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The Yellow River Basin (YRB) is a significant grain base, energy base and natural ecological barrier in China. It is also an area with scarce water resources, and there was a constraint relationship with water-energy-food-ecosystems (WEFE). Studying the synergistic WEFE relationship has a favorable impact on the promotion of high-quality and sustainable development. This study developed a comprehensive index system for WEFE and analyzed the evolution of coupling relationship over time. Geographical detector was used to quantify the driving factors of coupling coordination degree. Social network analysis (SNA) model was used to evaluate the network characteristics and spatial patterns of coupling coordination of WEFE. The results indicated that: 1) the coupling coordination degree of WEFE Nexus had increased from moderate incoordination to good coordination during 2006–2020; 2) production and waste emission processes of energy and food were key constraints to coupling relationships; 3) Henan was the center of WEFE coupling coordination network in YRB, and the spatial network was divided into the net beneficial block, net spillover block, bidirectional spillover block, brokers block. However, regional disparities existed, coupling coordination degree showed downstream spillovers and upstream benefits; 4) accordingly, we proposed measures to enhance the balanced development of regional coupling coordination, what's the most important of which was identifying one's own position and actively broadening the channels of factor mobility. This study helps to understand the characteristics of resources from the perspective of complex networks, and provides a scientific basis for strengthening the regional integrated management, and achieving regional synergistic development. [Display omitted] • The coupling coordination degree has shown an increasing trend during 2006–2020. • Social Network Analysis model was used to analyze spatial network characteristics. • The upper reach is the beneficiary area of coupling coordination development. • Explored the targeted measures to enhance regional sustainable development. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA), as one of the most important and harmful mycotoxins, is classed as possible human carcinogen (group 2B). As we all know, DNA damage may cause genomic instability, cell cycle disorder, activation of DNA damage pathway, and stimulation of DNA repair system. To explore the roles of DNA damage repair protein (hMLH1) on OTA-induced G 2 arrest, the DNA damage, chromosome aberration, cell cycle distribution and p53-p21 signaling pathway were evaluatd after different time OTA exposure (6, 12, 24, 48 h) in immortalized human gastric epithelial cells (GES-1). Our results demonstrated that OTA exposure could trigger genomic instability, DNA damage and G 2 phase arrest of GES-1 cells. At the same time, OTA treatment could increase the expression of hMLH1, and induce phosphorylation of the p53 protein, as well as p21, in response to DNA damage. Finally, inhibition of hMLH1 by siRNA effectively prevented the activation of p53-p21 signaling pathway and rescued the G 2 arrest elicited by OTA. This study demonstrated that hMLH1-p53-p21 signaling pathway played an important role in DNA damage and G 2 cell cycle arrest the mediated by OTA in GES-1 cells. • OTA treatment for different amounts of time in GES-1 cells could induce chromosomal aberrations, DNA damage and G 2 /M phase arrest. • OTA treatment for different amounts of time induced GES-1 cells to arrest at G 2 /M phase by regulating the expression of Cdc2, p-Cdc2 and CyclinB1. • The hMLH1-p53-p21 signaling pathway play an important role in OTA-caused G 2 phase arrest in GES-1 cells. [ABSTRACT FROM AUTHOR]

This study aims to explore psychological experience and influential factors of pregnant women who decided elective caesarean section after the COVID-19 pandemic.Methods: This is a cross-sectional study carried out in a hospital in Shanghai, according to the inclusion and exclusion criteria, we selected pregnant women who selected elective cesarean section as the study objects, all participants provided informed consent and completed questionnaires, including sociodemographic questionnaire, Generalized Anxiety Disorder scale (GAD-7) and General Well-Being Schedule (GWBS). Software SPSS 23.0 was used to analyze and explore the influencing factors.Results: Eligible 595 questionnaires were included in the study, the mean score of GAD-7 was 4.855 ± 3.254 and 90.699 ± 13.807 of GWBS. Generalized linear regression analysis revealed several factors that were statistically significant with the two scales, including birthplace, average monthly income, number of abortion and pregnancy complication (p < 0.01).Conclusion: The COVID-19 infection status and symptoms around infection have no statistical difference in anxiety level and general well-being after they experience the COVID-19 pandemic. However, through this study, we found some influencing factors that worth further exploration. In the future, we will expand the sample size to explore the different situation of multi-center, and we hope provide psychological nursing interventions based on existing results to offer a better delivery experience. [ABSTRACT FROM AUTHOR]

To analyze the expression trends and clinical significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 ( APE1/Ref-1) and Nucleophosmin ( NPM1) proteins in high-grade serous ovarian adenocarcinoma ( HGSC). The expressions of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were determined using the immunohistochemical ( IHC) method, and their relationships with clinicopathological features were analyzed by the χ2 test or Fisher's exact test. The follow-up data, Cox proportional hazards univariate and multivariate survival analyses were integrated to evaluate the prognostic factors affecting patients with HGSC. In the normal fallopian tubes, APE1/Ref-1 and NPM1 protein were mainly distributed in the nuclear. The HGSC experienced changes in the cellular localization of APE1/Ref-1 and NPM1 protein expressions, which were abnormally expressed in the cytoplasm. The rates of abnormal cytoplasmic expression of APE1/Ref-1 and NPM1 proteins in 94 patients with HGSC were 69.1% and 73.4%, respectively, which were significantly higher than the normal fallopian tube tissues (p < 0.05). The abnormal cytoplasmic APE1/Ref-1 and NPM1 are significantly correlated with the lymph node metastasis, chemosensitivity, FIGO staging, and prognosis. The COX multivariate survival analysis showed that the abnormal expression of APE1/Ref-1 protein, FIGO staging, and lymph node metastasis are independent prognostic factors. Collectively, the abnormal cytoplasmic APE1/Ref-1 and NPM1 proteins are associated with the oncogenic progression and chemoresistance of HGSC, and predict a poor prognosis. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) causes tremendous harm to a patient's physical, mental, and financial health. Moreover, recovery of SCI is affected by many factors, inflammation is one of the most important as it engulfs necrotic tissue and cells during the early stages of injury. However, excessive inflammation is not conducive to damage repair. Macrophages are classified into either blood-derived macrophages or resident microglia based on their origin, their effects on SCI being two-sided. Microglia first activate and recruit blood-derived macrophages at the site of injury—blood-borne macrophages being divided into pro-inflammatory M1 phenotypes and anti-inflammatory M2 phenotypes. Among them, M1 macrophages secrete inflammatory factors such as interleukin-β (IL-β), tumor necrosis factor-α (TNF-α), IL-6, and interferon-γ (IFN-γ) at the injury site, which aggravates SCIs. M2 macrophages secrete IL-4, IL-10, IL-13, and neurotrophic factors to inhibit the inflammatory response and inhibit neuronal apoptosis. Consequently, modulating phenotypic differentiation of macrophages appears to be a meaningful therapeutic target for the treatment of SCI. Biomaterials are widely used in regenerative medicine and tissue engineering due to their targeting and bio-histocompatibility. In this review, we describe the effects of biomaterials applied to modulate macrophage phenotypes on SCI recovery and provide an outlook. [ABSTRACT FROM AUTHOR]

Salinity and alkalinity are important indicators of the aquatic environment, and saline-alkali stress has negative effects on aquatic organisms. Dietary supplementation with probiotics can improve the overall health and productivity of aquatic animals. Bacillus subtilis is a widely used probiotic in aquaculture. A total of 240 Carassius auratus gibelio (13.85 ± 0.15 g) were assigned to four groups. This experiment used a completely randomized design with three replicates and a 2 × 2 factorial scheme, with two saline-alkali concentrations (0 g/L NaCl + 0 g/L NaHCO3 and 5 g/L NaCl + 2.52 g/L NaHCO3) and two diets (control and supplemented with 108 CFU/g B. subtilis). After 12, 24, 48, 72, and 96 h of saline-alkali exposure, fish blood samples were collected and serum levels of immunoglobulin M, alkaline phosphatase, and acid phosphatase were measured. Gills and kidneys were sampled to analyze superoxide dismutase activity, catalase activity, malondialdehyde content, and histopathological alterations. The results suggested that a B. subtilis-supplemented diet may enhance immunity, improve antioxidant ability, and reduce tissue damage in C. gibelio exposed to saline-alkali stress. [ABSTRACT FROM AUTHOR]

Objective: This study explored the colorectal cancer exosome lncRNA prostate cancer associated transcript 1- (PCAT1) mediated circulating tumors and the mechanism of cell colorectal cancer liver metastasis.Methods: Exosomes were extracted from the primary colorectal cancer (CRC) cell lines HCT116 and SW480 and cultured with T84 and human umbilical vein endothelial (HUVE) cells. The expression of PCAT1 and miR-329-3p was detected by real-time quantitative polymerase chain reaction (RT-qPCR), the expression of Netrin-1, CD146, and epithelial mesenchymal transition (EMT) related proteins was detected by Western blot, the proliferation activity of T84 cells was detected by cell counting kit 8 (CCK-8), and cell migration was detected by Transwell. The expression of the F-actin signal was detected by immunofluorescence after coculture of exosomes with human umbilical vein endothelial cells (HUVECs). Changes in subcutaneous tumor and liver nodule size after PCAT1 deletion were observed in a mouse model of liver metastasis from rectal cancer.Results: PCAT1 expression was upregulated in primary cell lines and their exosomes. After exosomes were cocultured with colorectal cancer tumor circulating T84 cells, the expression of Netrin-1 and CD146 was upregulated, the expression of miR-329-3p was downregulated, the proliferation and migration ability of T84 cells were enhanced, and EMT occurred. After knocking down PCAT1, the above phenomenon was reversed. Similarly, after exosomes were cocultured with HUVECs, the expression of the F-actin signal increased, and after PCAT1 was knocked down, the F-actin signal also decreased. PCAT1 regulates miR-329-3p/Netrin-1 and affects the biological behavior of T84 and F-actin signal expression in HUVECs. In a mouse model of colorectal cancer liver metastasis, knocking down PCAT1 significantly reduced the nodules formed by liver metastasis in mice.Conclusions: LncRNA PCAT1 derived from colorectal cancer exosomes regulates the activity of the Netrin-1-CD146 complex in circulating tumor cells (CTCs) to promote the occurrence of colorectal cancer EMT and liver metastasis and provides new molecular targets for the treatment of colorectal cancer liver metastasis. [ABSTRACT FROM AUTHOR]

Objective. Glioma is a common malignant tumor of the central nervous system with extremely poor prognosis. An efficient molecular marker for diagnosis and treatment is urgently needed. Fatty acid binding protein 7(FABP7), which regulates intracellular lipid metabolism, is highly expressed in nervous system tumors, but its prognostic value remains undetermined. The present study investigated the relationship between FABP7 expression and prognosis in glioma patients by bioinformatics analysis, as well as immunohistochemically evaluating the effect of FABP7 expression on the efficacy of antiangiogenic drugs. Methods. Gene expression and clinical data on patients with glioma were collected from the China Glioma Genome Atlas (CGGA) database, The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases. Levels of FABP7 expression and their association with the clinicopathologic characteristics of glioma patients were analyzed in the CGGA database. The relationships between FABP7 expression and clinical findings, such as survival and prognostic, were determined and used for nomogram construction. Mechanisms of action of FABP7 were assessed using GSEA software. FABP7 expression in the tissues of glioma patients treated with apatinib was evaluated immunohistochemically. Results. FABP7 was highly expressed in glioma samples, with higher FABP7 expression associated with poorer patient prognosis and more advanced clinicopathological features. Bioinformatics analysis, including survival, receiver operating characteristic curve, and univariate and multivariate Cox analyses, showed that FABP7 was independently prognostic of outcomes in glioma patients. GSEA analysis showed that FABP7 was associated with angiogenesis, with FABP7 having correlation coefficients > 0.4 with seven factors in the angiogenic pathway, POSTN, TIMP1, PDGFA, FGFR1, S100A4, COL5A2, and STC1, and the expression of these factors related to patient prognosis. Immunohistochemistry showed that FABP7 expression was higher in glioma patients with poor survival after apatinib treatment. Conclusions. High FABP7 expression is associated with poor prognosis in glioma patients. FABP7, which is important for glioma angiogenesis, may serve as an independent prognostic predictor in glioma patients. [ABSTRACT FROM AUTHOR]

Background: Fish is favored by consumers, while amino acids and fatty acids are the main nutrients of muscle. At present, it has been found that the gut microbial community may be involved in the regulation of host material anabolism. Juvenile and adult bighead carp (A. nobilis) from Chagan lake and Xinlicheng reservoir were selected, and divided into four groups to compare the differences of gut microbial communities, free amino acid and fatty acids in muscle. Results: The results showed that fish in different lakes or ages contained specific microbiota, the gut microbial structure was similar, but the microbial content was significantly different. Gut microbial abundance of juvenile fish in Chagan lake was significantly higher than that of other groups. Phylum level analysis Proteobacteria was the dominant gut bacteria of fish in both adult and juvenile fish from two separate lakes. Actinobacteria was another dominant bacterial phylum in juvenile fish in both lakes. Contents of free amino acids and fatty acids in muscle were detected, and the relationships between them and gut microbial communities were analyzed. Bighead carp grew from juvenile to adult, Actinobacteria abundance decreased (P < 0.05) and Proteobacteria increased (P < 0.05). Proteobacteria was positively correlated with the contents of Thr, Lys, Pro, Asp, Gly and Glu, Actinobacteria was negatively correlated with Met and His. Meanwhile, EPA and DHA were positively correlated with Proteobacteria, EPA and DHA were not significantly associated with Actinobacteria. Conclusion: It was speculated that the contents of free amino acids and fatty acids in muscle might be affected by the difference of gut microbiota, thus affecting the taste and nutritional quality. [ABSTRACT FROM AUTHOR]

Purpose: Long noncoding RNAs (lncRNAs) are emerging as key regulators in cancer initiation and progression. LINC01137 is a recently identified lncRNA of which the functional role in the development of oral squamous cell carcinoma (OSCC) has not been determined yet. Methods: We analyzed the expression of LINC01137 using a microarray-based OSCC gene expression dataset (GSE31056), and validated the results obtained using RT-qPCR in 26 pairs of primary OSCC tumor tissues and adjacent non-tumor tissues. The proliferative and invasive effects of LINC01137 on OSCC cells were determined using CCK-8, colony formation and transwell assays, respectively. Targeted binding between miR-22-3p and LINC01137 was verified using a dual luciferase reporter assay. Results: We found that LINC01137 was significantly upregulated in primary OSCCs. LINC01137 knockdown inhibited OSCC cell proliferation, migration and invasion, whereas LINC01137 overexpression induced opposite effects. LINC01137 upregulation along with p53 inhibition enhanced the malignant transformation of oral cells. In addition, we found that miR-22-3p can directly target LINC01137 through interaction with a putative miR-22-3p-binding site present within the LINC01137 sequence. A significant negative correlation was observed between LINC01137 and miR-22-3p expression in primary OSCC specimens. Exogenous overexpression of miR-22-3p markedly reduced the endogenous expression level of LINC01137 in OSCC cells. Additional functional assays showed that miR-22-3p overexpression enhanced the inhibitory effect of siRNA-mediated LINC01137 silencing on OSCC cell proliferation, migration and invasion, whereas miR-22-3p inhibition had the opposite effect. Conclusions: Our results indicate that LINC01137 functions as an oncogenic lncRNA in OSCC. miR-22-3p can directly target LINC01137 and negatively regulate its expression and function. [ABSTRACT FROM AUTHOR]

Background: Low risk pregnancy ending in a vaginal birth is best served and guided by a midwife. Utilizing a midwife in such cases offers many emotional and economic advantages and does not increase the risks for mother or neonate. However, women's experience and satisfaction of midwife-led maternity care is rarely reported in China. The primary objective of this study is to describe the experience of Chinese women receiving midwife-led maternity care, and to report their satisfaction level of the experience.Methods: The study is a cross-sectional survey of 4192 women who had natural birth from March-June 2019 in a maternity care center, Shanghai, China. We used a self-administered questionnaire addressing items related to women's experience during childbirth, as well as their satisfaction with midwife-led maternity care. We also included demographic and perinatal characteristics of each participant. Descriptive statistics and correlations analysis between groups of different experience and satisfaction were used.Results: In this sample, 87.7% of women had a Doula and a family member present during childbirth. Epidural anesthesia was used in 75.6% and episiotomy was needed in 23.2%. Free positioning during the first stage of labor and free positioning during the second stage of labor and delivery were adopted in 84.3 and 67.9% of the cases, respectively. Moderate to severe perineal pain and moderate to severe perineal edema were reported in 43.1 and 12.2% of the participants, respectively. High satisfaction level was found when there was midwife-led prenatal counseling and presence of Doula and family member, Lamaze breathing techniques, warm perineal compresses, epidural anesthesia, free positioning during the first stage of labor, and midwifes' postpartum guidance. Negative satisfaction was seen with perineal pain and edema.Conclusion: Women in this survey generally had high satisfaction with midwife-led maternity care. This satisfaction is probably felt because of the prenatal counseling by the midwife and allowing a Doula and a family member in the room during childbirth. Other intangible factors to improve the satisfaction level were Lamaze breathing techniques, warm perineal compresses, epidural anesthesia, free positioning during first stage of labor, and early skin to skin contact. [ABSTRACT FROM AUTHOR]

Purpose: Gefitinib is a first-line treatment option for epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma. However, most patients inevitably develop gefitinib resistance. The mechanism underlying this resistance is not fully understood. Y-box binding protein 1 (YB-1) has been reported to play a role in modulating drug sensitivity, but its role in gefitinib resistance is currently unknown. Here, we investigated the role of YB-1 in gefitinib resistance of lung adenocarcinoma. Methods: We determined the expression of YB-1, epithelial–mesenchymal transition (EMT) and AKT signaling markers, as well as the viability of lung adenocarcinoma cell lines bearing mutant (HCC827, PC-9) or wild-type (H1299) EGFR. We also evaluated PC-9 cell migration and invasion using transwell assays. The clinical importance of YB-1 and major vault protein (MVP) was evaluated using primary lung adenocarcinoma patient samples. Results: We found that YB-1 was significantly upregulated in gefitinib-resistant lung adenocarcinoma cells compared to gefitinib-sensitive cells. YB-1 augmented gefitinib resistance by activating the AKT pathway and promoting EMT. Decreased migration and invasion was observed upon MVP silencing in YB-1-overexpressing PC-9 cells, as well as restored gefitinib sensitivity. A retrospective analysis of 85 patients with lung adenocarcinoma revealed that YB-1 levels were significantly increased in tyrosine kinase inhibitor (TKI)-resistant patients compared to those in TKI-sensitive patients, indicating that YB-1 may serve as a biomarker to clinically predict acquired gefitinib resistance. Conclusion: YB-1 activates AKT signaling and promotes EMT at least in part by directly activating MVP. Hence, targeting the YB-1/MVP axis may help to overcome gefitinib resistance in lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

• Ochratoxin A(OTA) induces aerobic glycolysis of GES-1 cells. • OTA increases the glycolytic-associated enzymes (HK2, PFK1, LDHA) in GES-1 cells. • OTA promotes the phosphorylation and nuclear translocation of PKM2. • OTA reduces the TCA-cycle-associated enzymes (IDH1 and ODGH) in GES-1 cells. Ochratoxin A (OTA) is a ubiquitous mycotoxin with potential nephrotoxic, hepatotoxic and immunotoxic effects. We previously demonstrated that OTA could cause mitochondrial function disturbance in GES-1 cells in vitro , which lead to the presumption that the glucose metabolism of GES-1 cells will be altered by OTA. Therefore in the present study, we explored the toxicity of OTA on glucose metabolism of GES-1 cells and the molecular mechanism. We found that OTA could induce aerobic glycolysis, evidenced shown by increase of glucose consumption, lactate production and cellular ATP concentration. We further detected expressions of GLUT1 and glycolytic enzymes including HK2, PFK1, PKM2 and LDHA as well as tricarboxylic acid (TCA) cycle-associated enzymes including IDH1, OGDH and CS. The results showed that expression of GLUT1 as well as the activities and expressions of HK2, PFK1 and LDHA were significantly increased while IDH1 and OGDH were reduced by OTA. As to PKM2, western blot showed that OTA could elevated the phospho-PKM2 Ser37 protein level and induce the nuclear accumulation of PKM2, which was further supported by immunofluorescence analyses, in addition, pyruvate kinase activity was reduced by OTA. In conclusion, these findings suggest that OTA exposure induces the metabolic shift from oxidative phosphorylation to aerobic glycolysis via regulating the activities and expressions of glycolysis and TCA-cycle associated molecules in GES-1 cells. [ABSTRACT FROM AUTHOR]

Saline lakes represent a particularly interesting aquatic environment for harboring high microbial diversity. However, the microbial diversity in different states and locations of saline lake is often overlooked. We studied for the first time the diversity and relative composition of the microbial communities in the Chagan Lake, NE China, and investigated the differences in microbial species and physical and chemical factors in different geographical localities of the lake. After extracting the total DNA of the sample, we tested the library with the established library, sequenced the qualified library with Illumina HiSeq 2500, and studied the bacterial diversity by 16S rRNA targeted metagenomics analysis. Results reveal that the highest microbial abundance in Chagan Lake at genus level was Proteobacterium followed by Actinomycetes and Bacteroides. In addition, we compared the microbial composition within the lake using alpha- and beta-diversity indices, showing that both diversity and evenness were the highest in the middle of the lake and lowest in the west of lake areas, and in the upper, middle, and lower depth of water columns, the low water column had the highest species number in the whole water environment, but the difference was not significant. We believe that physicochemical factors contribute to the formation of microbial community composition and diversity. In aquaculture industry, it is impossible apply horticulture for making full use of the spatial differences in the microbial composition of the water. Therefore, combining cultured aquatic animal with the most suitable microbial species is a good way to boost the breeding effect for greater economic value. [ABSTRACT FROM AUTHOR]

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant inherited condition affecting multiple endocrine organs, resulting in significant morbidity and decreased life expectancy. Early tumor identification allows for timely patient management, reduces morbidity, and improves disease outcomes. Patients with MEN1 typically present with primary hyperparathyroidism caused by multiple parathyroid tumors, however, thymic and bronchial carcinoid tumors are also less common manifestations. MEN1-related neuroendocrine tumors often show hematogenous metastasis, with the liver being the most common metastatic site. Skeletal metastases from neuroendocrine tumors are extremely rare. As few as 50 case reports were identified in a recently published literature review on skeletal metastases from carcinoid tumors. To our knowledge, studies related to MEN1 have not been previously conducted.Case Presentation: We present a case of MEN1-related atypical ovarian carcinoid presenting as the first disease manifestation in a 30-year old woman. After two years, another atypical carcinoid was incidentally diagnosed in the contralateral ovary during a caesarean section. Syndromic MEN1 was not diagnosed clinically despite her young age and bilateral involvement. The patient remained disease-free for two years without further adjuvant treatment prior to clinic presentation with complaints of chest discomfort and body pain. Radiologic and pathologic investigations identified multifocal simultaneous neuroendocrine tumors involving the parathyroid, thymus, pancreas, and adrenal glands, in addition to multiple other metastatic sites. The findings ultimately resulted in the patient being diagnosed with MEN1.Conclusions: This extremely rare case emphasizes that ovarian carcinoids, especially when bilateral, could be the initial manifestation of MEN1. The significance of this differential diagnosis was highlighted by the subsequent detection of widespread skeletal metastasis resulting from the carcinoid tumors. A low threshold of suspicion, systemic diagnostic work-up, and regular follow-up are of utmost importance to timely diagnosis of MEN1. [ABSTRACT FROM AUTHOR]

Sterigmatocystin (ST), being a precursor of aflatoxin, is categorized as Group 2B carcinogen. Our previous studies found that both mismatch repair (MMR) pathways and p53 signaling pathway were involved in ST-induced G 2 cell cycle arrest in human esophageal squamous epithelial cell line, HET-1A, in vitro . Studies showed that ERK, JNK and p38 signaling pathways played important roles in cell cycle arrest induced by several other carcinogens. However, the role of MAPK pathway and the links between the MMR and p53 signaling pathways in ST induced G 2 phase arrest is still not clarified. In the present study, we first explored the role of MAPK pathway upon ST induced G 2 arrest, and found that ST up-regulated the expression of G 2 /M regulatory factors through MAPK signaling pathway (both ERK and p38, but not JNK pathway). The inhibition of ERK and p38 significantly inhibited p53 activation by ST. Blockage of MMR pathway by silencing hMLH1 expression inhibited ERK, p38 and p53 activation and then attenuated G 2 arrest by ST. Thus, in conclusion, the current study demonstrated that in response to ST induced DNA damage, hMLH1 was first activated, then triggered ERK, p38 and p53 activation and finally resulted in G 2 arrest in HET-1A cells. [ABSTRACT FROM AUTHOR]

Bacillus can not only improve the ecological environment of aquaculture water, but also improve the immunity of aquaculture animals, inhibit the reproduction of pathogenic microorganisms and reduce the incidence of disease. The present study represented the effect of different combinations of Bacillus on immunity and antioxidant activities in common carp. A total of 240 fish were randomly divided into four groups: control group (basal diet), experimental group I (add B. subtilis), experimental group II (add B. subtilis and B. licheniformis), and experimental group III ( B. subtilis, B. licheniformis, and B. cereus). Compared with the control group, the carp in experimental group II displayed a significantly elevated phagocytic percentage (up to a 20.2% increase; P < 0.05), phagocytic index (up to a 41.5% increase; P < 0.05), serum immunoglobulin M (up to a 26.1% increase; P < 0.05), serum lysozyme activity (up to a 21.9% increase; P < 0.05), intestinal mucosal secretory immunoglobulin A content (up to a 53.1% increase; P < 0.05), and peripheral blood lymphocyte proliferation ratio (up to a 32.8% increase; P < 0.05). Further analysis of liver antioxidants showed that, compared with the control group, carp in experimental group II displayed elevated superoxide dismutase (69.4%; P < 0.05), glutathione peroxidase (25.4%; P < 0.05), catalase (76.4%; P < 0.05), total antioxidant (41.1%; P < 0.05), maleic dialdehyde (28.9%; P < 0.05), and glutathione (35.6%; P < 0.05) activities. There was no significant difference between the experimental group I and the experimental group III ( P > 0.05). Our results indicated that dietary Bacillus enhanced the performance of the common carp immune response and that a mixture of strains elevated the antioxidant ability. [ABSTRACT FROM AUTHOR]

[Display omitted] • Porous hollow carbon spheres (HCSs) with adjustable size and pore width distribution were synthesized. • The clearance rate of HCSs to interleukin 6 (IL-6) in PBS buffer solution was up to 99.8%. • HCSs had a high adsorption rate and removal efficiency for PTH, β 2 -MG, IL-6 and TNF-α in the serum of uremic patients. • The selective adsorption of middle-macromolecular toxins or cytokines was achieved by regulating the pore structure of HCSs. Abnormally elevated middle-macromolecular toxins such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF- α) in human blood are fatal precipitating factors for patients suffered from immune-related diseases, especially for uremia and COVID-19 critical patients, while the effective clearance of them has always been problematic in clinic. In this work, porous hollow carbon spheres (HCSs) with different size and pore structure has been successfully prepared. The removal efficiency for IL-6 in PBS solution is about 99.8 %, even in the serum of uremic patients, HCSs could remove 94.75 % and 98.33 % of parathyroid hormone (PTH) and β 2 -microglobulin (β 2 -MG) efficiently within 5–10 min, and particularly, the adsorption of IL-6 and TNF- α is 17.6 and 11.4 times higher over that of the existing commercial hemoperfusion adsorbents. The adsorption balance can be achieved in 60 min, which would greatly shorten the current clinical treatment duration. Moreover, HCSs with different pore structure exhibit distinct adsorption selectivity for IL-6 and TNF- α, which is of special significance for modifying the middle-macromolecular cytokine level in the complicated human blood environment. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a mycotoxin produced by Aspergillus and Penicillium species that greatly threatens human health. We previously showed that OTA induced cycle arrest, apoptosis and autophagy in human gastric epithelium cells (GES-1). However, the mechanism underlying these effects is still unclear. Here, we showed that OTA exposure increased the expression of endoplasmic reticulum (ER) stress indicators (GRP78, PERK, ATF6, eIF2α, and CHOP), suggesting the activation of the unfolded protein response pathway. 4-phenylbutyric acid (4-PBA), an ER stress-specific inhibitor, attenuated OTA-induced loss of cell viability and apoptosis in GES-1 cells. It also attenuated the G2 phase arrest and autophagy induced by OTA, as evidenced by upregulated G2 phase-related proteins (Cdc2, Cdc25C, and cyclinB1) and downregulated autophagy markers (LC3B and Beclin-1). Moreover, OTA was found to increase ROS generation, and the inhibition of ROS formation by N-acetylcysteine (NAC), an ROS inhibitor, attenuated OTA-induced ER stress and subsequent apoptosis, cell cycle arrest, and autophagy. Collectively, these results suggest that the ROS-mediated ER stress pathway contributes to the OTA toxin-induced cytotoxicity in GES-1 cells. This study offers new insights into the molecular mechanisms underlying OTA toxicity in gastric cells. • Ochratoxin A(OTA) induces ER stress of gastric epithelium cells. • OTA induces apoptosis of GES-1 cells through ER stress. • ER stress is involved in G2 phase arrest caused by OTA in GES-1 cells. • ER stress participate in OTA-induced autophagy in GES-1 cells. • ROS regulates the ER stress-mediated OTA-induced apoptosis, cell cycle arrest as well as autophagy in GES-1 cells. [ABSTRACT FROM AUTHOR]

• Transportation network framework based on OD-grid using real-life GPS data. • Resilience metrics given transportation resilience main factors. • Resilience-oriented recovery optimization algorithm based on GA. Transportation is the key to a city's prosperity, however, there is possibility that the development and expansion of city make the transportation system complicated, uncertain and vulnerable, especially when in the face of damage. Although resilience is a critical factor for understanding and managing the damage and recovery of the transportation system, study on model of transportation resilience, which is able to effectively utilize actual data and is based on real cases, is still not enough. Therefore, this paper proposes a resilience model and investigates the optimization of the recovery strategy according to this model. It constructs a modeling framework based on the OD-grid network and provides a brand-new performance metric for transportation network resilience analysis based on grid capacity. It also develops two resilience assessment models and compares their characters. Focusing on the recovery of transportation resilience process, it presents two recovery strategies considering recovery sequence and resource allocation respectively and uses the GA algorithm to optimize them and solve the problem. It then demonstrates the effectiveness of the proposed model and the recovery algorithm through the resilience analysis and recovery strategy optimization of a city's transportation network model, which is built according to the real GPS data. [ABSTRACT FROM AUTHOR]

Benzoxazine/epoxy copolymers were prepared by solution blending bis(4-(8-allyl-2 H-benzo[e][1,3]oxazin-3(4 H)-yl)phenyl)methane ( oAP-ddm) with bisphenol-A type novolac epoxy resin (bis-ANER), followed by thermally polymerization of the blend. The copolymerization behavior of oAP-ddm/bis-ANER was investigated by Fourier transform infrared spectroscopy and differential scanning calorimetry (DSC). With the increasing of bis-ANER fraction, the exothermic peak in DSC curve changes from one to two overlapped peaks, and the second peak shifts to higher temperatures. Dynamic mechanical analysis results show that a single peak appears in each tan δ curve of the oAP-ddm/bis-ANER copolymers. With the bis-ANER content increasing, the storage modulus and the peak temperature of tan δ peak increase, whereas the tan δ peak height decreases. Thermogravimetric analysis results indicate that the onset temperatures of mass loss and the char yields at 800 °C of the oAP-ddm/bis-ANER copolymers decrease with the increase of bis-ANER content. [ABSTRACT FROM AUTHOR]

In this study, a total of 420 healthy crucian carp (9.77 ± 0.04 g) were randomly divided into CK, B·S , XOS and B·S + XOS group, and cultured for 8 weeks. Results showed that the dietary Bacillus subtilis (B. subtilis) and xylo-oligosaccharides (XOS) can significantly increased the final weight, weight gain, specific growth rate, feed efficiency, protein efficiency and survival rate of crucian carp. Dietary B. subtilis and XOS can significantly increased the activities of catalase, glutathione, superoxide dismutase and total antioxidant capacity, significantly decreased the contents of malondialdehyde, and significantly increased the activities of alkaline phosphatase, acid phosphatase, lysozyme and the contents of complement component 3,4 and immunoglobulin M in crucian carp serum. In addition, compared with CK group, the expression levels of TGF-β and IL-10 in B·S , XOS and B·S + XOS group were significantly increased, and the expression levels of TNF-α, HSP90, IL-1β, TLR4 and MyD88 were significantly decreased. Supplementation of B. subtilis and XOS can also improve the intestinal tissue morphology of crucian carp. After injection of 1 × 107 CFU/mL Aeromonas hydrophila (A. hydrophila), compared with CK group, the survival rates of the B·S group, the XOS group and the B·S + XOS group were increased by 13.98%, 10.56% and 30.74%, respectively. These results show that dietary B. subtilis and XOS can significantly improve the growth performance, antioxidant capacity, immunity and resistance to A. hydrophila of crucian carp, and the combined effect is better than that of single addition. The graphical abstract of CBC 109296 (Title: Boosted growth performance, immunity, antioxidant capacity and disease resistance of crucian carp (Carassius auratus) by single or in combination dietary Bacillus subtilis and xylo-oligosaccharides). [Display omitted] • Dietary B. subtilis and XOS can improve the growth performance, immunity and antioxidant capacity of crucian carp. • Supplementation of B. subtilis and XOS in feed can significantly improve the intestinal tissue morphology of crucian carp. • Dietary B. subtilis and XOS can significantly improve the resistance of crucian carp to Aeromonas hydrophila infection. [ABSTRACT FROM AUTHOR]

This experiment was conducted to evaluate the immunomodulatory effect and antiviral activity of Astragalus polysaccharides (APS) in crucian carp and epithelioma papulosum cyprinid (EPC) cells. Two diets containing 0 and 2 g/kg, APS were fed crucian carp for 56 days. The results showed that supplementation with APS significantly upregulated the immune-related indices including the levels of IgM, the activities of LZM, AKP and ACP, and the contents of C3 and C4. At the same time, compared with the CK group, adding APS to the feed significantly upregulated the expression of IL-8, IL-10, IL-1β, IFN-α, IFN-γ, MyD88, TGF-β and TNF-α in the spleen, kidney, liver and intestine of crucian carp. In addition, when the crucian carp were injected with SVCV, the survival rates of fish in the APS group and the control group were 48.87% and 13.76%, respectively. These results indicated that dietary APS could improve the resistance of crucian carp against SVCV infection. APS also significantly decreased viral titer and inhibited apoptosis induced by SVCV in EPC cells. These results indicated that APS could stimulate the immune response of crucian carp and improve the abilities of crucian carp and EPC cells to resist SVCV infection. • Supplementing Astragalus polysaccharides can significantly up-regulate immune parameters and enhance the immune response of crucian carp. • Dietary Astragalus polysaccharides could improve the resistance of crucian carp against SVCV infection. • Astragalus polysaccharides could significantly decrease viral titer and inhibited apoptosis induced by SVCV in EPC cells. [ABSTRACT FROM AUTHOR]

Lead is an environmental toxicant that has toxicity effect to the health of aquatic organisms. Gut microbiota has been reported to be closely related to human health. The aim of this study was to investigate the effects of lead exposure on the composition of gut microbiota. The composition of gut microbiota alteration was detected by 16S rRNA gene sequencing, following a 42-day exposure of lead (1 mg/L). The results showed that compared with the normal control group, the carp of lead group showed severe intestinal tissues injury and decreased Zona Occludens 1 (ZO-1) and occludin expression. The production of LPS in serum was increased by the treatment of lead exposure. Our results showed gut bacterial diversity in lead-treated common carp was lower than the control group. At the phylum level, the abundance of Bacteroidetes (LPS producing bacteria) and Fusobacteria in lead-treated carp were much higher than the control carp. And the abundance of Actinobacteria decreased by lead exposure. At the genus level, we found the abundance of Bacteroides (LPS producing bacteria) and Plesiomonas (an important pathogenic bacteria), increased significantly by lead exposure. And the abundance of Akkermansia , a critical probiotics, was markedly inhibited by lead exposure. In conclusion, this study indicated exposure of carp to lead causes gut microbiota alterations and intestinal structural integrity destruction. Unlabelled Image • The carp of lead group showed severe intestinal tissues injury and decreased ZO-1 and occludin expression. • Gut bacterial diversity in lead-treated common carp was lower than the control group. • At the phylum level, the abundance of Bacteroidetes and Fusobacteria increased significantly by lead exposure. • At the genus level, the abundance of Bacteroides and Plesiomonas increased significantly by lead exposure. • And the abundance of Akkermansia was markedly inhibited by lead exposure. [ABSTRACT FROM AUTHOR]

Mercury (Hg) poisoning in humans and fish represents a significant global problem. Hg is one of the most dangerous threats to the aquatic ecosystem due to its high toxicity. Mercury has a high oxidative stress-inducing potential, and can compounds exert toxic effects by interacting with many important enzymes involved in the regulation of antioxidants. Selenium (Se) supplementation can reactivate the mercury-inhibited enzymes viability. The probiotic Bacillus subtilis is widely used in aquaculture, and it has a certain adsorption effect on heavy metals. The interactions between Hg and Se have been rigorously investigated, particularly due to the observed protective effects of Se against Hg toxicity. The objective of this study was to evaluate whether Se-rich B. subtilis ameliorated Hg-induced toxicity in C. carpio var. specularis. Fish were exposed to waterborne Hg (0.03 mg/L) and fed a diet supplemented with 105 cfu/g Se-rich B. subtilis for 30 days. Fish were sampled, antioxidant activity, and Intestinal damage repair were assessed. Our results indicated that Se-rich B. subtilis protected the Intestinal from Hg-induced morphological changes. Hg treatment significantly decreased the activity levels of SOD, CAT and GSH-PX while increasing the activity levels of MDA, GST, and GSH. Hg treatment also upregulated the mRNA expression of Nrf2 , CAT , GSH-PX and HO-1 , and reduced expression of keap1. Se-rich B. subtilis had a significant protective effect against Hg-induced oxidative stress. Unlabelled Image • Dietary selenium-rich Bacillus subtilis significantly alleviates mercury induced oxidative stress. • Selenium-rich Bacillus subtilis protected the intestinal from the histological damage induced by Hg exposure. [ABSTRACT FROM AUTHOR]

Ginseng exhibits multiple medicinal properties, including the improvement of immune function and enhancing disease resistance. In this study, we investigated the inhibitory effects of ginsenoside Rg3 on grass carp reovirus (GCRV) infection of grass carp ovarian (CO) epithelial cells, in order to provide a baseline framework for future high-efficacy antiviral drug screening investigations. Ginsenoside Rg3 was added to GCRV-infected CO cells, and cells were cultured at 27 °C before cell proliferation was measured by MTT assays. Label-free real-time cellular analysis (RTCA) after 72 h of experimentation demonstrated that 100 μg/mL ginsenoside Rg3 treatment had the highest inhibitory effect on GCRV (among 1,10,100 μg/mL treatments). We then measured the capacity for cellular antioxidant ability. Cells treated with 1,10,100 μg/mL ginsenoside Rg3 exhibited increases in Total Antioxidant Capacity activity relative to controls, respectively. Furthermore, Antioxidant assay and reverse transcript quantitative polymerase chain reaction (RT-qPCR) showed that ginsenoside Rg3 were efficient to restrain the replication of GCRV in CO cells. Expression analysis of immune-related genes via RT-qPCR showed that treatment with ginsenoside Rg3 promoted expression of IRF-3 and IRF-7 increases, respectively. Moreover, expression of IFN-1 was induced, which then inhibition the expression of tumor necrosis factor-alpha (TNF-α). In conclusion, we demonstrated that ginsenoside Rg3 promotes CO cell proliferation, inhibits GCRV activity, promotes CO cell immune activities, and thereby enhances the resistance of CO to GCRV infection. • GCRV infection lead to high morbidity and mortality in fish. • Ginsenosides Rg3 were first used to study the effects on GCRV -infected CO cells. • Ginsenosides Rg3 increase the Total Antioxidant Capacity activity of GCRV -infected CO cells. • Ginsenoside Rg3 promoted expression of IRF-3 , IRF-7 and IFN-1. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, the coexistence of PTC and medullary thyroid carcinoma (MTC) is uncommon. While the simultaneous occurrence of both cancers with small lymphocytic lymphoma (SLL) in lymph nodes with PTC metastasis is very rare. This study presents a unique case of concurrent PTC, MTC, and SLL, highlighting the exceptional rarity of these coexisting tumors., Methods: A 75-year-old female with a thyroid tumor underwent total thyroidectomy, bilateral central neck lymph node dissection, and right radical neck lymph node dissection. Histopathological examination revealed a low-grade medullary thyroid carcinoma (MTC) in the left lobe and classical papillary thyroid carcinoma (PTC) in the right lobe, with PTC metastasis in the cervical lymph nodes and concurrent SLL in the affected lymph nodes., Results: Coexistence of PTC, MTC and SLL in the same patient is rare, there are currently no standardized treatment guidelines due to the limited literature. However, it is essential to consider not only the treatment for each type of tumor but also the potential risks or conflicts associated with the treatments. In the case reported in this paper, the papillary carcinoma invaded the capsule of the right lobe of the thyroid and metastasized to the cervical lymph nodes, warranting radioactive iodine therapy. However, considering the potential negative impact of radioactive iodine on the pre-existing lymphoma, the radioactive iodine therapy was postponed. Meanwhile, constant monitoring of calcitonin and thyroid globulin should be performed to monitor tumor recurrence as was performed in the present case., Conclusion: Since MTC, PTC, and SLL may coexist, patients with PTC deserve careful surveillance for the other disease entities. This case underscores the need for heightened awareness among clinicians, radiologists, and pathologists regarding the possibility of concurrent thyroid tumors and abnormal lymph nodes, guiding comprehensive pre-operative evaluations and postoperative monitoring strategies. This study aims to provide a warning for routine pathological diagnosis and contribute data for related research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Glioblastoma (GBM) is the most common malignant diffuse glioma of the brain. Although immunotherapy with immune checkpoint inhibitors (ICIs), such as programmed cell death protein (PD)-1/PD ligand-1 inhibitors, has revolutionized the treatment of several cancers, the clinical benefit in GBM patients has been limited. Lymphocyte-activation gene 3 (LAG-3) binding to human leukocyte antigen-II (HLA-II) plays an essential role in triggering CD4 + T cell exhaustion and could interfere with the efficiency of anti-PD-1 treatment; however, the value of LAG-3-HLA-II interactions in ICI immunotherapy for GBM patients has not yet been analyzed. Therefore, we aimed to investigate the expression and regulation of HLA-II in human GBM samples and the correlation with LAG-3 + CD4 + T cell infiltration. Human leukocyte antigen-II was highly expressed in GBM and correlated with increased LAG-3 + CD4 + T cell infiltration in the stroma. Additionally, HLA-II High LAG-3 High was associated with worse patient survival. Increased interleukin-10 (IL-10) expression was observed in GBM, which was correlated with high levels of HLA-II and LAG-3 + T cell infiltration in stroma. HLA-II High IL-10 High GBM associated with LAG-3 + T cells infiltration synergistically showed shorter overall survival in patients. Combined anti-LAG-3 and anti-IL-10 treatment inhibited tumor growth in a mouse brain GL261 tumor model. In vitro, CD68 + macrophages upregulated HLA-II expression in GBM cells through tumor necrosis factor-α (TNF-α). Blocking TNF-α-dependent inflammation inhibited tumor growth in a mouse GBM model. In summary, T cell-tumor cell interactions, such as LAG-3-HLA-II, could confer an immunosuppressive environment in human GBM, leading to poor prognosis in patients. Therefore, targeting the LAG-3-HLA-II interaction could be beneficial in ICI immunotherapy to improve the clinical outcome of GBM patients., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Sarcoidosis is a multisystem granulomatous disease of an unknown aetiology. It can exist in many organs. Pulmonary and intrathoracic lymph nodes are most commonly involved. Lung sarcoidosis is uncommon in Asia. However, due to the large population of our country and the development of bronchoscopy, percutaneous lung puncture, and other medical technologies, the number of pulmonary sarcoidosis patients is on the rise. Pulmonary sarcoidosis patients have no obvious symptoms in the early stage, and the clinical manifestations in the later stage may vary from person to person. Eventually, the disease progresses to life-threatening pulmonary fibrosis. Therefore, patients with pulmonary sarcoidosis should receive a timely diagnosis. In recent years, the imaging features and serologic biomarkers of pulmonary sarcoidosis have been continuously studied. The diagnostic value of imaging and serologic biomarkers for pulmonary sarcoidosis is summarized below.

AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. Activation of AMPK enhances the expression of proliferator-activated receptor γ coactivator 1α (PGC1-α) and subsequently activates mitochondrial transcription factor A (TFAM) to regulate mitochondrial oxidative respiratory function. The possible functions of AMPK, p-AMPK, PGC-1α, and TFAM and their interactions in astrocytomas are not known. Here, the levels, clinicopathological characteristics, and prognostic potential of AMPK, p-AMPK, PGC-1α, and TFAM expression levels in astrocytomas were evaluated. The results showed that levels of AMPK, p-AMPK, PGC-1α, and TFAM expression was increased in astrocytomas. Strong correlations were observed between AMPK, p-AMPK, PGC-1α, and TFAM expression in patients with astrocytomas. The analysis indicated that the levels of AMPK, p-AMPK, PGC-1α, and TFAM were associated with the survival. AMPK levels, tumor grade, and age were independent prognostic factors predicting poor outcomes in patients with astrocytoma. Together, these results indicate that these 4 targets may play a crucial role in the progression and prognosis of human astrocytomas and that AMPK may represent a potential therapeutic target., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Cardiac valve calcification is closely related to cardiovascular disease. The aim of this study was to investigate the magnesium level and cardiac valve calcification in hemodialysis patients., Methods: A cross-sectional study was conducted in 105 maintenance hemodialysis patients with complete follow-up data from June 2020 to May 2021 in Beijing Tsinghua Changgung Hospital, Tsinghua University. Baseline data, including sex, age, primary disease, liver and kidney function, electrolytes and parathyroid hormone, were recorded. According to their echocardiograms, patients were divided into a cardiac valve calcification group and a noncardiac valve calcification group, and the correlations between valve calcification and clinical data were analyzed., Results: Of 105 patients under hemodialysis, 60 (56.6%) were male, with an average age of 62.1 ± 13.5 years and a mean dialysis duration of 58.8 ± 45.4 months. The majority of primary renal diseases were diabetic nephropathy (55, 51.9%). Approximately 64.8% of the 105 maintenance hemodialysis patients had cardiac valve calcification, and 35.2% were in the noncardiac valve calcification group. The independent t test and the chi-square test analysis showed that the cardiac valve calcification group had older age, higher smoking rate, diabetes mellitus, lower extremity arterial occlusion, coronary heart disease, and coronary artery calcification ratio but lower parathyroid hormone, serum calcium, serum magnesium, albumin, prealbumin, and high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis showed that age, diabetes mellitus, coronary artery calcification, lower serum magnesium, lower serum calcium, and lower parathyroid hormone levels were associated with valve calcification., Conclusion: The presence of cardiac valve calcification was associated with age, calcium, phosphorus and lower magnesium level. These factors we should pay more attention in clinical practice., (© 2023. The Author(s).)

Cyclophilin D (CypD) is a mitochondrial matrix peptidyl prolidase that regulates the mitochondrial permeability transition pore. Inhibition of CypD was suggested as a therapeutic strategy for acute pancreatitis. Peptide inhibitors emerged as novel binding ligand for blocking receptor activity. In this study, we present our computational approach for designing peptide inhibitors of CypD. The 3-D structure of random peptides were built, and docked into the active center of CypD using Rosetta script integrated FlexPepDock module. The peptide displayed the lowest binding energy against CypD was further selected for virtual iterative mutation based on virtual mutagenesis and molecular docking. Finally, the top 5 peptides with the lowest binding energy was selected for validating their affinity against CypD using inhibitory assay. We showed 4 out of the selected 5 peptides were capable for blocking the activity of CypD, while WACLQ display the strongest affinity against CypD, which reached 0.28 mM. The binding mechanism between WACLQ and CypD was characterized using molecular dynamics simulation. Here, we proved our approach can be a robust method for screening peptide inhibitors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The present study evaluated the presentations and outcomes of coronavirus disease 2019 (COVID-19) among patients undergoing maintenance hemodialysis (MHD) and the impact of the Omicron BF.7 variant. Adult patients (age ≥ 18 years), who underwent MHD (dialysis vintage ≥ 3 months) at the Hemodialysis Center at Beijing Tsinghua Changgung Hospital between December 2022 and January 2023, were included based on predefined eligibility criteria. Clinical and laboratory characteristics were retrospectively collected. Among 131 patients who underwent MHD (10.7% vaccination rate), 106 (80.9%) tested positive for COVID-19. The prevalence of asymptomatic, mild, moderate, and severe COVID-19 was 8.5%, 58.5%, 17%, and 16%, respectively. Among the 97 patients with symptoms, 23 (23.7%) were hospitalized and six (5.7%) died. Fever was experienced by 74.2% of patients and respiratory symptoms were the most common (81.4%). Residual symptoms persisted in 20.9% of patients one month after the onset of COVID-19. COVID-19-positive hemodialysis patients were more likely to experience weight loss and exhibit reduced albumin levels compared to those without COVID-19 ( p  < .05). Compared with the asymptomatic group, patients with symptoms were younger, and exhibited higher interleukin-6 levels and lower post-infection phosphate levels ( p  < .05). Age, dialysis vintage, comorbidities, and inflammatory factors were positively associated with disease severity, while baseline albumin and hemoglobulin levels were associated with death ( p  < .05). In conclusion, COVID-19 was prevalent among patients undergoing MHD, even during the Omicron variant epidemic. Age, nutritional status, comorbidities, and inflammatory factors were associated with disease severity and prognosis.

Introduction: It is a rare case of continuous ambulatory peritoneal dialysis-related peritonitis associated with Acremonium spp infection., Case Presentation: Symptoms of Acremonium infection peritonitis are hidden and atypical, leucocytes in ascites are moderately elevated, and general bacterial culture difficulty obtains positive results. In this report, a patient with peritoneal dialysis-related peritonitis caused by Acremonium species was successfully treated without catheter removal in our hospital. The organism species was cultured from a catheter and PD effluent fluid. The patient's peritonitis did not relapse within 6 months., Conclusions: Once a patient on peritoneal dialysis was infected with fungal peritonitis, the outcome was usually to remove the tube and stop peritoneal dialysis. In this case, our experience is that using a catheter-salvage therapy method, we can successfully cure PD-related peritonitis associated with Acremonium sp., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Zhen Zhuang, Yuehong Li, Xianglan Wu, Wei Wang, Mingxia Cao, Nan Xiao.)

High environment ammonia (HEA) poses a deadly threat to aquatic animals and indirectly impacts human healthy life, while nutritional regulation can alleviate chronic ammonia toxicity. α-lipoic acid exhibits antioxidative effects in both aqueous and lipid environments, mitigating cellular and tissue damage caused by oxidative stress by aiding in the neutralization of free radicals (reactive oxygen species). Hence, investigating its potential as an effective antioxidant and its protective mechanisms against chronic ammonia stress in crucian carp is highly valuable. Experimental fish (initial weight 20.47 ± 1.68 g) were fed diets supplemented with or without 0.1% α-lipoic acid followed by a chronic ammonia exposure (10 mg/L) for 42 days. The results revealed that chronic ammonia stress affected growth (weight gain rate, specific growth rate, and feed conversion rate), leading to oxidative stress (decreased the activities of antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase; decreased total antioxidant capacity), increased lipid peroxidation (accumulation of malondialdehyde), immune suppression (decreased contents of nonspecific immune enzymes AKP and ACP, 50% hemolytic complement, and decrease of immunoglobulin M), impaired ammonia metabolism (reduced contents of Glu, GS, GSH, and Gln), imbalance of expression of induced antioxidant-related genes (downregulation of Cu/Zu SOD, CAT, Nrf2, and HO-1; upregulation of GST and Keap1), induction of pro-apoptotic molecules (transcription of BAX, Caspase3, and Caspase9), downregulation of anti-apoptotic gene Bcl-2 expression, and induction of endoplasmic reticulum stress (upregulation of IRE1, PERK, and ATF6 expression). The results suggested that the supplementation of α-lipoic acid could effectively induce humoral immunity, alleviate oxidative stress injury and endoplasmic reticulum stress, and ultimately alleviate liver injury induced by ammonia poisoning (50-60% reduction). This provides theoretical basis for revealing the toxicity of long-term ammonia stress and provides new insights into the anti-ammonia toxicity mechanism of α-lipoic acid., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

As a new type of pollutant, microplastics have attracted much attention. As the third largest freshwater lake in China, Taihu Lake is characterized by severe eutrophication caused by external pollution and frequent occurrence of cyanobacterial blooms. Although there have been previous investigations into the spatial distribution of microplastics in Taihu Lake, research on the relationships among microplastics, pollutants, and cyanobacterial blooms, as well as the spatiotemporal distribution and changing characteristics of microplastics, is deficient. This study investigated the characteristics of microplastics, pollutants, and cyanobacterial blooms in the surface water and sediments of Taihu Lake. The abundances of microplastics were 0-3.7 items/L in the surface water and 44.42-417.56 items/kg (dry weight) in the sediments. Microplastics are most abundant in the western, southern, and northern lake areas. The northern and western lake areas are severely polluted, and cyanobacterial blooms are prone to occur in these areas. This study found that microplastics exist in the surface water of the southeastern lake area, which is a source of drinking water, and the microplastics may thus have adverse effects on drinking water quality. As the main organisms in the cyanobacterial blooms, Microcystis and microplastics have similar spatial distributions in Taihu Lake and are both affected by wind. Based on a combination of the investigations of this paper with the existing research on the microplastics in Taihu Lake, the spatiotemporal distribution of microplastics was obtained: the abundance of microplastics in surface water has continuously decreased, there are no obvious spatial distribution differences, and the spatial distribution of microplastics in the sediments is the same as that in the surface water., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Targeted immunotherapies have emerged as a transformative approach in cancer treatment, offering enhanced specificity to tumor cells, and minimizing damage to healthy tissues. The targeted treatment of the tumor immune system has become clinically applicable, demonstrating significant anti-tumor activity in both early and late-stage malignancies, subsequently enhancing long-term survival rates. The most frequent and significant targeted therapies for the tumor immune system are executed through the utilization of checkpoint inhibitor antibodies and chimeric antigen receptor T cell treatment. However, when using immunotherapeutic drugs or combined treatments for solid tumors like osteosarcoma, challenges arise due to limited efficacy or the induction of severe cytotoxicity. Utilizing nanoparticle drug delivery systems to target tumor-associated macrophages and bone marrow-derived suppressor cells is a promising and attractive immunotherapeutic approach. This is because these bone marrow cells often exert immunosuppressive effects in the tumor microenvironment, promoting tumor progression, metastasis, and the development of drug resistance. Moreover, given the propensity of myeloid cells to engulf nanoparticles and microparticles, they are logical therapeutic targets. Therefore, we have discussed the mechanisms of nanomedicine-based enhancement of immune therapy through targeting myeloid cells in osteosarcoma, and how the related therapeutic strategies well adapt to immunotherapy from perspectives such as promoting immunogenic cell death with nanoparticles, regulating the proportion of various cellular subgroups in tumor-associated macrophages, interaction with myeloid cell receptor ligands, activating immunostimulatory signaling pathways, altering myeloid cell epigenetics, and modulating the intensity of immunostimulation. We also explored the clinical implementations of immunotherapy grounded on nanomedicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Fan, Xia, Wang, Li, Feng and Fu.)

Macrophages are a heterogeneous cell type with high plasticity, exhibiting unique activation characteristics that modulate the progression and resolution of diseases, serving as a key mediator in maintaining tissue homeostasis. Macrophages display a variety of activation states in response to stimuli in the local environment, with their subpopulations and biological functions being dependent on the local microenvironment. Resident tissue macrophages exhibit distinct transcriptional profiles and functions, all of which are essential for maintaining internal homeostasis. Dysfunctional macrophage subpopulations, or an imbalance in the M1/M2 subpopulation ratio, contribute to the pathogenesis of diseases. In skeletal muscle disorders, immune and inflammatory damage, as well as fibrosis induced by macrophages, are prominent pathological features. Therefore, targeting macrophages is of great significance for maintaining tissue homeostasis and treating skeletal muscle disorders. In this review, we discuss the receptor-ligand interactions regulating macrophages and identify potential targets for inhibiting collateral damage and fibrosis in skeletal muscle disorders. Furthermore, we explore strategies for modulating macrophages to maintain tissue homeostasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhu, Fan, Xia, Wang, Li, Feng and Fu.)

Background: Short-term and long-term blood pressure variability (BPV) in hemodialysis (HD) population are risk factors of cardiovascular diseases (CVD) and all-cause mortality. There is no full consensus on the best BPV metric. We compared the prognostic role of intra-dialytic and visit-to-visit BPV metrics for CVD morbidity and all-cause mortality in HD patients., Methods: A retrospective cohort of 120 patients on HD was followed up for 44 months. Systolic blood pressure (SBP) and baseline characteristics were collected for 3 months. We calculated intra-dialytic and visit-to-visit BPV metrics, including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV) and residual. The primary outcomes were CVD events and all-cause mortality., Results: In Cox regression analysis, both intra-dialytic and visit-to-visit BPV metrics were associated with increased CVD events (intra-dialytic CV: HR 1.70, 95% CI 1.28-2.27, p < 0.01; visit-to-visit CV: HR 1.55, 95% CI 1.12-2.16, p < 0.01), but not associated with increased all-cause mortality (intra-dialytic CV: HR 1.32, 95% CI 0.99-1.76, p = 0.06; visit-to-visit CV: HR 1.22, 95% CI 0.91-1.63, p = 0.18). Overall, intra-dialytic BPV showed greater prognostic ability than visit-to-visit BPV for both CVD event (AUC of intra-dialytic BPV and visit-to-visit BPV metrics respectively: SD 0.686, 0.606; CV 0.672, 0.425; VIM 0.677, 0.581; ARV 0.684, 0.618; residual 0.652, 0.586) and all-cause mortality (SD 0.671, 0.608; CV 0.662, 0.575; VIM 0.669, 0.581; ARV 0.529, 0.588; residual 0.651, 0.602)., Conclusion: Compared to visit-to-visit BPV, intra-dialytic BPV is a greater predictor of CVD event in HD patients. No obvious priority was found among various BPV metrics., (© 2023. The Author(s).)

With the aging of the population and changes in lifestyle, the incidence of spine-related diseases is increasing, which has become a major global public health problem; this results in a huge economic burden on the family and society. Spinal diseases and complications can lead to loss of motor, sensory, and autonomic functions. Therefore, it is necessary to identify effective treatment strategies. Currently, the treatment of spine-related diseases includes conservative, surgical, and minimally invasive interventional therapies. However, these treatment methods have several drawbacks such as drug tolerance and dependence, adjacent spondylosis, secondary surgery, infection, nerve injury, dural rupture, nonunion, and pseudoarthrosis. Further, it is more challenging to promote the regeneration of the interstitial disc and restore its biomechanical properties. Therefore, clinicians urgently need to identify methods that can limit disease progression or cure diseases at the etiological level. Platelet-rich plasma (PRP), a platelet-rich form of plasma extracted from venous blood, is a blood-derived product. Alpha granules contain a large number of cytokines, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor, platelet factor 4 (PF-4), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β). These growth factors allow stem cell proliferation and angiogenesis, promote bone regeneration, improve the local microenvironment, and enhance tissue regeneration capacity and functional recovery. This review describes the application of PRP in the treatment of spine-related diseases and discusses the clinical application of PRP in spinal surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zhu, Xia, Li and Fu.)

Spinal cord injury (SCI) has considerable impact on patient physical, mental, and financial health. Secondary SCI is associated with inflammation, vascular destruction, and subsequent permanent damage to the nervous system. Mesenchymal stem cells (MSCs) have anti-inflammatory properties, promoting vascular regeneration and the release neuro-nutrients, and are a promising strategy for the treatment of SCI. Preclinical studies have shown that MSCs promote sensory and motor function recovery in rats. In clinical trials, MSCs have been reported to improve the American Spinal Injury Association (ASIA) sensory and motor scores. However, the effectiveness of MSCs in treating patients with SCI remains controversial. MSCs promote tumorigenesis and ensuring the survival of MSCs in the hostile environment of SCI is challenging. In this article we examine the evidence on the pathophysiological changes occurring after SCI. We then review the underlying mechanisms of MSCs in the treatment of SCI and summarize the potential application of MSCs in clinical practice. Finally, we highlight the challenges surrounding the use of MSCs in the treatment of SCI and discuss future applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, Zhu, Yang, Wang, Li and Fu.)

Mesenchymal stem cell (MSC) chondrogenesis in three-dimensional (3D) culture involves dynamic changes in cytoskeleton architecture during mesenchymal condensation before morphogenesis. However, the mechanism linking dynamic mechanical properties of matrix to cytoskeletal changes during chondrogenesis remains unclear. Here, we investigated how viscoelasticity, a time-dependent mechanical property of collagen hydrogel, coordinates MSC cytoskeleton changes at different stages of chondrogenesis. The viscoelasticity of collagen hydrogel was modulated by controlling the gelling process without chemical cross-linking. In slower-relaxing hydrogels, although a disordered cortical actin promoted early chondrogenic differentiation, persistent myosin hyperactivation resulted in Rho-associated kinase (ROCK)-dependent apoptosis. Meanwhile, faster-relaxing hydrogels promoted cell-matrix interactions and eventually facilitated long-term chondrogenesis with mitigated myosin hyperactivation and cell apoptosis, similar to the effect of ROCK inhibitors. The current work not only reveals how matrix viscoelasticity coordinates MSC chondrogenesis and survival in a ROCK-dependent manner but also highlights viscoelasticity as a design parameter for biomaterials for chondrogenic 3D culture.

Background: The aim of the study was to explore the changes and the possible influencing factors of phosphorus excretion in chronic kidney disease (CKD) patients., Methods: A database with 204 patients who met the CKD diagnostic criteria was established. Clinical data, including 24-hour urine phosphorus excretion (24-hour UPE), were collected. The demographic and clinical characteristics of CKD patients in different stages and the changes in serum phosphorus (P) and 24-hour UPE with renal function were studied. After exploring the factors influencing 24-hour UPE by multiple linear regression analysis, the effects of gender on 24-hour UPE was assessed., Results: Among 204 patients, there were significant differences in serum calcium (Ca), P, 24-hour UPE, intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D [25(OH)-VD] among different CKD stages. Twenty-four-hour UPE fluctuated greatly, but serum P was relatively stable, which was > 1.46 mmol/L at an estimated glomerular filtration rate (eGFR) < 10 mL/minute/1.73 m2. Male gender (β = 3.42, p < 0.00) and eGFR (β = 0.06, p < 0.00) were related to 24-hour UPE, while age, body weight, albumin (ALB), iPTH, and serum P were not related to 24-hour UPE according to regression analysis. There were significant differences in 24-hour UPE and serum P between males and females., Conclusions: Urinary phosphorus excretion decreased with decreasing renal function in CKD patients. Urinary phosphorus excretion might be affected by eGFR and gender.

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain. Although IVDD cannot directly cause death, it can cause pain, psychological burdens, and economic burdens to patients. Current conservative treatments for IVDD can relieve pain but cannot reverse the disease. Patients who cannot tolerate pain usually resort to a strategy of surgical resection of the degenerated disc. However, the surgical removal of IVDD can affect the stability of adjacent discs. Furthermore, the probability of the reherniation of the intervertebral disc (IVD) after surgery is as high as 21.2%. Strategies based on tissue engineering to deliver stem cells for the regeneration of nucleus purposes (NP) and annulus fibrosus (AF) have been extensively studied. The developed biomaterials not only locally withstand the pressure of the IVD but also lay the foundation for the survival of stem cells. However, the structure of IVDs does not provide sufficient nutrients for delivered stem cells. The role of immune mechanisms in IVDD has recently become clear. In IVDD, the IVD that was originally in immune privilege prevents the attack of immune cells (mainly effector T cells and macrophages) and aggravates the disease. Immune regulatory and inflammatory factors released by effector T cells, macrophages, and the IVD further aggravate IVDD. Reversing IVDD by regulating the inflammatory microenvironment is a potential approach for the treatment of the disease. However, the biological factors modulating the inflammatory microenvironment easily degrade in vivo . It makes it possible for different biomaterials to modulate the inflammatory microenvironment to repair IVDD. In this review, we have discussed the structures of IVDs and the immune mechanisms underlying IVDD. We have described the immune mechanisms elicited by different biological factors, including tumor necrosis factors, interleukins, transforming growth factors, hypoxia-inducible factors, and reactive oxygen species in IVDs. Finally, we have discussed the biomaterials used to modulate the inflammatory microenvironment to repair IVDD and their development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, Wang, Yang, Hou, Li, Zhu and Fu.)

Pleomorphic xanthoastrocytoma (PXA) is a rare tumor ranging from World Health Organization (WHO) grades 2-3 and can potentially recur and metastasize throughout the central nervous system (CNS). Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion is a frequent genomic alteration of PXA. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in PXA. Therefore, we performed CDKN2A fluorescence in situ hybridization and MTAP immunohistochemistry on specimens from 23 patients with CNS WHO grades 2 (n = 10) and 3 (n = 13) PXAs, including specimens from primary and recurrent tumors, and determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 30% (3/10) and 76.9% (10/13) of CNS WHO grades 2 and 3 PXAs, respectively. In addition, MTAP loss was inconsistent with CDKN2A homozygous deletion (sensitivity = 86.7%, specificity = 100%). Furthermore, CDKN2A homozygous deletion was correlated with WHO grade (p = 0.026) and the Ki-67 labeling index (p = 0.037). Therefore, MTAP immunostaining can be a suitable surrogate marker for CDKN2A homozygous deletions in PXAs, and CDKN2A homozygous deletions may be an important prognostic factor for PXAs., (© 2022. The Author(s), under exclusive licence to The Japan Society of Brain Tumor Pathology.)

Objective: To investigate the effects of glucose-free and glucose-containing dialysates during dialysis in maintenance hemodialysis (MHD) patients by the prospective cross-over study, and detect glucose control methods in MHD patients., Methods: A total of 66 MHD 18-75 years old patients in our hospital from Nov. 2019 to Mar. 2020 were recruited. All patients underwent HD with 4 hours per time, three times per week. Glucose-free dialysate (glucose-free group) and then 5.55 mmol/L glucose-containing dialysate (glucose-5.55 group) were used alternately in dialysis. The demographics and parameters of pre- and post-dialysis were recorded., Results: A total of 60 patients were analyzed, and 28 patients among them had type 2 diabetes. Serum glucose pre and post dialysis were 8.64 ± 4.18 mmol/L versus 5.74 ± 1.82 mmol/L (p < 0.01) in glucose-free dialysate, and 9.31 ± 4.89 mmol/L versus 7.80 ± 2.59 mmol/L (p < 0.01) in glucose-5.55 dialysate. The post-dialysis blood glucose of glucose-free group was lower than glucose-5.55 group (5.74 ± 1.82 vs 7.80 ± 2.59, p < 0.01). About 18 (30.00%) patients in glucose-free group and 1 patient (1.67%) in glucose-5.55 group whose blood glucose was lower than 4.44 mmol/L (p < 0.01). About 29 patients (48.33%) in glucose-free group and 17 patients (28.33%; p = 0.02) in glucose-5.55 group have hunger feeling. Serum sodium level in the glucose-free group was higher than that in Glucose-5.55 group (137.92 ± 1.64 vs 136.70 ± 1.64, p < 0.01). Post-dialysis blood glucose had no significant differences between patients not using diabetes-related medication (13 patients) and patients using diabetes-related medication (15 patients) in glucose-free group (7.13 ± 1.78 mmol/L vs 6.08 ± 2.84 mmol/L, p = 0.23) and glucose-5.55 group (9.22 ± 2.59 mmol/L vs 9.35 ± 2.88 mmol/L, p = 0.90)., Conclusions: Glucose-free and glucose-5.55 dialysate both decrease the blood glucose post-dialysis. Dialysates containing 5.55 mmol/L glucose can reduce the incidence of hypoglycemia and lower serum sodium, but have no effect on blood pressure during dialysis. Stopping insulin and oral anti-diabetic drugs once before dialysis may not affect the control of blood glucose.

Mercury is a heavy metal which causes irreversible toxicity to fish and is detected in aquatic environment around the world. We aimed to explore the relative mechanism of mercury exposure on the brain injury. In this study, high-throughput sequencing RNA-Seq technology was carried out to analyze the changes of gene expression of brain tissues exposed to mercury. A large number of differentially expressed genes were identified. And 366 genes were up-regulated and 688 genes were down-regulated. Gene Ontology (GO) functional enrichment analysis showed that DNA-templated and transport were highly enriched in the biological process. Membrane, nucleus, and cytoplasm were highly enriched in the cellular component, and metal ion binding and DNA binding were highly enriched in molecular function. The differential genes were enriched in ferroptosis, necroptosis, calcium signaling pathway, and ion channels. Real-time quantitative reverse transcription PCR (qRT-PCR) results demonstrated the selected genes exhibited the same trends with the RNA-Seq results, which indicates the transcriptome sequencing data is reliable. Our results may provide an insightful view for the toxic effects of mercury on brain injury of common carp., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)