Search

ABSTRACT: Dietary energy density influences feed intake (FI) and development of layer-type pullets. A total of 384 nine-wk-old Hy-Line Brown pullets were randomly assigned to one of 3 dietary treatments: fed a diet with 2,600, 2,750, and 2,900 Kcal metabolizable energy/kg (ME/kg) from 10 to 21 wk of age. The results showed that the 2,900 and 2,600 ME groups had lower feed and ME intake (P < 0.01) from 10 to 21 wk of age. The 2,600 ME pullets had heavier body weight (BW) and longer shank length (P < 0.05) at 21 wk of age than the 2,750 ME group. The eggshell percentage was increased by the 2,600 and 2,900 kcal/kg treatments (P = 0.002). Serum concentration of 17-β-estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) decreased at 70 wk of age (P < 0.05). Pullet diet and its interaction with age had a significant influence (P < 0.001) on the expression of gonadotropin-releasing hormone 1 (GnRH-1) and gonadotropin-inhibitory hormone (GnIH) in the hypothalamus and of gonadotropin releasing hormone 1 receptor (GnRH-1R) and gonadotropin-inhibitory hormone receptor (GnIHR) in the pituitary. In the hypothalamus, GnRH-1 expression increased from 9 to 40 wk of age and then decreased; however, GnIH expression was highest at 70 wk of age. Follicle-stimulating hormone receptor (FSHR) expression increased (P < 0.001) at wk 40 and decreased at wk 70 compared to wk 21 at various follicular stages. In conclusion, the energy level of pullet diet had no unfavorable influence on feed intake, laying rate, egg mass, and FCR, whereas change egg weight and mortality during the laying period from 21 to 70 wk of age. during the laying period. These results suggest that pullet dietary energy can activate the expression of genes related to reproduction in the hypothalamus, whereas it plays a minor role in the regulation of genes in the pituitary and ovary. Age-induced gene expression in the hypothalamus-pituitary-gonadal (HPG) axis is associated with laying performance in hens.

Temperature and dissolved oxygen (DO) are important biological environmental factors for aquatic animal. The sea cucumber Apostichopus japonicus was an important aquaculture species in China, which was highly impacted by temperature and DO. In the present study, the transcriptomics expression profiles under high temperature (HT), hypoxia (LO), and these combined stressors (HL) were investigated by RNA-seq technique. Compared with the control group, 275, 409 and 434 differential expressed genes (DEGs) were detected in HT, LO and HL groups respectively. Further analysis of KEGG pathways revealed that “protein processing in endoplasmic reticulum” pathway was significantly enriched in both HT vs C and HL vs C comparisons. Protein folding-related genes in this pathway, such as HSPs, were up-regulated in the two comparisons. In LO vs C comparison, “fatty acid metabolism” pathway was significantly enriched, and genes related to de novo biogenesis of fatty acids was significantly down-regulated. Some genes related to anti-apoptosis, such as BCL-2 and BAG3, were up-regulated in HL vs C comparison, which revealed that the combined stress threatened the survival of cells. The present research provided new insights for the response to different stressful environments in A. japonicus.

ABSTRACT: The present study was designed to investigate whether L-arginine (Arg) supplementation would influence the production performance and reproductive traits of laying hens fed low crude protein (LCP) diets. Hy-Line brown laying hens were randomly assigned to dietary treatments of control, LCP, and LCP supplemented with 0.05, 0.10, 0.15, or 0.20% Arg for 7 wk. The results showed no significant variations on the production performance, and relative organ indexes of hens. However, significant transcriptional and structural changes were evident along the HPG axis of hens. Arg supplementation linearly upregulated (P < 0.05) the gonadotropin-releasing hormone 1 (GnRH1), and gonadotropin inhibitory hormone in the hypothalamus. The pituitary growth hormone, GnRH receptor, and follicle-stimulating hormone (FSHβ) were also increased (P < 0.05). In the ovary, GnRH1, and estrogen receptor β were linearly increased by Arg, and the ovarian morphology revealed that LCP induced structural alterations which were minimally recovered by Arg supplementation. Serum insulin-like growth factor 1 (IGF-1) and nitric oxide (NO) were increased (P < 0.05) at higher levels of Arg supplementation. Therefore, supplementing high Arg (0.20%) to LCP hens influenced the ovarian morphology and modulated the gene expression of reproductive hormones in the hypothalamic-pituitary-gonadal axis of laying hens via actions that may be related to NO and IGF-1 activity.

ABSTRACT: Calcium (Ca) and phosphorus (P) transporters are responsible for their absorption and transport in small intestine and kidney, contributing to eggshell formation. The light-dark cycle is a primary cue in the reproduction of laying hen. In this study, we investigated the effect of different light-dark programs on eggshell quality and the expression of genes related to Ca and P transportation in laying hens. Seventy-two 56-week-old laying hens were randomly divided into two groups and reared at 16-h light and 8-h dark (control) or 9-h light and 15-h dark regime (long dark phase, LDP). The expressions of calcium transporter calbindin-D28k (CaBP-D28k), plasma membrane Ca ATPase 1b (PMCA1b), and phosphorus transporter NaPi-IIb (NPt2b) and NaPi-IIa (NPt2a) were measured in the small intestine, kidney, and eggshell gland. The results showed that feed intake (P < 0.001) and egg weight (P = 0.05) were decreased by LDP treatment. Compared with control, the eggshell hardness was increased (P = 0.011) by LDP treatment, but the eggshell thickness and the percentage of eggshell were not changed. The Ca and P contents in eggshell were increased by LDP treatment. During the scotophase, LDP-hens showed higher serum Ca (P = 0.0056) and P levels (P = 0.079) but lower alkaline phosphatase (ALP) activity than that of control hens. In the duodenum, the relative higher expression of CaBP-D28k and PMCA1b in scotophase compared to photophase was masked by LDP treatment. The expression of CaBP-D28k and osteopontin (OPN) in the eggshell gland were increased by LDP treatment, compared to control hens. In the jejunum, the protein expression levels of CaBP-D28k and PMCA1b decreased during photophase in LDP-hens. The result indicates that the increased blood Ca and P concentration during scotophase by LPD treatment is beneficial to the deposition of Ca and P in the eggshell. The result offers an alternative strategy for managing laying hens with poor eggshell quality.

Climate change is causing the surface temperature to rise and the extreme weather events to increase in frequency and intensity, which will pose potential threats to the survival and health of residents. Beijing is facing multiple challenges such as coping with climate change, urbanization, and population aging, which puts huge decision-making pressure on decision maker. However, few studies that systematically consider the health effects of climate change, urbanization, and population aging for China. Based on the distributed lag nonlinear model (DLNM) and 13 global climate models in the Coupled Model Intercomparison Project Phase 6 (CMIP6), this study obtained the temporal and spatial distribution of surface temperature through statistical downscaling methods, and comprehensively explored the independent and comprehensive effects of urbanization and population aging on the projection of future temperature-related cardiovascular disease (CVD) mortality in the context of climate and population change. The results showed that only improving urbanization can reduce future temperature-related CVD mortality by 1.7–18.3%, and only intensified aging can increase future temperature-related CVD mortality by 48.8–325.9%. Taking into account the improving urbanization and intensified aging, future temperature-related CVD mortality would increase by 44.1–256.6%, and the increase was slightly lower than that of only intensified aging. Therefore, the intensified aging was the biggest disadvantage in tackling climate change, which would obviously magnify the mortality risks of temperature-related CVD in the future. Although the advancement of urbanization would alleviate the adverse effects of the intensified aging population, the mitigation effects would be limited. Even so, Urbanization should be continued to reduce health risks for residents. These findings would contribute to formulate policies related to mitigate climate change and reduce baseline mortality rate (especially the elderly) in international mega-city - Beijing. In addition, relevant departments should improve the medical health care level and optimize the allocation of social resources to better cope with and adapt to climate change.

Excess production of reactive oxygen species (ROS) causes oxidative stress, which is associated with oxidative damage and a number of human chronic diseases. Here, novel antioxidant hydrolysates were obtained from fish skin, pig skin, pig bone and bovine skin gelatins using ginger protease, and were compared with those produced using pepsin-pancreatin. Ginger protease could hydrolyze the gelatin from fish skin to peptides with low average molecular weights (

The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards models were performed for both PFS and OS for all assumed predictor variables. Statistically significant predictor variables (P < .05) on univariate analysis were then included in multivariate Cox proportional-hazards models, which were performed to compare the effects of RT delay on PFS and OS. A total of 316 patients were finally enrolled in this prospectively multicentric study. Time to RT after surgery varied from 12 days to over 60 days (median, 26 days). Multivariate analysis showed that delay to RT longer than the median does not appear to be a survival cost. There was also no statistically difference in PFS (P = .513) or OS (P = .236) between patients stratified by quartiles (≤21 days vs ≧35 days). However, patients with particularly long delays (≧42 days) demonstrated a detrimental impact on OS (P = .021) but not PFS (P = .580). Delaying postoperative RT of esophageal cancer does not impact PFS, but results in a significant reduction on OS if delaying longer than 6 weeks.

Non-small cell lung cancer (NSCLC) is a highly malignant tumor, with a significant mortality and morbidity. With the development of tumor immunotherapy, chimeric antigen receptor T cells (CART) gets increasingly attention and achieves prominent contributions in the treatment of hematologic malignancies. However, CART therapy for NSCLC proceeds slowly and further researches need to be investigated. In our study, we performed bioinformatics analysis to evaluate the significant role of CD147 in NSCLC. The expression level of CD147 was detected in human NSCLC cell lines and NSCLC tissues. Meanwhile, CD147-CART was constructed and identified. Cell cytotoxicity and cytokine secretion were performed to evaluate the efficacy of CD147-CART. We also constructed cell-derived xenograft (CDX) model and patient-derived xenograft (PDX) model, which was used to further investigate the safety and efficacy of CD147-CART in vivo. Our observations show that CD147 is a specific tumor antigen of NSCLC and plays an essential role in NSCLC progression, which can be used as a target for CART therapy in NSCLC. CD147-CART cells exhibit robust cytotoxicity and cytokine production in vitro, suggesting a strong anti-tumor activity against NSCLC tumor cells. Importantly, CD147-CART cells have strong anti-tumor activity against NSCLC cells in vivo in both CDX and PDX models and no adverse side effects. Our findings show that CD147-CART immunotherapy for NSCLC is safe and effective, which is an ideal and promising medical patch for treating NSCLC.

Little information is available on the influence of substantial precipitation and particulate matter entering during the monsoon process on the release of potentially toxic elements (PTEs) into lake sediments. Sediments from a typical subtropical lake across three periods, pre-monsoon, monsoon, and post-monsoon, were collected to determine the chemical forms of 12 PTEs (As, Cd, Co, Cr, Cu, Fe, Hg, Pb, Mn, Ni, Sb, and Zn), magnetic properties, and physicochemical indicators. Feature importance, Shapley additive explanations, and partial dependence plots were used to explore the factors influencing bioavailable PTEs. The proportion of bioavailable forms of PTEs decreased from 3.85 % (Cd) to 87.84 % (Hg) after the monsoon. Gradient extreme boosting demonstrated robust fitting accuracy for the prediction of the bioavailable forms of the 12 PTEs (R 2  > 0.84). Shapley additive explanations identified that the bioavailable forms were influenced by the total PTE concentrations, wind, shortwave radiation, and particle inputs (25.1 %-88.5 % for total importance), either individually or in combination. The partial dependence plots highlighted the influence thresholds of background values and anthropogenic factors on the bioavailable forms of PTEs. Changes in environmental properties could indicate the process of external sediment influx into lakes. The optimized model combined with magnetic parameters showed strong performance in other cases (coefficient of determination>0.58), confirming the ubiquitous decrease in bioavailable forms of PTEs in sediments across subtropical lakes after monsoons., (Copyright © 2024. Published by Elsevier B.V.)

Environmental microplastics (MPs) vary in abundance, shape, size, color, and polymer type in freshwater ecosystems, yet their impact on bacterial community assembly in natural lakes is unclear. Here, we examined MPs and bacterial compositions in water and sediments of Taihu Lake, China, to reveal the influence of complex MPs on the bacterial community assembly. The results showed that the complexity index of MPs significantly influenced the turnover and nestedness components of bacterial communities. In the colder season, MP complexity was significantly correlated with the turnover componentin sediments (R 2 = 0.19, P < 0.0001), with turnover increasing as MP complexity increased. Conversely, under warmer season, MP complexity was significantly correlated with turnover and nestedness components. Additionally, the interaction effect of environmental and MP factors affected almost all components of beta diversity, particularly in cold water and sediment, with impacts on nestedness of 0.17 and 0.12, respectively, and should thus not be ignored. Our findings indicate for the first time that complex MPs significantly influence the assembly of bacterial communities in lake systems. The impact varies across seasons and future warming may exacerbate this effect, rendering it more uncertain and complex., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The magnetic properties of lake sediments account for close relationships with heavy metal(loid)s (HMs), but little is known about their relationships with chemical fractions (CFs) of HMs. Establishing an effective workflow to predict HMs risk among various machine learning (ML) methods in conjunction with magnetic measurement remains challenging. This study evaluated the simulation efficiency of nine ML methods in predicting the risk assessment code (RAC) and ratio of the secondary and primary phases (RSP) of HMs with magnetic parameters in sediment cores of a shallow lake. The sediment cores were collected and sliced, and the total amount and CFs of HMs, as well as magnetic parameters, were determined. Support vector machine (SVM) outperformed other models, as evidenced by coefficient of determination (R 2 ) > 0.8. Interpretable machine learning (IML) methods were employed to identify key indicators of RAC and RSP among the magnetic parameters. Values of χ ARM, HIRM, χ ARM/χ , and χ ARM /SIRM of sediments ranging in 220-500 × 10 -8 m 3 /kg, 30-40 × 10 -5 Am 2 /kg, 15-25, and 0.5-1, respectively, indicated the potential ecological risks of Cd, Hg, and Sb. This study offers new perspectives on the risk assessment of HMs in lake sediments by combining magnetic measurement with IML workflow., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The pervasive issue of microplastics pollution has garnered public attention, yet urban residents remain unaware of the threat within their living spaces. Urban road dust, as primary reservoirs for environmental microplastics, offers an insightful perspective into their occurrence and characteristics. This study investigated microplastics in the urban road dust in Nanjing, a megacity in eastern China, to reveal their spatiotemporal pattern. The abundance of microplastics in the road dust measured 143.3 ± 40.8 particles/m 2 , with predominant fragments and suspected tire wear particles, particularly those below 100 µm. Significant spatial variations were observed across urban functional zones (P < 0.05), with commercial and heavy industrial areas experiencing the highest microplastic pollution (up to 223.5 particles/m 2 ). Infrared spectroscopy analysis identified 29 polymer types, with polystyrene (PS), polyamide (PA), and polyvinylidene difluoride (PVDF) prevailing. Light industrial zones exhibited slight contamination (mean = 93.4 particles/m 2 ) but with diverse polymer components (24 types). Redundancy analysis and variation partitioning revealed that urban functional zoning, 7-day accumulated precipitation, and monthly PM 2.5 primarily influenced the occurrence and characteristics of microplastics in urban road dust (P = 0.001). This study deepened our understanding of microplastics pollution in urban environments, providing novel insights for effective urban environmental management and improvement., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bisphenol analogues (BPs), as one of the endocrine disruptors, have received wide attention due to their adverse impacts on ecosystems. However, the seasonal spatiotemporal distribution, source apportionment, and ecological risk of BPs in natural basins are poorly understood. Especially in highly urbanized river basins with the extensive economic development and anthropogenic activities threaten these critical but ecologically fragile regions. In this study, field investigations of BPs in the waters of the entire Qinhuai River Basin (QRB) were conducted in June (before the annual flood period) and August (after the annual flood period) 2023. The Qinhuai River, an important primary tributary of the lower Yangtze River, is located in eastern China and the QRB is characterized by a high population density and dense urbanization. Thirty-two sites were sampled for six types of BPs known to be ubiquitous in the surface water of the QRB. Significant differences in the concentrations of those BPs were found. Specifically, the concentration of total BPs (ΣBPs) was significantly higher before than after the flood period: 20.3-472 ng/L (mean = 146 ng/L) and 14.1-105 ng/L (mean = 35.9 ng/L), respectively. BPA was the main contributor to ΣBPs before the flood, and BPB followed by BPA after the flood. ΣBP concentrations were 12-241 % higher downstream than upstream of wastewater treatment plants (WWTPs). The results of a principal component analysis followed by multiple linear regression (PCA-MLR) suggested that untreated wastewater discharge from the WWTPs is an important source of BPs in the basin, with urban rainfall runoff as another potential source after the flood period. An assessment of the ecological risk of BPs, based on a calculation of the risk quotient, showed that BPA and BPS should be given due attention, and overall ecological risk of BPs pose a low risk to local algae but high and medium risks to invertebrates and fish, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Atmospheric microplastics (AMPs) transmitted through the atmosphere are critical to global microplastic pollution. However, little is known about the long-term dynamics and distribution patterns of deposited (DAMPs) and suspended (SAMPs) AMPs. In this study, simultaneous sampling was conducted over one year to examine the deposition-suspension distribution of AMPs. Monthly and seasonal variations in abundance were evident, with an annual average of 302.31 ± 107.40 items/m 2 /day for DAMPs and 1.31 ± 0.62 items/m 3 for SAMPs. The dynamics of DAMP and SAMP abundance demonstrated the dynamic distribution of AMPs between deposition and suspension. Both meteorological factors and particle features were found to influence the AMP distribution, manifesting as morphological differences and abundance variations. AMPs were most likely derived from traffic, industry, construction, and synthetic textiles, with diverse source areas up to 1750 km away. The estimated deposition flux of 7.28 × 10 14 items per year and inhalation exposure of up to 12,777 items per year highlight the potential ecological and health risks of AMPs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

SEMA4D-modified titanium surfaces can indirectly regulate macrophages through endothelial cells to achieve an anti-inflammatory effect, which is beneficial for healing soft tissues around the gingival abutment. However, the mechanism of surface-induced cellular phenotypic changes in SEMA4D-modified titanium has not yet been elucidated. SEMA4D activates the RhoA signaling pathway in endothelial cells, which coordinates metabolism and cytoskeletal remodeling. This study hypothesized that endothelial cells inoculated on SEMA4D-modified titanium surfaces can direct M2 polarization of macrophages via metabolites. An indirect co-culture model of endothelial cells and macrophages was constructed in vitro, and specific inhibitors were employed. Subsequently, endothelial cell adhesion and migration, metabolic changes, Rho/ROCK1 expression, and inflammatory expression of macrophages were assessed via immunofluorescence microscopy, specific kits, qRT-PCR, and Western blotting. Moreover, an in vivo rat bilateral maxillary implant model was constructed to evaluate the soft tissue healing effect. The in vitro experiments showed that the SEMA4D group had stronger endothelial cell adhesion and migration, increased Rho/ROCK1 expression, and enhanced release of lactate. Additionally, decreased macrophage inflammatory expression was observed. In contrast, the inhibitor group partially suppressed lactate metabolism and motility, whereas increased inflammatory expression. The in vivo analyses indicated that the SEMA4D group had faster and better angiogenic and anti-inflammatory effects, especially in the early stage. In conclusion, via the Rho/ROCK1 signaling pathway, the SEMA4D-modified titanium surface promotes endothelial cell adhesion and migration and lactic acid release, then the paracrine lactic acid promotes the polarization of macrophages to M2, thus obtaining the dual effects of angiogenesis and anti-inflammation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Dye released by industrial is one of the main known pollutants in wastewater, which is harmfully affected to the human health. Adsorptive method by absorbents and photocatalytic degradation technique are advanced technologies to remove dyes from wastewater. However, the single technique mentioned above has imperfections limiting its application. Herein, in order to integrate the two techniques and take both advantages, bacterial cellulose (BC) based titanium dioxide (TiO 2 )‑cadmium sulfide (CdS) nanocomposite gel was prepared by microwave-assisted solvothermal synthesis. The BC@TiO 2 -CdS nanocomposite gel was characterized by SEM, EDS, XRD, XPS, Raman spectral and TG, its photocatalytic mechanism was proved by PL. The results showed the TiO 2 -CdS nanophotocatalyst exhibited binary hierarchical structure and followed the Z-scheme type photocatalytic system. The Z-scheme heterojunction is advantageous for photo-generated charge separation and migration. The photocatalytic performance of BC@TiO 2 -CdS nanocomposite gel was evaluated by MB degradation under visible light irradiation. Due to synergistic effect of BC matrix and TiO 2 -CdS, the as-prepared BC@TiO 2 -CdS nanocomposite gel possesses enhanced photocatalytic activity with 94.47 % removal of methylene blue (MB) after 180 min visible light irradiation. Therefore, this work provides a facile route to fabricate bio-mass based efficient nanophotocatalytic material for pretreating the water pollution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Convolutional neural network (CNN) has promoted the development of diagnosis technology of medical images. However, the performance of CNN is limited by insufficient feature information and inaccurate attention weight. Previous works have improved the accuracy and speed of CNN but ignored the uncertainty of the prediction, that is to say, uncertainty of CNN has not received enough attention. Therefore, it is still a great challenge for extracting effective features and uncertainty quantification of medical deep learning models In order to solve the above problems, this paper proposes a novel convolutional neural network model named DM-CNN, which mainly contains the four proposed sub-modules : dynamic multi-scale feature fusion module (DMFF), hierarchical dynamic uncertainty quantifies attention (HDUQ-Attention) and multi-scale fusion pooling method (MF Pooling) and multi-objective loss (MO loss). DMFF select different convolution kernels according to the feature maps at different levels, extract different-scale feature information, and make the feature information of each layer have stronger representation ability for information fusion HDUQ-Attention includes a tuning block that adjust the attention weight according to the different information of each layer, and a Monte-Carlo (MC) dropout structure for quantifying uncertainty MF Pooling is a pooling method designed for multi-scale models, which can speed up the calculation and prevent overfitting while retaining the main important information Because the number of parameters in the backbone part of DM-CNN is different from other modules, MO loss is proposed, which has a fast optimization speed and good classification effect DM-CNN conducts experiments on publicly available datasets in four areas of medicine (Dermatology, Histopathology, Respirology, Ophthalmology), achieving state-of-the-art classification performance on all datasets. DM-CNN can not only maintain excellent performance, but also solve the problem of quantification of uncertainty, which is a very important task for the medical field. The code is available: https://github.com/QIANXIN22/DM-CNN., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A new homogeneous polysaccharide (TPS3A) was isolated and purified from Tianzhu Xianyue fried green tea by DEAE-52 cellulose and Sephacryl S-500 column chromatography. Structural characterization indicated that TPS3A mainly consisted of arabinose, galactose, galacturonic acid and rhamnose in a molar ratio of 5.84: 4.15: 2.06: 1, with an average molecular weight of 1.596 × 10 4  kDa. The structure of TPS3A was characterized as a repeating unit consisting of 1,3-Galp, 1,4-Galp, 1,3,6-Galp, 1,3-Araf, 1,5-Araf, 1,2,4-Rhap and 1-GalpA, with two branches on the C6 of 1,3,6-Galp and C2 of 1,2,4-Rhap, respectively. To investigate the preventive effects of TPS3A on atherosclerosis, TPS3A was administered orally to ApoE-deficient (ApoE -/- ) mice. Results revealed that TPS3A intervention could effectively delay the atherosclerotic plaque progression, modulate dyslipidemia, and reduce the transformation of vascular smooth muscle cells (VSMCs) from contractile phenotype to synthetic phenotype by activating the expression of contractile marker alpha-smooth muscle actin (α-SMA) and inhibiting the expression of synthetic marker osteopontin (OPN) in high-fat diet-induced ApoE -/- mice. Our findings suggested that TPS3A markedly alleviated atherosclerosis by regulating dyslipidemia and phenotypic transition of VSMCs, and might be used as a novel functional ingredient to promote cardiovascular health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Porosity and channel structure has important effects on the performance of hydrogen evolution reaction (HER) of nanostructured electrocatalysts in acid solution and seawater. Mesopore usually helps to enhance the reaction kinetics and mass transfer, while the macroporous channel structure also affects the electrocatalyst. Traditional graphene materials do not have such structure. Therefore, this paper designs a method to synthesize Mo 2 C composite nanomaterial in situ on corn straw biochar, inspires by the natural channel structure of conducting water, salt and organic matter in plants. Characteristic characterization shows that the material also has a large number of mesoporous and vertical distribution of large porous channel structure, through the decrease of tortuosity and porosity, ensure the catalyst surface electrolyte transport and hydrogen timely escape, alleviate the process of metal ion precipitation blocking pore channel, so as to improve the rate of hydrogen evolution reaction. The results shows that the overpotential of the catalyst was 48 mV and 251 mV under 10 mA cm -2 acidic electrolyte and simulated seawater electrolyte, respectively. This method provides new ideas for the design of efficient electrocatalysts for seawater decomposition, then the HER performance in alkaline and neutral environments needs to be further explored., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

High ambient temperature is a major environmental stressor affecting poultry production, especially in the tropical and subtropical regions of the world. Nutritional interventions have been adopted to combat thermal stress in poultry, including the use of amino acids. L-citrulline is a nonessential amino acid that is involved in nitric oxide generation and thermoregulation, however, the molecular mechanisms behind L-citrulline's regulation of body temperature are still unascertained. This study investigated the global gene expression in the hypothalamus of chickens fed either basal diet or L-citrulline-supplemented diets under different housing temperatures. Ross 308 broilers were fed with basal diet (CON) or 1% L-citrulline diet (LCT) from day-old, and later subjected to 2 environmental temperatures in a 2 by 2 factorial arrangement as follows; basal diet-fed chickens housed at 24°C (CON-TN); L-citrulline diet-fed chickens housed at 24°C (LCT-TN); basal diet-fed chickens housed at 35°C (CON-HS), and L-citrulline diet-fed chickens housed at 35°C (LCT-HS) from 22 to 42 d of age. At 42-days old, hypothalamic tissues were collected for mRNA analyses and RNA sequencing. A total of 1,019 million raw reads were generated and about 82.59 to 82.96% were uniquely mapped to genes. The gene ontology (GO) term between the CON-TN and LCT-TN groups revealed significant enrichments of pathways such as central nervous system development, and Wnt signaling pathway. On the other hand, GO terms between the CON-HS and LCT-HS groups revealed enrichments in the regulation of corticosteroid release, regulation of feeding behavior, and regulation of inflammatory response. Several potential candidate genes were identified to be responsible for central nervous system development (EMX2, WFIKKN2, SLC6A4 Wnt10a, and PHOX2B), and regulation of feed intake (NPY, AgRP, GAL, POMC, and NMU) in chickens. Therefore, this study unveils that L-citrulline can influence transcripts associated with brain development, feeding behavior, energy metabolism, and thermoregulation in chickens raised under different ambient temperatures., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Endophytic bacteria residing within host plants can significantly impact on the host's growth, health, and overall relationship with its surrounding environment. However, the process that shape the community assembly of stem bacterial endophytes (SBEs) remains poorly understood. This study explored the community structure, co-occurrence patterns, and ecological processes of the SBEs inhabiting the shrub host, Mussaenda pubescens, across seven locations in southeastern China. We found that the absolute abundances, alpha diversity, and community composition of SBE communities exhibited notable differences among various host populations. Stem chemical characteristics were the most important factors influencing SBE community distribution, followed by geographic distance and climatic factors. The beta diversity decomposition analyses indicated that SBE community dissimilarities between sites were nearly equally driven by similarity, replacement diversity, and richness difference. The co-occurrence network analysis revealed that the keystone taxa were mostly observed in rare species, which may be essential for preserving the ecosystem's functions. Conditionally abundant taxa (CAT) showcased the highest closeness centrality, while exhibiting the lowest degree centrality and betweenness centrality as opposed to rare taxa. In addition, stochastic processes also played an important role in structuring SBE communities, with ecological drift being the dominant factor for both abundant and rare taxa. This study would deepen our understanding of the ecological dynamics and microbial interactions within plant endophytic microbiomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

River regulation has a key role in water resource management, but the introduced pollutants cannot be underestimated. This study reported spatiotemporal variations of perfluoroalkyl acids (PFAAs) significantly affected by river regulations in a standard example of urban river network with bidirectional flow in China. Perfluoroalkyl sulfonic acids (PFSAs), mostly of domestic origin, dominated during discharge, and perfluoroalkyl carboxylic acids (PFCAs), industrial pollutants, during diversion. The estimated PFAA flux into the Yangtze River during discharge was 1.22 × 10 2  kg with 62.5 % from Taihu Lake and 37.5 % from the river network. And that from the Yangtze River during diversion was 90.2 kg with 72.2 % into Taihu Lake and 27.8 % into the river network. Our findings show that PFAAs can exert pressure on regional water security that most of the urban river network was at medium risk. This study improves understandings of the role of river regulations in urban water networks and provides solid reference for risk assessment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The extensive use of organophosphorus insecticides poses a threat to the survival of non-target organisms. Ecotoxicological outcomes of embryonic exposure to insecticides are rarely evaluated in various oviparous species. In this study, soft-shelled turtle (Pelodiscus sinensis) eggs were incubated in moist substrate containing different levels (0, 2, 20 and 200 μg/kg) of chlorpyrifos to investigate its toxic effects on embryonic development and survival, and hatchling physiological performance. Chlorpyrifos exposure had no significant impacts on embryonic development rate and egg survival in P. sinensis. Similarly, embryonic chlorpyrifos exposure neither obviously affected the size and locomotor performance of hatchlings, nor changed the activities of superoxide dismutase and catalase, and content of malondialdehyde in their erythrocytes. Based on liquid chromatography-mass spectrometry analysis, minor metabolic perturbations related to amino acid, lipid and energy metabolism in hatchlings after embryonic chlorpyrifos exposure were revealed by hepatic metabolite profiling. Overall, our results suggested that embryonic exposure to environmentally relevant levels of chlorpyrifos had only a limited impact on physiological performances of hatchlings, although it would result in a potential risk of hepatotoxicity in P. sinensis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t 1/2  = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B 12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (∼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology., Competing Interests: Declaration of competing interest There are no conflicts to declare for this work., (Copyright © 2023. Published by Elsevier Inc.)

The development of cereal foods with slow starch digestibility is important for the general improvement of human health. In this study, the quality properties of noodles with added okara, in vitro starch digestibility, and the underlying mechanisms of the influence of okara on noodles were studied. Low concentrations (5 and 10 %) of okara improved the texture, cooking, and sensory properties of the noodles. Okara decreased the rapidly digestible starch (RDS) content, increased the resistant starch (RS) content, and reduced the predicted glycaemic index (pGI) of noodles. The pasting viscosity, thermal stability, and dynamic rheological results indicated that okara improved the starch crystallite stability of wheat flour and viscoelasticity of dough. Moreover, Fourier transform infrared (FTIR) spectroscopy showed that okara promoted the formation of starch-lipid complexes and improved the short-range structural order of starch. Additionally, microstructure imaging and protein network analysis (PNA) indicated that low addition of okara promoted the compactness of the okara-gluten-starch matrix, thus reducing the contact between starch and hydrolytic enzymes. These results reveal the effect of okara on the quality properties and starch digestibility in a starch-gluten complex system., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Endocrine-disrupting chemicals (EDCs) in environmental water samples, a rapid, sensitive, and high-throughput method should be developed. In this study, an in situ-synthesized composite material of three-dimensional mesoporous graphene (3D-MG) and zirconium-based metal-organic frameworks (MOFs), denoted as MG@UiO-66, was used as both the adsorbent and matrix in surface-assisted laser desorption/ionization time-of-flight mass spectrometry (SALDI-TOF MS) for steroid detection. Both graphene-based materials and MOFs have proven to be ineffective in detecting steroids as a matrix; however, their composites can detect steroids with higher sensitivity and lower interference. After screening different types of MOFs, a composite of UiO-66 and 3D-MG was selected as the new matrix for steroid detection. The combination of 3D-MG and UiO-66 further enhanced the ability of the material to enrich steroids, and reduced the limit of detection (LOD) of steroids. The method was evaluated for linearity, LODs, limit of quantitation (LOQs), reproducibility, and precision under optimized conditions. The results showed that the linear relationships of three steroids are kept in the range of 0-300 nM/L with a correlation coefficient r ≥ 0.97. The LODs and LOQs of the steroids were in the range of 3-15 and 10-20 nM/L, respectively. Recoveries (n = 5) of 79.3-97.2% were obtained at three spiked levels in the blank water samples. This fast and efficient method of using SALDI-TOF MS can be extended to detect the steroids in EDCs in environmental water samples., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Current methods for the rapid detection of trace antibiotics in the environment remains problems of low accuracy and false negative or false positive, making the development of fast, and accurate, and reliable methods for antibiotic testing a major challenge that needs to be addressed. Herein, we developed a novel label-free colorimetric and fluorescent dual-mode aptasensor assembled by the strong interaction of layered MoSe 2 nanosheets (MoSe 2 NSs) with ampicillin (AMP) aptamer functionalized silver nanoclusters (Apt-AgNCs) that specifically bind AMP to allow the sensitive and selective detection of AMP. Apt-AgNCs could be adsorbed on the surface of MoSe 2 NSs via van der Waals force to form a nanocomposite, Apt-AgNCs/MoSe 2 NSs. Interestingly, Apt-AgNCs/MoSe 2 NSs act together to construct dual mode aptasensor through modulation of the intrinsic peroxidase activity of MoSe 2 NSs and the fluorescence of Apt-AgNCs. In the presence of AMP, Apt-AgNCs could specifically bind AMP, triggering desorption from the MoSe 2 NSs surface, leading to a decrease in the peroxidase activity of the system with the recovery in Apt-AgNCs fluorescence. The dual-signal aptasensor exhibited good linear colorimetric and fluorescence responses in the AMP concentration ranges of 0.115-2.00 μM and 6-100 nM, respectively. Furthermore, the aptasensor was successfully measured AMP levels in commercially-bought milk and lake water with satisfactory results. Unlike single-signal aptasensors, the constructed dual-signal aptasensor could not only improve the detection precision, but also reduce the false positive or false negative results. These promising results suggest that the dual-readout strategy as demonstrated is general mode for the detection of other antibiotics or compounds using various aptamers functionalized AgNCs in concert with MoSe 2 NSs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is a great need for timely monitoring and rapid water quality assessment to control the algal blooms that often occur in eutrophic lakes. While algal cell density (ACD) is a critical indicator of algal growth, field monitoring is laborious and time-consuming, and rapid assessment of algal blooms based on ACD is often not possible. To address the limitations of conventional ACD detection, we proposed a soft sensor approach that uses surrogate indicators to simulate ACD in machine learning models. We conducted a case study using monitoring data from Chaohu Lake collected between 2016 and 2019. We found that ensemble learning models, especially extreme gradient boosting (XGBoost), outperformed traditional machine learning algorithms by comparing various machine learning algorithms. Also, considering the influence of input variable selection on model performance, we combined the results of different filter methods in the multi-stage variable selection process. Finally, we screened out seven key variables out of the 43 initial candidate variables, including dissolved oxygen (DO), chlorophyll-a (Chl-a), Secchi disk depth (SD), pH, permanganate index (COD Mn ), week of the year (WOY), and wind velocity (WV). Their inclusion substantially improved data accessibility and supported the development of a rapid simulation model. The final model was capable of reliable spatiotemporal generalization, with an overall R 2 value of 0.761. On the theoretical side, our study makes a new attempt to simulate ACD values in a eutrophic lake. For practical purposes, the soft sensor can facilitate the rapid assessment of bloom conditions, which helps the local administration with emergency prevention and control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Osseointegration is a prerequisite for the function of dental implants, and macrophage-dominated immune responses triggered by implantation determine the outcome of ultimate bone healing mediated by osteogenic cells. The present study aimed to develop a modified titanium (Ti) surface by covalently immobilizing chitosan-stabilized selenium nanoparticles (CS-SeNPs) to sandblasted, large grit, and acid-etched (SLA) Ti substrates and further explore its surface characteristics as well as osteogenic and anti-inflammatory activities in vitro. CS-SeNPs were successfully prepared by chemical synthesis and characterized their morphology, elemental composition, particle size, and Zeta potential. Subsequently, three different concentrations of CS-SeNPs were loaded to SLA Ti substrates (Ti-Se1, Ti-Se5, and Ti-Se10) using a covalent coupling strategy, and the SLA Ti surface (Ti-SLA) was used as a control. Scanning electron microscopy images revealed different amounts of CS-SeNPs, and the roughness and wettability of Ti surfaces were less susceptible to Ti substrate pretreatment and CS-SeNP immobilization. Besides, X-ray photoelectron spectroscopy analysis showed that CS-SeNPs were successfully anchored to Ti surfaces. The results of in vitro study showed that the four as-prepared Ti surfaces exhibited good biocompatibility, with Ti-Se1 and Ti-Se5 groups showing enhanced adhesion and differentiation of MC3T3-E1 cells compared with the Ti-SLA group. In addition, Ti-Se1, Ti-Se5, and Ti-Se10 surfaces modulated the secretion of pro-/anti-inflammatory cytokines by inhibiting the nuclear factor kappa B pathway in Raw 264.7 cells. In conclusion, doping SLA Ti substrates with a modest amount of CS-SeNPs (1-5 mM) may be a promising strategy to improve the osteogenic and anti-inflammatory activities of Ti implants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Microplastics (plastic particles < 5 mm; MPs) are ubiquitous in aquatic environments but their potential adverse ecological effects on biota remain poorly understood. This is in part because in typical ecotoxicology tests the toxic effects of MPs were found to be limited. To capture the potential find-scale effects of MPs on freshwater organisms, we employed ultra-performance liquid chromatography-tandem mass spectrometry based untargeted metabolomics to investigate the metabolic impact of polystyrene microbeads microplastics (PS-MPs) of different sizes (0.1, 1, 10, 100 μm) and concentrations (1, 10, 100 mg/L) on a common freshwater microalga, Microcystis aeruginosa, after a 96-h exposure test. The phenotype-based results illustrated that while PS-MPs had no discernible effects on microalgal growth and photosynthesis, both oxidative stress and microcystin production were slightly increased. Metabolomics analysis revealed that the PS-MPs altered the global metabolic profile of the microalga. Specially, PS-MPs of larger size and higher concentration induced a larger number of differentially expressed metabolites. The PS-MPs significantly disturbed metabolisms involved in amino acid synthesis, membrane formation, nitrogen storage, and antioxidant defense of the microalga, consistent with the phenotypic observations. These results suggested several perturbed metabolic pathways, especially arginine-related pathways, as the mechanism. Our study showed that the insights provided by metabolomics-based approaches can enhance assessments of the ecological impacts of MPs on freshwater organisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background & Aims: Although it is well known dietary factors are closely correlated with bone health, the association between macronutrients intake distribution and bone mineral density (BMD) is still unclear. The aims of this study were to investigate how macronutrients distribution was correlated with BMD, and to evaluate how the substitution between macronutrients could be associated with BMD., Methods: We conducted a cross-sectional study based on data from National Health and Nutrition Examination Survey. Dietary recall method was used to assessed the intake of macronutrients. Macronutrient intake distribution including carbohydrate, protein and fat was calculated as percentages of energy intake from total energy. BMD was converted to T-score and low BMD was defined as T-score less than -1.0. The association between the percentages of energy intake from carbohydrate, protein and fat with T-score and risk of low BMD was evaluated using multivariate regression models. Isocaloric substitution analysis was conducted using the multivariate nutrient density method., Results: Data form 4447 adults aged 20 years and older who underwent BMD examination were included in this study. Higher percentage of energy intake from carbohydrate was associated with lower T-score (-0.03 [95%CI, -0.05 to -0.01]; P = 0.001) and higher risk of low BMD (1.05 [95%CI, 1.02-1.08]; P = 0.003), while higher percentage of energy intake from protein was associated with higher T-score (0.05 [95%CI, 0.01-0.08]; P = 0.009) and lower odds of low BMD (0.92 [95%CI, 0.87-0.98]; P = 0.007). The percentage of energy intake from fat seemed to be positively correlated with T-score, but the correlation became insignificant after adjusting for metabolism related confounders. Isocaloric substitution analysis showed that only the substitution between carbohydrate and protein was significantly and independently associated with T-score (-0.05 [95%CI, -0.08 to -0.01]; P = 0.01) and the risk of low BMD (1.08 [95%CI, 1.02-1.15]; P = 0.008)., Conclusions: Based on the results from this study, we hypothesized that a high-protein diet coupled with low carbohydrate intake would be beneficiary for prevention of bone loss in adults. However, randomized clinical trials or longitudinal studies are needed to further assessed our findings., Competing Interests: Conflict of interest All authors declare that there is no conflict of interest involved., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

This study demonstrates the utility of internal nutrient loads as an additional parameter to improve the performance of machine learning models in predicting the temporal variations of aqueous TN and TP concentrations in Taihu Lake, a large shallow lake. Internal loads, as a potential input parameter for machine learning models, were estimated using a mass balance calculation. The results showed that between 2011 and 2018 the maximum monthly internal loads of nitrogen and phosphorus in Taihu Lake were 4200 t and 178 t, respectively. Monthly changes in the aqueous TN and TP concentrations of Taihu Lake did not correlate significantly with inflow loads whereas the correlations with estimated internal loads were positive and significant. Long short-term memory (LSTM), random forest (RF), and gradient boosting regression tree (GBRT) models were built, and for all of them the inclusion of internal loads in the input parameters improved their performance. LSTM model III, whose input parameters included both inflow loads and internal loads, had the best performance, based on a testing root mean square error of 0.11 mg TN/L and 0.017 mg TP/L. A 28 % decrease in the annual aqueous TP concentration in Taihu Lake in 2018 simulated by LSTM model III was achieved by lowering the average water level from 3.29 m to 2.99 m, suggesting a possible strategy to control the TP concentration in the lake. In summary, our study showed that aqueous TN and TP concentrations in shallow lakes can be simulated using machine learning, with LSTM models outperforming RF and GBRT models; in these models, internal loads should be included as an input parameter. Additionally, our study identified the water level as an important factor affecting the aqueous TP concentration in Taihu Lake., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Targeting EGFR and HER-2 is an essential direction for cancer treatment. Here, a series of N-(1,3,4-thiadiazol-2-yl)benzamide derivatives containing a 6,7-methoxyquinoline structure was designed and synthesized to serve as EGFR/HER-2 dual-target inhibitors. The kinase assays verified that target compounds could inhibit the kinase activity of EGFR and HER-2 selectively. The results of CCK-8 and 3D cell viability assays confirmed that target compounds had excellent anti-proliferation ability against breast cancer cells (MCF-7 and SK-BR-3) and lung cancer cells (A549 and H1975), particularly against SK-BR-3 cells, while the inhibitory effect on healthy breast cells (MCF-10A) and lung cells (Beas-2B) was weak. Among them, the hit compound YH-9 binded to EGFR and HER-2 stably in molecular dynamics studies. Further studies found thatYH-9could induce the release of cytochrome c and inhibit proliferation by promoting ROS expression in SK-BR-3 cells. Moreover,YH-9could diminish the secretion of VEGF and bFGF factors in SK-BR-3 cells, then inhibited tube formation and angiogenesis. Notably,YH-9could effectively inhibit breast cancer growth and angiogenesis with little toxicity in the SK-BR-3 cell xenograft model. Taken together,in vitroandin vivoresults revealed that YH-9 had high drug potential as a dual-target inhibitor of EGFR/HER-2 to inhibit breast cancer growth and angiogenesis., (Copyright © 2021. Published by Elsevier Inc.)

Objective: Psychobiotics, as a novel class of probiotics mainly acting on the gut-brain axis, have shown promising prospects in treating psychiatric disorders. Bifidobacterium breve CCFM1025 was validated to have an antidepressant-like effect in mice. This study aims to assess its psychotropic potential in managing major depression disorder (MDD) and unravel the underlying mechanisms., Methods: Clinical Trial Registration: https://www.chictr.org.cn/index.aspx (identifier: NO. ChiCTR2100046321). Patients (n = 45) diagnosed with MDD were randomly assigned to the Placebo (n = 25) and CCFM1025 (n = 20) groups. The freeze-dried CCFM1025 in a dose of viable bacteria of 10 10 CFU was given to MDD patients daily for four weeks, while the placebo group was given maltodextrin. Changes from baseline in psychometric and gastrointestinal symptoms were evaluated using Hamilton Depression Rating scale-24 Items (HDRS-24), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Psychiatric Rating Scale (BPRS), and Gastrointestinal Symptom Rating Scale (GSRS). Serum measures were also determined, i.e., cortisol, TNF-α, and IL-β. Serotonin turnover in the circulation, gut microbiome composition, and tryptophan metabolites were further investigated for clarifying the probiotics' mechanisms of action., Results: CCFM1025 showed a better antidepressant-like effect than placebo, based on the HDRS-24 (placebo: M = 6.44, SD = 5.44; CCFM1025: M = 10.40, SD = 6.85; t(43) = 2.163, P = 0.036, d = 0.640) and MADRS (placebo: M = 4.92, SD = 7.15; CCFM1025: M = 9.60, SD = 7.37; t(43) = 2.152, P = 0.037, d = 0.645) evaluation. The factor analysis of BPRS and GSRS suggested that patients' emotional and gastrointestinal problems may be affected by the serotonergic system. Specifically, CCFM1025 could significantly and to a larger extend reduce the serum serotonin turnover compared with the placebo (placebo: M = -0.01, SD = 0.41; CCFM1025: M = 0.27, SD = 0.40; t(43) = 2.267, P = 0.029, d = 0.681). It may be due to changes in gut microbiome and gut tryptophan metabolism under the probiotic treatment, such as changes in alpha diversity, tryptophan, and indoles derivatives., Conclusion: B. breve CCFM1025 is a promising candidate psychobiotic strain that attenuates depression and associated gastrointestinal disorders. The mechanisms may be relevant to the changes in the gut microbiome and tryptophan metabolism. These findings support the future clinical applications of psychobiotics in the treatment of psychiatric disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Microplastics have been reported in environmental media for decades, but gaps in our knowledge about them still remain. We investigated the third biggest freshwater lake in China - Taihu Lake - and the 30 major rivers around it. Microplastics were detected in lake water and sediment, and in river water, at abundances varying from 1.7 to 8.5 items/L, 460 to 1380 items/kg and 1.8 to 18.2 items/L, respectively. Inflow rivers were more polluted with microplastics than outflow rivers. The most common shape was fragment. Microplastic sizes of <100 μm dominated in inflow rivers, 100-200 μm dominated in lake water and outflow rivers. The average size of microplastics in outflow rivers (200.4 μm) was larger than that in inflow rivers (166.2 μm). Microplastics of <100 μm only accounted for 28% in the lake surface water but were as high as 70% in the sediment, indicating that smaller microplastics may more easily settle in the lake. The main components of the microplastics were identified as being polyvinyl chloride and polyethylene. There were about 1.2E06 items/s microplastics entered Taihu Lake. Four main rivers located at northwestern lake accounted for 79% of the total inflow microplastic fluxes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ferroptosis, as a newly discovered cell death form, has become an attractive target for precision cancer therapy. Several ferroptosis therapy strategies based on nanotechnology have been reported by either increasing intracellular iron levels or by inhibition of glutathione (GSH)-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4). However, the strategy by simultaneous iron delivery and GPX4 inhibition has rarely been reported. Herein, novel tumor microenvironments (TME)-activated metal-organic frameworks involving Fe & Cu ions bridged by disulfide bonds with PEGylation (FCSP MOFs) were developed, which would be degraded specifically under the redox TME, simultaneously achieving GSH-depletion induced GPX4 inactivation and releasing Fe ions to produce ROS via Fenton reaction, therefore causing ferroptosis. More ROS could be generated by the acceleration of Fenton reaction due to the released Cu ions and the intrinsic photothermal capability of FCSP MOFs. The overexpressed GSH and H 2 O 2 in TME could ensure the specific TME self-activated therapy. Better tumor therapeutic efficiency could be achieved by doxorubicin (DOX) loading since it can not only cause apoptosis, but also indirectly produce H 2 O 2 to amplify Fenton reaction. Remarkable anti-tumor effect of obtained FCSP@DOX MOFs was verified via both in vitro and in vivo assays., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Magnetic measurement was provided to substitute for time-consuming conventional methods for determination of potentially toxic elements. Both the concentrations of 12 elements and 9 magnetic parameters were determined in 700 muscle tissue samples from the snail Bellamya aeruginosa, shrimp species Exopalaemon modestus and Macrobrachium nipponense, and fish species Hemisalanx prognathous Regan, Coilia ectenes taihuensis, and Culer alburnus Basilewsky collected from Chaohu Lake during different hydrological periods. Spherical and irregular iron oxide particles were observed in the muscle tissues of the studied aquatic products. A field survey of the exposure parameters in humans, such as per capita intake dose of local aquatic products, found no evidence that consumption of the tested species poses a potential health risk. Redundancy analysis revealed different degrees of correlation between the magnetic parameters and concentrations of elements in aquatic products. Back-propagation artificial neural network (BP-ANN) and support vector machine (SVM) models were applied to predict elemental concentrations in aquatic products, using magnetic parameters as input. SVM models performed well in predicting the presence of Cr and Ni, with R and index of agreement values of >0.8 in both training and validation stages as well as relatively low errors. The BP-ANN and SVM models both performed relatively poorly in predicting the presence of Cd and Zn in aquatic products, with R values between 0.333 and 0.718 for Cd and between 0.454 and 0.664 for Zn in training and validation stages. For most of the elements, a better R value was obtained with the SVM than with BP-ANN model. The R of Co, Cr, Cu, Ni, and Ti in the training and validation stages of snail in the SVM model were >0.8. This study is a first step in developing a novel approach allowing the rapid monitoring of potentially toxic elements concentrations in aquatic products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Environmental magnetism in combination with machine learning can be used to monitor heavy metal pollution in sediments. Magnetic parameters and heavy metal concentrations of sediments from Chaohu Lake (China) were analyzed. The magnetic measurements, high- and low-temperature curves, and hysteresis loops showed the primary magnetic minerals were ferrimagnetic minerals in sediments. For most metals, their concentrations were highest during the wet season and lowest during the medium-water period. Cd, Hg, and Zn were moderately enriched and Cd and Hg posed a considerable ecological risk. A redundancy analysis indicated a relationship between physicochemical indexes and magnetic parameters and heavy metal concentrations. An artificial neural network (ANN) and support vector machine (SVM) were used to construct six models to predict the heavy metal concentrations and ecological risk index. The inclusion of both the physicochemical indexes and magnetic parameters as input factors in the models were significantly ameliorated the simulation accuracy for the majority of heavy metals. The training and test R, for Be, Fe, Pb, Zn, As, Cu, and Cr were > 0.8. The SVM showed better performance and hence it has potential for the efficient and economical long-term tracking and monitoring of heavy metal pollution in lake sediments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Microbial remediation is a promising technique to reduce Cd accumulation in rice (Oryza sativa). In present study, a set of pot experiments were conducted to evaluate the effects of Cd-tolerate Pseudomonas TCd-1 inoculation on rice Cd uptake, soil enzyme activities and Cd bioavailability in the rhizosphere soils under Cd contaminated conditions. The results showed that at the ripening stage, with the inoculation of TCd-1, Cd contents in root, culm, leaf, hull and brown rice significantly reduced by 60.7%, 47.7%, 50.6%, 58.1% and 47.9%, respectively, and the cadmium bioconcentration factor (BCF) of rice lowered by 66.2% under 5 mg kg -1 Cd treatment. At the meantime, in the rhizosphere soils, pH increased by 0.05, the contents of exchangeable Cd (EX-Cd) and Fe-Mn oxides (OX-Cd) increased by 107.8% and 33.5%, whereas organic matter (OM-Cd) and residual (Res-Cd) decreased by 31.9% and 60.0%, respectively. The activity of acid phosphatase (ACP) increased by 28.3%, catalase (CAT), saccharase (SUC) activity decreased by 28.5% and 26.0%. Similarly, the Cd contents in root, culm, leaf, hull and brown rice reduced by 42.1%, 42.5%, 58.0%, 50.3%, and 68.8%, respectively, and the BCF lowered by 57.1%, under 10 mg kg -1 Cd treatment. Simultaneously, the soil pH increased by 0.06, the activities of CAT, SUC, urease (URE), ACP decreased by 26.4%, 34.6%, 63.8% and 15.3%, respectively. Furthermore, the correlation analysis showed that the inoculation of TCd-1 changed the correlation between rice Cd content and the biomass of roots, leaves, soil pH, CAT, PPO, URE activities, OM-Cd in rhizosphere soils. It suggested that Pseudomonas TCd-1 effectively reduced Cd uptake and Cd accumulation in rice was closely linked to the changes of soil pH, enzyme activities and Cd availability., (Copyright © 2021. Published by Elsevier Inc.)

Human induced pluripotent stem cell (hiPSC)-derived endothelial cell (hiPSC-EC) transplantation is a promising therapy for treating peripheral artery disease (PAD). However, the poor differentiation of hiPSCs limits their clinical application. Therefore, finding key factors that regulate cellular differentiation is crucial for improving the therapeutic efficacy of hiPSC-EC transplantation. Sterol regulatory element binding protein 1 (SREBP1) is a key regulator of lipid metabolism and stem cell differentiation. However, it remains unknown whether SREPBP1 modulates hiPSC differentiation. In this study, we showed that SREBP1 expression was negatively associated with hiPSC differentiation and EC function. The results show that SREBP1 binds to the promoter region of miR199b-5p and suppresses its transcription, resulting in the activation of Notch1 signaling. Blocking SREBP1 increased both hiPSC differentiation and EC angiogenesis. These findings demonstrate a novel role for SREBP1 in hiPSC differentiation and EC angiogenesis., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO 2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: To explore the biological function and mechanism of Syntaxin2 (STX2) in Colorectal cancer (CRC) proliferation., Main Methods: A series of gain- and loss-of-function analysis were conducted the to explore the biological function of STX2 in CRC proliferation in vivo and in vitro. Western blot, Co-immunoprecipitation (Co-IP) and the functional analyses were taken to analyze the regulative role of STX2 on Exosome Complex 4 (EXOSC4) in CRC proliferation; Immunohistochemistry (IHC) and Real-time quantitative polymerase chain reaction (qPCR) were used to further verify the relationship between the expression of STX2 and EXOSC4 in human CRC samples., Key Findings: Our study revealed that the over-expression of STX2 promoted CRC proliferation, while knockdown of STX2 repressed CRC proliferation; STX2 promoted CRC proliferation via increasing EXOSC4 protein; There was a positive correlation between STX2 and EXOSC4 expression., Significance: The current data verify that STX2 drives the proliferation of CRC via increasing the expression of EXOSC4., (Copyright © 2020. Published by Elsevier Inc.)

Background and Aims: Phenotypic switch of vascular smooth muscle cells (VSMC) plays a key role in the pathogenesis of atherosclerosis and restenosis after artery intervention. Transcription repressor element 1-silencing transcription factor (REST) has been identified as key regulator of VSMC proliferation. In the present study, we sought to investigate the potential association of E3-ubiquitin ligase β-TRCP mediated REST protein degradation with Kv1.3 expression during VSMC phenotypic switch., Methods: Protein and mRNA expression was measured in ex vivo and in vitro models. Protein interaction and ubiquitination were analyzed by immunoprecipitation assays. ChIP assays were performed to assess the relationship between REST and targeted DNA binding site., Results: We found that the expression level of E3-ubiquitin ligase β-TRCP is significantly increased during VSMC phenotypic switch. REST protein ubiquitination mediated by β-TRCP is critical for VSMC proliferation and migration. We also found that the gene KCNA3 encoding potassium channel protein Kv1.3 contains a functional REST binding site and is repressed by REST. Downregulation of REST by β-TRCP and consequently upregulation of Kv1.3 are important events during VSMC phenotypic switch. Furthermore, upregulated Kv1.3 accelerates β-TRCP modulated REST degradation through Erk1/2 signaling., Conclusions: Our results reveal a fundamental role for regulatory interactions between β-TRCP modulated REST degradation and Kv1.3 in the control of the multilayered regulatory programs required for VSMC phenotype switch., (Copyright © 2020. Published by Elsevier B.V.)

Electrochemical reduction of carbon dioxide (CO 2 ) is considered a promising renewable energy conversion technology, but it remains challenging to find active, stable, low-cost, and highly efficient electrocatalysts for the CO 2 conversion. Here, we develop an in situ nitrogen-doped, metal-free, porous biochar from plant moss to catalyze the electrochemical reduction of CO 2 into methane (CH 4 ), methanol (CH 3 OH) and ethanol (C 2 H 5 OH) at high current densities and low overpotentials. Using this metal-free biochar electrocatalyst, production rates of approximately 36.1, 32.1, and 18.1 μg h -1  cm -2 towards CH 4 , C 2 H 5 OH, and CH 3 OH are obtained with Faradaic efficiencies of 56.0%, 26.0% and 10.5%, respectively. In addition, the total faradaic efficiency reaches 92.6% at -1.2 V (vs. Ag/AgCl) with good stability. A favorable pathway for the electrochemical reduction of CO 2 over the metal-free biochar is also provided. This study presents a new approach to produce cost-effective, in situ nitrogen-doped porous biochars with excellent efficiency and durability for the electrochemical reduction of CO 2 ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A series of novel (E)-N-phenyl-4-(pyridine-acylhydrazone) benzamide derivatives were designed, synthesized, and evaluated for their anti-proliferative activity against two different human cancer cell lines and one human normal cell line. Compound 8b had the best anti-proliferative activity (IC 50  = 0.12 ± 0.09 μM, RPMI8226 cells) than the other compounds. And compound 8b had lower toxicity than imatinib. Flow cytometry analysis showed that compound 8b could arrest the cell cycle at the G0/G1 phase, and induce apoptosis of RPMI8226 cells by promoting mitochondrial ROS release, thereby effectively inhibiting cell proliferation. Our findings provided a promising lead compound 8b for further structural optimization and will be instructive for the discovery of more potent antitumor drugs with high selectivity and low toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Few studies have focused on the impact of particulate matter (PM) exposure with respect to the relationship between PM-induced inflammation and the levels of trace metals in tissues and organs. In this study, C57BL/6 male mice were exposed to ambient air alongside control mice breathing air filtered through a high-efficiency particulate air (HEPA) filter. In both groups, mRNA levels of pro- and anti-inflammatory cytokines were measured after 4, 8 and 12 weeks together with the trace metal contents of the lungs, heart, liver, hippocampus and blood. PM exposure resulted in a general upward trend in the levels of pro-inflammatory cytokines in lung, heart, liver and hippocampus. By contrast, IL-10 mRNA expression varied depending on the organ, with a continuous upward trend in heart and liver and an up-regulation at 8 weeks followed by a down-regulation at 12 weeks in lung and hippocampus. The disturbed homeostasis of inflammatory cytokines was accompanied by changes in trace metal levels in the mice. These alterations may have constituted a compensatory effect conferring protection from inflammatory damage. However, prolonged PM exposure finally resulted in the deficiency of several essential trace metals in the lungs and hippocampus, which may have contributed to the observed histological changes typical of an inflammatory response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Since December 2019, new COVID-19 outbreaks have occurred and spread around the world. However, the clinical characteristics of patients in other areas around Wuhan, Hubei Province are still unclear. In this study, we performed epidemiological and clinical characteristics analysis on these regional cases., Methods: We retrospectively investigated COVID-19 patients positively confirmed by nucleic acid Q-PCR at Taihe Hospital from January 16 to February 4, 2020. Their epidemiological, clinical manifestations, and imaging characteristics were analysed., Results: Among the 73 patients studied, 12.3 % developed symptoms after returning to Shiyan from Wuhan, and 71.2 % had a history of close contact with Wuhan personnel or confirmed cases. Among these patients, 9 cases were associated with family clustering. The first main symptoms presented by these patients were fever (84.9 %) and cough (21.9 %). The longest incubation period was 26 days, and the median interval from the first symptoms to admission was 5 days. Of the patients, 67.1 % were originally healthy people with no underlying diseases, others mostly had common comorbidities including hypertension (12.3 %) and diabetes (5.5 %), 10.9 % were current smokers, 30.1 % had low white blood cell counts and 45.2 % showed decreased lymphocytes at the first time of diagnosis. CT scans showed that multiple patchy ground glass shadows outside of the patient lungs were commonly observed, and a single sub-pleural sheet of ground glass shadow with enhanced vascular bundles was also found located under the pleura. Patient follow-up to February 14 presented 38.4 % severe cases and 2.7 % critical cases. After follow-up, the parameter of lymphocyte counts below 0.8 × 10 9 /L cannot be used to predict severe and critical groups from the ordinary group, and a lower proportion of smokers and higher proportion of diabetes patients occur in the poor outcome group. Other co-morbidities are observed but did not lead to poor outcomes., Conclusion: The epidemiological characteristics of patients in the area around Wuhan, such as Shiyan, at first diagnosis are described as follows: Patients had histories of Wuhan residences in the early stage and family clustering in the later period. The incubation period was relatively long, and the incidence was relatively hidden, but the virulence was relatively low. The initial diagnosis of the patients was mostly ordinary, and the percentage of critical patients who evolved into the ICU during follow-up is 2.7 %, which is lower than the 26.1 % reported by Wuhan city. According to the Shiyan experience, early diagnosis with multiple swaps of the Q-PCR test and timely treatment can reduce the death rate. Diabetes could be one of the risk factors for progression to severe/critical outcomes. No evidence exists that smoking protects COVID-19 patients from developing to severe/critical cases, and the absolute number of lymphocytes at initial diagnosis could not predict the progression risk from severe to critical condition. Multivariate regression analysis should be used to further guide the allocation of clinical resources., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Mesenchymal stem cell therapy has drawn much attention as a promising therapeutic option for the treatment of different diseases. Due to insufficient cell population derived from freshly isolated tissues, in vitro propagation is required prior to clinical use. However, reduced cell viability of aging mesenchymal stem cell (MSCs) with repeated propagations has yet not be fully investigated, especially for the biological characteristics of immunoregulatory ability and paracrine factors. In this study, we compared the biological properties of human umbilical cord-MSCs (hUC-MSCs) at different passages, especially for immunomodulatory ability and secretions. Our results showed that hUC-MSCs at early passage (P2) and late passage (P8) exhibited similar morphology and surface marker expression, but hUC-MSCs at P8 displayed reduced proliferation and differentiation potential, immunoregulatory and secretory ability. In particular, hUC-MSCs at P2 and P5 could significantly suppress the population of proinflammatory Th1 and Th17 cell subsets and upregulate Treg cells, but not with hUC-MSCs at P8. For paracrine mechanism, higher level of secretions such as growth factors, cell adhesions, anti-inflammatory factors of hUC-MSCs were observed at P2 and P5 compared to that at P8. Therefore, it is essential to verify and validate the biological characteristics of hUC-MSCs that possess a good vitality before they are released for clinical use. Altogether, this study provides a rationale and two important parameters for how to select appropriate passage and vitality of MSCs for cell therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)