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Despite playing a fundamental role in plant population dynamics, the considerable variability and control of belowground bud banks in grasslands currently remain unknown globally. Here, we explored the size and driver of belowground bud bank both in alpine (Qinghai-Tibet Plateau: QTP) and temperate (Inner Mongolia Plateau: IMP) grasslands across China, using a dataset comprising 209 observations at 171 sites compiled from laboratory and published data. We found that temperate grassland had higher density (912 no./m2) dominated by tiller buds (72.26 %) than alpine grasslands (768 no./m2) dominated by rhizome buds (51.56 %). Moreover, belowground bud of alpine grassland exhibited longitudinal, latitudinal and altitudinal patterns, more diverse than those of longitudinal and latitudinal pattern in temperate grassland. Furthermore, climate, particularly the precipitation, is the factor controlling belowground bud in alpine grassland, while soil nutrient predominantly controls those in temperate grassland. Our study advances understanding of the variability and its climate and soil regulation on belowground buds in grasslands, sheds new light on differing management respectively for alpine and temperate grasslands in the context of climate change.

Reprogramming of cancer metabolism has become increasingly concerned over the last decade, particularly the reprogramming of glucose metabolism, also known as the ''Warburg effect''. The reprogramming of glucose metabolism is considered a novel hallmark of human cancers. A growing number of studies have shown that reprogramming of glucose metabolism can regulate many biological processes of cancers, including carcinogenesis, progression, metastasis, and drug resistance. In this review, we summarize the major biological functions, clinical significance, potential targets and signaling pathways of glucose metabolic reprogramming in human cancers. Moreover, the applications of natural products and small molecule inhibitors targeting glucose metabolic reprogramming are analyzed, some clinical agents targeting glucose metabolic reprogramming and trial statuses are summarized, as well as the pros and cons of targeting glucose metabolic reprogramming for cancer therapy are analyzed. Overall, the reprogramming of glucose metabolism plays an important role in the prediction, prevention, diagnosis and treatment of human cancers. Glucose metabolic reprogramming-related targets have great potential to serve as biomarkers for improving individual outcomes and prognosis in cancer patients. The clinical innovations related to targeting the reprogramming of glucose metabolism will be a hotspot for cancer therapy research in the future. We suggest that more high-quality clinical trials with more abundant drug formulations and toxicology experiments would be beneficial for the development and clinical application of drugs targeting reprogramming of glucose metabolism.This review will provide the researchers with the broader perspective and comprehensive understanding about the important significance of glucose metabolic reprogramming in human cancers.

A series of experiments was conducted to study the performance and mechanisms of Cemented Ultrafine Tailings Backfill (CUTB). Firstly, the optimum fiber type was selected by single factor multilevel test. Secondly, the effects of cement content, rice husk ash content, fiber content and fiber length on backfill properties were analyzed by orthogonal test and microstructure test, and the influence mechanism of fiber and rice husk ash content was revealed. Finally, fuzzy mathematics theory is used to optimize the ratio parameters. The results show, compared to glass and basalt fiber, polypropylene fiber yields the most substantial enhancement in backfill strength. The increase of cement content, polypropylene fiber content and length can reduce slump, but the change of rice husk ash content has no obvious effect. Increased cement or fiber content effectively restrained the formation of primary fractures in CUTB, thus enhancing its integrity. Adding an optimal dosage range of 0–4 % of rice husk ash boosted the early compressive strength, albeiting at the expense of later compressive strength. Fiber addition with the optimum content range between 0.1 and 0.4 % enhanced the strengthening effect of cement content on compressive strength. Fiber primarily enhances the macroscopic strength of backfill through the dispersion and co-loading of forces, whereas rice husk ash enhances strength by optimizing void structure distribution. The optimal ratio parameters of a cement content of 310 kg/m³, rice husk ash content of 8.0 %, fiber content of 0.4 %, and fiber length of 9 mm were proposed finally.

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remains unclear. Methods We discovered through GEO and TCGA databases that USP14 may play an important role in liver cancer. Using bioinformatics analysis based on the Cancer Genome Atlas (TCGA) database, we screened and identified USP14 as highly expressed in liver cancer. We detected the growth and metastasis of HCC cells promoted by USP14 through clone formation, cell counting kit 8 assay, Transwell assay, and flow cytometry. In addition, we detected the impact of USP14 on the downstream protein kinase B (AKT) and epithelial-mesenchymal transition (EMT) pathways using western blotting. The interaction mechanism between USP14 and HK2 was determined using immunofluorescence and coimmunoprecipitation (CO-IP) experiments. Results We found that sh-USP14 significantly inhibits the proliferation, invasion, and invasion of liver cancer cells, promoting apoptosis. Further exploration revealed that sh-USP14 significantly inhibited the expression of HK2. Sh-USP14 can significantly inhibit the expression of AKT and EMT signals. Further verification through immunofluorescence and CO-IP experiments revealed that USP14 co-expressed with HK2. Further research has found that USP14 regulates the glycolytic function of liver cancer cells by the deubiquitination of HK2. USP14 regulates the autophagy function of liver cancer cells by regulating the interaction between SQSTM1/P62 and HK2. Conclusions Our results indicate that USP14 plays a crucial role in the carcinogenesis of liver cancer. We also revealed the protein connections between USP14, HK2, and P62 and elucidated the potential mechanisms driving cancer development. The USP14/HK2/P62 axis may be a new therapeutic biomarker for the diagnosis and treatment of HCC.

Abstract Background Macrophages phenotypic deviation and immune imbalance play vital roles in pregnancy-associated diseases such as spontaneous miscarriage. Trophoblasts regulate phenotypic changes in macrophages, however, their underlying mechanism during pregnancy remains unclear. Therefore, this study aimed to elucidate the potential function of trophoblast-derived miRNAs (miR-410-5p) in macrophage polarization during pregnancy. Methods Patient decidual macrophage tissue samples in spontaneous abortion group and normal pregnancy group (those who had induced abortion for non-medical reasons) were collected at the Reproductive Medicine Center of Renmin Hospital of Wuhan University from April to December 2021. Furthermore, placental villi and decidua tissue samples were collected from patients who had experienced a spontaneous miscarriage and normal pregnant women for validation and subsequent experiments at the Shenzhen Zhongshan Obstetrics & Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital), from March 2021 to September 2022. As an animal model, 36 female mice were randomly divided into six groups as follows: naive-control, lipopolysaccharide-model, agomir-negative control prevention, agomir-410-5p prevention, agomir-negative control treatment, and agomir-410-5p treatment groups. We analyzed the miR-410-5p expression in abortion tissue and plasma samples; and supplemented miR-410-5p to evaluate embryonic absorption in vivo. The main source of miR-410-5p at the maternal–fetal interface was analyzed, and the possible target gene, signal transducer and activator of transcription (STAT) 1, of miR-410-5p was predicted. The effect of miR-410-5p and STAT1 regulation on macrophage phenotype, oxidative metabolism, and mitochondrial membrane potential was analyzed in vitro. Results MiR-410-5p levels were lower in the spontaneous abortion group compared with the normal pregnancy group, and plasma miR-410-5p levels could predict pregnancy and spontaneous abortion. Prophylactic supplementation of miR-410-5p in pregnant mice reduced lipopolysaccharide-mediated embryonic absorption and downregulated the decidual macrophage pro-inflammatory phenotype. MiR-410-5p were mainly distributed in villi, and trophoblasts secreted exosomes-miR-410-5p at the maternal–fetal interface. After macrophages captured exosomes, the cells shifted to the tolerance phenotype. STAT1 was a potential target gene of miR-410-5p. MiR-410-5p bound to STAT1 mRNA, and inhibited the expression of STAT1 protein. STAT1 can drive macrophages to mature to a pro-inflammatory phenotype. MiR-410-5p competitive silencing of STAT1 can avoid macrophage immune disorders. Conclusion MiR-410-5p promotes M2 macrophage polarization by inhibiting STAT1, thus ensuring a healthy pregnancy. These findings are of great significance for diagnosing and preventing spontaneous miscarriage, providing a new perspective for further research in this field.

Pedestrian detection is a critical task in computer vision; however, mainstream algorithms often struggle to achieve high detection accuracy in complex scenarios, particularly due to target occlusion and the presence of small objects. This paper introduces a novel pedestrian detection algorithm, YOLO-ESL, based on the YOLOv7 framework. YOLO-ESL integrates the ELAN-SA module, designed to enhance feature extraction, with the LGA module, which improves feature fusion. The ELAN-SA module optimizes the flexibility and efficiency of small object feature extraction, while the LGA module effectively integrates multi-scale features through local and global attention mechanisms. Additionally, the CIOUNMS algorithm addresses the issue of target loss in cases of high overlap, improving boundary box filtering. Evaluated on the VOC2012 pedestrian dataset, YOLO-ESL achieved an accuracy of 93.7%, surpassing the baseline model by 3.0%. Compared to existing methods, this model not only demonstrates strong performance in handling occluded and small object detection but also remarkable robustness and efficiency.

Objective: The purpose of this overview is to assess systematic reviews (SRs)/ meta-analyses (MAs) of Huachansu (HCS) combination chemotherapy for treating non-small cell lung cancer (NSCLC) and provide summarized evidence for clinical decision making. Methods: From the creation of the database to JUNE 2023, 8 databases in English and Chinese were searched. SRs/MAs that met the inclusion and exclusion criteria were included. Two reviewers independently screened research, extracted data and assessed methodological quality, risk of bias, report quality and evidence quality by using relevant criteria from AMSTAR-2, ROBIS scale, PRISMA, and GRADE system. Results: The short-term effect, long-term effect, quality of life improvement, safety and pain relief effect in 8 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory, with the results of the AMSTAR-2 assessment showing that all of them were of low or critically low quality; the number of items in the included research that were fully reported (compliance was 100%) by the PRISMA checklist was only 50%, while there were 38.10% of the research reporting less than 60% completeness; the ROBIS assessment showed a small number of systems to be low risk of bias. In addition, 26 items were rated as moderate quality, while 50.94% of items were rated as low or critically low quality by GRADE. Conclusion: HCS may be a promising adjuvant therapy for NSCLC. However, high-quality SRs/MAs and randomized control trials (RCTs) should be conducted to provide sufficient evidence so as to draw a definitive conclusion.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer with bleak prognosis. Its optimal treatment remains undetermined due to its malignancy. A 66-year-old man diagnosed with unresectable locally advanced LCNEC exhibited partial radiographic response to chemo-immunotherapy. He underwent salvage surgery after 4 rounds of docetaxel/nedaplatin (DP) regimen plus sintilimab, a highly selective monoclonal antibody which targets human anti-programmed death-ligand 1 (PD-L1). In addition, the pathologic examination of the excision demonstrated that there were no viable residuary tumor cells. This case indicates that neoadjuvant chemo-immunotherapy might benefit patients with locally advanced LCNEC, which deserves further investigation.

BackgroundThe bioinformatics analysis on glioma has been a hot point recently. The purpose of this study was to provide an overview of the research in this field using a bibliometric method.MethodsThe Web of Science Core Collection (WOSCC) database was used to search for literature related to the bioinformatics analysis of gliomas. Countries, institutions, authors, references, and keywords were analyzed using VOSviewer, CiteSpace, and Microsoft Excel software.ResultChina was the most productive country, while the USA was the most cited. Capital Medical University had the largest number of publications and citations. Institutions tend to collaborate more with other institutions in their countries rather than foreign ones. The most productive and most cited author was Jiang Tao. Two citation paths were identified, with literature in basic research journals often cited in clinical journals. Immune-related vocabularies appeared frequently in recent studies.ConclusionGlioma bioinformatics analyses spanned a wide range of fields. The international communication in this field urgently needs to be strengthened. Glioma bioinformatics approaches are developing from basic research to clinical applications. Recently, immune-related research has become a focus.

ObjectivesMisinformation about the COVID vaccines poses a significant challenge to vaccination efforts in many countries. This study examined Chinese citizens’ ability to correctly identify COVID-19 vaccine misinformation in geographic areas with and without a regional outbreak. We also investigated the associations between misinformation identification and information source usage, source trust, perceived information quality, and demographic characteristics.SettingThe online survey was conducted in four cities from June 8th to 15th, 2021 in Guangdong Province, two of which were experiencing a regional surge of COVID-19 delta variant infections, and four cities in Hunan Province, a neighboring province largely unaffected.ParticipantsA total of 4,479 individuals aged 18 and above completed the online questionnaire. Given survey length, those who finished the study under 5 min were excluded, resulting in a final sample of 3,800.Outcome measurementsMisinformation identification, source exposure, source trust, and perceived information quality.ResultsResults showed slightly higher levels of correct misinformation identification in surge vs. non-surge areas. Trust in official information sources was positively associated with correct misinformation identification in full sample analysis, while trust in informal sources was negatively associated with the same outcome. Perceived information quality was positively associated with correct misinformation identification in the full sample.ConclusionInformation providers in China should enhance the quality of the vaccine information they provide, and the Chinese public should balance their usage of different sources of information to acquire vaccine knowledge.

IntroductionSafranal is an active component of the traditional Tibetan medicine (TTM) saffron, which has potential anticancer activity.Methods and resultsHere, we studied the therapeutic effect and mechanism of safranal on GBM. CCK-8, GBM-brain organoid coculture experiments and 3D tumour spheroid invasion assays showed that safranal inhibited GBM cell proliferation and invasion in vitro. Network pharmacology, RNA-seq, molecular docking analysis, western blotting, apoptosis, and cell cycle assays predicted and verified that safranal could promote GBM cell apoptosis and G2/M phase arrest and inhibit the PI3K/AKT/mTOR axis. In vivo experiments showed that safranal could inhibit GBM cell growth alone and in combination with TMZ.ConclusionThis study revealed that safranal inhibits GBM cell growth in vivo and in vitro, promotes GBM cell apoptosis and G2/M phase arrest, inhibits the PI3K/AKT/mTOR axis and cooperate with TMZ.

Abstract Background Resveratrol is a plant-derived phenylpropanoid with diverse biological activities and pharmacological applications. Plant-based extraction could not satisfy ever-increasing market demand, while chemical synthesis is impeded by the existence of toxic impurities. Microbial production of resveratrol offers a promising alternative to plant- and chemical-based processes. The non-conventional oleaginous yeast Rhodotorula toruloides is a potential workhorse for the production of resveratrol that endowed with an efficient and intrinsic bifunctional phenylalanine/tyrosine ammonia-lyase (RtPAL) and malonyl-CoA pool, which may facilitate the resveratrol synthesis when properly rewired. Results Resveratrol showed substantial stability and would not affect the R. toruloides growth during the yeast cultivation in flasks. The heterologus resveratrol biosynthesis pathway was established by introducing the 4-coumaroyl-CoA ligase (At4CL), and the stilbene synthase (VlSTS) from Arabidopsis thaliana and Vitis labrusca, respectively. Next, The resveratrol production was increased by 634% through employing the cinnamate-4-hydroxylase from A. thaliana (AtC4H), the fused protein At4CL::VlSTS, the cytochrome P450 reductase 2 from A. thaliana (AtATR2) and the endogenous cytochrome B5 of R. toruloides (RtCYB5). Then, the related endogenous pathways were optimized to affect a further 60% increase. Finally, the engineered strain produced a maximum titer of 125.2 mg/L resveratrol in YPD medium. Conclusion The non-conventional oleaginous yeast R. toruloides was engineered for the first time to produce resveratrol. Protein fusion, co-factor channeling, and ARO4 and ARO7 overexpression were efficient for improving resveratrol production. The results demonstrated the potential of R. toruloides for resveratrol and other phenylpropanoids production.

ObjectiveA surgical simulation of an endoscope-dominated side-to-end hypoglossal-facial anastomosis was performed to evaluate the feasibility.MethodsEight anatomical cadaver heads (16 sides) were recruited. The steps in conventional procedures were abbreviated or omitted. A facial nerve was first harvested near its external genu and was used for a side-to-end hypoglossal-facial anastomosis. The stump of the used facial nerve was truncated and recycled immediately caudal to the facial recess in another anastomosis and then recycled again at the stylomastoid foramen. As a recycled stump becomes too short to ensure a side-to-end anastomosis, the hypoglossal nerve was transected in situ, and an endoscopic end-to-end hypoglossal-facial anastomosis was attempted. Surgical simulation and quantitative measurement methods were used to analyze the anastomosis effects of different harvested sites of the facial nerve.ResultsSeveral steps in the conventional procedures provide little benefit in endoscopic surgery. A facial nerve stump recycled at the stylomastoid foramen is too short to ensure a tensionless side-to-end anastomosis. An endoscopic end-to-end hypoglossal-facial anastomosis was feasible, although it required more time than the classical microsurgical anastomosis. The greater agility of an endoscope enables the conventional surgical steps to be overlapped or interweaved into the procedure.ConclusionsThe multiple surgical fields and ability to manipulate the viewpoint provided by an endoscope have brought about breakthroughs in classical surgical paradigms. In addition, it is best to choose the sites of the facial nerve harvested near the external genu. If unavailable, an alternative section site could be selected immediately caudal to the facial recess, but cannot be distal to the stylomastoid foramen. The length of the stump should be individualized and preferably optimized with a nerve stimulator.

Aflatoxin is one of the most toxic mycotoxins and causes server threaten to human health and food safety issues. It is crucial to develop efficient materials to remove and degrade aflatoxins. In this work, we adopted PVP modified ZIF-8 as precursor to prepare novel ZnO@NPC core–shell heterostructures (NPC is N-doped porous carbon) via “pyrolysis-in situ transformation-pyrolysis” strategy and used it as catalyst for degradation of aflatoxin B1 (AFB1). Various technologies were adopted to characterize to the structures and properties of the catalyst, such as XRD, SEM, BET, and TEM. The results show that the coating of N-doped porous carbon on ZnO can extend its light absorption wavelength to 800 nm, enhancing its photocatalytic activity for degradation of AFB1 (94.8%). The synergetic effect of high absorption capacity on N-doped porous carbon and excellent photocatalytic activity on ZnO was proven to contribute high degradation performance of ZnO@NPC. ZnO@NPC also shows excellent reparation and reusability. The photocatalytic activity of ZnO@NPC reduces only 1.71% after five repeated cycles. The developed ZnO@NPC may bring a promising solution for toxin degradation.

Persimmon wine has various nutritional elements and high commercial potential. However, the high content of methanol, which is derived from the fruit’s pectin, always hinders persimmon wine production. To reduce the methanol level in the wine, the effects of persimmon cultivar, starter, pectinase, and pretreatment methods were investigated via single-factor and orthogonal experiments. The persimmon cultivar ‘MaoKui’ was finally used throughout the study owing to its lowest pectin concentration (24.5 g/kg). The best treatment conditions against the persimmon pulp were pectinase (0.04 g/kg) at 30 °C for 4 h, then boiled at 115 °C for 15 min before fermentation started. The optimized fermentation conditions for wine production were pectinase (0.03 g/kg), 250 mg/kg starter (BO213 and SPARK with equal amounts), at 28 °C for 6 d. The obtained wine had 77.7 mg/L methanol and a 68.4% raw juice yield. The fruit wine had 111.4 mg/L methanol and a 90.6 sensory evaluation score. Forty-nine volatile aromas were identified. Ethyl acetate content was the highest, followed by 3-methyl-1-butanol, 2,3-butanediol, and lactate ethyl ester. The persimmon wine had a unique style with transparent color, elegant aroma, and pure taste.

A novel bis-γ-butyrolactone grifolamine A (1), the first γ-butyrolactone dimer from nature, together with three known γ-butyrolactones (2–4), was isolated from the byproduct from Grifola frondosa polysaccharides preparation process. The structure and stereochemistry of grifolamine A (1) were elucidated by extensive spectroscopic analysis combined with quantum chemical calculation. The biosynthetic origin of compound 1, as well as 2–4 was proposed. Grifolamine A (1) showed an intense inhibition against α-glucosidase in vitro. The underlying inhibitory mechanism was revealed by surface plasmon resonance (SPR), molecular docking, molecular dynamics (MD) simulation and binding free energy calculation. SPR revealed that grifolamine A exhibited a strong affinity to α-glucosidase with an equilibrium dissociation constant (KD) value of 1.178 × 10−4 M. Molecular docking manifested that grifolamine A sat at the active pocket of α-glucosidase by van der Waals force, alkyl interaction and carbon hydrogen bonds, and consequently changed the micro-environmental structure of α-glucosidase. MD simulation revealed that grifolamine A had high binding affinity to α-glucosidase with average free energy of −25.2 ± 3.2 kcal/mol. Free energy decomposition indicated amino acid residues including PHE298, PHE308, PHE309, PHE155 and ARG310 at the binding pocket played a strongly positive effect on the interaction between grifolamine A and α-glucosidase. Our findings provide valuable information for the design and development of novel α-glucosidase inhibitors based on γ-butyrolactone skeleton.

Abstract Background Sepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Early identifying high risk patients for AKI progression is a major challenge in patients with septic AKI. Methods This is a prospective, multicenter cohort study which enrolled adult patients with sepsis and initially developed stage 1 or 2 AKI in the intensive care unit from January 2014 to March 2018. AKI was diagnosed and staged according to 2012 KDIGO-AKI guidelines. Renal cell arrest biomarkers (urinary TIMP2*IGFBP7, u[TIMP-2]*[IGFBP7]) and renal damage biomarkers (urinary KIM-1[uKIM-1] and urinary IL-18 [uIL-18]) were measured at time of AKI clinical diagnosis, and the performance of biomarkers for predicting septic AKI progression alone or in combination were evaluated. The primary outcome was AKI progression defined as worsening of AKI stage. The secondary outcome was AKI progression with subsequent death during hospitalization. Results Among 433 screened patients, 149 patients with sepsis and stage 1 or 2 AKI were included, in which 63 patients developed progressive AKI and 49 patients subsequently died during hospitalization. u[TIMP-2]*[IGFBP7], uKIM-1 and uIL-18 independently predicted the progression of septic AKI in which u[TIMP-2]*[IGFBP7] showed the greatest AUC (0.745; 95%CI, 0.667-0.823) as compared to uKIM-1 (AUC 0.719; 95%CI 0.638-0.800) and uIL-18 (AUC 0.619; 95%CI 0.525-0.731). Combination of u[TIMP-2]*[IGFBP7] with uKIM-1 improved the performance of predicting septic AKI progression with AUC of 0.752. u[TIMP-2]*[IGFBP7], alone or combined with uKIM-1/uIL-18, improved the risk reclassification over the clinical risk factor model alone both for the primary and secondary outcomes, as evidenced by significant category-free net reclassification index. Conclusions Combination of renal cell arrest and damage biomarkers enhanced the prediction of AKI progression in patients with sepsis and improved risk reclassification over the clinical risk factors.

Abstract Background Limonene is a widely used monoterpene in the production of food, pharmaceuticals, biofuels, etc. The objective of this work was to engineer Rhodosporidium toruloides as a cell factory for the production of limonene. Results By overexpressing the limonene synthase (LS), neryl pyrophosphate synthase (NPPS)/geranyl pyrophosphate synthase and the native hydroxy-methyl-glutaryl-CoA reductase (HMGR), we established a baseline for limonene production based on the mevalonate route in Rhodosporidium toruloides. To further enhance the limonene titer, the acetoacetyl-CoA thiolase/HMGR (EfMvaE) and mevalonate synthase (EfMvaS) from Enterococcus faecalis, the mevalonate kinase from Methanosarcina mazei (MmMK) and the chimeric enzyme NPPS-LS were introduced in the carotenogenesis-deficient strain. The resulting strains produced a maximum limonene titer of 393.5 mg/L. Conclusion In this study, we successfully engineered the carotenogenesis yeast R. toruloides to produce limonene. This is the first report on engineering R. toruloides toward limonene production based on NPP and the fusion protein SltNPPS-CltLS. The results demonstrated that R. toruloides is viable for limonene production, which would provide insights into microbial production of valuable monoterpenes.

Summary: Background: The role of the IL6 family members in organ fibrosis, including renal interstitial fibrosis (TIF), has been widely explored. However, few studies have ever simultaneously examined them in the same cohort of patients. Besides, the role of leukemia inhibitory factor (LIF) in TIF remains unclear. Methods: RNA-seq data of kidney biopsies from chronic kidney disease (CKD) patients, in both public databases and our assays, were used to analyze transcript levels of IL6 family members. Two TIF mouse models, the unilateral ureteral obstruction (UUO) and the ischemia reperfusion injury (IRI), were employed to validate the finding. To assess the role of LIF in vivo, short hairpin RNA, lenti-GFP-LIF was used to knockdown LIF receptor (LIFR), overexpress LIF, respectively. LIF-neutralizing antibody was used in therapeutic studies. Whether urinary LIF could be used as a promising predictor for CKD progression was investigated in a prospective observation patient cohort. Findings: Among IL6 family members, LIF is the most upregulated one in both human and mouse renal fibrotic lesions. The mRNA level of LIF negatively correlated with eGFR with the strongest correlation and the smallest P value. Baseline urinary concentrations of LIF in CKD patients predict the risk of CKD progression to end-stage kidney disease by Kaplan–Meier analysis. In mouse TIF models, knockdown of LIFR alleviated TIF; conversely, overexpressing LIF exacerbated TIF. Most encouragingly, visible efficacy against TIF was observed by administering LIF-neutralizing antibodies to mice. Mechanistically, LIF–LIFR-EGR1 axis and Sonic Hedgehog signaling formed a vicious cycle between fibroblasts and proximal tubular cells to augment LIF expression and promote the pro-fibrotic response via ERK and STAT3 activation. Interpretation: This study discovered that LIF is a noninvasive biomarker for the progression of CKD and a potential therapeutic target of TIF. Fundings: Stated in the Acknowledgements section of the manuscript.

Abstract Background The prognostic significance of programmed cell death‐ligand 1 (PD‐L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta‐analysis to systematically evaluate its prognostic value in human cancers. Methods Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre‐treatment and post‐treatment PD‐L1+ CTCs with progression‐free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD‐L1 detection method, cut‐off, and specifically the comparison model were performed. Results We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre‐treatment PD‐L1+ CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28–1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36–1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non‐ICI therapies (PFS: HR = 1.85, 95% CI 1.21–2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69–3.51, p

Selenium nanoparticles (SeNPs) have gained extensive attention for their excellent biological activity and low toxicity. However, SeNPs are extremely liable to aggregate into non-bioactive or gray elemental selenium, which limits their application in the biomedicine field. This study aimed to prepare stable SeNPs by using lentinan (LNT) as a template and evaluate its anti-colon cancer activity. The average particle diameter of obtained lentinan-selenium nanoparticles (LNT-SeNPs) was approximately 59 nm and presented zero-valent, amorphous, and spherical structures. The monodisperse SeNPs were stabilized by LNT through hydrogen bonding interactions. LNT-SeNPs solution remained highly stable at 4°C for at least 8 weeks. The stability of LNT-SeNPs solution sharply decreased under high temperature and strong acidic conditions. LNT-SeNPs showed no obvious cytotoxic effect on normal cells (IEC-6) but significantly inhibited the proliferation of five colon cancer cells (HCT-116, HT-29, Caco-2, SW620, and CT26). Among them, LNT-SeNPs exhibited the highest sensitivity toward HCT-116 cells with an IC50 value of 7.65 μM. Also, LNT-SeNPs displayed better cancer cell selectivity than sodium selenite and selenomethionine. Moreover, LNT-SeNPs promoted apoptosis of HCT-116 cells through activating mitochondria-mediated apoptotic pathway. Meanwhile, LNT-SeNPs induced cell cycle arrest at G0/G1 phase in HCT-116 cells via modulation of cell cycle regulatory proteins. The results of this study indicated that LNT-SeNPs possessed strong potential application in the treatment of colorectal cancer (CRC).

BackgroundRheumatoid arthritis (RA) is the most common inflammatory arthropathy. Immune dysregulation was implicated in the pathogenesis of RA. Thus, the aim of the research was to determine the immune related biomarkers in RA.MethodsWe downloaded the gene expression data of RA in GSE89408 and GSE45291 from Gene Expression Omnibus public database (GEO). Differentially expressed genes (DEGs) were identified between RA and control groups. Infiltrating immune cells related genes were obtained by ssGSEA and weighted gene co-expression network analysis (WGCNA). We performed functional enrichment analysis of differentially expressed immunity-related genes (DEIRGs) by “clusterProfiler” R package, key genes screening by protein-protein interaction (PPI) network of DEIRGs. And mice collagen-induced arthritis (CIA) model was employed to verify these key genes.ResultsA total of 1,885 up-regulated and 1,899 down-regulated DEGs were identified in RA samples. The ssGSEA analysis showed that the infiltration of 25 cells was significantly different. 603 immune related genes were obtained by WGCNA, and 270 DEIRGs were obtained by taking the intersection of DEGs and immune related genes. Enrichment analyses indicated that DEIRGs were associated with immunity related biological processes. 4 candidate biomarkers (CCR7, KLRK1, TIGIT and SLAMF1) were identified from the PPI network of DEIRGs and literature research.In mice CIA model, the immunohistochemical stain showed SLAMF1 has a significantly high expression in diseased joints. And flow cytometry analysis shows the expression of SLAMF1 on CIA mice-derived CTL cells, Th, NK cells, NKT cells, classical dendritic cell (cDCs) and monocytes/macrophages was also significantly higher than corresponding immune cells from HC mice.ConclusionOur study identified SMLAF1 as a key biomarker in the development and progression of RA, which might provide new insight for exploring the pathogenesis of RA.

Metal–organic frameworks (MOFs) have been widely used in various fields, including gas storage, separation, sensors, and catalysis, owing to their excellent performance. In this study, a zinc-based MOF [MIL-125(Zn)] was successfully synthesized using the solvothermal method, and Ag-doped ZnO (Ag/ZnO) was prepared by pyrolyzing Ag/MIL-125(Zn). The fabricated Ag/ZnO was used as a photocatalyst for rhodamine (RhB) degradation. Results showed that the MIL-125(Zn) derived from Ag/ZnO exhibits superior photocatalytic activity. It can degrade 99.4% of RhB under 20-min ultraviolet (UV) light irradiation, higher than those achieved using ZnO (73.2%) and MIL-125(ZnO) (19.6%). Furthermore, Ag/ZnO shows excellent stability. After four photocatalytic degradation cycles, the photocatalytic activity of Ag/ZnO reduces by only 3.6%. The excellent photocatalytic performance of Ag/ZnO may be attributed to the synergistic effect of Ag nanoparticles and ZnO. The possible photocatalytic mechanism of RhB degradation on the Ag/ZnO photocatalyst under UV light irradiation was proposed.

Photocatalytic degradation method has been recognized as an effective way to eliminate the contamination of environment. However, developing photocatalysts with excellent photocatalytic properties are still a big challenge. In this paper, Ag doped ZnO coating with a layer of N doped porous carbon (Ag/ZnO@N-carbon) was successfully synthesized by using polyvinyl pyrrolidone (PVP) modified ZIF-8 as precursor via adsorption, hydrothermal treatment, in situ growth and carbonization processes. The physical and chemical properties of all samples were characterized by X-ray powder diffraction (XRD), scanning electron microscope (SEM), electron transmission microscopy (TEM) and so on. The results show that Ag doping does not change the crystallinity of ZnO, but broaden its photo-response property. The coating of N doped carbon can improve the specific surface area of photocatalyst. The photocatalytic activity of all samples was evaluated by degradation of rhodamine B (RhB) solution under UV light irradiation for 25 min. Ag/ZnO@N-carbon exhibits the highest photocatalytic activity for degradation of RhB with a degradation of 98.65%. Furthermore, Ag/ZnO@N-carbon also has high stability. Based on the characterization, possible mechanism for degradation of RhB by Ag/ZnO@N-carbon under UV light irradiation was proposed.

Limonene is a valuable monoterpenoid with diverse applications in food, medicine, agriculture, etc. Currently, the commercial production of limonene from citrus pomace cannot meet the evergrowing market demand. With the development of synthetic biology, microbial biosynthesis is offering a sustainable alternative to plant-based extraction. However, the performance of engineered strains can be affected by many factors including the microbial host, the cultivation conditions, etc. Therefore, in the present study, potential factors that influence the limonene production of the engineered strains were investigated through single-factor and orthogonal experiments. The optimized medium was MM, with a working volume of 50 mL, inoculum OD600 = 0.6, 22 °C, pH 6, and a dodecane coverage (v/v) of 20%. The final limonene titer was improved from 52.5 to 358.1 mg/L, a 586% net increase in titer and 34.8-fold improvement in production efficiency (mg/OD600) on 250-mL flasks. The results here demonstrated that R. toruloides could be explored as an efficient limonene producer and could facilitate the study of the biosynthesis of other terpenes using R. toruloides.

To understand how different types of cues in vaccine education messages affect attitude toward campaign messages and vaccination intention, this study examined the impact of the presence of social norm appeals (individual vs. group cues) and the presence of fear appeals in coronavirus disease 2019 (COVID-19) vaccine campaign posters on perceived communication quality and vaccination intention. A 2 (social norm appeal: individual cue vs. group cue) × 2 (fear appeal: absence vs. presence) × 3 (repetition) within-subject factorial design experiment was conducted in China. Findings demonstrated that the presence of fear appeals in COVID-19 vaccine campaign posters elicited lower levels of perceived communication quality and vaccination intention than those without fear appeals. The interactive effect of fear appeals and social norm appeals was also found to be significant. Specifically, positive-framed messages (i.e., absence of fear appeals) with group cues and fear appeal messages with individual cues elicited higher perceived information quality and stronger vaccination intention than other types of messages. Understanding how these cues function jointly in COVID-19 vaccine campaign messages will help public health practitioners create more effective intervention strategies.

Pectin is the most studied compound. However, recently, more attention has been paid to the health care of pectin oligosaccharides, especially the potential of prebiotics. In order to obtain lower molecular weight molecules with improved bioactivities, the pectin (ALP2) was partially degraded by acid and enzymatic hydrolysis. The molecular weights of acid hydrolyzed fragment (ALP2-A) and enzymatic hydrolyzed fragment (ALP2-E) were 2.4 × 104 Da and 5.8 × 103 Da, respectively. ALP2-A was composed of rhamnose and galacturonic acid while ALP2-E contained rhamnose, glucuronic acid, galacturonic acid, galactose, and arabinose. Rheological experiments showed that ALP2-A and ALP2-E solutions had lower viscosity than that of ALP2 solution, exhibited shear-thinning behavior and belonged to pseudoplastic fluids. ALP2-A could alleviate the constipation symptoms of mice while ALP2-A and ALP2-E had better intestinal flora regulation activity than that of ALP2. Therefore, the results indicated that ALP2-A and ALP2-E could be recommended as potential prebiotic or functional food that could benefit the host by regulating human gut microbiota.

The type VI secretion system (T6SS) is a transmembrane protein nanomachine employed by many gram-negative bacteria to directly translocate effectors into adjacent cells or the extracellular milieu, showing multiple functions in both interbacterial competition and bacteria-host interactions. Metal ion transport is a newly discovered T6SS function. This review summarizes the identified T6SS functions and highlights the features of metal ion transport mediated by T6SS and discusses its regulation.

BackgroundRenal cell carcinoma (RCC) is associated with poor prognostic outcomes. The current stratifying system does not predict prognostic outcomes and therapeutic benefits precisely for RCC patients. Here, we aim to construct an immune prognostic predictive model to assist clinician to predict RCC prognosis.MethodsHerein, an immune prognostic signature was developed, and its predictive ability was confirmed in the kidney renal clear cell carcinoma (KIRC) cohorts based on The Cancer Genome Atlas (TCGA) dataset. Several immunogenomic analyses were conducted to investigate the correlations between immune risk scores and immune cell infiltrations, immune checkpoints, cancer genotypes, tumor mutational burden, and responses to chemotherapy and immunotherapy.ResultsThe immune prognostic signature contained 14 immune-associated genes and was found to be an independent prognostic factor for KIRC. Furthermore, the immune risk score was established as a novel marker for predicting the overall survival outcomes for RCC. The risk score was correlated with some significant immunophenotypic factors, including T cell infiltration, antitumor immunity, antitumor response, oncogenic pathways, and immunotherapeutic and chemotherapeutic response.ConclusionsThe immune prognostic, predictive model can be effectively and efficiently used in the prediction of survival outcomes and immunotherapeutic responses of RCC patients.

Previous studies showed that CXCR7 expression was upregulated after enzalutamide (ENZ) treatment, and an increased level of CXCR7 could increase the invasion, migration, and angiogenesis of castration-resistant prostate cancer (CRPC) cells. This study demonstrated that the levels of p-JAK2, p-STAT1, C-Myc, and VEGFR2 were significantly reduced after CCX771, a specific CXCR7 inhibitor, treatment. This effect further increased after the combination treatment of ENZ and CCX771. Then, we verified that targeting the inhibition of JAK2 or STAT1 could remarkably increase apoptosis and DNA damage and decrease the migration of CRPC cells. More importantly, the combination treatment of ENZ + JAK2/STAT1 led to much greater suppression than the single-agent treatment of JAK2 or STAT1. Subcutaneous CRPC xenograft tumor growth was also reduced by single-agent ENZ treatment and single-agent FLUD, a specific STAT1 antagonist, treatment; but much superior effect was elicited by the combination treatment of ENZ + FLUD. The proliferative indices significantly decreased following combination treatment in tumor tissues compared with control-treatment tissues and single-agent-treatment tissues. Our results demonstrated that CXCR7, which signifies an androgen receptor (AR)-independent signaling pathway, caused CRPC progression via the downstream JAK2/STAT1 signal transduction cascade. Combined inhibition targeting both the AR and JAK2/STAT1 resulted in substantial tumor suppression due to the reduction in DNA damage repair ability and increment in apoptosis.

Despite the adoption of a national immunization program in China, the incidence of mumps remains high. This study aimed to describe the epidemiological characteristics, including the time, region, occupation, and age, of mumps in Wuhan from 2005 to 2018 and to evaluate its transmissibility. In this study, the susceptible–exposed–infectious–asymptomatic–recovered (SEIAR) model fitted the actual incidence data of mumps. The effective reproduction number (Rt) was used to evaluate and compare the transmission capacity in different areas. From 2005 to 2018, there were 36,415 cases. The incidence of mumps was highest among people aged 5–10 years (460.02 per 100,000). The SEIAR model fitted the reported mumps data well (P < 0.01). The median transmissibility (Rt) was 1.04 (range = 0–2.50). There were two peak spreads every year (from March to May and from October to December). The Rt peak always appeared in the first 2 months of the peak incidence rate. The peak time of the epidemic spread of mumps was 1–2 months earlier than the peak incidence rate. The prevention and control measures of vaccination for children aged 5–10 years should be taken before the peak transmission capacity each year, 2 months before the peak of the outbreak, to reduce the spread of mumps.

Insufficient acidity in grape berries from warm climate regions has been exacerbated due to global warming, thereby becoming a major concern for winemaking. The wine lactic acid bacterium Lactiplantibacillus plantarum has potential to ameliorate wine acidity by producing lactic acid from hexose metabolism, but its impact on wine compositions and sensory outcomes is not well studied. Here, we evaluated acidification and fermentation performance of indigenous L. plantarum in two inoculation regimes (i.e., reverse inoculation and co-inoculation) by conducting pilot-scale vinification using Cabernet Sauvignon with low acidity. Important parameters of the bio-acidified wines, including fermentation kinetics, basic oenological parameters, volatile and sensory profile were compared to those in wines produced by single Saccharomyces cerevisiae with/without chemical acidification. Total titratable acidity in L. plantarum wines were either comparable or significantly higher compared to the chemical acidification control. Chemical profiling reviewed remarkable differences in certain organic acids and major volatile compounds, especially an up to a five-fold, six-fold, and nine-fold increase in lactic acid, ethyl lactate and isoamyl lactate, respectively. Changes in chemical compositions of the bio-acidified wines resulted in differentiated sensory perception compared to the control wines. Except having higher scores for “wine acidity”, the flavour profile of the bio-acidified wines was shifted towards “jammy fruit” and “butter” aromas. Together, these findings highlighted the applicability of using L. plantarum to induce biological acidification along with modulation of wine flavour.

Kaolin clay is an inexpensive and abundant material with potential for use as a low-dielectric-constant ceramic; however, the natural metallic oxides the clay contains hinder such applications. In this study, kaolin clay ceramics with excellent physical and dielectric properties were synthesized using kaolin clay as the raw material by chemical cleaning and sintering. Characterization of the resulting samples showed that the sulfuric acid treatment has a significant influence on the metallic oxide content and dielectric properties of the kaolin clay ceramics. When the kaolin clay raw material was treated with sulfuric acid three times, the dielectric constant decreased from 5.12 to 3.75 and the Vickers hardness increased from 946 to 1,214 kg/mm2 relative to the ceramic prepared from the untreated clay. Therefore, these ceramics exhibit significant potential for use in the microelectronics industry.

Prostate cancer (PCa) is one of the most common malignancies for males, but very little is known about its pathogenesis. This study aimed to identify novel biomarkers associated with PCa prognosis and elucidate the underlying molecular mechanism. First, The Cancer Genome Atlas (TCGA) RNA-sequencing data were utilized to identify differentially expressed genes (DEGs) between tumor and normal samples. The DEGs were then applied to construct a co-expression and mined using structure network analysis. The magenta module that was highly related to the Gleason score (r = 0.46, p = 3e–26) and tumor stage (r = 0.38, p = 2e–17) was screened. Subsequently, all genes of the magenta module underwent function annotation. From the key module, CCNA2, CKAP2L, NCAPG, and NUSAP1 were chosen as the four candidate genes. Finally, internal (TCGA) and external data sets (GSE32571, GSE70770, and GSE141551) were combined to validate and predict the value of real hub genes. The results show that the above genes are up-regulated in PCa samples, and higher expression levels show significant association with higher Gleason scores and tumor T stage. Moreover, receiver operating characteristic curve and survival analysis validate the excellent value of hub genes in PCa progression and prognosis. In addition, the protein levels of these four genes also remain higher in tumor tissues when compared with normal tissues. Gene set enrichment analysis and gene set variation analysis for a single gene reveal the close relation with cell proliferation. Meanwhile, 11 small molecular drugs that have the potential to treat PCa were also screened. In conclusion, our research identified four potential prognostic genes and several candidate molecular drugs for treating PCa.

To resolve the limited large-scale methods of disposal of low calcium fly ash with poor activity, based on the double excitation principle, clinker and desulfurized gypsum are used as alkali/salt activators to activate fly ash and slag, avoiding the inconvenience of strong alkali activating fly ash in industry. Firstly, the strength test of a filling body with multiple ratio composite cementing material is carried out, and the weight coefficient of each material to strength is analyzed by grey correlation degree. The composition of the hydration products, microstructure, and pore structure of the filling body was analyzed by X-ray diffractometer, scanning electron microscope, thermogravimetric test, and mercury compression test. The strength mechanism of the cemented body was confirmed. The results show that cemented backfill prepared by composite cementitious material, which contained high content and low-quality fly ash, can meet the strength requirements of subsequent backfill in a mine. The degree of composite cementitious material influence on 7 d strength is slag > desulfurized gypsum > fly ash > clinker; the degree of influence on 28 d strength is: fly ash > slag > desulfurized gypsum > clinker. The main hydration products of the composite cementable material with high content low-quality fly ash are C–S–H gel and ettringite, and the unreacted fly ash particles can still be seen at 28 d. As the curing age grows, the difference in the number of hydration products under different proportioning conditions has a weaker effect on the strength, while the influence of raw materials and product morphology on the pore structure determines the development trend of the strength. Therefore, the threshold pore size can be used to characterize the strength advantages and disadvantages reasonably.

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

The use of ground granulated blast furnace slag (GGBFS) is environmentally sustainable and prevalent in the cement industry, but the original alkali-activated slag binder cannot be used for mine backfilling. Few reports have studied slag binders with high slag proportions (>90%) and low-cost activators (solid waste is used) that have higher performance than cement for backfilling. To increase the utilization of slag in the mining industry, this work presents a new slag binder (SB) comprised of 91% slag powder and 9% activator (3% clinker, 5% desulfurized gypsum, and 1% mirabilite). Its performance was evaluated by testing its strength, yield stress, and viscosity, which are three key properties for backfilling. We also investigated its microstructure using SEM, XRD and thermogravimetric analysis (TG/DTG). The results showed that the SB composites have a slightly lower early-age (28 d). Although the SB backfilling composites had a twofold higher yield stress and nearly the same viscosity as Portland cement, the pressure drop in a pipe was only slightly higher through friction factor modeling. The proposed SB may provide a sustainable binder for the mining industry with better performance and lower cost.

Fatigue life prediction is an important part of the reliability and durability analysis of automobile components. Based on Wang and Brown’s framework, multiaxial random fatigue damage was adopted to predict the fatigue life of half-shaft. The stress analysis of half-shaft was resolved analytically to determine the local stress tensor in the potential area of fracture. The maximum shear strain fatigue damage parameter and the normal stress fatigue damage parameter were evaluated to predict the fatigue life of half-shaft. The results show that the prediction method is reliable and meets the service life and safety requirements.

Background: Insulin resistance (IR) complicates chronic kidney disease (CKD). We tested the hypothesis that CKD activates a broad reflex response from the kidneys and the white adipose tissue to impair peripheral glucose uptake and investigated the role of salt intake in this process. Methods: 5/6-nephrectomized rats were administered normal- or high-salt for 3 weeks. Conclusions were tested in 100 non-diabetic patients with stage 3–5 CKD. Findings: High-salt in 5/6-nephrectomized rats decreased insulin-stimulated 2-deoxyglucose uptake >25% via a sympathetic nervous system (SNS) reflex that linked the IR to reactive oxygen species (ROS) and the renin-angiotensin system (RAS) in brain and peripheral tissues. Salt-loading in CKD enhanced inflammation in adipose tissue and skeletal muscle, and enhanced the impairment of insulin signaling and Glut4 trafficking. Denervation of the kidneys or adipose tissue or deafferentation of adipose tissue improved IR >40%. In patients with non-diabetic CKD, IR was positively correlated with salt intake after controlling for cofounders (r = 0.334, P = 0.001) and was linked to activation of the RAS/SNS and to impaired glucose uptake in adipose tissue and skeletal muscle, all of which depended on salt intake. Interpretation: CKD engages a renal/adipose-cerebral-peripheral sympathetic reflex that activates the RAS/ROS axes to promote IR via local inflammation and impaired Glut4 trafficking that are enhanced by high-salt intake. The findings point to a role for blockade of RAS or α-and-β-adrenergic receptors to reduce IR in patients with CKD. Fund: National Natural Science Foundation of China. Keywords: Insulin resistance, Salt, Sympathetic reflex, Adipose tissue, Renin-angiotensin system, Chronic kidney disease

Abstract Background Cancer-related fatigue (CRF) is the most common symptom in patients with advanced non-small cell lung cancer (NSCLC) undergoing treatment with chemotherapy. However, evidence upon which to base management strategies is scarce. Traditional Chinese Medicine (TCM) has been shown to be beneficial to patients with CRF. Chinese herbal injections should be administered under an evidence-based approach. This trial aims to assess the efficacy and safety of the addition of the Shenmai injection (SMI) to conventional therapy for CRF in NSCLC patients undergoing chemotherapy. Methods/design The study is a two-group, prospective, randomized controlled trial (RCT) designed to evaluate the efficacy and safety of SMI for CRF NSCLC patients undergoing chemotherapy. Eligible participants will be randomized to either a treatment group receiving a 5-day Shenmai injection regimen plus conventional therapy or a control group receiving only conventional therapy. The primary outcome is fatigue, assessed using severity scores from the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F) measurement system. Secondary outcomes include symptom distress scores, depression, sleep disorders, quality of life, and levels of immunologic indicators. Assessments will be carried out at baseline and on day 5 (the end of the intervention). Discussion This study can provide evidence to support clinical decision-making in the management of CRF in NSCLC patients undergoing chemotherapy in a way that can be scaled up and used throughout China. Trial registration Chinese Clinical Trial Registry (chictr.org.cn), ChiCTR-INR-17013737. Registered on 6 December 2017.

Combination chemotherapy is widely exploited for suppressing drug resistance and achieving synergistic anticancer efficacy in the clinic. In this paper, the nanostructured targeting methotrexate (MTX) plus pemetrexed (PMX) chitosan nanoparticles (CNPs) were developed by modifying methoxy polye (thylene glycol) (mPEG), in which PEGylation CNPs was used as stealth nanocarriers (PCNPs) and MTX was employed as a targeting ligand and chemotherapeutic agent as well. Studies were undertaken on human lung adenocarcinoma epithelial (A549) and Lewis lung carcinoma (LLC) cell lines, revealing the anti-tumor efficacy of nanoparticle drug delivery system. The co-delivery nanoparticles (MTX-PMX-PCNPs) had well-dispersed with sustained release behavior. Cell counting kit-8 (CCK8) has been used to measure A549 cell viability and the research showed that MTX-PMX-PCNPs were much more effective than free drugs when it came to the inhibition of growth and proliferation. Cell cycle assay by flow cytometry manifested that the MTX-PMX-PCNPs exhibited stronger intracellular taken up ability than free drugs at the same concentration. In vivo anticancer effect results indicated that MTX-PMX-PCNPs exhibited a significantly prolong blood circulation, more tumoral location accumulation, and resulted in a robust synergistic anticancer efficacy in lung cancer in mice. The results clearly demonstrated that such unique synergistic anticancer efficacy of co-delivery of MTX and PMX via stealth nanocarriers, providing a prospective strategy for lung cancer treatment.

Abstract Herein, Co3O4 nanoparticles/nitrogen-doped carbon (Co3O4/NPC) composites with different structures were prepared via a facile method. Structure control was achieved by the rational morphology design of ZIF-67 precursors, which were then pyrolyzed in air to obtain Co3O4/NPC composites. When applied as catalysts for the oxygen evolution reaction (OER), the M-Co3O4/NPC composites derived from the flower-like ZIF-67 showed superior catalytic activities than those derived from the rhombic dodecahedron and hollow spherical ZIF-67. The former M-Co3O4/NPC composite displayed a small over-potential of 0.3 V, low onset potential of 1.41 V, small Tafel slope of 83 mV dec−1, and a desirable stability. (94.7% OER activity was retained after 10 h.) The excellent performance of the flower-like M-Co3O4/NPC composite in the OER was attributed to its favorable structure.

The contact-dependent type VI secretion system (T6SS) in diverse microbes plays crucial roles in both inter-bacterial and bacteria-host interactions. As numerous microorganisms inhabit the intestinal ecosystem at a high density, it is necessary to consider the functions of T6SS in intestinal bacteria. In this mini-review, we discuss T6SS-dependent functions in intestinal microbes, including commensal microbes and enteric pathogens, and list experimentally verified species of intestinal bacteria containing T6SS clusters. Several seminal studies have shown that T6SS plays crucial antibacterial roles in colonization resistance, niche occupancy, activation of host innate immune responses, and modulation of host intestinal mechanics. Some potential roles of T6SS in the intestinal ecosystem, such as targeting of single cell eukaryotic competitors, competition for micronutrients, and stress resistance are also discussed. Considering the distinct activities of T6SS in diverse bacteria residing in the intestine, we suggest that T6SS research in intestinal microbes may be beneficial for the future development of new medicines and clinical treatments.

The type VI secretion system (T6SS) is a versatile secretion system widely distributed in Gram-negative bacteria that delivers multiple effector proteins into either prokaryotic or eukaryotic cells, or into the extracellular milieu. T6SS participates in various physiological processes including bacterial competition, host infection, and stress response. Three pathogenic Yersinia species, namely Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica, possess different copies of T6SSs with distinct biological functions. This review summarizes the pathogenic, antibacterial, and stress-resistant roles of T6SS in Yersinia and the ion-transporting ability in Y. pseudotuberculosis. In addition, the T6SS-related effectors and regulators identified in Yersinia are discussed.

Lignocellulosic biomass is an abundant and renewable resource for biofuels and bio-based chemicals. Vanillin is one of the major phenolic inhibitors in biomass production using lignocellulose. To assess the response of Corynebacterium glutamicum to vanillin stress, we performed a global transcriptional response analysis. The transcriptional data showed that the vanillin stress not only affected the genes involved in degradation of vanillin, but also differentially regulated several genes related to the stress response, ribosome/translation, protein secretion, and the cell envelope. Moreover, deletion of the sigH or msrA gene in C. glutamicum resulted in a decrease in cell viability under vanillin stress. These insights will promote further engineering of model industrial strains, with enhanced tolerance or degradation ability to vanillin to enable suitable production of biofuels and bio-based chemicals from lignocellulosic biomass.

Type VI protein secretion systems (T6SSs) are specialized transport apparatus which can target both eukaryotic and prokaryotic cells and play key roles in host–pathogen–microbiota interactions. Therefore, T6SSs have attracted much attention as a research topic during the past ten years. In this review, we particularly summarized the T6SS antibacterial function, which involves an interesting offensive and defensive mechanism of the effector–immunity (E–I) pairs. The three main categories of effectors that target the cell wall, membranes, and nucleic acids during bacterial interaction, along with their corresponding immunity proteins are presented. We also discuss structural analyses of several effectors and E–I pairs, which explain the offensive and defensive mechanisms underpinning T6SS function during bacterial competition for niche-space, as well as the bioinformatics, proteomics, and protein–protein interaction (PPI) methods used to identify and characterize T6SS mediated E–I pairs. Additionally, we described PPI methods for verifying E–I pairs.

BACKGROUND: Although there was a report about the seasonal variation in Wuhan city, it only analyzed the prevalence data of pulmonary tuberculosis (TB) cases, and just studied the seasonality by subgroup of smear positive and negative from 2006 to 2010 by spectral analysis. In this study, we investigated the seasonality of the total newly notified pulmonary TB cases by subgroups such as time period, sex, age, occupation, district, and sputum smear result from 2004 to 2013 in Wuhan by a popular seasonal adjustment model (TRAMO-SEATS). METHODS: Monthly pulmonary TB cases from 2004 to 2013 in Wuhan were analyzed by the TRAMO-SEATS seasonal adjustment program. Seasonal amplitude was calculated and compared within the subgroups. RESULTS: From 2004 to 2013, there were 77.76 thousand newly notified pulmonary TB cases in Wuhan, China. There was a dominant peak spring peak (March) with seasonal amplitude of 56.81% and a second summer peak (September) of 43.40%, compared with the trough month (December). The spring seasonal amplitude in 2004-2008 was higher than that of 2009-2013(P0.05). However, there were significant differences in spring seasonal amplitude by occupation, with amplitude ranging from 59.37% to 113.22% (P0.05). There were significant differences in summer seasonal amplitude by age, with amplitude ranging from 36.05% to 100.09% (P