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Using electrocatalysts is effective in solving the slow reaction kinetics of polysulfides in Li-S batteries, but designing stable electrocatalysts with an integrated adsorption-catalysis-desorption system is challenging. Here, we report a stable metal-semiconductor (Co-ZrO 2 ) heterojunction electrocatalyst fabricated by assembling electron-coupled Co-ZrO 2 nanodots into macroporous carbon nanofibers. The Co-ZrO 2 contact causes interfacial electron enrichment and electron transfer from Co to ZrO 2 , which creates abundant Lewis-acid sites on Co that can adsorb polysulfides. Simultaneously, the enriched interfacial electrons can activate the S-S bond and boost the catalytic conversion of long-chain polysulfides, while the ZrO 2 with Lewis-base sites facilitate the desorption of short-chain polysulfides from the electrocatalyst. Moreover, the nanodot heterojunctions show great chemical stability and high redox reaction kinetics of polysulfides. Li-S batteries show high discharge capacities of 954.5 mA h·g -1 at 0.5 C with a retention of 84.9% over 200 cycles, and 710.2 mA hg -1 at 1 C with a retention of 98.6% over 200 cycles. This study provides an effective strategy for developing active and durable electrocatalysts for Li-S batteries.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the digestive malignancy with poor prognosis, and there is still a lack of effective diagnostic biomarkers., Objective: We aimed to explore the diagnostic efficiency of DNA methylation in peripheral blood monocytes (PBMCs) in PDAC., Methods: 850K BeadChips were used to detect genome-wide methylation of PBMCs. For the selected sites, MethylTarget assays was used for further verification. The support vector machine was used to establish the combined panel., Results: A total of 167 PDAC patients and 113 healthy controls were included in this study and were divided into three sets. In the discovery set, we found 4625 differentially methylated positions (DMPs) between cancer group and healthy controls. ZFHX3 (0.16 ± 0.04 vs. 0.18 ± 0.04, P = 0.001), cg01904886 (0.84 ± 0.05 vs. 0.81 ± 0.04, P = 0.02) and NUMBL (0.96 ± 0.005 vs. 0.957 ± 0.005, P = 0.04) were found to be significantly different in training set. The locus with more significant differences, namely ZFHX3, was used for further validation and to establish a combined diagnostic panel with CA19-9. In the validation set, the ROC curve indicated that the AUC value of ZFHX3 was 0.75. The AUC value of the combined model (AUC = 0.92) was higher than that of CA19-9 alone (AUC = 0.88). In patients with normal CA19-9 levels, the ZFHX3 methylation biomarker still maintained good diagnostic efficacy (AUC = 0.71)., Conclusion: Our study preliminarily suggests that ZFHX3 methylation combined with CA19-9 can improve the detection rate of PDAC. Especially in patients with normal CA19-9, ZFHX3 methylation can maintain stable diagnostic efficacy. The diagnostic value of ZFHX3 methylation still needs to be prospectively validated., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: HBP, a novel biomarker released from neutrophils, may induce inflammatory responses and exacerbate vascular permeability, representing the pathophysiological characteristics of sepsis and septic shock. However, it remains uncertain whether the combination of HBP with other biomarkers yields enhanced diagnostic capacity for sepsis. We hypothesized that measurements included IL-6·IL-8·HBP, IL-6·IL-8·HBP/ALB and HBP/ALB which based on HBP will improve its diagnostic efficacy and even better than the traditional infection biomarkers., Methods: Between July 2021 and June 2022, we carried out a comprehensive, multi-center, observational cohort study spanning six leading tertiary hospitals located in Heilongjiang Province, China. Patients were stratified into three categories based on the severity of infection: non-sepsis, sepsis, and septic shock. We collected clinical and laboratory data, along with infection and inflammation biomarkers, for analysis., Results: A total of 195 patients were enrolled. Among the three groups, patients with septic shock (n = 75, 38.5%) had significantly higher baseline levels of HBP, WBC, Lac, CRP, PCT, IL-6, IL-8, and IL-10 compared to non-sepsis patients (n = 43, 22.0%) and sepsis patients (n = 77, 39.5%), with statistically significant differences (p < 0.05) observed for all parameters. When compared to SOFA score and traditional markers of CRP, PCT, IL-6 and IL-8, the combined indexes of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB demonstrated significantly improved diagnostic performance for sepsis and septic shock (AUC 0.911 and 0.902 respectively, p < 0.001)., Conclusions: The combined measurements of IL-6·IL-8·HBP and IL-6·IL-8·HBP/ALB can augment the diagnostic capacity of HBP for sepsis, and offer reliable early supplementary indicators to traditional biomarkers for assessing disease severity in patients with infection., (© 2024. The Author(s).)

Polycarboxylate superplasticizers BMC-L and BMC-S were utilized as modifiers in the formulation of novel cement-based grouting materials. Indoor tests were conducted on 32 groups of cement slurries, varying by water-cement ratio (0.5:1 and 0.6:1) and modifier content (0, 2‱, 4‱, 6‱, 8‱, 10‱, 12‱, and 14‱), to test their density, funnel viscosity, water separation rate, and stone rate. Four groups of slurry modified with BMC-L were selected as the preferred slurry, and the apparent viscosity test, uniaxial, and triaxial compression test of the slurry stone body were conducted. The study investigated the influence of BMC-L on various properties of the slurry, including its apparent viscosity, uniaxial compressive strength, stress-strain relationships, shear strength parameters, and elastic modulus. Ultimately, the pore structure and phase composition of the slurry stone body were detected by Nuclear Magnetic Resonance (NMR) and X-ray Diffraction (XRD), and the impact of BMC-L on slurry performance was examined from a microstructural perspective. Results indicate that the two polycarboxylate superplasticizers exert minimal influence on the density and water separation rate of the slurry. Within the effective incorporation range of the polycarboxylate superplasticizer, increasing the dosage correlates with a decrease in both the stone rate and viscosity of the slurry. BMC-L significantly enhances the mechanical properties of the slurry stone body by promoting more complete cement hydration and reducing porosity. The uniaxial compressive strength of slurry stone body with a 6 ‱ BMC-L dosage reached 29.7 MPa after 7 days and 38.5 MPa after 28 days of curing, representing increases of 118.4% and 64%, respectively, compared to masonry with 0 BMC-L dosage. The shear strength parameters and elastic modulus of the slurry stone body also showed corresponding increases.

As the understanding of natural gas hydrates as a vast potential resource deepens, their importance as a future clean energy source becomes increasingly evident. However, natural gas hydrates trend towards secondary generation during extraction and transportation, leading to safety issues such as pipeline blockages. Consequently, developing new and efficient natural gas hydrate inhibitors has become a focal point in hydrate research. Kinetic hydrate inhibitors (KHIs) offer an effective solution by disrupting the nucleation and growth processes of hydrates without altering their thermodynamic equilibrium conditions. This paper systematically reviews the latest research progress and development trends in KHIs for natural gas hydrates, covering their development history, classification, and inhibition mechanisms. It particularly focuses on the chemical properties, inhibition effects, and mechanisms of polymer inhibitors such as polyvinylpyrrolidone (PVP) and polyvinylcaprolactam (PVCap). Studies indicate that these polymer inhibitors provide an economical and efficient solution due to their low dosage and environmental friendliness. Additionally, this paper explores the environmental impact and biodegradability of these inhibitors, offering guidance for future research, including the development, optimization, and environmental assessment of new inhibitors. Through a comprehensive analysis of existing research, this work aims to provide a theoretical foundation and technical reference for the commercial development of natural gas hydrates, promoting their safe and efficient use as a clean energy resource.

A novel air-lifting loop reactor combines anoxic, oxic, and settling zones to achieve organic and nutrient removal, as well as solid-liquid separation. To address sludge settling ability and operation stability issues caused by low dissolved oxygen in aerobic zones, this study proposes using modified polypropylene carriers to establish a fixed-film activated sludge (IFAS) system. A pilot-scale demonstration of the IFAS-based air-lifting loop reactor is conducted, and the results show successful operation for approximately 300 days. The pilot-scale reactor achieves a maximum aerobic granulation ratio of 16% in the bulk liquid. The IFAS system contributes to efficient removal of organic matter (96%) and nitrogen (94%) by facilitating simultaneous nitrification and denitrification, as well as fast solid-liquid separation with a low sludge volume index of 34 mL/g. Microbial analysis reveals enrichment of functional bacteria involved in nitrification, denitrification, and flocculation throughout the operation process., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Ion transport efficiency, the key to determining the cycling stability and rate capability of all-solid-state lithium metal batteries (ASSLMBs), is constrained by ionic conductivity and Li + -migration ability across the multicomponent phases and interfaces in ASSLMBs. Here, we report a robust strategy for the large-scale fabrication of a practical solid electrolyte composite with high-throughput linear Li + -transport channels by compositing an all-trans block copolymer PVDF- b -PTFE matrix with ferroelectric BaTiO 3 -TiO 2 nanofiber films. The electrolyte shows a sustainable electromechanical-coupled deformability that enables the rapid dissociation of anions with Li + to create more movable Li + ions and spontaneously transform the battery internal strain into Li + -ion migration kinetic energy. The ceramic framework homogenizes the interfacial potential with electrodes, endowing the electrolyte with a high conductivity of 0.782 mS·cm -1 and stable ion transport ability in ASSLMBs at room temperature. The batteries of LiFePO 4 /Li can stably cycle 1000 times at 0.5 C with a high capacity retention of 96.1%, and Ah-grade pouch or high-voltage Li(Ni 0.8 Mn 0.1 Co 0.1 )O 2 /Li batteries also exhibit excellent rate capability and cycling performance.

Gallbladder cancer (GBC) is the most common malignant tumor of the biliary system with the worst prognosis. Even after radical surgery, the majority of patients with GBC have difficulty achieving a clinical cure. The risk of tumor recurrence remains more than 65%, and the overall 5-year survival rate is less than 5%. The gut microbiota refers to a variety of microorganisms living in the human intestine, including bacteria, viruses and fungi, which profoundly affect the host state of general health, disease and even cancer. Over the past few decades, substantial evidence has supported that gut microbiota plays a critical role in promoting the progression of GBC. In this review, we summarize the functions, molecular mechanisms and recent advances of the intestinal microbiota in GBC. We focus on the driving role of bacteria in pivotal pathways, such as virulence factors, metabolites derived from intestinal bacteria, chronic inflammatory responses and ecological niche remodeling. Additionally, we emphasize the high level of correlation between viruses and fungi, especially EBV and Candida spp., with GBC. In general, this review not only provides a solid theoretical basis for the close relationship between gut microbiota and GBC but also highlights more potential research directions for further research in the future., 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 © 2024 Liu, Li, Chen, Li, Geng, Liu and Wu.)

Background: CXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4., Methods: This study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis., Results: 100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively)., Conclusion: Differential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis., 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 © 2024 Pang, Li, Shi, Fan, Gao, Meng, Liu, Gao, Su, Wang and Zhan.)

Introduction: The dietary protein level plays a crucial role in maintaining the equilibrium of rumen microbiota in yaks. To explore the association between dietary protein levels, rumen microbiota, and muscle metabolites, we examined the rumen microbiome and muscle metabolome characteristics in yaks subjected to varying dietary protein levels., Methods: In this study, 36 yaks were randomly assigned to three groups ( n = 12 per group): low dietary protein group (LP, 12% protein concentration), medium dietary protein group (MP, 14% protein concentration), and high dietary protein group (HP, 16% protein concentration)., Results: 16S rDNA sequencing revealed that the HP group exhibited the highest Chao1 and Observed&#95;species indices, while the LP group demonstrated the lowest. Shannon and Simpson indices were significantly elevated in the MP group relative to the LP group ( P < 0.05). At the genus level, the relative abundance of Christensenellaceae&#95;R-7&#95;group in the HP group was notably greater than that in the LP and MP groups ( P < 0.05). Conversely, the relative abundance of Rikenellaceae&#95;RC9&#95;gut&#95;group displayed an increasing tendency with escalating feed protein levels. Muscle metabolism analysis revealed that the content of the metabolite Uric acid was significantly higher in the LP group compared to the MP group ( P < 0.05). The content of the metabolite L-(+)-Arabinose was significantly increased in the MP group compared to the HP group ( P < 0.05), while the content of D-(-)-Glutamine and L-arginine was significantly reduced in the LP group ( P < 0.05). The levels of metabolites 13-HPODE, Decanoylcarnitine, Lauric acid, L-(+)-Arabinose, and Uric acid were significantly elevated in the LP group relative to the HP group ( P < 0.05). Furthermore, our observations disclosed correlations between rumen microbes and muscle metabolites. The relative abundance of NK4A214&#95;group was negatively correlated with Orlistat concentration; the relative abundance of Christensenellaceae&#95;R-7&#95;group was positively correlated with D-(-)-Glutamine and L-arginine concentrations., Discussion: Our findings offer a foundation for comprehending the rumen microbiome of yaks subjected to different dietary protein levels and the intimately associated metabolic pathways of the yak muscle metabolome. Elucidating the rumen microbiome and muscle metabolome of yaks may facilitate the determination of dietary protein levels., 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 © 2024 Pang, Wang, Chai, Yang, Wang, Liu, Ding and Wang.)

The stacking of phosphogypsum has caused considerable phosphorus pollution in water bodies near phosphogypsum yards through surface runoff and underground infiltration. The phosphate oxygen isotope (δ 18 O p ) tracing method has served as a valuable tool for tracing phosphorus pollution in water. However, the existing δ 18 O p enrichment and purification methods are complex, costly, and inefficient for phosphate recovery, particularly for phosphogypsum leachate with complex compositions. Herein, a simplified and optimized pretreatment method for δ 18 O p measurement in phosphogypsum leachate was developed. Zirconium/polyvinyl alcohol (Zr/PVA) gel beads showed good selectivity for phosphate enrichment from water at different initial phosphate concentrations with appropriate Zr/PVA dosage. The optimal enrichment pH value was <7, and the concentrated phosphate on the Zr/PVA gel beads could be effectively eluted in an alkaline environment. Compared with the traditional Fe or Mg coprecipitation enrichment methods, impurities in the solution showed no obvious adverse effects on the phosphate enrichment process. Further, the phosphate solution eluted from the Zr/PVA gel beads was purified by a simple adjustment of the pH instead of cation exchange in the traditional purification process. Magnesium ions in the solution could be completely removed when the pH ranged from 3.17 to 6.15, and the phosphate recovery rate could reach 98.66% when the eluent pH was 5.02. Fourier-transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy revealed that similar to traditional pretreatment method, the proposed method can obtain high-purity Ag 3 PO 4 solids for δ 18 O P measurement and no isotope fractionation of δ 18 O P was observed. Therefore, this study provides a promising and reliable pretreatment method for δ 18 O P measurement, especially in complex phosphogypsum leachate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Ovarian cancer is one of the most common cancers in women. Profiles changes of microRNAs (miRNAs) are closely linked to malignant tumors. In the present study, we investigated expression of miR-451a in high-grade serous ovarian cancer (HGSOC). We also investigated the potential pathological roles and the likely mechanism of miR-451a in the development of HGSOC using animal models and cell lines., Methods: Using bioinformatics techniques and a real-time PCR, we analyzed differently expressed miRNAs in HGSOC compared to normal tissue. MTT (i.e. 3-[4, 5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide), EDU (i.e. 5-ethynyl-2'-deoxyuridine) and transwell assays were performed to investigate the effect of miR-451a on the proliferation and migration of HGSOC SKOV-3 cells. A dual luciferase reporter assay was performed to verify the targeting relationship of miR-451 and RAB5A (one of the Rab GTPase proteins that regulates endocytosis and vesicle transport). Also, we analyzed levels of the RAB5A mRNA and protein by real-time PCR, western blotting and immunohistochemistry assays in HGSOC cells and tissues. Finally, we performed in vivo experiments using HGSOC mice., Results: miR-451a was substantially upregulated in HGSOC and associated with favorable clinical characteristics. miR-451a knockdown significantly increased growth and metastasis of HGSOC cell line SKOV-3 through Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling. In addition, RAB5A, an early endosome marker, was shown to be a direct target of miR-451a. Moreover, RAB5A is correlated with unfavorable clinical features and shows independent prognostic significance in HGSOC., Conclusions: We found that the miR-451a/RAB5A axis is associated with tumorigenesis and progression through the Ras/Raf/MEK/ERK pathway, providing prognostic indicators and therapeutic targets for patients with HGSOC., (© 2024 John Wiley & Sons, Ltd.)

Polyethylene glycol-coated magnetic nanoparticles (PEGylated MNPs) have demonstrated prominent advantages in cancer diagnosis and hyperthermia therapy. However, there is currently lack of standard mode and sufficient toxicity data for determining the delayed risk of PEGylated MNPs. Nevertheless, the toxicity potentials, especially those associated with the oxidative stress, were ubiquitously reported. In this study, PEGylated MNPs and p-PEGylated MNPs were administrated to SD (Sprague Dawley) rats by single intravenously injection, and various toxicity indicators were monitored till 56 days post-administration for a comprehensive toxicity evaluation. We revealed that both nanoparticles could be rapidly cleared from plasma and enter tissues, such as, liver, kidneys and spleen, and p-PEGylated MNP is less prone to be accumulated in the tissues, indicating a lower toxicity risk. PEGylated MNPs were more likely to up-regulate the expression levels of Th2 type cytokines and trigger inflammatory pathways, but no related pathological change was found. Both MNPs are not mutagenic, while recoverable mild DNA damage associated with the presence of nanoparticles might also be observed. This study demonstrated a research approach for the non-clinical safety evaluation of nanoparticles. It also provided comprehensive valuable safety data for PEGylated and p-PEGylated MNPs, for promoting the clinical application and bio-medical translation of such MNPs with PEG modifications in the cancer diagnosis and therapy., (© 2023. The Author(s).)

The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the regulatory mechanisms of the gut microbiota in animal organisms hypobaric hypoxia exposure require further study. We conducted a research by comparing SD rats treated with an antibiotic (ABX) cocktail and untreated SD rats that were housed in a low-pressure oxygen chamber (simulating low pressure and hypoxic environment at 6000 m altitude) for 30 days. After the experiment, blood, feces, and lung tissues from SD rats were collected for analysis of blood, 16S rRNA amplicon sequencing, and non-targeted metabolomics. The results demonstrated that the antibiotic cocktail-treated SD rats exhibited elevated counts of neutrophil (Neu) and monocyte (Mon) cells, an enrichment of sulfate-reducing bacteria (SBC), reduced levels of glutathione, and accumulated phospholipid compounds. Notably, the accumulation of phospholipid compounds, particularly lysophosphatidic acid (LPA), lipopolysaccharide (LPS), and lysophosphatidylcholine (LPC), along with the aforementioned changes, contributed to heightened oxidative stress and inflammation in the organism. In addition, we explored the resistance mechanisms of SD rats in low-oxygen and low-pressure environments and found that increasing the quantity of the Prevotellaceae and related beneficial bacteria (especially Lactobacillus) could reduce oxidative stress and inflammation. These findings offer valuable insights into enhancing the adaptability of low-altitude animals under hypobaric hypoxia exposure., 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.)

Craniofacial anomalies are one of the most frequent birth defects worldwide and are often caused by genetic and environmental factors such as pharmaceuticals and chemical agents. Although identifying adverse outcome pathways (AOPs) is a central issue for evaluating the teratogenicity, the AOP causing craniofacial anomalies has not been identified. Recently, zebrafish has gained interest as an emerging model for predicting teratogenicity because of high throughput, cost-effectiveness and availability of various tools for examining teratogenic mechanisms. Here, we established zebrafish sox10-EGFP reporter lines to visualize cranial neural crest cells (CNCCs) and have identified the AOPs for craniofacial anomalies. When we exposed the transgenic embryos to teratogens that were reported to cause craniofacial anomalies in mammals, CNCC migration and subsequent morphogenesis of the first pharyngeal arch were impaired at 24 hours post-fertilization. We also found that cell proliferation and apoptosis of the migratory CNCCs were disturbed, which would be key events of the AOP. From these results, we propose that our sox10-EGFP reporter lines serve as a valuable model for detecting craniofacial skeletal abnormalities, from early to late developmental stages. Given that the developmental process of CNCCs around this stage is highly conserved between zebrafish and mammals, our findings can be extrapolated to mammalian craniofacial development and thus help in predicting craniofacial anomalies in human., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology.)

Obesity is an essential risk factor for pancreatic cancer (PC). Macrophage-induced inflammation plays a pivotal role in obesity-associated carcinogenesis and disease progression; however, the underlying molecular mechanisms remain unclear. In this study, we found that fatty acid-binding protein 4 (FABP4) overexpressed in serum of obese patients and was associated with poor overall survival. In vivo and in vitro experiments have revealed that FABP4 induces macrophage-related inflammation to promote cancer cell migration, invasion and metastasis under obese conditions. Mechanistically, FABP4 participates in transferring saturated fatty acid to induce macrophages pyroptosis in a caspase-1/GSDMD-dependent manner and mediates NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/IL-1β axis in macrophages, which further regulates epithelial-mesenchymal transition signals to promote the migration, invasion, and metastasis of PC cells. Our results suggest that FABP4 in macrophages is a crucial regulator of the NLRP3/IL-1β axis to promote the progression of PC under obese conditions, which could act as a promising molecular target for treating of PC patients with obesity., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The use of noninvasive ventilation (NIV) during and after extubation is common. We designed this study to determine the optimal strategy to compensate for mask leaks and achieve effective ventilation during NIV by comparing commonly used operating room ventilator systems and a regular facemask., Methods: We tested four operating room ventilator systems (Dägger Zeus, Dägger Apollo, Dägger Fabius Tiro, and General Electric Healthcare Carestation 650) on a lung model with normal compliance and airway resistance and evaluated pressure control ventilation (PCV), volume control ventilation (VCV), and AutoFlow mode (VAF). We set the O 2 flow at 10 L/min and the maximal flow at 13, 16, or 26 L/min. We simulated five leak levels, from no leak to over 40 L/min (I to V levels), using customized T-pieces placed between the lung model and the breathing circuit. We recorded the expired tidal volume (Vte) from the lung model and peak inspiratory pressure via two flow/pressure sensors that were placed distally and proximally to the T-pieces., Results: 1. Comparison of four ventilators: with any given ventilation mode, an increase in leak level caused a decrease in Vte. With PCV, only Zeus produced Vte larger than 150 ml at leak level V. 2. Effect of ventilation mode on Vte: across all four ventilators, PCV resulted in a higher Vte than VCV and VAF (P < 0.01). PCV mode with all ventilators at leak level II provided Vte values that were equal to or greater than those obtained with no leak. 3. Effect of O 2 flow on Vte Using PCV mode: only Carestation 650 Vte at leak level II during PCV were significantly greater with 16 L/min O 2 flow compared with 10 L/min O 2 flow (P < 0.01). 4. Actual leak: increasing the O 2 flow from 10 L/min to the maximum O 2 flow dramatically increased the real leak with all 4 ventilators at any fixed leak level (P < 0.01). 5. Preset PIP vs. actual PIP with PCV: at low preset PIP and leak levels such as leak II and III, the discrepancy between preset PIP and actual PIP was small. The disparity between the preset and actual PIP grew when the target PIP and the leak level were raised., Conclusion: For NIV using a mask, the ventilator is preferred whose Pressure generator is Turbine, the PCV mode is preferred in the ventilation mode and the oxygen flow is set to 10 L/min or maximum oxygen flow., Competing Interests: 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., (© 2023 The Authors.)

Achieving simultaneous carbon and nitrogen removal with sludge-liquid separation in a single reactor offers a solution to land shortages and improves treatment efficiency in municipal wastewater treatment plants of megacities. This study proposes a novel air-lifting continuous-flow reactor configuration with an alternative-aeration strategy that creates multi-functional zones for anoxic, oxic, and settlement processes. The optimal operating conditions for the reactor include a long anoxic hydraulic retention time, low dissolved oxygen (DO) in the oxic zone, and no specific reflux for external nitrifying liquid, which exhibit a high nitrogen removal efficiency of over 90% in treating real sewage with C/N < 4 in the pilot-scale study. Results show that a high sludge concentration and a low DO concentration facilitate simultaneous nitrification and denitrification, and a well mixing of sludge and substrate in different reaction zones promotes mass transfer and microbial activity. The long-term operation enriches functional microbes for carbon storage and nutrient removal., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Yak ( Bos grunniens ) is an important economic animal species on the Qinghai-Tibet Plateau. Yaks grazed in the cold season often suffer from nutritional stress, resulting in low production performance. This situation can be improved by properly feeding the grazing yaks in the cold season; however, there is still little information about the effect of different feeding levels on the intestinal microflora and metabolites of yaks. Therefore, this study aimed to explore the effect of feeding different doses of concentrate supplements on rumen bacterial communities and metabolites in grazing yaks during the cold season. Feed concentrate supplementation significantly improved the production performance and rumen fermentation status of grazing yaks during the cold season, and switched the type of ruminal fermentation from acetic acid fermentation to propionic acid fermentation. Ruminal fermentation parameters and ruminal bacterial abundance correlated strongly. At the phylum level, the abundance of Firmicutes increased with increasing concentrate supplementation, while the opposite was true for Bacteroidota . At the genus level, the abundance of Christensenellaceae&#95;R-7&#95;group , NK4A214&#95;group , Ruminococcus , norank&#95;f&#95;&#95;Eubacterium&#95;coprostanoligenes&#95;group , norank&#95;f&#95;&#95;norank&#95;o&#95;&#95; Clostridia&#95;UCG-014 , Lachnospiraceae&#95;NK3A20&#95;group , Acetitomaculum , and Family&#95;XIII&#95;AD3011&#95;group increased with increasing concentrate supplementation, while the abundance of Rikenellaceae&#95;RC9&#95;gut&#95; group decreased. Dietary concentrate supplementation altered the concentration and metabolic mode of metabolites in the rumen, significantly affecting the concentration of metabolites involved in amino acid and derivative metabolism (e.g., L-aspartic acid, L-glutamate, and L-histidine), purine metabolism (e.g., guanine, guanosine, and hypoxanthine), and glycerophospholipid metabolism (e.g., phosphatidate, phosphatidylcholine, and phosphocholine), and other metabolic pathways. The strong correlation between yak rumen microorganisms and metabolites provided a more comprehensive understanding of microbial community composition and function. This study showed significant changes in the composition and abundance of bacteria and metabolites in the rumen of cool season grazing yaks fed with concentrate supplements. Changes in ruminal fermentation parameters and metabolite concentration also showed a strong correlation with ruminal bacterial communities. These findings will be helpful to formulate supplementary feeding strategies for grazing yaks in the cold season from the perspective of intestinal microorganisms., 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 Yi, Wu, Liu, Dai, Meng, Chai, Liu and Zhou.)

Copper, manganese, and iodine are part of a yak's required trace elements. However, knowledge about their dietary requirements is scarce. Therefore, an experiment was conducted to evaluate rumen fermentation, blood parameters, and growth performance and screen out the optimum levels of trace elements in yaks' diet. Here, 18 three-year-old castrated yaks were randomly divided into four groups, which fed with diets containing basal (CON: 4.40, 33.82, and 0 mg/kg) and low-level (LL: 10.00, 40.00, and 0.30 mg/kg), middle-level (ML: 15.00, 50.00, and 0.50 mg/kg), and high-level (HL: 20.00, 60.00, and 0.70 mg/kg) copper, manganese, and iodine for 30 days. With the increase in trace elements, yaks' daily weight gain (DWG), rumen pH, ammonia nitrogen, microbial protein (MCP), and volatile fatty acids levels and serum triglycerides and urea nitrogen levels showed firstly increasing and then decreasing trends and reached the highest values in ML, and serum ceruloplasmin and total superoxide dismutase (T-SOD) activities showed continuously increasing trends. Yaks' DWG, rumen MCP, butyrate, and valerate levels and serum triglycerides, urea nitrogen, ceruloplasmin, and T-SOD levels in ML were significantly higher than CON. Therefore, the recommended levels of copper, manganese, and iodine in growing yaks' diet are 15.00, 50.00, and 0.50 mg/kg (ML), respectively.

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), two immunosuppressive myeloid components within the tumor microenvironment (TME), represent fundamental barriers in cancer immunotherapy, whereas current nanomedicines rarely exert dual modulatory roles on these cell types simultaneously. Reactive oxygen species (ROS) not only mediates MDSC-induced immunosuppression but also triggers differentiation and polarization of M2-TAMs. Herein, an ROS scavenging nanozyme, Zr-CeO, with enhanced superoxide dismutase- and catalase-like activities for renal tumor growth inhibition is reported. Mechanistically, intracellular ROS scavenging by Zr-CeO significantly attenuates MDSC immunosuppression via dampening the unfolded protein response, hinders M2-TAM polarization through the ERK and STAT3 pathways, but barely affects neoplastic cells and cancer-associated fibroblasts. Furthermore, Zr-CeO enhances the antitumor effect of PD-1 inhibition in murine renal and breast tumor models, accompanied with substantially decreased MDSC recruitment and reprogrammed phenotype of TAMs in the tumor mass. Upon cell isolation, reversed immunosuppressive phenotypes of MDSCs and TAMs are identified. In addition, Zr-CeO alone or combination therapy enhances T lymphocyte infiltration and IFN-γ production within the TME. Collectively, a promising strategy to impair the quantity and function of immunosuppressive myeloid cells and sensitize immunotherapy in both renal and breast cancers is provided., (© 2023 Wiley-VCH GmbH.)

A relatively stable microbial ecological balance system in the rumen plays an important role in rumen environment stability and ruminant health maintenance. No studies have reported how rumen fluid transplantation (RFT) affects the composition of rumen microorganisms and yak growth performance. In this experiment, we transplanted fresh rumen fluid adapted to house-feeding yaks to yaks transitioned from natural pastures to house-feeding periods to investigate the effects of rumen fluid transplantation on rumen microbial community regulation and production performance. Twenty yaks were randomly divided into the control group (CON; n = 10) and the rumen fluid transplantation group (RT; n = 10). Ten yaks that had been adapted to stall fattening feed in one month were selected as the rumen fluid donor group to provide fresh rumen fluid. Ruminal fluid transplantation trials were conducted on the 1st, 3rd, and 5th. Overall, 1 L of ruminal fluid was transplanted to each yak in the RT and CON group. The formal trial then began with both groups fed the same diet. After this, growth performance was measured, rumen fluid was collected, and rumen microbial composition was compared using 16s rRNA sequencing data. The results showed that rumen fluid transplantation had no significant effect on yak total weight gain or daily weight gain ( p > 0.05), and feed efficiency was higher in the RT group than in the CON group at 3 months (treatment × month: p < 0.01). Ruminal fluid transplantation significantly affected rumen alpha diversity ( p < 0.05). Up to day 60, the RT group had significantly higher OTU numbers, Shannon diversity, and Simpson homogeneity than the CON group. Principal coordinate analysis showed that the rumen microbiota differed significantly on days 4 and 7 ( p < 0.05). Bacteroidota, Firmicutes, Proteobacteria, and Spirochaetes were the most abundant phyla in the rumen. The relative abundances of Bacteroidota, Proteobacteria, and Spirochaetes were lower in the RT group than in the CON group, with a decrease observed in Bacteroidota in the RT group on days 7 and 28 after rumen fluid transplantation ( p = 0.013), while Proteobacteria showed a decreasing trend in the CON group and an increasing trend in RT; however, this was only at day 4 ( p = 0.019). The relative abundance of Firmicutes was significantly higher in the RT group than in the CON group on days 4, 7, and 28 ( p = 0.001). Prevotella and Rikenellaceae&#95;RC9&#95;gut&#95;group were the predominant genera. In conclusion, our findings suggest that rumen fluid transplantation improves yak growth performance and rumen microbial reshaping. The findings of this study provide new insights into yak microbial community transplantation and a reference for improving feed efficiency in the yak industry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflict of interest.

The efficacy of radiotherapy (RT) is usually restricted by the hypoxic microenvironment and the poor radiation attenuation coefficient of tumor tissue. Theranostic probes that simultaneously evaluate the hypoxia degree and sensitize cancer cells toward RT are promising for improving the treatment efficacy and avoiding overtreatment. We rationally designed a metal-organic framework (MOF)-derived multifunctional nanoprobe for hypoxia imaging-guided radiosensitization. Hf-MOF was carbonized to obtain a porous carbonous nanostructure containing ultrasmall HfO 2 (HfC); then, a fluorophore-labeled HIF-α mRNA antisense sequence was readily adsorbed and quenched by HfC to obtain the nanoprobe (termed HfC-Hy). The antisense sequence could easily hybridize with HIF-α mRNA and recover its fluorescence signal to evaluate the degree of hypoxia, while the HfC nanostructure could deposit more radiation energy in cancer cells for radiosensitization. A series of in vitro and in vivo experiments demonstrated that the nanoprobe could be successfully utilized for imaging the hypoxic degree of cancer cells/tumor tissue and guiding radiosensitization. This work not only developed a highly efficient and safe nanosensitizer but also offered a potential solution for customized clinical RT.

Nanozymes are functional nanomaterials with enzyme-mimicking activities, which have found wide applications in various fields. Investigation on nanozyme inhibitors not only helps to apply nanozymes in a controlled manner but also deepens our insight into the catalysis mechanism. Herein, we report an inorganic ion inhibitor, HCO 3 - , which can significantly inhibit the alkaline phosphatase-mimicking activities of Ce 6 cluster-based metal-organic framework (Ce-MOF) nanozymes. The inhibition of adsorption of the negatively charged fluorescence sodium on Ce 6 clusters in Ce-MOF nanoparticles (NPs) by HCO 3 - proves that HCO 3 - ions occupy and deactivate Ce 6 clusters (i.e., catalytic active sites), leading to the activity inhibition of Ce-MOF nanozymes. Tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) buffer is widely employed as the alkaline reaction medium. HCO 3 - ions can be formed in Tris-HCl buffer through adsorption of CO 2 in the air during storage in a sealed tube, which significantly inhibits the activity of Ce-MOF nanozymes. To our knowledge, this study is the first to demonstrate an air-derived inhibitor of nanozymes.

As a widely used material in underground engineering, clay-cement slurry grouting is characterized by poor initial anti-seepage and filtration capacity, low strength of the resulting stone body, and a tendency to brittle failure. In this study, a novel type of clay-cement slurry was developed by adding of graphene oxide (GO) as a modifier to ordinary clay-cement slurry. The rheological properties of the improved slurry were studied through laboratory tests, and the effects of varying amounts of GO on the slurry's viscosity, stability, plastic strength, and stone body mechanical properties were analyzed. The results indicated that the viscosity of clay-cement slurry increases by a maximum of 163% with 0.05% GO, resulting in a decrease in the slurry's fluidity. The stability and plastic strength of GO-modified clay-cement slurry were significantly enhanced, with the plastic strength increasing by a 5.62 time with 0.03% GO and a 7.11 time with 0.05% GO at the same curing time. The stone body of the slurry exhibited increased uniaxial compressive strength and shear strength, with maximum increases of 23.94% and 25.27% with 0.05% GO, respectively, indicating a significant optimization effect on the slurry's durability. The micro-mechanism for the effect of GO on the properties of slurry was investigated using scanning electron microscopy (SEM) and a diffraction of X-rays (XRD) test. Moreover, a growth model of the stone body of GO-modified clay-cement slurry was proposed. The results showed that after the GO-modified clay-cement slurry was solidified, a clay-cement agglomerate space skeleton with GO monolayer as the core was formed inside the stone body, and with an increase in GO content from 0.03% to 0.05%, the number of clay particles increased. The clay particles filled the skeleton to form a slurry system architecture, which is the primary reason for the superior performance of GO-modified clay-cement slurry when compared with traditional clay-cement slurry.

Introduction: Manganese (Mn) is an essential trace element for livestock, but little is known about the optimal Mn source and level for yak., Methods: To improve yak's feeding standards, a 48-h in vitro study was designed to examine the effect of supplementary Mn sources including Mn sulfate (MnSO 4 ), Mn chloride (MnCl 2 ), and Mn methionine (Met-Mn) at five Mn levels, namely 35 mg/kg, 40 mg/kg, 50 mg/kg, 60 mg/kg, and 70 mg/kg dry matter (includes Mn in substrates), on yak's rumen fermentation., Results: Results showed that Met-Mn groups showed higher acetate ( p < 0.05), propionate, total volatile fatty acids ( p < 0.05) levels, ammonia nitrogen concentration ( p < 0.05), dry matter digestibility (DMD), and amylase activities ( p < 0.05) compared to MnSO4 and MnCl2 groups. DMD ( p < 0.05), amylase activities, and trypsin activities ( p < 0.05) all increased firstly and then decreased with the increase of Mn level and reached high values at 40-50 mg/kg Mn levels. Cellulase activities showed high values ( p < 0.05) at 50-70 mg/kg Mn levels. Microbial protein contents ( p < 0.05) and lipase activities of Mn-Met groups were higher than those of MnSO4 and MnCl2 groups at 40-50 mg/kg Mn levels., Discussion: Therefore, Mn-met was the best Mn source, and 40 to 50 mg/kg was the best Mn level for rumen fermentation of yaks., Competing Interests: HL, CS, and YX were employed by Qinghai Pure Yak Biotechnology Co., LTD. The remaining 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 Lu, Liu, Liu, Zhao, Bai, Cheng, Zhang, Sun, Hao and Xue.)

Molecular therapeutics are limited for Candida vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing the recurrence. To tackle this limitation, through the combination of peroxidase-like rGO@FeS 2 nanozymes [reduced graphene oxide (rGO)] with Lactobacillus -produced lactic acid and H 2 O 2 , a responsive hyaluronic acid (HA) hydrogel rGO@FeS 2 / Lactobacillus @HA (FeLab) is developed. FeLab has simultaneous anti- Candida albicans and vaginal microbiota-modulating activities. In particular, the hydroxyl radical produced from rGO@FeS 2 nanozymes and Lactobacillus kills C. albicans isolated from clinical specimens without affecting Lactobacillus . In mice with Candida vaginitis, FeLab has obvious anti- C. albicans activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of Firmicutes (especially Lactobacillus ) and a decrease in Proteobacteria reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for Candida vaginitis therapy.

According to the 2020 global cancer data released by the World Cancer Research Fund (WCRF) International, gastric cancer (GC) is the fifth most common cancer worldwide, with yearly increasing incidence and the second-highest fatality rate in malignancies. Despite the contemporary ambiguous molecular mechanisms in GC pathogenesis, numerous in-depth studies have demonstrated that zinc finger proteins (ZFPs) are essential for the development and progression of GC. ZFPs are a class of transcription factors with finger-like domains that bind to Zn 2+ extensively and participate in gene replication, cell differentiation and tumor development. In this review, we briefly outline the roles, molecular mechanisms and the latest advances in ZFPs in GC, including eight principal aspects, such as cell proliferation, epithelial-mesenchymal transition (EMT), invasion and metastasis, inflammation and immune infiltration, apoptosis, cell cycle, DNA methylation, cancer stem cells (CSCs) and drug resistance. Intriguingly, the myeloid zinc finger 1 (MZF1) possesses reversely dual roles in GC by promoting tumor proliferation or impeding cancer progression via apoptosis. Therefore, a thorough understanding of the molecular mechanism of ZFPs on GC progression will pave the solid way for screening the potentially effective diagnostic indicators, prognostic biomarkers and therapeutic targets of GC.

Long noncoding RNAs (lncRNAs) play crucial roles in various biological processes, and they are considered to be closely associated with the pathogenesis of intestinal diseases. However, the role and expression of lncRNAs in intestinal damage during weaning stress remain unknown. Herein, we investigated the expression profiles of jejunal tissue from weaning piglets at 4 and 7 d after weaning (groups W4 and W7, respectively) and from suckling piglets on the same days (groups S4 and S7, respectively). Genome-wide analysis of lncRNAs was also performed using RNA sequencing technology. A total of 1809 annotated lncRNAs and 1612 novel lncRNAs were obtained from the jejunum of piglets. In W4 vs. S4, a total of 331 lncRNAs showed significant differential expression, and a total of 163 significantly differentially expressed lncRNAs (DElncRNAs) was identified in W7 vs. S7. Biological analysis indicated that DElncRNAs were involved in intestinal diseases, inflammation, and immune functions, and were mainly enriched in the Jak-STAT signaling pathway, inflammatory bowel disease, T cell receptor signaling pathway, B cell receptor signaling pathway and intestinal immune network for IgA production. Moreover, we found that lnc&#95;000884 and target gene KLF5 were significantly upregulated in the intestine of weaning piglets. The overexpression of lnc&#95;000884 also significantly promoted the proliferation and depressed apoptosis of IPEC-J2 cells. This result suggested that lnc&#95;000884 may contribute to repairing intestinal damage. Our study identified the characterization and expression profile of lncRNAs in the small intestine of weaning piglets and provided new insights into the molecular regulation of intestinal damage during weaning stress.

In this study, we used a combination of animal nutrition and nontargeted metabolomics to investigate the effects of feeding different sources forages rations on the morphology and function of the pancreas in preweaning yak calves, providing theoretical guidance and important references for the healthy and high-quality rearing of yak calves. At 45 days old, 21 yak calf males were divided into OP, AP, and AOP groups, with seven animals in each group, which were fed with oat hay, alfalfa hay, and mixed oat and alfalfa hay, respectively. Five calves from each group were selected randomly to slaughter after a pretest period of 21 days and the official period of 120 days, when the average daily feed intake reached 1 kg. During the test, the growth and pancreas weight of yak calves were recorded, and the morphology and function of the pancreas tissues were determined using tissue sectioning methods, enzyme-linked immunosorbent assay (ELISA) tests, and nontargeted metabolomics strategies. The results showed that the body weight and pancreatic organ index of yak calves in the AOP group were significantly higher than those of the AP and OP groups. Compared to the AP and OP groups, the AOP group had considerably lower ratios of the area of the pancreatic endocrine component and overall percentage of that section of the organ, and the AOP group increased pancreatic amylase activity and a higher concentration of growth inhibitor. The AP group had significantly higher levels of the differential metabolites L-ascorbic acid, spermidine, spermine, and dopaquinone in the glutathione, β-alanine, and tyrosine metabolic pathways than the OP group. The AOP group had significantly lower levels of the differential metabolites spermine and phenylacetylglycine in the glutathione and phenylalanine metabolic pathways than the AP group. In summary, compared to feeding oat or alfalfa hay alone, combined feeding oat hay and alfalfa hay is more beneficial to promote the morphological and functional development of the pancreas in preweaning yak calves, so as to enhance the digestion and absorption of nutrients in the diet and maintain the positive regulation of blood glucose levels. This provides an important basis for the optimized forage supply of healthy and high-quality rearing in preweaning yak calves.

DNA methylation profiles are in dynamic equilibrium via the initiation of methylation, maintenance of methylation and demethylation, which control gene expression and chromosome stability. Changes in DNA methylation patterns play important roles in carcinogenesis and primarily manifests as hypomethylation of the entire genome and the hypermethylation of individual loci. These changes may be reflected in blood-based DNA, which provides a non-invasive means for cancer monitoring. Previous blood-based DNA detection objects primarily included circulating tumor DNA/cell-free DNA (ctDNA/cfDNA), circulating tumor cells (CTCs) and exosomes. Researchers gradually found that methylation changes in peripheral blood mononuclear cells (PBMCs) also reflected the presence of tumors. Blood-based DNA methylation is widely used in early diagnosis, prognosis prediction, dynamic monitoring after treatment and other fields of clinical research on cancer. The reversible methylation of genes also makes them important therapeutic targets. The present paper summarizes the changes in DNA methylation in cancer based on existing research and focuses on the characteristics of the detection objects of blood-based DNA, including ctDNA/cfDNA, CTCs, exosomes and PBMCs, and their application in clinical research., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

With diversification of yak breeding, it is important to understand the effects of feed type on the rumen, especially microbiota and metabolites. Due to the unique characteristics of yak, research on rumen microbes and metabolites is limited. In this study, the effects of two diet types on rumen eukaryotic microflora and metabolites were evaluated using the Illumina MiSeq platform and liquid chromatography-mass spectrometry (LC-MS). All identified protozoa belonged to Trichostomatia . At the genus level, the relative abundance of Metadinium and Eudiplodinium were significantly ( p < 0.05) higher in the roughage group than that of concentrate group, while the concentrate group harbored more Isotricha . Ascomycota, Basidiomycota , and Neocallimastigomycota were the main fungal phyla, and the Wallemia, Chordomyces, Chrysosporium, Cladosporium, Scopulariopsis , and Acremonium genera were significantly ( p < 0.05) more abundant in the roughage group than the concentrate group, while the concentrate group harbored more Aspergillus, Neocallimastix, Thermoascus , and Cystofilobasidium ( p < 0.05). Metabolomics analysis showed that feed type significantly affected the metabolites of rumen protein digestion and absorption (L-proline, L-phenylalanine, L-tryosine, L-leucine, L-tryptophan, and β-alanine), purine metabolism (hypoxanthine, xanthine, guanine, guanosine, adenosine, and adenine), and other metabolic pathway. Correlation analysis revealed extensive associations between differential microorganisms and important metabolites. The results provide a basis for comprehensively understanding the effects of feed types on rumen microorganisms and metabolites of yaks. The findings also provide a reference and new directions for future research., 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 © 2022 Cui, Liu, Wu, Meng, Liu, Chai, Hao and Zhou.)

This study aimed to examine the relations between perceived teacher emotional support, Covid-19 anxiety, resilience, and mental well-being among Chinese vocational college students during Covid-19 pandemic. A sample of Chinese vocational college students ( n  = 1469) were surveyed with an online questionnaire composed of Teacher Emotional Support, Covid-19 Anxiety Scale, Brief Resilience Scale and Mental Well-being in Chinese version. Path analysis was employed in the study and the results showed that teacher emotional support was an important promoter for building up mental well-being but not a buffer for Covid-19 within Chinese cultural context, and the Covid-19 anxiety was significantly and negatively related to mental well-being. Resilience hindered the incidences of Covid-19 anxiety and was a significant protector for mental well-being. Covid-19 anxiety mediated the both relations between teacher emotional support and mental well-being, and resilience and mental well-being. These findings provided practical implications for coping with psychological problems and flourishing mental well-being among Chinese vocational college students., Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-04112-9., Competing Interests: Conflict of interestThe authors claim that there is no any potential conflicts of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Zika virus (ZIKV) targets the neural progenitor cells (NPCs) in brain during intrauterine infections and consequently causes severe neurological disorders, such as microcephaly in neonates. Although replicating in the cytoplasm, ZIKV dysregulates the expression of thousands of host genes, yet the detailed mechanism remains elusive. Herein, we report that ZIKV encodes a unique DNA-binding protein to regulate host gene transcription in the nucleus. We found that ZIKV NS5, the viral RNA polymerase, associates tightly with host chromatin DNA through its methyltransferase domain and this interaction could be specifically blocked by GTP. Further study showed that expression of ZIKV NS5 in human NPCs markedly suppressed the transcription of its target genes, especially the genes involved in neurogenesis. Mechanistically, ZIKV NS5 binds onto the gene body of its target genes and then blocks their transcriptional elongation. The utero electroporation in pregnant mice showed that NS5 expression significantly disrupts the neurogenesis by reducing the number of Sox2- and Tbr2-positive cells in the fetal cortex. Together, our findings demonstrate a molecular clue linking to the abnormal neurodevelopment caused by ZIKV infection and also provide intriguing insights into the interaction between the host cell and the pathogenic RNA virus, where the cytoplasmic RNA virus encodes a DNA-binding protein to control the transcription of host cell in the nuclei.

Objective: This study aimed to determine the role of COL17A1 in tumor progression and predict the prognosis of pancreatic cancer (PC)., Methods: RNA-seq data from The Cancer Genome Atlas and Genotype-Tissue Expression were analyzed using bioinformatics methods. "Limma" package was used to screen differentially expressed genes (DEGs). Prognostic-associated data were further analyzed using univariate Cox regression and verified using the GSE28375 and GSE62452 datasets. Protein-protein interaction (PPI) network analysis was integrated to screen for hub genes. In vitro quantitative real-time PCR (qPCR) and western blotting were used to detect gene expression. The functional attributes of PC cells were verified by wound healing assays, migration and invasion assays, Cell Counting Kit 8 (CCK8), and 5-ethynyl-2'-deoxyuridine (EdU) assay., Results: On analyzing PC data, 4637 DEGs were identified. Of these, 2399 genes were upregulated and 2238 were downregulated. Through PPI network analysis, we identified that COL17A1 expression was highly correlated with poor prognosis of patients with PC. Functional attribute assays in the in vitro study showed that COL17A1 knockdown inhibited PC cell proliferation, migration, and invasion., Conclusions: According to our results, COL17A1 promotes PC cell proliferation, migration, and invasion mediated by the epithelial-mesenchymal transition (EMT) pathway. Thus, COL17A1 could be used as a prognostic marker in PC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A novel vertical dual-loop reactor (VDLR) was developed to start and conduct a single-stage partial nitritation (PN) and anammox (PN/A) process for treating landfill leachate. Results showed that the total nitrogen (TN) removal reached 1.54 kg N/m 3 ·d in the VDLR. It exhibited excellent mixing uniformity and buffer performance, which can increase the nitrogen removal performance up to 42.1 % via the improvement of anammox granular sludge activity (a particle size of 0.5-1 mm). Mass balance and microbial analysis indicated that the VDLR achieved efficient TN removal via anammox (99.24 %) and AOB (Nitrosomonas and Ellin6067) and anAOB (Candidatus kuenenia) played a vital role in this process., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

According to the global cancer burden data for 2020 issued by the World Health Organization (WHO), colorectal cancer has risen to be the third-most frequent cancer globally after breast and lung cancer. Despite advances in surgical treatment and chemoradiotherapy for colon cancer, individuals with extensive liver metastases still have depressing prognoses. Numerous studies suggest ZFPs are crucial to the development of colon cancer. The ZFP family is encoded by more than 2% of the human genome sequence and is the largest transcriptional family, all with finger-like structural domains that could combine with Zn 2+ . In this review, we summarize the functions, molecular mechanisms and recent advances of ZFPs in colon cancer. We also discuss how these proteins control the development and progression of colon cancer by regulating cell proliferation, EMT, invasion and metastasis, inflammation, apoptosis, the cell cycle, drug resistance, cancer stem cells and DNA methylation. Additionally, several investigations have demonstrated that Myeloid zinc finger 1 (MZF1) has dual functions in colon cancer, which may both promote cancer proliferation and inhibit cancer progression through apoptosis. Generally, a comprehensive understanding of the action mechanisms of ZFPs in colon cancer will not only shed light on the discovery of new diagnostic and prognosis indicators but will also facilitate the design of novel targeted therapies.

Yaks living on the Qinghai-Tibetan Plateau for a long time have evolved a series of mechanisms to adapt to the unique geographical environment and climate characteristics of the plateau. Compared with other ruminants, yaks have higher energy utilization and metabolic efficiency. This paper presents possible mechanisms responsible for the efficient energy utilization, absorption and metabolism resulting from the unique evolutionary process of yaks. It is hoped that the information discussed in this review will give a better insight into the uniqueness and superiority of yaks in regards to energy metabolism and utilization compared with cattle and open new avenues for the targeted regulation of energy utilization pathways of other ruminants., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2022 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

This study examined the effect of the ratio of dietary metabolizable energy (MJ) to nitrogen (g) content (ME:N) on average daily gain (ADG), blood biochemical indices, rumen fermentation parameters, and rumen bacterial community in yaks. Thirty-six male yaks, aged 2-3 years, were divided into three groups and received a ME:N ratio of 0.42 (HY), 0.36 (MY,) or 0.32 (LY) MJ/g. Dry matter intake ranged between 3.16 and 3.63 kg/d and was lesser ( p  < 0.001) in the LY group than the other two groups. ME intake increased ( p  < 0.001) with an increase in the ME:N ratio, while N intake did not differ among groups. The ADG was 660 g/day for the MY group, which was higher ( p  < 0.005) than the 430 g/day in the LY group, while the HY group gained 560 g/day and did not differ from the other two groups. Feed intake to ADG ratio ranged between 5.95 and 7.95, and numerically was highest in the LY group and lowest in the MY group. In general, the concentration of ruminal total volatile fatty acids ( p  < 0.03) and molar proportions of propionate ( p  < 0.04), increased, while the molar proportion of acetate ( p  < 0.005) and the acetate:propionate ratio decreased ( p  < 0.001) with a decrease in the ME:N ratio. The molar proportion of butyrate did not differ among groups ( p  = 0.112). Group MY had higher ruminal NH 3 -N content than group HY and had a higher serum glucose content but lower urea content, lactate dehydrogenase, and creatine kinase content than group LY. In ruminal bacteria at the phylum level, the relative abundance of Firmicutes (F) was greater and of Bacteroidetes (B) was lesser, while the F:B ratio was greater in group MY than in groups HY an LY. We concluded that the yaks consuming the diet containing a ME:N ratio of 0.36 MJ/g had the best performance of the three groups., 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 © 2022 Liu, Li, Hao, Degen, Wang, Ma, Niu, Cheng and Liu.)

Ruminal microflora is closely correlated with the ruminant's diet. However, information regarding the effect of high concentrate diets on rumen microflora in yaks is lacking. In the current study, 24 healthy male yaks were randomly assigned to two groups, each fed with different diets: less concentrate (LC; concentrate: coarse = 40: 60) and high concentrate (HC; concentrate: coarse = 80: 20) diets. Subsequently, a 21-day feeding trial was performed with the yaks, and rumen fluid samples were collected and compared using 16 s rRNA sequencing. The results showed that NH 3 -N, total VFA, acetate, butyrate, isobutyrate, and isovalerate were significantly higher in the HC group than that in the LC group ( p  < 0.05), while microbial diversity and richness were significantly lower in the HC group ( p  < 0.05). Principal coordinate analysis indicated that rumen microflora was significantly different in LC and HC groups ( p  < 0.05). In the rumen, phyla Firmicutes and Bacteroidota were the most abundant bacteria, with Firmicutes being more abundant, and Bacteroidota being less abundant in the HC group than those found in the LC group. Christensenellaceae&#95;R-7&#95;group and Prevotella are the highest abundant ones at the genus level. The relative abundance of Acetitomaculum , Ruminococcus , and Candidatus&#95;Saccharimonas were significantly higher in the HC group than that in the LC group ( p  < 0.05), while the relative abundance of Olsenella was significantly lower in the HC group than in the LC group ( p  < 0.05). Compared to the LC group, the relative abundance of Prevotella , Ruminococcus , and Candidatus&#95;Saccharimonas was significantly higher in the HC group. The relative abundances of Prevotella , Prevotellaceae&#95;UCG-003 , Olsenella , Ruminococcus , Acetitomaculum , Candidatus&#95;Saccharimonas , and NK4A214&#95;group were correlated with ruminal fermentation parameters ( p  < 0.05). Furthermore, PICRUSt 2 estimation indicated that microbial genes associated with valine, leucine, and isoleucine biosynthesis were overexpressed in the rumen microflora of yaks in the HC group ( p  < 0.05). Conclusively, our results suggest that high concentrate diets affect the microflora composition and fermentation function in yak rumen. The present findings would provide new insights into the health of yaks under high concentrate feeding conditions and serve as a potent reference for the short-term fattening processes of yaks., 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 © 2022 Pang, Dai, Yang, Wang, Liu, Huang, Xue, Chai and Wang.)

This experiment was conducted to investigate the effect of supplemental concentrate feeding on the pancreatic development of yak calves. Twenty one-month-old yak calves with healthy body condition and similar body weight were selected as experimental animals and randomly divided into two groups, five replicates in each group. The control group yak calves were fed milk replacer and alfalfa hay, the experimental group yak calves were fed milk replacer, alfalfa hay and concentrate. The pre-feeding period of this experiment was thirty days, the trial period was one hundred days. At the end of feeding trail, five yak calves from each group were selected and slaughtered and the pancreas tissues of yak calves were collected and determined. The results showed that: (1) Dry matter and body weight of yak calves in the test group were significantly higher than those of the control group. (2) The apparent nutrient digestibility of crude protein, crude fat, calcium and phosphorus in the test group of yak calves was significantly higher than that of the control group, while the apparent nutrient digestibility of neutral detergent fiber and acid detergent fiber in the test group was significantly lower than that of the control group. (3) Pancreatic weight, organ index, total ratio of exocrine part area and total ratio of endocrine area of yak calves in the test group were significantly higher than those in the control group, while the ratio of exocrine area was significantly lower in the test group than that of the control group. (4) The activities of the main pancreatic digestive enzymes: pancreatic amylase, pancreatic lipase, pancreatic protease and chymotrypsin were significantly higher in the test group than those of the control group, as were the hormonal contents of glucagon, insulin and pancreatic polypeptide. (5) The main differential metabolites of the pancreas in the test group were significantly higher than those of the control group, such as D-proline, hypoxanthine, acetylcysteine, gamma-glutamylcysteine, thiazolidine-4-carboxylic acid, piperidinic acid, ellagic acid, nicotinamide, tropolone, D-serine, ribulose-5-phosphate, (+/-)5(6)-epoxyeicosatrienoic acid(EET), 2-hydroxycinnamic acid, L-phenylalanine, creatinine, tetrahydrocorticosterone, pyridoxamine, xanthine, 5-oxoproline, asparagine, DL-tryptophan, in-dole-3-acrylic acid, thymine, trehalose, docosapentaenoic acid, docosahexaenoic acid, fatty acid esters of hydroxy fatty acids(FAHFA) (18:1/20:3), fatty acid esters of hydroxy fatty acids(FAHFA) (18:2/20:4), adrenic acid and xanthosine. In conclusion, supplemental concentrate feeding promoted the good development of morphological and functional properties of the pancreas in early weaned yak calves to improve the digestion and absorption of feed nutrients, so as to enhance the growth and development quality of early weaned yak calves.

(1) Background: This study aimed to investigate the effects of different dietary concentrate to roughage ratios on growth performance and fecal microbiota composition of yaks by 16S rRNA gene sequencing. (2) Methods: In the present study, three diets with different dietary forage-to-concentrate ratios (50:50, 65:35, and 80:20) were fed to 36 housed male yaks. (3) Results: The result shows that Final BW, TWG, and ADG were higher in the C65 group than in the C50 and C80 groups, but the difference was not significant (p > 0.05). DMI in the C65 group was significantly higher than in the other two groups (p < 0.05). The DMI/ADG of the C65 group was lower than that of the other two groups, but the difference was insignificant (p > 0.05). At the phylum level, Firmicutes were the most abundant in the C65 group, and the relative abundance of Bacteroidetes was lower in the C65 group than in the other two groups. At the genus level, the relative abundances of Ruminococcaceae&#95;UCG&#95;005, Romboutsia, and Christensenellaceae&#95;R-7 were higher in the C56 group than in the C50 and C80 groups. The relative abundance of Lachnospiraceae&#95;NK3A20 and Rikenellaceaewas&#95;RC9&#95;gut is lower in the C65 group, but the difference was insignificant (p > 0.05). At KEGG level 2, the relative abundance of lipid metabolism and energy metabolism were lowest in the C50 group, and both showed higher relative abundance in the C65 group. (4) Conclusions: In conclusion, the structure of fecal microbiota was affected by different concentrate-to-forage ratios. We found that feeding diets with a concentrate-to-forage ratio of 65:35 improved yaks’ growth and energy metabolism.

Physical tenderization technologies for beef have been of particular interest to the meat industry. Here a novel tenderization technology by mechanical resonance vibration was proposed. The fundamental natural frequency (NF f ) of the yak longissimus thoracis et lumborum (LTL) was obtained through a hammer impacting on the muscle, and was reported to be 24.89 Hz. The tensile stress and Warner-Bratzler shear force of the yak meat were decreased by using the obtained NF f as the frequency of resonance vibration (RV), and only linear elastic deformation was found in stress-strain behavior of the vibrated meat. The variation of mechanical properties in post-rigor meat is responsible for the disappearance of the M-bands, shortening of the A-bands, and lengthening change in I-bands, rather than of the sarcomere length. The research demonstrated that RV treatment resulted in the M-band disappearance, the extensively detachment of endomysium from the myofibers, and the destruction of the linkages between α-actinin and thin filaments as well as other linkages., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The increasing prevalence of obesity worldwide is associated with an increased risk of various diseases, including multiple metabolic diseases, cardiovascular diseases, and malignant tumors. Fatty acid binding proteins (FABPs) are members of the adipokine family of multifunctional proteins that are related to fatty acid metabolism and are divided into 12 types according to their tissue origin. FABP4 is mainly secreted by adipocytes and macrophages. Under obesity, the synthesis of FABP4 increases, and the FABP4 content is higher not only in tissues but also in the blood, which promotes the occurrence and development of various cancers. Here, we comprehensively investigated obesity epidemiology and the biological mechanisms associated with the functions of FABP4 that may explain this effect. In this review, we explore the molecular mechanisms by which FABP4 promotes carcinoma development and the interaction between fat and cancer cells in obese circumstances here. This review leads us to understand how FABP4 signaling is involved in obesity-associated tumors, which could increase the potential for advancing novel therapeutic strategies and molecular targets for the systematic treatment of malignant tumors., 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 © 2022 Liu, Wu, Fan, Yang, Li, Meng, Gao and Zhan.)

Head and neck squamous cell carcinomas (HNSCCs) are a type of cancer originating in the mucosal epithelium of the mouth, pharynx, and larynx, the sixth most common cancer in the world. However, there is no effective treatment for HNSCCs. More than 90% of HNSCCs overexpress epidermal growth factor receptors (EGFRs). Although small molecule inhibitors and monoclonal antibodies have been developed to target EGFRs, few EGFR-targeted therapeutics are approved for clinical use. Ferroptosis is a new kind of programmed death induced by the iron catalyzed excessive peroxidation of polyunsaturated fatty acids. A growing body of evidence suggests that ferroptosis plays a pivotal role in inhibiting the tumor process. However, whether and how ferroptosis-inducers (FINs) play roles in hindering HNSCCs are unclear. In this study, we analyzed the sensitivity of different HNSCCs to ferroptosis-inducers. We found that only tongue squamous cell carcinoma cells and laryngeal squamous cell carcinoma cells, but not nasopharyngeal carcinoma cells, actively respond to ferroptosis-inducers. The different sensitivities of HNSCC cells to ferroptosis induction may be attributed to the expression of KRAS and ferritin heavy chain ( FTH1 ) since a high level of FTH1 is associated with the poor prognostic survival of HNSCCs, but knocked down FTH1 can promote HNSCC cell death. Excitingly, the ferroptosis-inducer RSL3 plays a synthetic role with EGFR monoclonal antibody Cetuximab to inhibit the survival of nasopharyngeal carcinoma cells (CNE-2), which are insensitive to both ferroptosis induction and EGFR inhibition due to a high level of FTH1 and a low level of EGFR , respectively. Our findings prove that FTH1 plays a vital role in ferroptosis resistance in HNSCCs and also provide clues to target HNSCCs resistant to ferroptosis induction and/or EGFR inhibition.