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Abstract Background There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts. Methods Our study included women between the ages of 18 and 70 who intended to undergo surgical intervention for benign lesions. Stratified blocked randomization was employed to allocate participants into groups. The main objective was to assess whether the assigned group adhered to the recommended surgical technique for ovarian cystectomy or adnexectomy, without any deviation to alternative surgical methods. Results A total of 196 patients were included in the study, with all surgeries in each group being conducted according to the assigned procedures. Among them, the ovarian cystectomy layer included 58 cases in the vNOTES group and 58 cases in the conventional laparoscopy (CL) groups. The adnexectomy layer included 40 cases in the vNOTES group and 40 cases in the CL group. Utilizing a sensitivity analysis, the two-sided 95% lower confidence limit was determined to be 5.5% for the disparity in proportions between the vNOTES groups and CL groups. These lower limits fell below the predetermined non-inferiority margin of 10%. Conclusions The study findings demonstrate that vNOTES was not inferior to CL in terms of adnexectomy or ovarian cystectomy. vNOTES can be considered a more minimally invasive surgical approach, as it results in reduced postoperative pain, faster recovery, and absence of visible incisions. Overall, vNOTES proves to be a safe, feasible, and less invasive treatment option. Trial registration This study retrospectively registered with the China Clinical Trial Registry with the registration number ChiCTR2100052223(22-10-2021).

Abstract Purpose The objective of this paper is to offer a thorough examination of the clinical presentations, etiology, and treatment strategies associated with perivascular epithelioid cell tumors (PEComas). Methods This retrospective study examined the comprehensive archival data of PEComa cases diagnosed at Beijing Hospital from 2015 to 2023. The pathology slides of all patients were thoroughly reassessed by two experienced pathologists. A thorough retrospective analysis was undertaken, incorporating clinicopathological data including gender, age at diagnosis, initial clinical manifestations, signs, disease onset site, tumor markers, imaging findings, therapeutic modalities, pathological features, immunohistochemical profiles, treatment responses, and prognostic indicators. Patients were evaluated for disease severity according to established pathological classification criteria and were followed up until the designated analysis cut-off date. In instances where patients were unable to be monitored on-site, they were contacted via telephone for postoperative follow-up inquiries. Results This study included 11 patients with ages ranging from 17 to 66 years old, presenting with the disease in multiple anatomical sites, including the retroperitoneum (2/11), liver (4/11), kidney (4/11), lung (1/11), and broad ligament of the uterus (1/11). Most patients presented with non-specific clinical symptoms and were subsequently diagnosed with space-occupying lesions upon physical examination. The tumor demonstrated progressive growth and enlargement, which could result in compression of neighboring organs. Preoperative imaging alone is insufficient for a definitive diagnosis of PEComa, but MRI can provide an initial evaluation of the tumor’s potential malignancy. Molecular marker testing specific to PEComa, such as HMB-45 (90.0%), SMA (81.8%), Melan-A (90.9%), vimentin (90.9%), and Desmin (36.3%), was conducted on all patients. No adjuvant therapies were administered postoperatively. Upon analysis, no instances of relapse at the primary site or the development of new tumors at other sites were observed. Regular imaging reviews of three patients with malignant PEComa post-surgery showed no evidence of recurrence. Conclusions The clinical presentation, tumor biomarkers, and imaging characteristics of PEComa lack specificity, necessitating dependence on pathology and immunohistochemistry for precise diagnosis. The mainstay of treatment consists of surgical resection, with patients typically experiencing a favorable prognosis.

Small cell lung cancer (SCLC) is a fatal tumor type that is prone to drug resistance. In our previous study, we showed that human rhomboid-5 homolog-1 (RHBDF1) was differentially expressed in 5 intrinsic cisplatin-resistant SCLC tissues compared with 5 intrinsic cisplatin-sensitive SCLC tissues by RNA sequencing, which intrigued us. We performed gain- and loss-of-function experiments to investigate RHBDF1 function, bioinformatics analysis, qRT-PCR, western blotting, and immunoprecipitation to elucidate the molecular mechanisms as well as detect RHBDF1 expression in SCLC by immunohistochemistry. We found that RHBDF1 knockdown promoted cell proliferation and cisplatin chemoresistance and inhibited apoptosis in vitro and in vivo. These effects could be reversed by overexpressing RHBDF1 in vitro. Mechanistically, RHBDF1 interacted with YAP1, which increased the phosphorylation of Smad2 and transported Smad2 to the nucleus. Among clinical specimens, the RHBDF1 was a low expression in SCLC and was associated with clinicopathological features and prognosis. We are the first to reveal that RHBDF1 inhibited cell proliferation and promoted cisplatin sensitivity in SCLC and elucidate a novel mechanism through RHBDF1/YAP1/Smad2 signaling pathway which played a crucial role in cisplatin chemosensitivity. Targeting this pathway can be a promising therapeutic strategy for chemotherapy resistance in SCLC.

Abstract Background This study aimed to identify an initial screening tool for congenital ectopia lentis (CEL) by comparing ocular biological parameters in children with myopia. Methods A retrospective case-control study was conducted at one tertiary referral centre, from October 2020 to June 2022. Axial length (AL), corneal curvature (CC), refractive astigmatism (RA), corneal astigmatism (CA), internal astigmatism (IA), the difference between the axis of RA and CA [AXIS(RA-CA)], white-to-white corneal diameter (WTW), and axial length-corneal radius ratio (AL/CR) were compared in 28 eyes of CEL patients, and 60 eyes of myopic patients matched for age and refraction. The spherical equivalent of each eye was < -3.00 D. Area under the curve (AUC) of the receiver operating characteristic curves were calculated. Results The differences in RA, AL, mean keratometry (Kmed), maximum keratometry (Kmax), minimum keratometry (Kmin), CA, IA, AXIS(RA-CA), WTW, and AL/CR between the CEL and myopic groups were statistically significant (p

Hard carbon is considered as the most commercially applicable anode for sodium-ion batteries. Lignin has the characteristics of sustainable, low cost, high carbon content (>60%) and abundant oxygen functional groups, which is expected to be used as a promising candidate precursor for low-cost hard carbons. The structure and electrochemical performances of hard carbons could be regulated by adjusting carbonization temperature. The microstructure and electrochemical performance of LDHC anode are highly dependent on the carbonization temperature. Increasing carbonization temperature could reduce specific surface area and improve initial coulombic efficiency. The slope and plateau capacity of the LDHC anode could also be adjusted by changing the carbonization temperature. The LDHC prepared at 1200 °C showed the best sodium-ion storage performance, with an initial coulombic efficiency of 78.9% and a reversible sodium-ion storage capacity of 284.7 mAh g−1.

Abstract MiRNA-375 has been reported to play critical roles in a variety of cancers. To unravel its biological roles, especially its specific mechanisms of action in lung squamous cell carcinoma (LUSC), LUSC tissue microarrays and miRNAscope were performed to identify the miR-375 expression. Associations with clinicopathologic features, survival, and the prognostic value of miR-375 in LUSC were clarified in a retrospective study of 90 pairs of LUSC tissues. In vitro and in vivo gain- and loss-of-function assays were conducted to validate the effects and mechanism of miR-375 in LUSC. The mechanism responsible for interactions was verified by dual-luciferase reporter gene assay, immunoprecipitation (IP) analysis, immunofluorescence (IF) assay and ubiquitination assay. We found that miR-375 had higher expression in noncancerous adjacent tissues than in LUSC tissues. Clinicopathologic analyses showed that miR-375 expression was correlated with pathologic stage and was an independent predictor of overall survival (OS) for LUSC. MiR-375, as a tumor inhibitor, inhibited proliferation and metastasis while promoting apoptosis of LUSC cells. Mechanistic research indicated that miR-375 targeted ubiquitin-protein ligase E3A (UBE3A), which in turn promoted the activity of the ERK signaling pathway via ubiquitin-mediated dual-specificity protein phosphatase 1 (DUSP1) degradation. Collectively, we propose a novel mechanism of tumorigenesis and metastasis of LUSC via the miR-375/UBE3A/DUSP1/ERK axis, which could potentially facilitate new strategies for the treatment of LUSC.

Summary: Background: Leritrelvir is a novel α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease. A preclinical study has demonstrated leritrelvir poses similar antiviral activities towards different SARS-CoV-2 variants compared with nirmatrelvir. A phase 2 clinical trial has shown a comparable antiviral efficacy and safety between leritrelvir with and without ritonavir co-administration. This trial aims to test efficacy and safety of leritrelvir monotherapy in adults with mild-to-moderate COVID-19. Methods: This was a randomised, double-blind, placebo-controlled, multicentre phase 3 trial at 29 clinical sites in China. Enrolled patients were from 18 to 75 years old, diagnosed with mild or moderate COVID-19 and not requiring hospitalization. Patients had a positive SARS-CoV-2 nucleic acid test (NAT) and at least one of the COVID-19 symptoms within 48 h before randomization, and the interval between the first positive SARS-CoV-2 NAT and randomization was ≤120 h (5 days). Patients were randomly assigned in a 1:1 ratio to receive a 5-day course of either oral leritrelvir 400 mg TID or placebo. The primary efficacy endpoint was the time from the first dose to sustained clinical recovery of all 11 symptoms (stuffy or runny nose, sore throat, shortness of breath or dyspnea, cough, muscle or body aches, headache, chills, fever ≥37 °C, nausea, vomiting, and diarrhea). The safety endpoint was the incidence of adverse events (AE). Primary and safety analyses were performed in the intention-to-treat (ITT) population. This study is registered with ClinicalTrials.gov, NCT05620160. Findings: Between Nov 12 and Dec 30, 2022 when the zero COVID policy was abolished nationwide, a total of 1359 patients underwent randomization, 680 were assigned to leritrelvir group and 679 to placebo group. The median time to sustained clinical recovery in leritrelvir group was significantly shorter (251.02 h [IQR 188.95–428.68 h]) than that of Placebo (271.33 h [IQR 219.00–529.63 h], P = 0.0022, hazard ratio [HR] 1.20, 95% confidence interval [CI], 1.07–1.35). Further analysis of subgroups for the median time to sustained clinical recovery revealed that (1) subgroup with positive viral nucleic acid tested ≤72 h had a 33.9 h difference in leritrelvir group than that of placebo; (2) the subgroup with baseline viral load >8 log 10 Copies/mL in leritrelvir group had 51.3 h difference than that of placebo. Leritrelvir reduced viral load by 0.82 log10 on day 4 compared to placebo. No participants in either group progressed to severe COVID-19 by day 29. Adverse events were reported in two groups: leritrelvir 315 (46.46%) compared with placebo 292 (43.52%). Treatment-relevant AEs were similar 218 (32.15%) in the leritrelvir group and 186 (27.72%) in placebo. Two cases of COVID-19 pneumonia were reported in placebo group, and one case in leritrelvir group, none of them were considered by the investigators to be leritrelvir related. The most frequently reported AEs (occurring in ≥5% of participants in at least one group) were laboratory finding: hypertriglyceridemia (leritrelvir 79 [11.7%] vs. placebo 70 [10.4%]) and hyperlipidemia (60 [8.8%] vs. 52 [7.7%]); all of them were nonserious. Interpretation: Leritrelvir monotherapy has good efficacy for mild-to-moderate COVID-19 and without serious safety concerns. Funding: This study was funded by the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine, Guangdong Science and Technology Foundation, Guangzhou Science and Technology Planning Project and R&D Program of Guangzhou Laboratory.

Abstract Binding kinetic properties of protein–ligand complexes are crucial factors affecting the drug potency. Nevertheless, the current in silico techniques are insufficient in providing accurate and robust predictions for binding kinetic properties. To this end, this work develops a variety of binding kinetic models for predicting a critical binding kinetic property, dissociation rate constant, using eight machine learning (ML) methods (Bayesian Neural Network (BNN), partial least squares regression, Bayesian ridge, Gaussian process regression, principal component regression, random forest, support vector machine, extreme gradient boosting) and the descriptors of the van der Waals/electrostatic interaction energies. These eight models are applied to two case studies involving the HSP90 and RIP1 kinase inhibitors. Both regression results of two case studies indicate that the BNN model has the state‐of‐the‐art prediction accuracy (HSP90: Rtest2=0.947, MAEtest = 0.184, rtest = 0.976, RMSEtest = 0.220; RIP1 kinase: Rtest2=0.745, MAEtest = 0.188, rtest = 0.961, RMSEtest = 0.290) in comparison with other seven ML models.

Abstract Background Oxidized soybean oil (OSO) has been shown to impair growth and exacerbate inflammation, leading to intestinal barrier injury in animals. Recent evidence suggests important roles for resveratrol (RES) in the promoting growth performance, antioxidant capacity, anti-inflammatory, and regulate intestinal barriers in animals. Therefore, The objectives of this study are to investigate the effects of dietary RES (purity 98%) supplementation on the growth performance, antioxidant capacity, inflammatory state, and intestinal function of weaned piglets challenged with OSO. Methods A total of 28 castrated weaned male piglets with a similar body weight of 10.19 ± 0.10 kg were randomly assigned to 4 dietary treatments for 28-d feeding trial with 7 replications per treatment and 1 piglet per replicate. Treatments were arranged as a 2 × 2 factorial with oil type [3% fresh soybean oil (FSO) vs. 3% OSO] and dietary RES (0 vs. 300 mg/kg). Results The results showed that relative to the FSO group, OSO stress tended to decrease the average daily feed intake (ADFI), and decreased the activity levels of lipase, villus/crypt ratio (VCR), the mRNA expression of FABP1, SOD2, IL-10 and ZO-1 in the jejunum, and SOD2, GPX1, occludin and ZO-1 in the colon, the levels of acetic acid in the colonic digesta, whereas up-regulated the mRNA expression of IL-1β and TNF-α in the jejunum (P

Abstract With the prohibition of antibiotics in feed, plant functional substances have been widely studied as feed additives. Resveratrol, a natural stilbene, and a non-flavonoid polyphenol found in plants, possesses antioxidant, anti-inflammatory, and metabolic regulatory features. Resveratrol generated intense scientific and public interest, primarily due to its widely reported ability to prevent cancer, delay aging and alleviate related metabolic diseases. Recently, resveratrol has been studied and applied as a feed additive in animal production. This review focuses on the outline of the absorption and metabolism and biological functions of resveratrol and summarizes the application of dietary resveratrol in animal production up to the present, including pigs, poultry, and ruminants. In pigs, dietary resveratrol improved intestinal health, mitochondrial function, meat quality, and more. In poultry, studies have shown that dietary resveratrol improves growth performance and meat and egg quality and alleviates heat stress induced adverse effects. There are few studies on dietary resveratrol in ruminants; however previous studies have indicated that dietary resveratrol increases nutrient digestibility and reduces methane emissions in sheep. It is hoped that this review could provide a specific theoretical basis and research ideas for the research and application of resveratrol.

Cancer remains the leading cause of death and an important barrier to increase life expectancy. It is desirable to develop therapeutics that can improve life quality and prolong the survival duration. Nano materials have long been considered as a potential tool for detection, diagnosis, and treatment of tumor. The application of nanotechnology for the treatment of cancer is highly based on nano drug delivery system. To meet specific clinical requirements in a superior degree, nanoparticles (NPs) with better biocompatibility, lower toxicity, and definite therapeutic effect are now being developed and designed for experiments and applications. This review presents an overview of the clinical application characteristics of NPs and summarizes the recent advances in the development of nano materials for cancer therapy.

Metabolic reprogramming is a phenomenon in which cancer cells alter their metabolic pathways to support their uncontrolled growth and survival. Platinum-based chemotherapy resistance is associated with changes in glucose metabolism, amino acid metabolism, fatty acid metabolism, and tricarboxylic acid cycle. These changes lead to the creation of metabolic intermediates that can provide precursors for the biosynthesis of cellular components and help maintain cellular energy homeostasis. This article reviews the research progress of the metabolic reprogramming mechanism of platinumbased chemotherapy resistance caused by three major nutrients in ovarian cancer.

Abstract Background EphrinA (EFNA) are Eph receptor ligands that regulate various disease processes. Nonetheless, the expression characteristics of EFNAs in pan-cancer, their relationship with tumor immune microenvironment, and prognostic value landscape remain unknown. Methods A comprehensive landscape of EFNAs was created using various statistical data extracted from 33 cancers. Subsequently, we identified differential expression, genetic variations, potential function enrichment, tumor immune-related analysis, and drug sensitivity. Further, we investigated the clinical features and diagnostic prognostic value of EFNAs. RT-qPCR, western blot and immunohistochemistry (IHC) were used to validate the expression level and significant clinical value of EFNA5 in lung adenocarcinoma cell lines and tissues. Results EFNAs were highly mutated in various cancers. Genomic and epigenetic alterations of EFNAs were observed in various tumors, where an oncogenic mutation in specific cancer types potentially affected EFNA expression. Moreover, tumor-derived EFNAs were significantly related to the tumor immune microenvironment, suggesting that they are promising therapeutic targets. The majority of EFNA family genes were significantly linked to patient prognosis. Eventually, EFNA5 was an independent prognostic factor in lung adenocarcinoma. Conclusion In summary, EFNAs are crucial in tumor immune regulation, and EFNA5 is a prognostic marker in lung adenocarcinoma. Our findings provide new insights into EFNAs from a bioinformatics standpoint and highlight the significance of EFNAs in cancer diagnosis and treatment.

Prostate cancer: stem cell treatment targets microRNA A microRNA shown to promote prostate cancer growth can be targeted through a treatment derived from stem cells. Prostate cancer is lethal for many men, and its growth is promoted by testosterone. However, some “castration-resistant” strains keep growing even after treatments that reduce testosterone levels. Xiaoyi Huang at Harbin Medical University Cancer Hospital, China, and co-workers examined the role of microRNA-375 in the progression of castration-resistant prostate cancer. They found that microRNA-375 was over-expressed in cancer tissue samples and promoted tumor growth by interfering with a specific signaling pathway. The team applied a treatment comprising extracellular vesicles called exosomes that are derived from human stem cells and loaded with molecules that suppress microRNA-375. The treatment inhibited microRNA-375 and thereby repressed the cancer growth, while also reducing the cancer’s resistance to the testosterone-blocking drug enzalutamide.

Abstract Background Disease resistance phenotypes are associated with immune regulatory functions and immune tolerance and have implications for both the livestock industry and human health. Microbiota plays an essential role in regulating immunity and autoimmunity in the host organism, but the influence of host-microbiota interactions on disease resistance phenotypes remains unclear. Here, multiomics analysis was performed to identify potential regulatory mechanisms of disease resistance at both the microbiome and host levels in two pig breeds. Results Acute colitis models were established in Min pigs and Yorkshire pigs, and control and diseased individuals were compared. Compared with Yorkshire pigs under the same nutritional and management conditions, Min pigs exhibited strong disease resistance, as indicated by a low disease activity index (DAI) and a low histological activity index (HAI). Microbiota sequencing analysis showed that potentially harmful microbes Desulfovibrio, Bacteroides and Streptococcus were enriched in diseased individuals of the two breeds. Notably, potentially beneficial microbes, such as Lactobacillus, Clostridia and Eubacterium, and several genera belonging to Ruminococcaceae and Christensenellaceae were enriched in diseased Min pigs and were found to be positively associated with the microbial metabolites related to intestinal barrier function. Specifically, the concentrations of indole derivatives and short-chain fatty acids were increased in diseased Min pigs, suggesting beneficial action in protecting intestinal barrier. In addition, lower concentrations of bile acid metabolites and short-chain fatty acids were observed in diseased Yorkshire pigs, which were associated with increased potentially harmful microbes, such as Bilophila and Alistipes. Concerning enrichment of the immune response, the increase in CD4+ T cells in the lamina propria improved supervision of the host immunity response in diseased Min pigs, contributing to the maintenance of Th2-type immune superiority and immune tolerance patterns and control of excessive inflammation with the help of potentially beneficial microbes. In diseased Yorkshire pigs, more terms belonging to biological processes of immunity were enriched, including Toll-like receptors signalling, NF-κB signalling and Th1 and Th17-type immune responses, along with the increases of potentially harmful microbes and damaged intestinal barrier. Conclusions Cumulatively, the results for the two pig breeds highlight that host-microbiota crosstalk promotes a disease resistance phenotype in three ways: by maintaining partial PRR nonactivation, maintaining Th2-type immune superiority and immunological tolerance patterns and recovering gut barrier function to protect against colonic diseases. Video abstract.

This study investigated the effects of adding corn distillers dried grains with solubles (DDGS) to the diet on the meat quality, chemical composition, fatty acid composition, and lipidomics profiling in the longissimus thoracis (LT) of finishing pigs. Twenty-four healthy crossbred pigs (average body weight 61.23 ± 3.25 kg) were randomly divided into two groups with three replicates per group and four pigs per pen. The control group (CON) was fed a basal diet, and the DDGS group was fed an experimental diet with 30% DDGS. The results show that adding DDGS to the diet increases the yellowness (b*), chroma (C*), linoleic acid (C18:2n-6) percentages, polyunsaturated fatty acid (PUFA) percentages and iodine value of LT (p < 0.05). Based on LC–ESI–MS/MS, 1456 lipids from 6 classes or 44 subclasses in LT were analyzed, and 50 differential lipids were observed. Triglyceride (TG) with C18:2n-6 side chains and ceramide alpha-hydroxy fatty acid-sphingosine (Cer–AS) contents increased significantly, and the decrease in multiple glycerophospholipids (GPs) content may be related to differences in the glycerophospholipid metabolic pathway. Correlation analysis suggests that triglycerides with C18:2n-6 side chains may be one of the reasons for the changes in b* and C* values in the LT. In conclusion, feeding DDGS affects the meat quality and fatty acid composition and may affect the lipid profile in the LT of finishing pigs by regulating lipid metabolism.

Abstract Background Immune checkpoint inhibitors (ICIs) are the standard treatment for advanced lung cancer, but immune‐related adverse events (irAEs) remain poorly understood, especially in a real‐world setting. Methods A multicenter observational study was conducted. Medical records of lung cancer patients treated with ICIs at 26 hospitals from January 1, 2015, to February 28, 2021, were retrieved. Types of ICIs included antiprogrammed cell death 1 or antiprogrammed cell death ligand 1 (PD‐L1) monotherapy, anticytotoxic T‐lymphocyte antigen‐4 monotherapy, or combination therapy. Results In total, 1905 patients with advanced lung cancer were evaluated. The median age was 63 (range 28–87) years, and the male/female ratio was 3.1:1 (1442/463). The primary histological subtype was adenocarcinoma (915). A total of 26.9% (512/1905) of the patients developed 671 irAEs, and 5.8% (110/1905) developed 120 grade 3–5 irAEs. Median duration from ICI initiation to irAEs onset was 56 (range 0–1160) days. The most common irAEs were thyroid dysfunction (7.2%, 138/1905), pneumonitis (6.5%, 124/1905), and dermatological toxicities (6.0%, 115/1905). A total of 162 irAEs were treated with steroids and 11 irAEs led to death. Patients with positive PD‐L1 expression (≥1%) and who received first‐line ICI treatment developed more irAEs. Patients who developed irAEs had a better disease control rate (DCR, 71.3% [365/512] vs. 56.0% [780/1145]; p

Rapid aerobic decomposition and a high cost/benefit ratio restrain the transformation of Chinese cabbage waste into livestock feed. Herein, anaerobically co-fermenting Chinese cabbage waste with wheat bran and rice bran at different dry matter levels (250, 300, 350 g/kg fresh weight) was employed to achieve the effective and feasible clean transformation of Chinese cabbage waste, and the related microbiological mechanisms were revealed by high-throughput sequencing technology. The bran treatments caused an increase in pH value (4.75–77.25%) and free amino acid content (12.09–152.66%), but a reduction in lactic acid concentration (54.58–77.25%) and coliform bacteria counts (15.91–20.27%). In addition, the wheat bran treatment improved the levels of short-chain fatty acids, nonprotein nitrogen, water-soluble carbohydrates and antioxidant activity and reduced the ammonia nitrogen contents. In contrast, the rice bran treatment decreased the levels of acetic acid, water-soluble carbohydrates, nonprotein nitrogen, ammonia nitrogen, and antioxidant activities. Microbiologically, the bran treatments stimulated Pediococcus, Lactobacillus, Enterobacter, and Weissella but inhibited Lactococcus and Leuconostoc, which were the primary organic acid producers reflected by the redundancy analysis. In addition, Chinese cabbage waste fermented with wheat bran at 350 g/kg fresh weight or with rice bran at 300 g/kg fresh weight increased the scale and complexity of bacteriome, promoted commensalism or mutualism and upregulated the global metabolism pathways, including carbohydrate and amino acid metabolisms. Furthermore, the bran treatments resulted in an increase in bacterial communities that were facultatively anaerobic, biofilm-formed, Gram-negative, potentially pathogenic and stress-tolerant. Collectively, the bran treatments inhibited effluent formation and protein degradation and improved nutrient preservation but reduced organic acid production during the anaerobic fermentation, which is linked to the variations in the bacteriome, indicating that the constructed fermentation system should be further optimized.

Pulmonary neuroendocrine tumors (PNETs) are a kind of epithelial tumors originating from pulmonary neuroendocrine cells, accounting for about 20% of primary lung tumors, including typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. The morphologic and clinical characteristics of these four types of PNETs are relatively highly heterogeneous. Immune checkpoint inhibitors (ICIs) have been shown robust antitumor activity in a variety of solid tumors. Treatment regimens of advanced PNETs have developed greatly in the past decade, but ICIs are still in their infancy in the field of PNETs. This review focuses on the landscape of current clinical trials and research as well as the situation of ICIs-related biomarkers in PNETs.

The objective of this study was to evaluate the effects of yeast culture (YC) on reproductive performance, gut microbiota, and milk composition in primiparous sows. A total of 60 primiparous sows were randomly assigned to the control group (CON) and YC group (0.5% YC during gestation and 0.8% YC during lactation) consisting of 30 replicates, with one sow in each. The results showed that dietary YC supplementation increased the piglet birth weight and backfat thickness at 28 d of lactation (p < 0.05). Dietary YC supplementation increased the apparent total tract digestibility (ATTD) of gross energy and calcium during lactation, the content of acetic acid and propionic acid at 110 d of gestation, and the content of acetic acid and butyric acid at 28 d of lactation in feces (p < 0.05). Furthermore, dietary YC supplementation decreased the abundance of Firmicutes, Lachnospiraceae_XPB1014_group, and Terrisporobacter (p < 0.05), and increased the abundance of Prevotellaceae_NK3B31_group and Rikenellaceae_RC9_gut_group (p < 0.05). Compared to the control group, dietary YC supplementation increased the fat and lactose content of the colostrum (p < 0.05). Metabolomics analysis showed that YC increased 26 different metabolites in the colostrum. Among them were mainly pantothenic acid, proline, isoleucine, phenylalanine, acylcarnitine, and other metabolites. In conclusion, these results suggested that dietary YC supplementation improves reproductive performance and gut health and increases the nutrient content in the colostrum of primiparous sows.

Objective: In this paper, we aim to show that the immunogenicity of the lyophilized human rabies vaccine (Vero cells) (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. in healthy participants aged 10–60 years old is non-inferior to the lyophilized PVRV (positive control) manufactured by Liaoning Chengda Biotechnology Co., Ltd. (Shenyang, China), and that its safety is clinically acceptable. Method: A total of 2776 participants were enrolled in this study and divided into four groups: a five-dose test group, a five-dose control group, a four-dose test group, and a four-dose control group. The patients in the four-dose groups (Zagreb) were vaccinated on Days 0 (two doses), 7 (one dose), and 21 (one dose), and those in the five-dose groups (Essen) were vaccinated on Days 0, 3, 7, 14, and 28 (one dose each). The rabies-virus-neutralizing antibody assay with the RFFIT was used to assess the immunogenicity, and the adverse events (AEs) and serious adverse events (SAEs) were identified and collated. Results: The positive seroconversion rate was up to 100% on Days 14 and 35/42 after vaccination following any procedures in pre-immunization antibody-negative participants, and the positive seroconversion rate and geometric mean concentration (GMC) of the test groups (Zagreb and Essen vaccination procedures) was not inferior to that of the control groups. On Day 7 after vaccination, the immunogenicity of the Zagreb procedure with two doses of the vaccine on Day 0 was superior to the Essen procedure with one dose of vaccine, that is, the former had a higher seroconversion rate and RVNA titer. The non-inferiority criterion of immunogenicity was met for the whole population, the population aged 10–18 years and ≥18 years, and the pre-immunization antibody-positive population. The incidences of all AEs, solicited AEs, and unsolicited AEs in both groups were not statistically significant, and no vaccination-related SAEs were observed. Conclusion: The investigated vaccine is safe, its immunogenicity is non-inferior to that of the control vaccine, and the efficacy of the Zagreb procedure is superior to that of the Essen procedure 7 days after the first dose.

Background: Lung cancer is a complex disease composed of neuroendocrine (NE) and non-NE tumors. Accurate diagnosis of lung cancer is essential in guiding therapeutic management. Several transcriptional signatures have been reported to distinguish between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) belonging to non-NE tumors. This study aims to identify a transcriptional panel that could distinguish the histological subtypes of NE tumors to complement the morphology-based classification of an individual.Methods: A public dataset with NE subtypes, including 21 small-cell lung cancer (SCLC), 56 large-cell NE carcinomas (LCNECs), and 24 carcinoids (CARCIs), and non-NE subtypes, including 85 ADC and 61 SCC, was used as a training set. In the training set, consensus clustering was first used to filter out the samples whose expression patterns disagreed with their histological subtypes. Then, a rank-based method was proposed to develop a panel of transcriptional signatures for determining the NE subtype for an individual, based on the within-sample relative gene expression orderings of gene pairs. Twenty-three public datasets with a total of 3,454 samples, which were derived from fresh-frozen, formalin-fixed paraffin-embedded, biopsies, and single cells, were used for validation. Clinical feasibility was tested in 10 SCLC biopsy specimens collected from cancer hospitals via bronchoscopy.Results: The NEsubtype-panel was composed of three signatures that could distinguish NE from non-NE, CARCI from non-CARCI, and SCLC from LCNEC step by step and ultimately determine the histological subtype for each NE sample. The three signatures achieved high average concordance rates with 97.31%, 98.11%, and 90.63%, respectively, in the 23 public validation datasets. It is worth noting that the 10 clinic-derived SCLC samples diagnosed via immunohistochemical staining were also accurately predicted by the NEsubtype-panel. Furthermore, the subtype-specific gene expression patterns and survival analyses provided evidence for the rationality of the reclassification by the NEsubtype-panel.Conclusion: The rank-based NEsubtype-panel could accurately distinguish lung NE from non-NE tumors and determine NE subtypes even in clinically challenging samples (such as biopsy). The panel together with our previously reported signature (KRT5-AGR2) for SCC and ADC would be an auxiliary test for the histological diagnosis of lung cancer.

Malignant pleural mesothelioma (MPM) is a malignant tumor with strong invasiveness, low survival rate and lack of effective treatment options. As the only first-line treatment plan for the advanced MPM, combination of pemetrexed and cisplatin chemotherapy have been existing since the last 20 years. Immunotherapy has long been considered as a potential treatment plan for MPM, mainly including immune checkpoint inhibitors (ICIs), immunotoxin therapy, anti-cancer vaccine and adoptive T-cell therapy. This review focuses on summarizing the current research status of immune checkpoint inhibitors in MPM, discusses the effect of tumor heterogeneity on ICIs treatment, and describes that the biomarker-oriented immunotherapy is a new vision for the realization of individualized treatment of MPM.

The transition of plants to land required several regulatory adaptive mechanisms. Little is known about these mechanisms, but they no doubt involved the evolution of transcription factor (TF) families. ETHYLENE-INSENSITIVE 3 (EIN3)/EIN3-LIKE (EIL) transcription factors (TFs) are core components of the ethylene signaling pathway that play important roles in almost every aspect of plant development and environmental responses by regulating the transcription of numerous genes. However, the evolutionary history of EIN3/EIL TFs, which are present in a wide range of streptophytes, is still not clear. Here, to explore the evolution and functions of EIN3/EIL TFs, we performed phylogenetic analysis of these TFs and investigated their gene and protein structures as well as sequence features. Our results suggest that the EIN3/EIL TF family was already was already present in the ancestor of streptophyte algae. Phylogenetic analysis divided the EIN3/EIL TFs into three groups (Group A–C). Analysis of gene and protein structure revealed that most of the structural features of these TFs had already formed in ancient lineages. Further investigation suggested that all groups have undergone several duplication events related to whole-genome duplications in plants, generating multiple, functionally diverse gene copies. Therefore, as plants colonized terrestrial habitats and evolved key traits, the EIN3/EIL TF family expanded broadly via multiple duplication events, which could have promoted their fundamental neo- and sub-functionalization to help plants adapt to terrestrial life. Our findings shed light on the functional evolution of the EIN3/EIL TF family in the streptophytes.

Abstract Chlorophyll (Chl) degradation is one of the most obvious signs of leaf senescence and fruit ripening. Stay-green (SGR) homologs that can remove magnesium from Chl a are the most important components in Chl degradation pathway in green plants. SGR homologs are not only universally involved in Chl breakdown during the senescence of green organs, but also play crucial roles in other organs during plant growth and development, such as fruit mature and nodule development. In this review, we focus on the diverse functions of SGR homologs in plant growth and development. A better understanding of SGR would be helpful for providing a theoretical basis for further illustrating the regulatory mechanism of SGR homologs.

Sonodynamic therapy (SDT) is a developing modality for cancer treatment based on the synergistic effect of ultrasound and chemical compounds which are known as sonosensitizers. The development of more efficient sonosensitizers has become an urgent issue in this field. In this study, a novel porphyrin derivative (BBTPP) mediated SDT was evaluated on PC-9 cells. Pulsed low-intensity ultrasound (PLIU) was used for its little thermal and mechanical damage. The accumulation of drugs in cells was evaluated through porphyrin fluorescence, and the cytotoxicity of BBTPP was evaluated using a cell counting kit-8 assay. The sonodynamic effect was investigated by Hoechst 33342/PI and Annexin V-FITC/PI double staining, which showed an apoptotic rate of 18.87% in the BBTPP-SDT group, as compared with 1.71%, 1.4%, 1.57%, 3.61%, 11.18% in the control, BBTPP, hematoporphyrin monomethyl ether (HMME), ultrasound, and HMME-SDT groups, respectively. The sono-toxic effect of BBTPP was significantly superior to HMME. Our results showed that BBTPP-SDT resulted in much higher intracellular reactive oxygen species (ROS) and lipid peroxidation levels which were evaluated by 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) and Liperfluo assay, respectively. The expressions of Bax, Bcl-2, caspase-9, caspase-8, and cleaved caspase-3 proteins were evaluated to investigate the apoptotic mechanism of BBTPP-SDT. The results of this study showed that the combination of BBTPP and PLIU induced the generation of ROS, resulting in lipid peroxidation, and activated both the extrinsic and intrinsic apoptotic pathways of PC-9 cells. Our results also suggested that the ether group introduced in the side chain of porphyrin could enhance the sono-toxicity of porphyrin-based sensitizers under the sonication of PLIU. These results supported the possibility of BBTPP as a promising sonosensitizer, and an appropriate side chain could enhance the sono-sensitivity of porphyrins.

Ferroptosis, as a recently discovered non-apoptotic programmed cell death with an iron-dependent form, has attracted great attention in the field of cancer nanomedicine. However, many ferroptosis-related nano-inducers encountered unexpected limitations such as immune exposure, low circulation time, and ineffective tumor targeting. Biomimetic nanomaterials possess some unique physicochemical properties which can achieve immune escape and effective tumor targeting. Especially, certain components of biomimetic nanomaterials can further enhance ferroptosis. Therefore, this review will provide a comprehensive overview on recent developments of biomimetic nanomaterials in ferroptosis-related cancer nanomedicine. First, the definition and character of ferroptosis and its current applications associated with chemotherapy, radiotherapy, and immunotherapy for enhancing cancer theranostics were briefly discussed. Subsequently, the advantages and limitations of some representative biomimetic nanomedicines, including biomembranes, proteins, amino acids, polyunsaturated fatty acids, and biomineralization-based ferroptosis nano-inducers, were further spotlighted. This review would therefore help the spectrum of advanced and novice researchers who are interested in this area to quickly zoom in the essential information and glean some provoking ideas to advance this subfield in cancer nanomedicine.

In the face of increasingly serious energy and environmental problems, the safety of offshore oil drilling and production platform, as a natural gas development platform, is of great significance. For offshore platforms, the offshore power system serves for oil and gas production, and the interruption or shutdown of oil and gas production caused by electric power is intrinsically unsafe; In addition, due to the weak interconnection between the offshore platform systems, with the characteristics of small unit, large load, wide application of frequency conversion equipment and poor environment, the security analysis of the offshore platform power system must take the power grid and gas network as a whole to analyze and take into account the low-voltage crossing capacity. For the coupling of power grid and gas network of offshore platform, multi-stage compression system and the “power to gas” system are proposed. For these voltage sag sensitive systems, the safe critical voltage and critical cut-off time are used to characterize the low-voltage crossing capability. The operation constraints considering the low-voltage crossing capability are also proposed, and the impact of voltage sag is taken into account in the safety analysis. The simulation results show the correctness of the safety analysis method considering the low voltage crossing capability, and the necessity of the safety analysis considering the gas network and the low crossing capability.

Abstract Background Pyrroloquinoline quinone (PQQ), which is a water soluble, thermo-stable triglyceride-quinone, is widely distributed in nature and characterized as a mammalian vitamin-like redox cofactor. The objective of this study was to investigate the effects of pyrroloquinoline quinone disodium (PQQ·Na2) on reproductive performance in sows. Results Dietary supplementation with PQQ·Na2 significantly increased the total number of piglets born, the number of piglets born alive and the born alive litter weight. It also increased the antioxidant status in the placenta, plasma and milk. The concentration of NO was significantly increased in the plasma and placenta. RNA-seq analysis showed that 462 unigenes were differentially expressed between the control (Con) treatment and PQQ treatment groups. Among these unigenes, 199 were upregulated, while 263 unigenes were downregulated. The assigned functions of the unigenes covered a broad range of GO categories. Reproduction (27, 7.03%) and the reproduction process (27, 7.03%) were assigned to the biological process category. By matching DEGs to the KEGG database, we identified 29 pathways. Conclusions In conclusion, dietary supplementation with PQQ·Na2 in gestating and lactating sows had positive effects on their reproductive performance.

Abstract Background Non-small cell lung cancer (NSCLC) is a devastating disease with a heterogeneous prognosis, and the molecular mechanisms underlying tumor progression remain elusive. Mammalian Eps15 homology domain 1 (EHD1) plays a promotive role in tumor progression, but its role in cancer angiogenesis remains unknown. This study thus explored the role of EHD1 in angiogenesis in NSCLC. Methods The changes in angiogenesis were evaluated through human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation assays. The impact of EHD1 on β2-adrenoceptor (β2AR) signaling was evaluated by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and enzyme-linked immunosorbent assay (ELISA). The interaction between EHD1 and β2AR was confirmed by immunofluorescence (IF) and coimmunoprecipitation (Co-IP) experiments, and confocal microscopy immunofluorescence studies revealed that β2AR colocalized with the recycling endosome marker Rab11, which indicated β2AR endocytosis. Xenograft tumor models were used to investigate the role of EHD1 in NSCLC tumor growth. Results The microarray analysis revealed that EHD1 was significantly correlated with tumor angiogenesis, and loss- and gain-of-function experiments demonstrated that EHD1 potentiates HUVEC proliferation, migration and tube formation. EHD1 knockdown inhibited β2AR signaling activity, and EHD1 upregulation promoted vascular endothelial growth factor A (VEGFA) and β2AR expression. Interestingly, EHD1 interacted with β2AR and played a novel and critical role in β2AR endocytic recycling to prevent receptor degradation. Aberrant VEGFA or β2AR expression significantly affected EHD1-mediated tumor angiogenesis. The proangiogenic role of EHD1 was confirmed in xenograft tumor models, and immunohistochemistry (IHC) analysis confirmed that EHD1 expression was positively correlated with VEGFA expression, microvessel density (MVD) and β2AR expression in patient specimens. Conclusion Collectively, the data obtained in this study suggest that EHD1 plays a critical role in NSCLC angiogenesis via β2AR signaling and highlight a potential target for antiangiogenic therapy.

Intramembrane proteases play very important roles in plants, such as chloroplast development, flower morphology, and response to abiotic stress. In this study, a putative metalloprotease gene, homologous to Ethylene-dependent Gravitropism deficient and Yellow-green2 (EGY2) of Arabidopsis, was isolated from tomato (Solanum lycopersicum) plants and named SlEGY2. We found that SlEGY2 was a member of the metalloprotease family M50 which contained conserved motifs HEXXH and NPDG and was localized in the chloroplast. SlEGY2 antisense transgenic tomato plants (AS) have similar hypocotyls phenotype to the Arabidopsis egy2 mutant. Heat (42 °C), PEG, ABA and MeJA treatments can upregulate the expression of SlEGY2. Under heat stress, SlEGY2 AS lines are more sensitive, with more water loss (lower fresh weight), seriously damaged membrane, and ROS accumulation, but lower activities of APX and CAT. In addition, suppression of SlEGY2 decreases the content of chlorophyll and photosynthetic activities, especially photosystem II. These results suggest that SlEGY2 can regulate the thermotolerance of tomatoes by affecting ROS accumulation and photosynthetic activities.

BackgroundLung cancer remains a common malignancy and the leading cause of cancer-related deaths in the world. Although dramatic progress made in multimodal therapies, it still has a poor prognosis. The Family with sequence similarity 83 (FAM83) of poorly characterized proteins are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini, most of which significantly elevated levels of expression in multiple cancers. However, the expression and prognostic values of different FAM83 family in lung cancer, especially in non-small-cell lung cancer (NSCLC), have not been clarified.MethodsONCOMINE, UALCAN, GEPIA, Kaplan–Meier Plotter, cBioPortal, and STRING databases were utilized in this study.ResultsThe transcriptional levels of FAM83A/B/C/D/F/G/H were up-regulated in patients with NSCLC. A noticeable correlation was found between the over-expressions of FAM83A/B/D/F/H and clinical cancer stages in NSCLC patients. Besides, higher mRNA expressions of FAM83A/B/C/D/F/H were discovered to be expressively associated with overall survival (OS) in lung cancer patients, furthermore, FAM83A, FAM83C, and FAM83H in OS group achieved 0.9475/1, 0.971897/1, and 0.9454545/0.8974359 specificity/sensitivity in distinguishing short survivors from long survivors, respectively. Moreover, a high mutation rate of FAM83 family (51%) was also observed in lung adenocarcinoma (LUAD) patients, and genetic alteration in the FAM83 family was associated with shorter OS and disease-free survival (DFS) in LUAD patients.ConclusionOur results indicated that FAM83A/H might play important roles in NSCLC tumorigenesis and might be risk factor for the survival of NSCLC patients.

Weaning transition usually impairs intestinal architecture and functions and results in gut-associated disorders in pigs. Understanding the changes in intestinal transcriptome and gut microbiota during weaning transition is important for elucidating the underlying mechanism of weaning stress. In the present study, we performed RNA-seq to determine the changes in intestinal transcriptome and 16S rRNA sequencing to measure the gut microbiota changes in the weaning transition. Transcriptome results indicated that weaning transition altered intestinal gene expression involved in nutrient transport and metabolism. Regarding fatty metabolism, fatty acid-binding protein 1 (FABP1), acyl-CoA dehydrogenase (ACADSB), and carnitine palmitoyltransferase 2 (CPT2) expression in the intestine was decreased by weaning. Genes related to bile acid metabolism were increased by weaning, including FABP6, farnesoid X receptor (FXR or NR1H4) and organic solute transporter-α (SLC51A). In addition, genes associated with oxidative stress were altered by weaning transition, including decreased catalase (CAT) and lactate dehydrogenase (LDHA) and increased glutathione peroxidase 2 (GPX2) and superoxide dismutase 3 (SOD3). Results of microbiota composition showed that the Firmicutes abundance and Firmicutes/Bacteroidetes ratio were increased and that the Proteobacteria abundance in the fecal microbiota was decreased by the weaning process; during the weaning transition, the Bacteroides and Fusobacterium abundances decreased markedly, and these bacteria nearly disappeared, while the Prevotella abundance showed a marked increase. Moreover, the levels of the microbial metabolites butyrate and acetate increased with changes in gut microbiota composition. In addition, predictive metagenome by PICRUSt analysis showed that the pathways related to D-glutamine and D-glutamate metabolism, citrate cycle (TCA cycle), peroxisome proliferators-activated receptor (PPAR) signaling, alpha-linolenic acid metabolism were decreased and the pathway related to retinol metabolism was increased in the gut microbiota of piglets during weaning transition. Our results showed that early weaning alters intestinal gene expression involved in nutrient metabolism, which may be due to the changes in microbiota composition.

Abstract Background Lung cancer stem cells have the ability to self-renew and are resistant to conventional chemotherapy. MicroRNAs (miRNAs) regulate and control the expression and function of many target genes; therefore, miRNA disorders are involved in the pathogenesis of human diseases, such as cancer. However, the effects of miRNA dysregulation on tumour stemness and drug resistance have not been fully elucidated. miR-181b has been reported to be a tumour suppressor miRNA and is associated with drug-resistant non-small cell lung cancer. Methods Cancer stem cell (CSC)-like properties were tested by a cell proliferation assay and flow cytometry; miR-181b expression was measured by real-time PCR; and Notch2 and related proteins were detected by Western blotting and immunohistochemistry. A mouse xenograft model was also established. Results In this study, we found that ectopic miR-181b expression suppressed cancer stem cell properties and enhanced sensitivity to cisplatin (DDP) treatment by directly targeting Notch2. miR-181b could inactivate the Notch2/Hes1 signalling pathway. In addition, tumours from nude mice treated with miR-181b were significantly smaller than tumours from mice treated with control agomir. Decreased miR-181b expression and increased Notch2 expression were observed to have a significant relationship with overall survival (OS) and CSC-like properties in non-small cell lung cancer (NSCLC) patients. Conclusions This study elucidates an important role of miR-181b in the regulation of CSC-like properties, suggesting a potential therapeutic target for overcoming drug resistance in NSCLC.

Abstract Background The highly refractory nature of non-small cell lung cancer (NSCLC) to chemotherapeutic drugs is an important factor resulting in its poor prognosis. Recent studies have revealed that tumour necrosis factor alpha-induced protein 8 (TNFAIP8) is involved in various biological and pathological processes of cells, but their underlying mechanisms in processes ranging from cancer development to drug resistance have not been fully elucidated. Methods TNFAIP8 expression in clinical NSCLC samples was examined through immunohistochemistry (IHC). After adjusting for patients’ characteristics with propensity score matching, Kaplan-Meier analysis and Cox regression analysis were performed for comparison of patients’ survival according to the TNFAIP8 level. Lentiviral transfection with TNFAIP8-specific shRNAs was used to establish stable TNFAIP8 knockdown (TNFAIP8 KD) NCI-H460, A549 and cis-diamminedichloroplatinum II resistant A549 (A549/cDDP) cell lines. Cell proliferation and viability were assessed by CCK-8 assay. Cell cycle was examined by flow cytometry. Multiple pathways regulated by TNFAIP8 KD were revealed by microarray analysis. Results We found that high TNFAIP8 expression was associated with advanced pT stage, advanced pTNM stage, lymph node metastasis and unfavourable survival in NSCLC patients. TNFAIP8 shRNAs reduced in vitro cancer cell proliferation and in vivo tumor growth. Additionally, TNFAIP8 KD increased the sensitivity of NSCLC cells to cisplatin in vitro and in vivo. Conversely, up-regulation of TNFAIP8 promoted the proliferation and drug resistance to cisplatin of NSCLC cells. TNFAIP8 influences cancer progression pathways involving the MDM2/p53 pathway. Indeed, we observed that TNFAIP8 KD mediated the MDM2 downregulation and the p53 ubiquitination, thereby decreasing the degradation of p53 protein. shRNA p53 reversed TNFAIP8 shRNA-mediated regulation of cell proliferation, cell cycle, cisplatin sensitivity, and expression levels of RAD51, a DNA repair gene. Conclusion Our work uncovers a hitherto unappreciated role of TNFAIP8 in NSCLC proliferation and cisplatin chemoresistance that is mediated through the MDM2/p53 pathway. These findings might offer potential therapeutic targets for reversing cisplatin resistance in NSCLC patients with high TNFAIP8 expression.

Abstract Background Resveratrol, a plant phenol, affords protection against inflammation and oxidative stress. The objective of this study was to investigate the effects of dietary resveratrol supplementation during pregnancy and lactation on the antioxidant status of sows and piglets and on antioxidant gene expression and pathway in placenta. Methods Forty sows were allotted to 2 dietary treatments 20 d after breeding. Sows were fed a control diet and a control diet with 300 mg/kg resveratrol. Oxidative stress biomarkers and antioxidant enzymes were measured in the placenta, milk, and plasma of sows and piglets. Antioxidant gene expression and protein expression of Kelch-like ECH-associated protein 1-Nuclear factor E2-related factor 2 (Keap1-Nrf2), nuclear factor kappa B-p65 (NFκB-p65) and sirtuin1 (Sirt1) were quantified in the placenta. Results Dietary resveratrol increased the litter and piglets weaning weights. Antioxidant status in the milk, placenta and plasma of sows and piglets was partially improved by dietary resveratrol. In placenta, Nrf2 protein expression was increased and Keap1 protein expression was decreased by dietary resveratrol. The mRNA expression of antioxidant genes including catalase (CAT), glutathione peroxidase 1 (GPX1), GPX4, superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO1), and phase 2 detoxification genes, including glutamate-cysteine ligase modifier (GCLM), microsomal glutathione S-transferase 1(MGST1) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1), was increased by dietary resveratrol. Dietary resveratrol also increased Sirt1 and phosphorylated NFκB-p65 protein expression in the placenta. We failed to observe any influences of dietary resveratrol on pro-inflammatory cytokine levels, including those of interleukin 1β (IL-1β), IL-6, IL-8 and tumor necrosis factor α (TNF-α). However, we observed that the mRNA expression of IL-8 in placenta was reduced by maternal resveratrol. In addition, dietary resveratrol showed interactive effects with day of lactation on activities of SOD and CAT and levels of malonaldehyde (MDA) and hydrogen peroxide (H2O2) in milk. Conclusions Dietary resveratrol supplementation during pregnancy and lactation improves the antioxidant status of sows and piglets, which is beneficial to the reproductive performance of sows. Dietary resveratrol regulates placental antioxidant gene expression by the Keap1-Nrf2 pathway and Sirt1 in placenta.

Background and objective Computed tomography-guided needle biopsy (CTNB) is a well-established and commonly used technique for diagnosing pulmonary nodules with high accuracy and safety. Needle-tract implantation after CTNB has been reported in various reports. The aim of this study is to evaluate whether preoperative CTNB affected the distant metastasis and overall survival in pathological stage I-II lung cancer patients. Methods A total of 1,234 patients with pathological stage I-II non-small cell lung cancer were collected. 113 patients received preoperative CTNB, and 1,121 patients did not receive any biopsy before surgical resection. Propensity score-matching method was adopted to balance observed covariates between two groups, 113 pairs were matched. Cox regression analysis and Kaplan-Meier estimates were used to process survival analysis. Results Distant metastasis free survival (DMFS) was significantly poorer in the preoperative CTNB group than in the non-biopsy group (P=0.032). But there was no difference in the overall survival between the two groups (P=0.086). Conclusion CTNB increased the risk of distant metastasis, not increasing the risk of mortality.

Cardiomyopeptidin is a kind of biological drug used in the perioperative period of cardiac surgery, and the main ingredient of it can help to repair myocardial damage. In the production of cardiomyopeptidin for injection, vacuum freeze drying is a key technology. However, it has to face many difficulties such as the long cycle of freeze drying process (78 h) and large deviation of quality in group which reduce the efficiency of product. Currently, the study of freeze drying process of cardiomyopeptidin for injection is rare. The experiments in this paper were conducted by a miniature freeze dryer, cutting down the cycle of freeze drying process to an ideal value (45 h) and diminishing the deviation of quality in group. At present, many key factors of freeze drying process of the cardiomyopeptidin have been investigated, the optimized freeze drying program successfully cuts down the cycle to 36 h in the pilot freeze dryer. Luckily, the research also found a new auxiliary material which could greatly improve the efficiency of freeze drying. This paper provides a new way for the research of freeze drying process of biological drugs.

Increasing emissions of greenhouse gases (GHGs) have been identified as the main contributor to global warming and climate change. Carbon dioxide (CO2) is the primary anthropogenic GHG. Carbon capture and storage (CCS) is widely recognized as a key mitigation technology that can significantly reduce CO2 emissions during combustion. It involves capturing CO2 from large stationary sources and subsequently storing it in various reservoirs such as depleted oil or gas reservoirs, saline aquifers and deep unmineable coal seams. In this work, a finite-scenario based two-stage stochastic mixed integer linear programming (MILP) model is developed for planning the retrofit of power plants with carbon capture (CC) technology and the subsequent CO2 source-sink matching in CCS supply chains under uncertainty. This model can be used to select appropriate sources, capture technologies and sinks and maximize the amount of captured and stored CO2 under the presence of uncertainty. Furthermore, to control risk at the optimal deployment of CCS systems, probabilistic financial risk metric is incorporated into the model. A case study is used to demonstrate the application of the proposed model. The computational results show that after risk management, risk of the expectation amount of captured and stored CO2 is reduced.

As a sort of emerging unconventional energy, shale gas has extensive market outlook by virtue of its enormous reserves, and concerns for shale gas exploitation and processing have been raised nowadays. Raw shale gas must be processed to achieve certain specifications before it can be transmitted in pipelines or utilized by consumers. Sweetening is a gas conditioning process to decrease the concentration of acid gases such as hydrogen sulfide and carbon dioxide which are not preferred in sales gas in consideration of heating value specification and corrosion prevention. However, the after-treatment of acid gases is not discussed in many research of sweetening process. In this paper, a flowsheet of shale gas sweetening process is established using Aspen Plus v8.6. Dissolution of light gases and weak electrolyte, absorption of acid gases and reactions in electrolyte solution are considered simultaneously in process modelling. Diethanolamine (DEA) solution is employed as the solvent to separate acid gases from raw shale gas. The optimal feed stage of rich solvent regeneration and reflux ratio of regenerator are analysed to optimize the sweetening flowsheet. A three-stage Claus process is simulated coupling with shale gas sweetening process to convert hydrogen sulfide in acid gas to element sulphur for pollution reduction. A principle is proposed to determine the operating temperature of each Claus reactor which is a decisive parameter on sulfur recovery efficiency and performance of Claus process. Ultimately, the sulfur recovery efficiency of the three-stage Claus process proposed in this paper is 97.35 %. The effectivity of the principle is confirmed by the results reported in literatures. Energy synthesis is then adopted to integrate sweetening process with Claus process in both mass and energy flow. The coupled process provides with more streams than a single sweetening or Claus process, promoting the reasonability of energy utilization. Streams are extracted and matched for heat exchanger network (HEN) synthesis to reduce the energy consumption and total annual cost of the whole process.

Ionic liquids (ILs) are recognized as a possible replacement of traditional organic solvents, and ILs have been widely applied to extract various compounds. The present work aims to extract ginsenosides from Panax ginseng flower buds using aqueous ionic liquid based ultrasonic assisted extraction (IL-UAE). The extraction yields of 1-alkyl-3-methylimidazolium ionic liquids with different anions and alkyl chains were evaluated. The extraction parameters of eight ginsenosides were optimized by utilizing response surface methodology (RSM). The model demonstrated that a high yield of total ginsenosides could be obtained using IL-UAE, and the optimum extraction parameters were 0.23 M [C4mim][BF4], ultrasonic time of 23 min, temperature of extraction set to 30 °C, and liquid-solid ratio of 31:1. After that, an aqueous biphasic system (ABS) was used to separate ginsenosides further. The nature and concentration of salt, as well as the value of pH in ionic liquid were evaluated, and the optimal conditions (6.0 mL IL extract, 3 g NaH2PO4, and pH 5.0) were obtained. The preconcentration factor was 2.58, and extraction efficiency reached 64.53%. The results indicate that as a simple and efficient method, an IL-UAE-ABS can be considered as a promising method for extracting and separating the natural active compounds from medicinal herbs.

Background and objective Galectin-3 is involved in many physical and pathologic process, and is closely correlated with tumorigenesis, development and metastasis. The aim of this study is to investigate the gene expression and significance of Galectin-3 in normal lung tissue and non-small cell lung cancer (NSCLC) tissue. Methods Gene expression was examined using the immunohistochemical S-P method in 62 NSCLC cases and in 17 cases with normal lung tissue. RT-PCR verified the expression of Galectin-3 at the transcriptional level. Results The expression rate of Galectin-3 in NSCLC tissue was 83.8% (52/62), which was significantly higher than that in normal lung tissue (P0.05), age (χ2=0.220, P>0.05), and histological type (χ2=0.012, P>0.05), but was negatively correlated with pathological differentiation (r=-0.292, P

The present study was conducted to investigate the effects of maternal zearalenone (ZEN) exposure on the intestine of pregnant Sprague-Dawley (SD) rats and its offspring. Ninety-six pregnant SD rats were randomly divided into four groups and were fed with diets containing ZEN at concentrations of 0.3 mg/kg, 48.5 mg/kg, 97.6 mg/kg or 146.0 mg/kg from gestation days (GD) 1 to 7. All rats were fed with mycotoxin-free diet until their offspring were weaned at three weeks of age. The small intestinal fragments from pregnant rats at GD8, weaned dams and pups were collected and studied for toxic effects of ZEN on antioxidant status, immune response, expression of junction proteins, and morphology. The results showed that ZEN induced oxidative stress, affected the villous structure and reduced the expression of junction proteins claudin-4, occludin and connexin43 (Cx43) in a dose-dependent manner in pregnant rats. Different effects on the expression of cytokines were also observed both in mRNA and protein levels in these pregnant groups. Ingestion of high levels of ZEN caused irreversible damage in weaned dams, such as oxidative stress, decreased villi hight and low expression of junction proteins and cytokines. Decreased expression of jejunal interleukin-8 (IL-8) and increased expression of gastrointestinal glutathione peroxidase (GPx2) mRNA were detected in weaned offspring, indicating long-term damage caused by maternal ZEN. We also found that the Nrf2 expression both in mRNA and protein levels were up-regulated in the ZEN-treated groups of pregnant dams and the high-dose of ZEN group of weaned dams. The data indicate that modulation of Nrf2-mediated pathway is one of mechanism via which ZEN affects gut wall antioxidant and inflammatory responses.

The net photosynthetic rate, chlorophyll content, chlorophyll fluorescence and 820 nm transmission were investigated to explore the behavior of the photosynthetic apparatus, including light absorption, energy transformation and the photoactivities of photosystem II (PSII) and photosystem I (PSI) during senescence in the stay-green inbred line of maize (Zea mays) Q319 and the quick-leaf-senescence inbred line of maize HZ4. The relationship between the photosynthetic performance and the decrease in chlorophyll content in the two inbred lines was also studied. Both the field and laboratory data indicated that the chlorophyll content, net photosynthetic rate, and the photoactivities of PSII and PSI decreased later and slower in Q319 than in HZ4, indicating that Q319 is a functional stay-green inbred line. In order to avoid the influence of different development stages and environmental factors on senescence, age-matched detached leaf segments from the two inbred lines were treated with ethephon under controlled conditions to induce senescence. The net photosynthetic rate, light absorption, energy transformation, the activities of PSII acceptor side and donor side and the PSI activities decreased much slower in Q319 than in HZ4 during the ethephon-induced senescence. These results suggest that the retention of light absorption, energy transformation and activity of electron transfer contribute to the extended duration of active photosynthesis in Q319. Although the chlorophyll content decreased faster in HZ4, with decrease of chlorophyll content induced by ethephon, photosynthetic performance of Q319 deteriorated much more severely than that of HZ4, indicating that, compared with Q319, HZ4 has an advantage at maintaining higher photosynthetic activity with decrease of chlorophyll although HZ4 is a quick-leaf-senescence inbred line. We conclude that attention should be paid to two favorable characteristics in breeding long duration of active photosynthesis hybrids: 1) maintaining more chlorophyll content during senescence and 2) maintaining higher photosynthetic activity during the loss of chlorophyll.

The title compound, C16H24O3, has a cage-type molecular structure and is of interest with respect to its photochemical properties. The structure displays non-classical intermolecular C—H...O hydrogen bonding, which links the molecules into a three-dimensional network.