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Abstract Background The Yangtze River Economic Belt, as a core economic region in China, is facing the dual challenges of an aging population and growing healthcare demand, and the balanced development and optimal allocation of nursing human resources is crucial to the region’s healthcare system. An in-depth study of the regional differences and convergence of nursing human resources in the region will provide a key basis for policy makers to achieve equity and efficiency in healthcare services and meet the growing demand for healthcare. Aim To analyze the regional differences and convergence characteristics of nursing human resource levels in the Yangtze River Economic Belt, and to provide scientific references for optimizing regional nursing human resource allocation. Methods Based on the panel data of 107 cities in the Yangtze River Economic Belt from 2010 to 2020, the regional differences and their sources were analyzed by using Dagum’s Gini coefficient, and the convergence characteristics were examined by the coefficient of variation and spatial convergence model. Results The average value of the number of nursing human resources in the Yangtze River Economic Belt is 2,132,300 people, with obvious regional differences, and the hypervariable density difference (53.01%) is the main source of the regional differences; there are obvious trends of σ-convergence and conditional β-convergence of the level of nursing human resources in the overall and the three major regions of the upstream, midstream, and downstream, and different factors have different moderating effects on the speed of spatial convergence in the other areas. Conclusion The implementation of precise policies for nursing human resources in different regions of the Yangtze River Economic Belt steadily reduces the regional differences between the upper, middle, and lower reaches and enhances the spatial linkage between regions of nursing human resources to improve the quality of nursing human resources.

Abstract RNA-binding proteins (RBPs) are a class of proteins that primarily function by interacting with different types of RNAs and play a critical role in regulating the transcription and translation of cancer-related genes. However, their role in the progression of hepatocellular carcinoma (HCC) remains unclear. In this study, we analyzed RNA sequencing data and the corresponding clinical information of patients with HCC to screen for prognostic RBPs. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was identified as an independent prognostic factor for liver cancer. It is upregulated in HCC and is associated with a poor prognosis. Elevated IGF2BP3 expression was validated via immunohistochemical analysis using a tissue microarray of patients with HCC. IGF2BP3 knockdown inhibited the proliferation of Hep3B and HepG2 cells, whereas IGF2BP3 overexpression promoted the expansion of HuH-7 and MHCC97H cells. Mechanistically, IGF2BP3 modulates cell proliferation by regulating E2F1 expression. DNA hypomethylation of the IGF2BP3 gene may increase the expression of IGF2BP3, thereby enhancing cell proliferation in HCC. Therefore, IGF2BP3 may act as a novel prognostic biomarker and a potential therapeutic target for HCC.

With the continuous application of new agricultural chemicals in agricultural systems, it is imperative to study the environmental fate and potential transformation products (TPs) of these chemicals to better assess their ecological and health risks, as well as guide scientific application. The dissipation of fluchloraminopyr was firstly evaluated under aerobic/anaerobic condition in four representative soils, with Dissipation Time 50 (DT50) values ranging from 0.107 to 4.76 days. Eight TPs generated by soil degradation were identified via Ultra-High Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-QTOF/MS) and Density Functional Theory (DFT) calculations. The predominant transformation reactions of fluchloraminopyr in soil include oxidation, dechlorination, hydroxylation, and acetylation. The predictions from toxicological software indicated that the acute and chronic toxicity of TPs to aquatic organisms was significantly lower than that of fluchloraminopyr. Moreover, both M267 and M221 exhibited higher acute oral toxicity to terrestrial organisms compared to the parent compound. Consequently, these findings offer essential ecological risk evaluation data for the judicious application of fluchloraminopyr.

Abstract Pyroptosis may play an important role in the resistance of ovarian cancer (OC) to chemotherapy. However, the mechanism by which pyroptosis modulation can attenuate chemotherapy resistance has not been comprehensively studied in OC. Here, we demonstrated that RAS‐associated C3 botulinum toxin substrate 1 (RAC1) is highly expressed in OC and is negatively correlated with patient outcomes. Through cell function tests and in vivo tumor formation tests, we found that RAC1 can promote tumor growth by mediating paclitaxel (PTX) resistance. RAC1 can mediate OC progression by inhibiting pyroptosis, as evidenced by high‐throughput automated confocal imaging, the release of lactate dehydrogenase (LDH), the expression of the inflammatory cytokines IL‐1β/IL‐18 and the nucleotide oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome. Mechanically, RNA‐seq, gene set enrichment analysis (GSEA), coimmunoprecipitation (Co‐IP), mass spectrometry (MS), and ubiquitination tests further confirmed that RAC1 inhibits caspase‐1/gasdermin D (GSDMD)‐mediated canonical pyroptosis through the P21‐activated kinase 4 (PAK4)/mitogen‐activated protein kinase (MAPK) pathway, thereby promoting PTX resistance in OC cells. Finally, the whole molecular pathway was verified by the results of in vivo drug combination tests, clinical specimen detection and the prognosis. In summary, our results suggest that the combination of RAC1 inhibitors with PTX can reverse PTX resistance by inducing pyroptosis through the PAK4/MAPK pathway.

Abstract Background Research has suggested significant correlations among ageing, immune microenvironment, inflammation and tumours. However, the relationships among ageing, immune microenvironment, cystitis and bladder urothelial carcinoma (BLCA) in the bladder have rarely been reported. Methods Bladder single-cell and transcriptomic data from young and old mice were used for immune landscape analysis. Transcriptome, single-cell and The Cancer Genome Atlas Program datasets of BLCA and interstitial cystitis/bladder pain syndrome (IC/BPS) were used to analyse immune cell infiltration and molecular expression. Bladder tissues from mice, IC/BPS and BLCA were collected to validate the results. Results Eight types of immune cells (macrophages, B-cells, dendritic cells, T-cells, monocytes, natural killer cells, γδ T-cells and ILC2) were identified in the bladder of mice. Aged mice bladder tissues had a significantly higher number of T-cells, γδ T-cells, ILC2 and B-cells than those in the young group (P

Plant growth regulators (PGRs) play an important role in increasing crop yield, and quality, and enhancing crop stress resistance in agricultural production, especially for important crops. PGRs can affect the transport and distribution of assimilates by changing the content and distribution of endogenous hormones in plants. Numerous empirical research results have proven that PGRs have an important impact on the growth, development, and yield composition of wheat. Taking wheat plants as an example, this study reviews the application of PGRs in wheat production and explores their impact on wheat growth and yield. Furthermore, residues and microbial degradation of PGRs are summarized in detail. Finally, future research directions on PGR application in wheat production are proposed. This summary is of great significance for understanding the role of PGRs in wheat production.

Summary: Isolation of antigen-specific plasma B cells had been challenging until the recent arrival of the Beacon platform. Leveraging light-sorting technology, Beacon can perform high-throughput screening of plasma B cells on a chip to sort single cells with the desired antigen specificity. Here, we present a protocol for isolating antigen-specific plasma B cells from immunized mice using Beacon, sequencing the encoded B cell receptors (BCRs), and cloning and expressing the resulting antibodies. This protocol can easily be extended to human samples. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Diazinon, an organophosphorus insecticide, is predominantly removed through photodegradation and biodegradation in the environment. However, photodegradation can generate diazoxon, a highly toxic oxidation byproduct, while biodegradation is hard to complete mineralize diazinon, showing limitations in both methods. In this study, we provided an efficient strategy for the complete and harmless removal of diazinon by synergistically employing biodegradation and photodegradation. The diazinon-degrading strain X1 was capable of completely degrading 200 μM of diazinon into 2-isopropyl-6-methyl-4-pyrimidinol (IMP) within 6 h without producing the highly toxic diazoxon. IMP was the only intermediate metabolite in biodegradation process, which cannot be further degraded by strain X1. Through RT-qPCR and prokaryotic expression analyses, the hydrolase OpdB was pinpointed as the key enzyme for diazinon degradation in strain X1. Photodegradation was further used to degrade IMP and a pyridazine ring-opening product of IMP was identified via high resolution mass spectrometry. The acute toxicity of this product to aquatic organisms were 123 times and 6630 times lower than that of diazinon and IMP, respectively. The stepwise application of biodegradation and photodegradation was proved to be a successful approach for the remediation of diazinon and its metabolite IMP. This integrated method ensures the harmless and complete elimination of diazinon and IMP within only 6 h. The research provides a theoretical basis for the efficient and harmless remediation of organophosphorus insecticide residuals in the environment.

Abstract Ubiquitination, catalyzed usually by a three-enzyme cascade (E1, E2, E3), regulates various eukaryotic cellular processes. E3 ligases are the most critical components of this catalytic cascade, determining both substrate specificity and polyubiquitination linkage specificity. Here, we reveal the mechanism of a naturally occurring E3-independent ubiquitination reaction of a unique human E2 enzyme UBE2E1 by solving the structure of UBE2E1 in complex with substrate SETDB1-derived peptide. Guided by this peptide sequence-dependent ubiquitination mechanism, we developed an E3-free enzymatic strategy SUE1 (sequence-dependent ubiquitination using UBE2E1) to efficiently generate ubiquitinated proteins with customized ubiquitinated sites, ubiquitin chain linkages and lengths. Notably, this strategy can also be used to generate site-specific branched ubiquitin chains or even NEDD8-modified proteins. Our work not only deepens the understanding of how an E3-free substrate ubiquitination reaction occurs in human cells, but also provides a practical approach for obtaining ubiquitinated proteins to dissect the biochemical functions of ubiquitination.

The black soil region experiences complex erosion due to natural processes and intense human activities, leading to soil degradation and adverse ecological and agricultural impacts. However, the complexities involved in quantifying regional erosion poses remarkable challenges in accurately assessing the current status of regional soil erosion for effective soil conservation. To solve this issue, we proposed a new method for monitoring soil erosion using Interferometric synthetic aperture radar (InSAR) technology and machine learning algorithms within the Google Earth Engine platform. The new method not only enables regional-scale monitoring, but also ensures high accuracy in measurement (millimeter-level). The erosion susceptibility of the study area (Yanshou County, Heilongjiang Province, Northeastern China) was also classified using random forest algorithms to refine the monitored and predicted soil erosion. The results indicate that the five-year (2016–2021) deformation in Yanshou County was −11.08 mm, with a significant mean cumulative deformation of −8.08 mm yr−1 occurring in 2017. The driving factor analysis shows that the region was subject to the compound effect of water and freeze–thaw erosion, closely related to crop phenological stages. The susceptibility analysis indicates that 73.3% of the region was susceptible to erosion, with a higher probability in river areas, at high altitudes, and on steep slopes. However, good vegetation cover can reduce the risk of soil erosion to some extent. This study offers a new perspective on monitoring regional soil erosion in the black soil region of China. The proposed method holds potential for future expansion to monitor soil erosion in a larger areas, thereby guiding the strategies development for protection of the agriculturally important black soil.

IntroductionAlternol is a natural compound isolated from the fermentation of a mutated fungus. We have demonstrated its potent anti-cancer effect via the accumulation of radical oxygen species (ROS) in prostate cancer cells in vitro and in vivo. In this study, we tested its anti-cancer spectrum in multiple platforms.MethodsWe first tested its anti-cancer spectrum using the National Cancer Institute-60 (NCI-60) screening, a protein quantitation-based assay. CellTiter-Glo screening was utilized for ovarian cancer cell lines. Cell cycle distribution was analyzed using flow cytometry. Xenograft models in nude mice were used to assess anti-cancer effect. Healthy mice were tested for the acuate systemic toxicity.ResultsOur results showed that Alternol exerted a potent anti-cancer effect on 50 (83%) cancer cell lines with a GI50 less than 5 µM and induced a lethal response in 12 (24%) of those 50 responding cell lines at 10 µM concentration. Consistently, Alternol displayed a similar anti-cancer effect on 14 ovarian cancer cell lines in an ATP quantitation-based assay. Most interestingly, Alternol showed an excellent safety profile with a maximum tolerance dose (MTD) at 665 mg/kg bodyweight in mice. Its therapeutic index was calculated as 13.3 based on the effective tumor-suppressing doses from HeLa and PC-3 cell-derived xenograft models.ConclusionTaken together, Alternol has a broad anti-cancer spectrum with a safe therapeutic index in vivo.

Background: Alternol is a small molecular compound isolated from the fermentation of a mutant fungus obtained from Taxus brevifolia bark. Our previous studies showed that Alternol treatment induced reactive oxygen species (ROS)-dependent immunogenic cell death. This study conducted a comprehensive investigation to explore the mechanisms involved in Alternol-induced immunogenic cell death.Methods: Prostate cancer PC-3, C4-2, and 22RV1 were used in this study. Alternol interaction with heat shock proteins (HSP) was determined using CETSA assay. Alternol-regulated ER stress proteins were assessed with Western blot assay. Extracellular adenosine triphosphate (ATP) was measured using ATPlite Luminescence Assay System.Results: Our results showed that Alternol interacted with multiple cellular chaperone proteins and increased their expression levels, including endoplasmic reticulum (ER) chaperone hypoxia up-regulated 1 (HYOU1) and heat shock protein 90 alpha family class B member 1 (HSP90AB1), as well as cytosolic chaperone heat shock protein family A member 8 (HSPA8). These data represented a potential cause of unfolded protein response (UPR) after Alternol treatment. Further investigation revealed that Alternol treatment triggered ROS-dependent (ER) stress responses via R-like ER kinase (PERK), inositol-requiring enzyme 1α (IRE1α). The double-stranded RNA-dependent protein kinase (PKR) but not activating transcription factor 6 (ATF6) cascades, leading to ATF-3/ATF-4 activation, C/EBP-homologous protein (CHOP) overexpression, and X-box binding protein XBP1 splicing induction. In addition, inhibition of these ER stress responses cascades blunted Alternol-induced extracellular adenosine triphosphate (ATP) release, one of the classical hallmarks of immunogenic cell death.Conclusion: Taken together, our data demonstrate that Alternol treatment triggered multiple ER stress cascades, leading to immunogenic cell death.

Abstract Background Alveolar echinococcosis (AE) is a lethal zoonosis caused by the fox tapeworm Echinococcus multilocularis. The disease is difficult to treat, and an effective therapeutic drug is urgently needed. Echinococcus multilocularis-associated angiogenesis is required by the parasite for growth and metastasis; however, whether antiangiogenic therapy is effective for treating AE is unclear. Methods The in vivo efficacy of sunitinib malate (SU11248) was evaluated in mice by secondary infection with E. multilocularis. Enzyme-linked immunosorbent assays (ELISAs) were used to evaluate treatment effects on serum IL-4 and vascular endothelial growth factor A (VEGFA) levels after SU11248 treatment. Gross morphological observations and immunohistochemical staining were used to evaluate the impact of SU11248 on angiogenesis and the expression of pro-angiogenic factors VEGFA and VEGF receptor 2 (VEGFR2) in the metacestode tissues. Furthermore, the anthelmintic effects of SU11248 were tested on E. multilocularis metacestodes in vitro. The effect of SU11248 on the expression of VEGFA, VEGFR2, and phosphorylated VEGFR2 (p-VEGFR2) in liver cells infected with protoscoleces in vitro was detected by western blotting, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). The influence of SU11248 on endothelial progenitor cell (EPC) proliferation and migration was determined using CCK8 and transwell assays. Results In vivo, SU11248 treatment markedly reduced neovascular lesion formation and substantially inhibited E. multilocularis metacestode growth in mice. Further, it exhibited high anti-hydatid activity as efficiently as albendazole (ABZ), and the treatment resulted in reduced protoscolex development. In addition, VEGFA, VEGFR2, and p-VEGFR2 expression was significantly decreased in the metacestode tissues after SU11248 treatment. However, no effect of SU11248 on serum IL-4 levels was observed. In vitro, SU11248 exhibited some anthelmintic effects and damaged the cellular structure in the germinal layer of metacestodes at concentrations below those generally considered acceptable for treatment (0.12–0.5 μM). Western blotting, RT-qPCR, and ELISA showed that in co-cultured systems, only p-VEGFR2 levels tended to decrease with increasing SU11248 concentrations. Furthermore, SU11248 was less toxic to Reuber rat hepatoma (RH) cells and metacestodes than to EPCs, and 0.1 μM SU11248 completely inhibited EPC migration to the supernatants of liver cell and protoscolex co-cultures. Conclusions SU11248 is a potential candidate drug for the treatment of AE, which predominantly inhibits parasite-induced angiogenesis. Host-targeted anti-angiogenesis treatment strategies constitute a new avenue for the treatment of AE. Graphical Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is a heterogeneity pathological malignant cancer with leading causes of morbidity and mortality. EGFR inhibitors, immune checkpoint inhibitors have become novel treatments. However, the mechanism still remained uncertain. Several studies have confirmed that the circadian rhythms induce multiple malignancies developing. We utilized multi-omics analysis to demonstrate the crosstalk between circadian clock genes and tumor microenvironment in HNSCC. Firstly, we performed the LASSO Cox regression analysis based on the 16 important clock genes. A 7-gene risk model was successfully established in TCGA and validated in GEO datasets. Next, CIBERSORT and ESTIMATE methods were performed to display the immune landscape of high risk and low risk groups, and the results showed that high abundance of mast cells activated, dendritic cells activated and neutrophils were positively correlated with poor OS. To further identify hub genes, Kaplan Meier plot was applied in all TCGA and GEO datasets and two hub genes (PER2, and PER3) were identified, especially PER3, which was found strongly associated with immune score, PDCD1, CD4 + and CD8 + T cells in HNSCCC. Moreover, to explore the innate mechanism of circadian-induced pathway, we constructed a circadian-related ceRNA regulatory network containing 34 lncRNAs, 3 miRNAs and 4 core circadian genes. In-vitro experiments also verified that Per2 or Per3 could suppressed the proliferation, migration and invasion of HNSC. This study unraveled the association between PER3 and prognosis in patients with HNSC and the innate mechanism remains to be elucidated.

Abstract Background Echinococcus granulosus can manipulate its host's immune response to ensure its own survival. However, the effect of histone modifications on the regulation of the NOD-like receptor protein 3 (NLRP3) inflammasome and downstream interleukin-1β (IL-1β) production in response to the parasite is not fully understood. Methods We evaluated IL-1β secretion through enzyme-linked immunosorbent assay and assessed reactive oxygen species levels using the dichlorodihydrofluorescein diacetate probe. Western blotting and quantitative real-time polymerase chain reaction were performed to examine the expression of NLRP3 and IL-1β in mouse peritoneal macrophages and Tohoku Hospital Pediatrics-1 cells, a human macrophage cell line. The presence of trimethylated histone H3 lysine 27 (H3K27me3) modification on NLRP3 and IL-1β promoters was studied by chromatin immunoprecipitation. Results Treatment with E. granulosus cyst fluid (EgCF) considerably reduced IL-1β secretion in mouse and human macrophages, although reactive oxygen species production increased. EgCF also suppressed the expression of NLRP3 and IL-1β. Mechanistically, EgCF prompted the enrichment of repressive H3K27me3 modification on the promoters of both NLRP3 and IL-1β in macrophages. Notably, the presence of EgCF led to a significant reduction in the expression of the H3K27me3 demethylase KDM6B. Conclusions Our study revealed that EgCF inhibits KDM6B expression and H3K27me3 demethylation, resulting in the transcriptional inhibition of NLRP3 and IL-1β. These results provide new insights into the immune evasion mechanisms of E. granulosus. Graphical Abstract

Abstract Background Peste des petits ruminants virus (PPRV) is a highly contagious pathogen that strongly influences the productivity of small ruminants worldwide. Acetylation is an important post-translational modification involved in regulation of multiple biological functions. However, the extent and function of acetylation in host cells during PPRV infection remains unknown. Methods Dimethylation-labeling-based quantitative proteomic analysis of the acetylome of PPRV-infected Vero cells was performed. Results In total, 1068 proteins with 2641 modification sites were detected in response to PPRV infection, of which 304 differentially acetylated proteins (DAcPs) with 410 acetylated sites were identified (fold change 1.2 and P

Abstract Background Echinococcus granulosus cyst fluid (EgCF) weakens macrophage inflammatory responses, thereby enabling the parasite to evade the immune system. However, the role of histone modification in this process remains to be explored. Methods The levels of IL-6, TNF-α, IL-10, H3K4me3, and KDM5B were detected using quantitative real-time PCR, ELISA, and Western blotting. The enrichment of H3K4me3 and KDM5B at the promoter of inflammatory factors was detected by chromatin immunoprecipitation. Results Based on EgCF-stimulated macrophage models, we found that EgCF significantly inhibited mRNA expression and protein secretion of IL-6 and TNF-α and upregulated mRNA expression of IL-10 under the influence of TLR4. EgCF lowered the level of H3K4me3 and promoted the transcription and protein stability of histone demethylase KDM5B. Chromatin immunoprecipitation analysis revealed that EgCF suppressed the enrichment of H3K4me3 modification at the promoters of TNF-α and IL-6 and downregulated their expression in macrophages. Additionally, the inhibition of KDM5B activity by CPI-455 weakened the anti-inflammatory effect of EgCF. Conclusions Our findings demonstrate a novel mechanism through which EgCF promotes KDM5B expression and inhibits the enrichment of H3K4me3 at the promoters of inflammatory cytokines to suppress the inflammatory response. Graphical Abstract

Abstract Purpose Flap endonuclease 1 (FEN1) is highly upregulated in prostate cancer and promotes the growth of prostate cancer cells. Androgen receptor (AR) is the most critical determinant of the occurrence, progression, metastasis, and treatment of prostate cancer. However, the effect of FEN1 on docetaxel (DTX) sensitivity and the regulatory mechanisms of AR on FEN1 expression in prostate cancer need to be further studied. Methods Bioinformatics analyses were performed using data from the Cancer Genome Atlas and the Gene Expression Omnibus. Prostate cancer cell lines 22Rv1 and LNCaP were used. FEN1 siRNA, FEN1 overexpression plasmid, and AR siRNA were transfected into cells. Biomarker expression was evaluated by immunohistochemistry and Western blotting. Apoptosis and the cell cycle were explored using flow cytometry analysis. Luciferase reporter assay was performed to verify the target relationship. Xenograft assays were conducted using 22Rv1 cells to evaluate the in vivo conclusions. Results Overexpression of FEN1 inhibited cell apoptosis and cell cycle arrest in the S phase induced by DTX. AR knockdown enhanced DTX‐induced cell apoptosis and cell cycle arrest at the S phase in prostate cancer cells, which was attenuated by FEN1 overexpression. In vivo experiments showed that overexpression of FEN1 significantly increased tumour growth and weakened the inhibitory effect of DTX on prostate tumour growth, while AR knockdown enhance the sensitivity of DTX to prostate tumour. AR knockdown resulted in FEN1, pho‐ERK1/2, and pho‐ELK1 downregulation, and the luciferase reporter assay confirmed that ELK1 can regulate the transcription of FEN1. Conclusion Collectively, our studies demonstrate that AR knockdown improves the DTX sensitivity of prostate cancer cells by downregulating FEN1 through the ERK/ELK1 signalling pathway.

Abstract Background Circular RNAs (circRNAs), which are involved in various human malignancies, have emerged as promising biomarkers. The present study aimed to investigate unique expression profiles of circRNAs in hepatocellular carcinoma (HCC) and identify novel biomarkers associated with HCC development and progression. Methods CircRNA expression profiles of HCC tissues were jointly analyzed to identify differentially expressed circRNAs. Overexpression plasmid and siRNA targeting candidate circRNAs were used in functional assays in vitro. CircRNA-miRNA interactions were predicted using miRNAs expressed in the miRNA-seq dataset GSE76903. To further screen downstream genes targeted by the miRNAs, survival analysis and qRT-PCR were conducted to evaluate their prognostic role in HCC and construct a ceRNA regulatory network. Results Three significantly upregulated circRNAs, hsa_circ_0002003, hsa_circ_0002454, and hsa_circ_0001394, and one significantly downregulated circRNA, hsa_circ_0003239, were identified and validated by qRT-PCR. Our in vitro data indicated that upregulation of hsa_circ_0002003 accelerated cell growth and metastasis. Mechanistically, DTYMK, DAP3, and STMN1, which were targeted by hsa-miR-1343-3p, were significantly downregulated in HCC cells when hsa_circ_0002003 was silenced and were significantly correlated with poor prognosis in patients with HCC. Conclusion Hsa_circ_0002003 may play critical roles in HCC pathogenesis and serve as a potential prognostic biomarker for HCC. Targeting the hsa_circ_0002003/hsa-miR-1343-3p/STMN1 regulatory axis could be an effective therapeutic strategy in patients with HCC.

We report a case of a male patient who presented with multiple abdominal and pelvic echinococcosis. The patient had been diagnosed with hepatic echinococcosis for 7 years and developed intermittent distension and discomfort in the upper abdomen after an accidental fall. In recent years, the patient’s abdominal distention increased gradually. Computed tomography revealed multiple hydatid cysts in the liver, spleen, abdominal cavity, and pelvic cavity. Abdominal organs were severely compressed, such that he could not eat normally except for a liquid diet. The patient underwent radical surgical resection based on the multi-disciplinary treatment (MDT) and the operation lasted 10 h, nearly 100 hydatid cysts were excised, about 18 liters of cyst fluid and cyst contents were removed, and the patient lost 20 kg of weight after surgery. The operation was successful, but there were still some postoperative complications such as hypovolemic shock, postoperative ascites, postoperative bile leakage. Treatment measures for the patient were anti-infection, antishock, clamping the abdominal drainage tube, and negative pressure abdominal puncture drainage. At follow up the patient’s quality of life had been significantly improved with 15 kg weight gain compared to before.

Coiled-coil domain-containing (CCDC)family proteins play an important role in tumour progression, however, the role of CCDC167 in hepatocellular carcinoma remains unclear. To investigate the role of coiled-coil structural domain 167 (CCDC167) in hepatocellular carcinoma progression, we downloaded three hepatocellular carcinoma datasets (TCGA-LIHC, ICGC-LIRI and GSE76427) and analysed the mechanisms by which CCDC167 regulates hepatocellular carcinoma progression using MetaScape, CPTAC, HPA, TISCH and TISIDB.“ pRRophetic” package predicted the chemotherapeutic agents associated with CCDC167. The results showed that CCDC167 was highly expressed in hepatocellular carcinoma tissues and was associated with poor prognosis in patients with hepatocellular carcinoma. Knockdown of CCDC167 inhibits the proliferative capacity of hepatocellular carcinoma cells. CCDC167 was involved in the regulation of cell cycle, DNA replication and oxidative phosphorylation. Hepatocellular carcinoma samples with high expression of CCDC167 showed higher immune scores and C4 (lymphocyte depleted) subtypes. CCDC167 was associated with a variety of immune molecules (CD274, IL6R, and KDR), not only that, but CCDC167 was positively correlated with Treg infiltration and negatively correlated with T cells CD4 memory resting. High expression of CCDC167 increased immune escape in hepatocellular carcinoma patients. CCDC167 was associated with sensitivity to cisplatin in hepatocellular carcinoma patients. CCDC167 promoted the proliferative capacity of hepatocellular carcinoma cells. Our study suggests that CCDC167 is a novel and potentially valuable prognostic marker for hepatocellular carcinoma, and that CCDC167 iCCDC167 not only promotes hepatocellular carcinoma cell proliferation but is also associated with immune function in hepatocellular carcinoma patients.

TMP269, a small molecular inhibitor of IIa histone deacetylase, plays a vital role in cancer therapeutic. However, the effect of TMP269 on the regulation of viral replication has not been studied. In the present study, we found that TMP269 treatment significantly inhibited RABV replication at concentrations without significant cytotoxicity in a dose-dependent manner. In addition, TMP269 can reduce the viral titers and protein levels of RABV at an early stage in the viral life cycle. RNA sequencing data revealed that immune-related pathways and autophagy-related genes were significantly downregulated after RABV infection treated with TMP269. Further exploration shows that autophagy enhances RABV replication in HEK-293T cells, while TMP269 can inhibit autophagy to decrease RABV replication. Together, these results provide a novel treatment strategy for rabies.

Agrochemicals are emergingly being implicated in the widespread dissemination of antibiotic resistance genes (ARGs) in agroecosystems. However, minimal research exists on the disturbance of fumigant on soil ARGs. Focusing on a typical fumigant dazomet in a simulated soil microcosm, we characterized the dazomet-triggered timely response and longstanding dynamic of ARGs at one-fold and two-fold field recommended doses using metagenome and quantitative PCR. Dazomet treatments reduced 13.17%-69.98% of absolute abundance of 16S rRNA gene and targeted ARGs, but, awfully, boosted diversity and relative abundance of ARGs up to 1.33–1.60 and 1.62–1.90 folds, respectively. Approximately 77.28% of changes in relative abundance of ARGs could be explained by bacterial community and mobile genetic elements (MGEs). Mechanistically, primary hosts of ARGs shifted from Proteobacteria (control) to Firmicutes and Actinobacteria (treatments) accompanied with corresponding changes in their abundance by combining community analysis, host tracking analysis and antibiotic resistant bacteria assay. Meanwhile, dazomet exposure significantly increased the incidence of MGEs and stimulated the conjugation of antibiotic-resistant plasmid. In addition, absolute abundance of targeted ARGs gradually recovered in the post-fumigation stage. Collectively, our results elucidate the dazomet-triggered emergence and spread of soil ARGs and highlight the importance of navigating toward rational use of fumigant in agricultural fields.

Machine learning can handle an ever-increasing amount of data with the ability to learn models from the data. It has been widely used in a variety of disciplines and is gaining increasingly more attention nowadays. As it is challenging to map soil and hydrological information that are characterised with high spatial and temporal variability, applications of machine learning in soil science and hydrology (AMLSH) have become popularised. To better understand the current state of AMLSH research, a scientific and quantitative approach was performed to statistically analyse publication information from 1973 to 2021 archived in the Scopus database using scientometric analysis tools, including VOSviewer, CiteSpace, and the open-source R package "bibliometrix". The results show a significant increase in the number of publications on AMLSH since 2006. The major contributions were identified based on country origins (China, the USA, and India), institutions (Hohai University, Islamic Azad University, and Wuhan University), and journals (Journal of Hydrology, Remote Sensing, and Geoderma). The keywords analysis of the AMLSH research demonstrates four research hotspots: neural network, artificial intelligence, machine learning, and soil. The most frequently utilised machine learning (ML) methods are neural networks, decision trees, random forests and other methods for image processing and predictive analysis. McBratney et al. 2003 is the most highly cited article. Our research sheds light on the research process on AMLSH and concludes with future research perspectives.

Abstract Background Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is an aminoacyl-tRNA synthase involved in the pathology of cancer and other diseases. In this study, we investigated the carcinogenic function, potential mechanism, and clinical significance of EPRS1 in human hepatocellular carcinoma (HCC). Methods The expression, clinical significance, and prognostic value of EPRS1 in HCC were assessed using the TCGA and GEO databases. The function of EPRS1 in HCC cells was detected by CCK-8, Transwell, and hepatosphere formation assays. Immunohistochemistry was used to explore the difference in EPRS1 levels in HCC tissues and peri-cancerous tissues. The mechanism of EPRS1 was studied using a proteomics method. Finally, cBioportal and MEXEPRSS were used to analyze the variations involved in the differential expression of EPRS1. Results EPRS1 was frequently upregulated at the mRNA and protein levels in liver cancer. Increased EPRS1 correlated with shortened patient survival. EPRS1 could promote cancer cell proliferation, characteristics of cell stemness, and mobility. Mechanistically, EPRS1 played a carcinogenic role by upregulating several downstream proline-rich proteins, primarily LAMC1 and CCNB1. In addition, copy number variation could contribute to the high expression of EPRS1 in liver cancer. Conclusion Together, our data imply that enhanced EPRS1 contributes to the development of HCC by increasing the expression of oncogenes in the tumor microenvironment. EPRS1 may be a successful treatment target.

Co-existence of NO3--N, antibiotics, phosphorus (P), and Cu2+ in aquaculture wastewater has been frequently detected, but simultaneous removal and relationship between enzyme and pollutants removal are far from satisfactory. In this study, simultaneous removal of NO3--N, P, antibiotics, and Cu2+ by moving bed biofilm reactor (MBBR) was established. About 95.51 ± 3.40% of NO3--N, 61.24 ± 3.51% of COD, 18.74 ± 1.05% of TP, 88% of Cu2+ were removed synchronously in stage I, and antibiotics removal in stages I-IV was 73.00 ± 1.32%, 79.53 ± 0.88%, 51.07 ± 3.99%, and 33.59 ± 2.73% for tetracycline (TEC), oxytetracycline (OTC), chlortetracycline hydrochloride (CTC), sulfamethoxazole (SMX), respectively. The removal kinetics and toxicity of MBBR effluent were examined, indicating that the first order kinetic model could better reflect the removal of NO3--N, TN, and antibiotics. Co-existence of multiple antibiotics and Cu2+ was the most toxicity to E. coli growth. Key enzyme activity, reactive oxygen species (ROS) level, and its relationship with TN removal were investigated. The results showed that enzymes activities were significantly different under the co-existence of antibiotics and Cu2+. Meanwhile, different components of biofilm were extracted and separated, and enzymatic and non-enzymatic effects of biofilm were evaluated. The results showed that 70.00%− 94.73% of Cu2+ was removed by extracellular enzyme in stages I-V, and Cu2+ removal was mainly due to the action of extracellular enzyme. Additionally, microbial community of biofilm was assessed, showing that Proteobacteria, Bacteroidetes, and Gemmatimonadetes played an important role in the removal of NO3--N, Cu2+, and antibiotics at the phylum level. Finally, chemical bonds of attached and detached biofilm were characterized by X-ray photoelectron spectroscopy (XPS), and effect of nitrogen (N) and P was proposed under the co-existence of antibiotics and Cu2+. This study provides a theoretical basis for further exploring the bioremediation of NO3--N, Cu2+, and antibiotics in aquaculture wastewater.

With the widespread adoption of flexible stealth materials (FSMs) in radar stealth application, understanding their electromagnetic scattering information has become increasingly crucial. However, acquiring the electromagnetic scattering properties of FSMs solely through measurement can be challenging. Hence, this study proposes an electromagnetic scattering model for FSMs based on random undulating units formed by sweeping two parabola functions. Specifically, the multi-layer fast multipole method (MLFMM) is applied to calculate the model’s monostatic RCS within 8–12 GHz, enabling a comprehensive analysis of FSM’s electromagnetic scattering characteristics (ESCs). We fabricate an FSM sample for experimental validation and conduct meticulous measurements alongside theoretical calculations. Impressively, the calculated results exhibit relatively good agreement with the measured data, signifying our model’s reliability. Furthermore, by leveraging the proposed model and the MLFMM, we delve into the influence of various electromagnetic parameters, the undulating angle, and the size of undulation units on the ESCs of FSM. Our numerical results demonstrate that the ESCs of FSM exhibit regular variations in response to the changes in these parameters. In addition, we meticulously examine the interaction between electromagnetic waves and the material, further enriching our understanding of the observed results. This research provides valuable references for ESC investigation of flexible stealth material and radar stealth experimental design.

Abstract Background Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. Methods The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. Results Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40–5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54–3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. Conclusion GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

In the family of histone-deacetylases, histone deacetylase 6 (HDAC6) stands out. The cytoplasmic class IIb histone deacetylase (HDAC) family is essential for many cellular functions. It plays a crucial and debatable regulatory role in innate antiviral immunity. This review summarises the current state of our understanding of HDAC6’s structure and function in light of the three mechanisms by which it controls DNA and RNA virus infection: cytoskeleton regulation, host innate immune response, and autophagy degradation of host or viral proteins. In addition, we summed up how HDAC6 inhibitors are used to treat a wide range of diseases, and how its upstream signaling plays a role in the antiviral mechanism. Together, the findings of this review highlight HDAC6’s importance as a new therapeutic target in antiviral immunity, innate immune response, and some diseases, all of which offer promising new avenues for the development of drugs targeting the immune response.

Abstract Artificial neural networks (ANNs) can understand the behavior of a given system from the historical measurements of its associated variables. Adjusting the weight and bias of the ANN model using an optimization algorithm is known as the training process. The ANN reliability is directly related to the success of the training process. Therefore, this study investigates the effect of optimization algorithms on the prediction accuracy of the multilayer perceptron neural networks (MLPNNs). The complex gas hydrate prevention unit is simulated using the MLPNN model trained by 20 different optimization algorithms. This study investigates the gradient‐based, evolutionary, and Bayesian‐based optimization algorithms. Combining statistical and ranking analyses confirms that the Levenberg–Marquardt (LM) is the most efficient optimization technique for training the MLPNN model. This training algorithm adjusts the weight and bis parameters of the MLPNN so that the highest accurate predictions have been achieved. On the other hand, the trained MLPNN by imperialist competitive algorithm shows the lowest accuracy for the considered task. The trained MLPNN by the LM algorithm predicts 239 laboratory‐measured data sets about the methanol (MeOH) loss with the absolute average relative deviation of 6.4% and regression coefficient of 0.9643. Coupling the developed MLPNN and differential evolution optimization algorithm shows that temperature = 263 K and pressure = 6.92 MPa are the optimum condition for minimizing the MeOH loss in the gas hydrate prevention unit. Economic analysis confirms that the annual cost of methanol loss for the daily processing of 100 × 106 m3 of gas is ~17 million US dollars.

PurposeRadiotherapy is one of the most important treatments for high-grade glioma (HGG), but the best way to delineate the target areas for radiotherapy remains controversial, so our aim was to compare the dosimetric differences in radiation treatment plans generated based on the European Organization for Research and Treatment of Cancer (EORTC) and National Research Group (NRG) consensus to provide evidence for optimal target delineation for HGG.MethodsWe prospectively enrolled 13 patients with a confirmed HGG from our hospital and assessed dosimetric differences in radiotherapy treatment plans generated according to the EORTC and NRG-2019 guidelines. For each patient, two treatment plans were generated. Dosimetric parameters were compared by dose–volume histograms for each plan.ResultsThe median volume for planning target volume (PTV) of EORTC plans, PTV1 of NRG-2019 plans, and PTV2 of NRG-2019 plans were 336.6 cm3 (range, 161.1–511.5 cm3), 365.3 cm3 (range, 123.4–535.0 cm3), and 263.2 cm3 (range, 116.8–497.7 cm3), respectively. Both treatment plans were found to have similar efficiency and evaluated as acceptable for patient treatment. Both treatment plans showed well conformal index and homogeneity index and were not statistically significantly different (P = 0.397 and P = 0.427, respectively). There was no significant difference in the volume percent of brain irradiated to 30, 46, and 60 Gy according to different target delineations (P = 0.397, P = 0.590, and P = 0.739, respectively). These two plans also showed no significant differences in the doses to the brain stem, optic chiasm, left and right optic nerves, left and right lens, left and right eyes, pituitary, and left and right temporal lobes (P = 0.858, P = 0.858, P = 0.701 and P = 0.794, P = 0.701 and P = 0.427, P = 0.489 and P = 0.898, P = 0.626, and P = 0.942 and P = 0.161, respectively).ConclusionThe NRG-2019 project did not increase the dose of organs at risk (OARs) radiation. This is a significant finding that further lays the groundwork for the application of the NRG-2019 consensus in the treatment of patients with HGGs.Clinical trial registrationThe effect of radiotherapy target area and glial fibrillary acidic protein (GFAP) on the prognosis of high-grade glioma and its mechanism, number ChiCTR2100046667. Registered 26 May 2021.

BackgroundHepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide. Lysosomes are organelles that play an important role in cancer progression by breaking down biomolecules. However, the molecular mechanisms of lysosome-related genes in HCC are not fully understood.MethodsWe downloaded HCC datasets from TCGA and GEO as well as lysosome-related gene sets from AIMGO. After univariate Cox screening of the set of lysosome-associated genes differentially expressed in HCC and normal tissues, risk models were built by machine learning. Model effects were assessed using the concordance index (C-index), Kaplan-Meier (K-M) and receiver operating characteristic curves (ROC). Additionally, we explored the biological function and immune microenvironment between the high- and low-risk groups, and analyzed the response of the high- and low-risk groups to immunotherapy responsiveness and chemotherapeutic agents. Finally, we explored the function of a key gene (RAMP3) at the cellular level.ResultsUnivariate Cox yielded 46 differentially and prognostically significant lysosome-related genes, and risk models were constructed using eight genes (RAMP3, GPLD1, FABP5, CD68, CSPG4, SORT1, CSPG5, CSF3R) derived from machine learning. The risk model was a better predictor of clinical outcomes, with the higher risk group having worse clinical outcomes. There were significant differences in biological function, immune microenvironment, and responsiveness to immunotherapy and drug sensitivity between the high and low-risk groups. Finally, we found that RAMP3 inhibited the proliferation, migration, and invasion of HCC cells and correlated with the sensitivity of HCC cells to Idarubicin.ConclusionLysosome-associated gene risk models built by machine learning can effectively predict patient prognosis and offer new prospects for chemotherapy and immunotherapy in HCC. In addition, cellular-level experiments suggest that RAMP3 may be a new target for the treatment of HCC.

Abstract Growing evidence has demonstrated the functional relevance of long intergenic noncoding RNAs (lincRNAs) to tumorigenesis and immune response. However, immune-related lincRNAs and their value in predicting the clinical outcomes of patients with liver cancer remain largely unexplored. Herein, we utilized the strategy of iterative gene pairing to construct a tumor-specific immune-related lincRNA pairs signature (IRLPS), which did not require specific expression levels, as an indicator of patient outcomes. The 18-IRLPS we developed was associated with overall survival, tumor progression, and recurrence in liver cancer patients. Multivariate analysis revealed that the risk model was an independent predictive factor. A high IRLPS risk was correlated suppressive immune microenvironment, and IRLPS-high patients might benefit more from CD276 blockade or TMIGD2 agonist. Patients in the high-risk group were associated with elevated tumor mutation, increased sensitivity to dopamine receptor antagonists, cisplatin, doxorubicin, and mitomycin but more resistance to vinblastine. Mechanistically, IRLPS high scores might lead to poor prognosis by promoting cell proliferation and metabolic reprogramming. The prognostic significance of the 18-IRLPS was confirmed in independent cancer datasets. These findings highlighted the robust predictive performances of the 18-IRLPS for prognosis and personalized treatment.

Solid-state sodium-ion batteries with sodium metal anodes possess high safety and reliability, which are considered as a promising candidate for the next generation of energy storage technology. However, poor electronic and ionic conductivities at the interface between electrodes and solid-state electrolytes restrict its practical application. Herein, we demonstrate a β″-Al2O3 electrolyte with a vertically porous-dense bilayer structure to solve this problem. The carbon-coated vertically porous layer serves as a high mass-loading host for Na3V2(PO4)3 cathode and provides fast electronically and ionically conductive pathways. In addition, the dense layer is produced to prevent sodium dendrite growth and improve mechanical strength of β″-Al2O3 electrolyte. Experimental results show that the cathode loading in vertically porous layer can reach to 8 mg cm−2, and the porous-dense bilayer β″-Al2O3 electrolyte-based battery exhibits a reversible specific capacity of 87 mAh g−1 and a capacity retention of 95.5% over 100 cycles at a current density of 0.1 C, which is superior to that of the traditional dense β″-Al2O3 electrolyte-based battery. This work based on electrolyte structure design represents an efficient strategy for the development of solid-state sodium-ion batteries with high mass-loading cathode.

Abstract Background The number of patients with diabetes is increasing worldwide. Diabetic testicular damage can cause spermiogenesis disorders and sexual dysfunction. We thus explored the role of miRNAs in diabetic testicular damage, and revealed that they could serve as effective prevention and treatment therapeutic targets. Methods Streptozotocin (STZ) was used to generate a rat model of type 2 diabetes. Rat testicular tissues were used for miRNA and mRNA sequencing. Through bioinformatics analysis, we constructed an miRNA–mRNA diabetic testicular damage regulatory network and screened for key miRNAs. We also used Leydig cells to generate a diabetic cell model and detected the downstream target genes of miRNAs, secretion of testosterone, and proliferation and apoptotic levels to elucidate the role and mechanism of the selected miRNAs in diabetic testicular damage. Results Using second-generation sequencing, we identified 19 differentially expressed miRNAs and 555 mRNAs in the testes of diabetic rats. Based on computational prediction of targets and negative regulation relationships, we constructed a miRNA–mRNA regulatory network, including 12 miRNAs and 215 mRNAs. KEGG enrichment analysis revealed that genes were more concentrated on the survival signalling pathway. Based on this, we screened 2 key miRNAs, miR-504 and miR-935. In vitro, glucose could induce an increase in miR-504 and miR-935, whereas a decrease in MEK5 and MEF2C in a dose-dependent manner. Overexpression of miR-504 and miR-935 led to the decreased expression of MEK5 and MEF2C, decreased proliferation rate of Leydig cells, increased apoptotic rate, and decreased secretion of testosterone. Whereas, knockdown of miR-504 and miR-935 displayed opposite tendencies. Conclusions miRNAs play important roles in diabetic testicular damage. miR-504 and miR-935 might regulate testicular damage through the classic survival pathway of MEK5-ERK5-MEF2C. Targeted inhibition of miR-504 and miR-935 could reverse the high-glucose-induced testicular complications, thus posing as a potential therapeutic approach in diabetic testicular injury.

Lumpy skin disease is caused by lumpy skin disease virus (LSDV), which can induce cattle with high fever and extensive nodules on the mucosa or the scarfskin, seriously influencing the cattle industry development and international import and export trade. Since 2013, the disease has spread rapidly and widely throughout the Russia and Asia. In the past few decades, progress has been made in the study of LSDV. It is mainly transmitted by blood-sucking insects, and various modes of transmission with distinct seasonality. Figuring out how the virus spreads will help eradicate LSDV at its source. In the event of an outbreak, selecting the most effective vaccine to block and eliminate the threat posed by LSDV in a timely manner is the main choice for farmers and authorities. At present, a variety of vaccines for LSDV have been developed. The available vaccine products vary in quality, protection rate, safety and side effects. Early detection of LSDV can help reduce the cost of disease. In addition, because LSDV has a huge genome, it is currently also used as a vaccine carrier, forming a new complex with other viral genes through homologous recombination. The vaccine prepared based on this can have a certain preventive effect on many kinds of diseases. Clinical detection of disease including nucleic acid and antigen level. Each method varies in convenience, accuracy, cost, time and complexity of equipment. This article reviews our current understanding of the mode of transmission of LSDV and advances in vaccine types and detection methods, providing a background for further research into various aspects of LSDV in the future.

Antibiotic resistance genes (ARGs) are important biological contamination factors in soil systems, posing direct or indirect threats to soil health, food safety and human health. The ubiquitous pollution of ARGs is usually implicated with the application of organic manures in agricultural soil ecosystem. However, little is known about the transmission and fate of ARGs after manure input concerning different soils. Herein, the transmission potential and temporal dynamics of manure-associated ARGs was characterized with three different agricultural soils collected from Jiangxi (JX), Zhejiang (ZJ), and Jilin (JL), respectively. The results show that manure input did not affect the total abundance of ARGs in the receiving soils, but remarkedly alter the compositions of ARGs in soils. The manure-associated ARGs were significantly enriched in the manure-amended soils, including genes conferring resistance to sulfonamide, aminoglycoside, tetracycline, chloramphenicol, and trimethoprim with the fold of 1.97 − 27.86. Variance partitioning analysis showed that the major variances of ARG community was explained by mobile genetic elements and bacterial profile (> 76%) but not the concentrations of heavy metals and antibiotics. Furthermore, 31, 37, and 38 ARG subtypes were identified as the potential extrinsic ARGs derived from manures in the JX, ZJ, and JL soils, respectively, including 13 shared ARG subtypes. It was also found that the manure-associated ARGs (aadA, sul1, sul2, tetC, and tetG) declined with the incubation time in the JX and ZJ soils, whereas they firstly decreased and then increased in the JL soil. The abundance of these five ARGs in the JL soil was significantly higher than that in the JX and ZJ soils. Collectively, this finding revealed that soil type was responsible for the transmission and fate of manure-associated ARGs in agroecosystem.

Nanotechnology has been widely used in the field of pesticides. Integration of nano-pesticides and carbon dot fluorescence can fully utilize the potential for high admission of pesticides on leaves and convenience observation of its distribution and transport in the tissues. In the present study, a fluorescent mesoporous nanosilica with double hollow shells for loading imidacloprid (Im@FL-MSNs) was designed and synthesized. The physical and chemical properties of the imidacloprid nanocarriers were characterized by transmission electron microscopy (TEM), FT-IR spectroscopy, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and N2 adsorption/desorption. When the mass ratio of FL MSNs to imidacloprid is 6:5, Im@FL-MSNs exhibits good fluorescence properties, high loading efficiency (∼30%), great slow-release performance as well as pH controllability. Besides, Im@FL-MSNs can improve the ability of imidacloprid to adhere on the leaf surface of bok choy (Initial contact angled is greater than 80°）. Importantly, Im@FL-MSNs did not reduce the biological activity of imidacloprid (LC50 (95% CI) = 1.43 mg/L). It was able to visually study the absorption and distribution of imidacloprid in bok choy plants, and provide theoretical and technical guidance for pesticide reduction.

To model the atmospheric dispersion of radionuclides released from nuclear accident is very important for nuclear emergency. But the uncertainty of model parameters, such as source term and meteorological data, may significantly affect the prediction accuracy. Data assimilation (DA) is usually used to improve the model prediction with the measurements. The paper proposed a parameter bias transformation method combined with Lagrangian puff model to perform DA. The method uses the transformation of coordinates to approximate the effect of parameters bias. The uncertainty of four model parameters is considered in the paper: release rate, wind speed, wind direction and plume height. And particle swarm optimization is used for searching the optimal parameters. Twin experiment and Kincaid experiment are used to evaluate the performance of the proposed method. The results show that the proposed method can effectively increase the reliability of model prediction and estimate the parameters. It has the advantage of clear concept and simple calculation. It will be useful for improving the result of atmospheric dispersion model at the early stage of nuclear emergency.

Tongue squamous cell carcinoma (TSCC) is a prevalent cancer of the oral cavity. Survival metrics are usually unsatisfactory, even using combined treatment with surgery, radiation, and chemotherapy. Immune checkpoint inhibitors can prolong survival, especially in patients with recurrent or metastatic disease. However, there are few effective biomarkers to provide prognosis and guide immunotherapy. Here, we utilized weighted gene co-expression network analysis to identify the co-expression module and selected the turquoise module for further scrutiny. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the innate pathways. The findings indicated that cell junction organization, response to topologically incorrect protein, and regulation of cell adhesion pathways may be essential. Eleven crucial predictive genes (PLXNB1, N4BP3, KDELR2, INTS8, PLAU, PPFIBP2, OAF, LMF1, IL34, ZFP3, and MAP7D3) were used to establish a risk model based on Cox and LASSO analyses of The Cancer Genome Atlas and GSE65858 databases (regarding overall survival). Kaplan–Meier analysis and receiver operating characteristic curve suggested that the risk model had better prognostic effectiveness than other clinical traits. Consensus clustering was used to classify TSCC samples into two groups with significantly different survival rates. ESTIMATE and CIBERSORT were used to display the immune landscape of TSCC and indicate the stromal score; specific types of immune cells, including naïve B cells, plasma cells, CD8 T cells, CD4 memory resting and memory activated T cells, follicular helper T cells, and T regulatory cells, may influence the heterogeneous immune microenvironment in TSCC. To further identify hub genes, we downloaded GEO datasets (GSE41613 and GSE31056) and successfully validated the risk model. Two hub genes (PLAU and PPFIBP2) were strongly associated with CD4+ and CD8+ T cells and programmed cell death protein 1 (PD1) and PD-ligand 1.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor is one of the important herbicides to solve the problem of weed control. With the widespread and continued use of HPPD inhibitor (HPPDi) herbicides, it may inevitably put pressure on the environment. Humic acid (HA) can effectively interact with pesticides through sorption or covalent bond formation and promote the degradation of pesticides, which can reduce the risk of pesticides in the environment. In the present study, the interactions of four HPPDi herbicides (sulcotrione, tembotrione, topramezone and mesotrione) with HA were reported and comparative assessment of the binding using multispectral technology, density functional theory (DFT) calculation and two-dimensional correlation spectroscopy (2D-COS). Time-resolved measurements and the Stern-Volmer constant at different temperature verified that HPPDi can bind with HA through the static quenching mechanism. From the thermodynamic parameters, the interaction force between HA and sulcotrione, tembotrione, topramezone and mesotrione was provided by electrostatic force. DFT, binding constant and three-dimensional (3D) fluorescence peak variation all indicated that the order of the binding ability of the four HPPDi and HA was mesotrione > tembotrione > sulcotrione > topramezone. According to dynamic light scattering (DLS), pH 7 is most conducive to the formation of HA-HPPDi complexes. Fourier transform infrared spectroscopy (FTIR) and 2D-COS showed that HA combined with HPPDi through aromatic C-H, CO and C-X, and the first binding group to HA was almost all CO. Sulcotrione, tembotrione, topramezone and mesotrione quench the endogenous fluorescence of HA by a static quenching mechanism and bind to HA through electrostatic interaction to form a complex. These results provide important insights into the combination of environmental pollutants with HA.

[This corrects the article DOI: 10.1371/journal.pntd.0008023.].

Change detection (CD) is a technique widely used in remote sensing for identifying the differences between data acquired at different times. Most existing 3D CD approaches voxelize point clouds into 3D grids, project them into 2D images, or rasterize them into digital surface models due to the irregular format of point clouds and the variety of changes in three-dimensional (3D) objects. However, the details of the geometric structure and spatiotemporal sequence information may not be fully utilized. In this article, we propose PBFormer, a transformer network with Siamese architecture, for directly inferring pointwise changes in bi-temporal 3D point clouds. First, we extract point sequences from irregular 3D point clouds using the k-nearest neighbor method. Second, we uniquely use a point transformer network as an encoder to extract point feature information from bitemporal 3D point clouds. Then, we design a module for fusing the spatiotemporal features of bi-temporal point clouds to effectively detect change features. Finally, multilayer perceptrons are used to obtain the CD results. Extensive experiments conducted on the Urb3DCD benchmark show that PBFormer outperforms other excellent approaches for 3D point cloud CD tasks.

Abstract Background The regulatory roles of circular RNAs (circRNAs) in tumorigenesis have attracted increasing attention. However, novel circRNAs with the potential to be used as serum/plasma biomarkers and their regulatory mechanism in the pathogenesis of hepatocellular carcinoma (HCC) remain explored. Methods CircRNA expression profiles of tumor tissues and plasma samples from HCC patients were compiled and jointly analyzed. CircRNA–miRNA–mRNA interactions were predicted by bioinformatics tools. The expression of interacting miRNAs and mRNA was verified in independent datasets. Survival analysis and pathway enrichment analysis were conducted on hub genes. Results We identified three significantly up-regulated circRNAs (hsa_circ_0009910, hsa_circ_0049783, and hsa_circ_0089172) both in HCC tissues and plasma samples. Two of them were validated to be indeed circular and could be excreted from hepatoma cells. We further revealed four miRNAs (hsa-miR-455-5p, hsa-miR-615-3p, hsa-miR-18a-3p, hsa-miR-4524a-3p) that targeting circRNAs and expressed in human HCC samples, and 95 mRNAs targeted by miRNAs and significantly up-regulated in two HCC cohorts. A protein-protein interaction network revealed 19 hub genes, 12 of them (MCM6, CCNB1, CDC20, NDC80, ZWINT, ASPM, CENPU, MCM3, MCM5, ECT2, CDC7, and DLGAP5) were associated with reduced survival in two HCC cohorts. KEGG, Reactome, and Wikipathway enrichment analysis indicated that the hub genes mainly functioned in DNA replication and cell cycle. Conclusions Our study uncovers three novel deregulated circRNAs in tumor and plasma from HCC patients and provides an insight into the pathogenesis from the circRNA–miRNA–mRNA regulatory network.

Humidity is a key factor affecting proton exchange membrane fuel cell (PEMFC) efficiency and output performance. Different working conditions have different requirements for humidity. Improper humidity may cause too high or too low water content inside the PEMFC, which will damage the output performance and even shorten the remaining useful life of PEMFC. Therefore, how to control humidity appropriately is a crucial subject. This paper establishes a PEMFC internal water management and inlet humidity model, and the influence of the change of anode inlet humidity on the performance of the PEMFC and the water content of the membrane is analyzed through computational fluid dynamics (CFD) simulation. And the direct control of the inlet humidity, which is difficult to be accurately measured, is converted to the temperature control of the bubble humidifier according to the proposed model, and a back propagation neural network proportion integration differentiation (BPPID) controller is proposed, which combines artificial neural network and digital PID control to adjust PID parameters in real time. The controller is applied to the temperature control of the bubble humidifier and compared with the traditional PID controller and the fuzzy PID controller. It is found that the performance of the BPPID controller is better through the comparison with the experimental results and the stabilization time it takes is only about 50% of that of other controllers.

To curb the pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple platforms have been employed toward a safe and highly effective vaccine. Here, we develop a novel cell-based vaccine candidate, namely K562-S, by utilizing human cell K562 as a cellular carrier to display Spike (S) protein of SARS-CoV-2 on the membrane. Analogous to the traditional inactivated vaccine, K562-S cells can be propagated to a large scale by culturing and completely lose their viability after exposure to X-ray irradiation or formalin. We in turn demonstrated high immunogenicity of formalin-inactivated K562-S vaccine in both mouse and non-human primates and its protective efficacy in mice. In mice, immunization with inactivated K562-S vaccines can elicit potent neutralizing antibody (nAb) responses persisting longer than 5 months. We consequently showed in a hACE2 mouse model of SARS-CoV-2 infection that a two-shot vaccination with adjuvanted K562-S rendered greater than 3 log reduction in viral lung load and concomitant ameliorated lung pathology. Of importance, the administration of the same regimen in non-human primates was able to induce a neutralizing antibody titer averaging three-fold higher relative to human convalescent serum. These results together support the promise of K562-based, S-protein-expressing vaccines as a novel vaccination approach against SARS-CoV-2. Importantly, with a powerful capacity to carry external genes for cell-based vectors, this platform could rapidly generate two- and multiple-valent vaccines by incorporating SARS-CoV-2 mutants, SARS-CoV, or MERS-CoV.