were detected, and their relationship with ferroptosis was clarified. Furthermore, the efficacy of nanocarriers in achieving in vivo therapeutic gene delivery was evaluated. Nanomedicine was further developed, with the anti-proliferative in vivo therapeutic effect validated using a subcutaneous xenograft cancer model. The expression level of miR-101–3p negatively correlated with clinical tumour size and TNM stage. miR-101–3p restores ferroptosis in tumour cells by directly targeting TBLR1, which in turn promotes apoptosis and inhibits proliferation. We developed nanomedicine that can deliver miR-101–3p to tumour cells in vivo to achieve ferroptosis recovery, as well as to inhibit in vivo tumour proliferation. The miR-101–3p/TBLR1 axis plays an important role in tumour ferroptosis. Nanopharmaceuticals that increase miR-101–3p levels may be effective therapies to inhibit tumour proliferation.

This experiment investigated the effect and interaction of dietary calcium (Ca) and nonphytate phosphorus (NPP) on growth performance, tibial characteristics, carcass traits, and meat quality for slow-growing yellow-feathered broilers during 56 to 84 d of age. A 3 × 3 factorial arrangement was used, and 720 56-day-old broilers were randomly divided into 9 groups and fed with diets containing different levels of Ca (0.70, 0.80, 0.90%) and NPP (0.30, 0.35, 0.40%) for 28 d. The dietary Ca level affected the ADFI of yellow-feathered broilers (P 0.05). The dietary Ca level did not affect carcass traits (P > 0.05). When broilers were fed with 0.30% P, the semieviscerated percentage was increased compared with birds fed with 0.40% NPP (P

Brominated flame retardants (BFRs) such as tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs) are of ecological concern due to their ubiquitous presence and adverse effects. There is a paucity of data on environmental fate of such compounds in mangrove wetlands, which are unique ecosystems in coastal intertidal areas and act as natural sinks for many pollutants. In this study, mangrove plants and sediments were collected from an urban nature reserve in South China to investigate bioaccumulation and translocation of TBBPA and HBCDs. The mean (range) concentrations of TBBPA and ΣHBCD in roots, stems and leaves were 67 (

In order to alleviate the environmental pollution from fluoropolymer, the biodegradable poly(l‑lactide) (PLLA) segments were introduced into fluorinated polyacrylate. The PLLA macromonomers with vinyl terminal group and different molecular weight, i.e. 2500, 7400 and 14,700, were synthesized by ring opening polymerization of l‑lactide (LLA) first, then copolymerized with hexafluorobutyl acrylate (HFBA) through free radical copolymerization. By changing the macromonomers and feeding ratio of the macromonomer and HFBA, the poly(l‑lactide)‑co‑poly(hexafluorobutyl acrylate) (PLLA-co-PHFBA) copolymers with different structures were obtained. Structures of the PLLA macromonomers and the copolymers were confirmed by FTIR, 1H NMR and GPC. The crystallization, thermal decomposition resistance, surface hydrophobicity and hydrolytic degradation were also investigated. The results show that the PLLA segments in the copolymers still have the crystallization capacity and the highest crystallinity reaches 36%. PLLA-co-PHFBA-4 with the longest PLLA segments has the highest initial decomposing temperature up to 355 °C. The hydrophobicity of the copolymers is mainly related to the content of PHFBA segments. The length of PLLA segments also have some effect on the hydrophobicity. An obvious mass loss of the copolymers was observed in 35 days under the hydrolytic degradation and it was related to PHFBA content and PLLA segment's length, exhibiting partially biodegradable behavior. Keywords: Poly(l‑lactide), Hexafluorobutyl acrylate, PLLA macromonomer, Copolymer, Property

Background: To develop a radiomics signature for predicting overall survival (OS)/progression-free survival (PFS) in patients with medulloblastoma (MB), and to investigate the incremental prognostic value and biological pathways of the radiomics patterns. Methods: A radiomics signature was constructed based on magnetic resonance imaging (MRI) from a training cohort (n = 83), and evaluated on a testing cohort (n = 83). Key pathways associated with the signature were identified by RNA-seq (GSE151519). Prognostic value of pathway genes was assessed in a public GSE85218 cohort. Findings: The radiomics-clinicomolecular signature predicted OS (C-index 0.762) and PFS (C-index 0.697) better than either the radiomics signature (C-index: OS: 0.649; PFS: 0.593) or the clinicomolecular signature (C-index: OS: 0.725; PFS: 0.691) alone, with a better calibration and classification accuracy (net reclassification improvement: OS: 0.298, P = 0.022; PFS: 0.252, P = 0.026). Nine pathways were significantly correlated with the radiomics signature. Average expression value of pathway genes achieved significant risk stratification in GSE85218 cohort (log-rank P = 0.016). Interpretation: This study demonstrated radiomics signature, which associated with dysregulated pathways, was an independent parameter conferring incremental value over clinicomolecular factors in survival predictions for MB patients. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Summary: Sensing stressful conditions and adjusting the cellular metabolism to adapt to the environment are essential activities for bacteria to survive in variable situations. Here, we describe a stress-related protein, YdiU, and characterize YdiU as an enzyme that catalyzes the covalent attachment of uridine-5′-monophosphate to a protein tyrosine/histidine residue, an unusual modification defined as UMPylation. Mn2+ serves as an essential co-factor for YdiU-mediated UMPylation. UTP and Mn2+ binding converts YdiU to an aggregate-prone state facilitating the recruitment of chaperones. The UMPylation of chaperones prevents them from binding co-factors or clients, thereby impairing their function. Consistent with the recent finding that YdiU acts as an AMPylator, we further demonstrate that the self-AMPylation of YdiU padlocks its chaperone-UMPylation activity. A detailed mechanism is proposed based on the crystal structures of Apo-YdiU and YdiU-AMPNPP-Mn2+ and on molecular dynamics simulation models of YdiU-UTP-Mn2+ and YdiU-UTP-peptide. In vivo data demonstrate that YdiU effectively protects Salmonella from stress-induced ATP depletion through UMPylation.

Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria Escherichia coli, which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12−L10 interaction and show bactericidal activity against E. coli. We used glutathione-S-transferase (GST) pull-down and surface plasmon resonance (SPR) assays to demonstrate that these compounds disrupt L12−L10 interaction in vitro and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12−L10 interaction by using yeast two-hybrid system. KEY WORDS: Yeast two-hybrid, Escherichia coli, Ribosome, L12/L10, Antimicrobial agents

Purpose: tumor-infiltrating immune cells are highly relevant to the progression and prognosis of colorectal cancer (CRC). The aim of this study is to explore the immune cells and immune-related gene expression in tumor microenvironment of CRC. Methods: CIBERSORT, a deconvolution algorithm, was used to analyze the infiltration of 22 immune cell types in the tumor microenvironment and immune-related gene expression in 404 CRC and 40 adjacent non-tumorous tissues. Results: a wide heterogeneity of immune cells among different paired tissues and in tumor stages was uncovered. M0 macrophages, M1 macrophages and CD4 memory activated T cells were infiltrated significantly more in CRC compared with normal tissues in both TCGA and GEO cohorts. CRC with T1–2 tumor stage showed increased CD4 memory activated T cells compared with T3–4 tumors. M0 macrophages were the highest in stage N1 tumors. Significant immune-related genes were identified to build prognostic models by Cox regression analysis. The concordance index of the prognostic model for TNM stage I–II was 0.69, and 0.71 for stage III–IV. The AUC values for 1-, 3-, and 5-year survivals were 0.674, 0.773, 0.812 for TNM stage I–II, respectively, and 0.764, 0.782, 0.803 for stage III–IV, respectively. Conclusion: these results could assist clinicians in selecting targets for immunotherapies and individualize treatment strategies for patients with CRC.

Objective: Ovarian cancer (OC) was one of the deadliest gynecological malignancy among women in global. Serum microRNAs (miRNAs) could serve as promising diagnostic biomarkers for patients with OC. Study design: Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel, we identified 27 differentially expressed miRNAs from one normal control (NC) pool and two OC pool samples in the initial screening stage. We further verified the miRNAs in the training (30 OC VS. 36 NCs) and validation stages (80 OC VS. 80 NCs) based on qRT-PCR. Later, the expression levels of the identified miRNAs were also evaluated in exosomes and tissues. Results: We found a serum microRNA signature including five overexpressed miRNAs (miR-200c-3p, miR-346, miR-127-3p, miR-143-3p and miR-205-5p) in OC in comparison with NCs. The areas under the receiver operating characteristic (ROC) curve (AUC) of the five-miRNA panel were 0.783 for the training stage and 0.745 for the validation stage. The diagnostic sensitivity and specificity of the combined five-miRNA panel was 0.818 and 0.609 when the cut-off value was 0.636. The levels of miR-200c-3p, miR-346 and miR-127-3p in serum were related to tumor grade and distant metastasis of OC. The expression levels of the five miRNAs were also significantly up-regulated in serum exosomes (32 OC VS. 32 NCs). Furthermore, miR-200c-3p was significantly elevated in OC tissues (22 OC VS. 22 NCs). But the levels of the miR-346 and miR-143-3p were significantly lower in OC tissues. Conclusion: Our findings showed a five-miRNA panel in serum for the detection of OC. Moreover, serum expression levels of miR-200c-3p, miR-346 and miR-127-3p were concerned with tumor grade and distant metastasis of OC. Keywords: microRNA, Ovarian cancer, Biomarker, Detection, Prediction, qRT-PCR

Summary: Type I interferons (IFNs) have therapeutic potential in CNS autoimmune diseases, such as uveitis, but the molecular mechanisms remain unclear. Using a T cell-transfer model of experimental autoimmune uveitis (EAU), we found that IFN-α/β treatment inhibited the migration of IFN-γ-producing pathogenic CD4+ T cells to effector sites. IFN-α/β upregulated the expression of the cognate ligands CXCL9, CXCL10, and CXCL11, causing ligand-mediated downregulation of CXCR3 expression and effector T cell retention in the spleen. Accordingly, type I IFN did not alter EAU progression in CXCR3−/− mice. In uveitis patients, disease exacerbations correlated with reduced serum IFN-α concentrations. IFN-α/β reduced CXCR3 expression and migration by human effector T cells, and these parameters were associated with the therapeutic efficacy of IFN-α in uveitis patients. Our findings provide insight into the molecular basis of type I IFN therapy for CNS autoimmune diseases and identify CXCR3 as a biomarker for effective type I IFN immunotherapy. : The mechanisms by which type I IFN therapy limits CNS autoimmune diseases remain unclear. Using animal models of experimental autoimmune uveitis and uveitis patient samples, Wang et al. reveal that type I interferon therapy inhibits CXCR3-mediated effector T cell trafficking into uveitogenic eyes to decrease disease pathogenesis. Keywords: type I interferon, CXCR3, experimental autoimmune uveitis, human uveitis