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Aim: This study aimed to investigate the biological functions of miRNAs in hepatobiliary tumors as the focus of targeted therapy research. Background: Hepatobiliary tumors are among the leading causes of cancer-related deaths worldwide. Many microRNAs (miRNAs) play an important regulatory role in tumor progression. Our study aims to explore some biologically functional miRNAs from different datasets of hepatobiliary tumors for disease diagnosis or treatment. Objective: In this study, we tried to filter out differentially expressed miRNAs in different tumor datasets from the GEO database. Methods: In this study, we first perform analyses in different GEO data sets. After taking the intersection, the initial scope is limited to several differential RNAs. Then, combined with the existing research results from Kaplan-Meier survival analysis and literature, the candidate molecule was finally identified to be studied. Furthermore, the biological characteristics analysis of the candidate molecule was performed on the basis of Cancermirnome online tool, including expression levels in tumors, KEGG and GO analysis, ROC analysis, and target gene prediction. Furthermore, the effect of the candidate molecule on the biological functions of liver cancer was verified by in vitro assay. Results: The preliminary analysis of bioinformatics shows that 16 differentially expressed miRNAs may play an important role in HCC or ICC. Ultimately, we identified miRNA-99a-5p as the only molecule to study. The results showed that miRNA-99a-5p is abnormally expressed in many tumors, and in liver cancer, its level of expression in tumor tissue is significantly lower than that in normal tissue. Then, the KEGG and GO analysis found that it functions in multiple pathways. At the same time, the ROC analysis found that it showed great potential for prognostic prediction in HCC and we also predicted that RUNDC3B is the most likely target to which it binds. Finally, the experimental results of overexpression and knockdown confirmed that miRNA-99a-5p could inhibit cell proliferation in HCC, which also suggested that it may be an important tumor suppressor in HCC. Conclusion: MiRNA-99a-5p was negatively correlated with HCC progression and could act as a novel therapeutic target for HCC.

Background. There is a significant role for peroxisome proliferator-activated receptors (PPARs) in the development of cancer. Nevertheless, the role of PPARs-related genes in ovarian cancer (OC) remains unclear. Methods. The open-accessed data used for analysis were downloaded from The Cancer Genome Atlas database, which was analyzed using the R software. Results. In our study, we comprehensively investigated the PPAR target genes in OC, including their biological role. Meanwhile, a prognosis signature consisting of eight PPAR target genes was established, including apolipoprotein A-V, UDP glucuronosyltransferase 2 family, polypeptide B4, TSC22 domain family, member 1, growth hormone inducible transmembrane protein, renin, dedicator of cytokinesis 4, enoyl CoA hydratase 1, peroxisomal (ECH1), and angiopoietin-like 4, which showed a good prediction efficiency. A nomogram was constructed by combining the clinical feature and risk score. Immune infiltration and biological enrichment analysis were applied to investigate the difference between high- and low-risk patients. Immunotherapy analysis indicated that low-risk patients might respond better to immunotherapy. Drug sensitivity analysis indicated that high-risk patients might respond better to bleomycin, nilotinib, pazopanib, pyrimethamine, and vinorelbine, yet worse to cisplatin and gefitinib. Furthermore, the gene ECH1 was selected for further analysis. Conclusions. Our study identified a prognosis signature that could effectively indicates patients survival. Meanwhile, our study can provide the direction for future studies focused on the PPARs in OC.

Goose astrovirus genotype 2 (GoAstV2), as a contagious pathogen of fatal visceral gout in goslings, has been widely distributed in major goose-producing regions in China since 2017, leading to significant economic losses to the Chinese goose industry. In this study, a novel goose astrovirus (GoAstV-SDHZ) was isolated and identified from laying hens with nephritis for the first time. Phylogenetic analysis of the sequenced genome of ORF2 gene revealed that the GoAstV-SDHZ strain clustered into Group 2 GoAstVs and shared the highest identity with the other representative GoAstV2 in the nucleotide (ORF1a: 97.2–99.7%; ORF1b: 98.4–99.8%; ORF2: 97.2–99.9%) and amino acid sequence (ORF1a: 98.2–100%; ORF1b: 98.8–99.6%; ORF2: 97.4–99.6%). In summary, this study provides the first evidence of the GoAstV2 infection in Chinese laying hens, which raises potential threat to the poultry industry in China.

Weizhou 11-4N oilfield is a medium-low-porosity and low-permeability reservoir. The oilfield was initially developed by edge and bottom water energy and then transferred to water injection development. Affected by poor physical properties and heterogeneity of the reservoir, the oilfield appeared in the process of water injection development. When the water injection pressure increases, the water injection volume continues to decrease, and it is difficult to meet the injection requirements. On the basis of the analysis of reservoir heterogeneity, void structure, and clay minerals of reservoir, the water injection compatibility experiment, damage evaluation experiment, and nuclear magnetic resonance-velocity sensitivity experiments were carried out to clarify the damage in the process of oilfield water flooding development. Experiments show that the main causes of damage in Weizhou 11-4N oilfield water flooding development process are water quality incompatibility and strong velocity-sensitive damage. The determination of water type shows that the injected water and formation water are MgCl2 water type and NaHCO3 water type, respectively, under the classification of Surin water type, resulting in the formation of scale with calcium carbonate as the main component in the reservoir. Incompatibility of water quality is an important cause of reservoir damage and scaling. In the reservoir-sensitive flow experiment, the experimental core showed strong velocity sensitivity, the average velocity sensitivity damage rate was 466.31%, and the average critical velocity was 2.98 m/d. Nuclear magnetic resonance experiments show that the core has a significant decrease in average pore size after water flooding. The main damage range is the tiny throat of 0-2 μm. In this paper, the main damage interval of velocity-sensitive damage in the Weizhou 11-4N area and the change trend of void structure after velocity-sensitive experiment are clarified by nuclear magnetic resonance and velocity sensitivity experiments. The main cause of block reservoir damage provides the basis for the oilfield to take targeted measures and provides a guarantee for the efficient development of the subsequent oilfield.

Fibroblast activation protein (FAP) generally shows low or undetectable expression in most normal tissues but is highly expressed in fibroblasts in almost all carcinomas. FAP is one of the potential molecules to detect activated fibroblasts and has multiple roles in tumour progression. We generated transgenic mice that specifically expressed tdTomato along with FAP promoter activity. Coculturing a mouse gastric cancer cell line and FAP-tdTomato transgenic mouse-derived fibroblasts showed that tdTomato expression was elevated in the cocultured fibroblasts. Moreover, stomach wall transplanted tumours in mice also showed FAP-tdTomato expression in fibroblasts of the stomach and each metastatic legion. These results indicated that FAP-tdTomato expression in fibroblasts was elevated by stimulation through the interaction with cancer cells. Functionally, collagen production was increased in FAP/tdTomato-positive fibroblasts cocultured with mouse cancer cells. These FAP-tdTomato transgenic mice have the potential to be used to investigate real-time FAP dynamics and the importance of FAP expression in tumour development.

The food safety issues caused by microorganisms are a great threat to human life and society.

A highly efficient and scalable total synthesis of pesimquinolone I (1) was accomplished in 5 steps with 3 chromatographic purifications.

The nonlinear optical responses of carbon nanohoop derivatives increase significantly with the increasing number and the length of π-bridges.

The designed defect MA2Z4 monolayer family is highly activated toward HER electrocatalysts.

To compare homoleptic [2]catenanes and single rings consisting of gold(i) thiolates, the geometric and electronic structures, absorption spectra, binding energy, interaction energy and composition of intramolecular forces were studied theoretically.

Excess stroma and cancer-associated fibroblasts (CAF) enhance cancer progression and facilitate immune evasion. Insights into the mechanisms by which the stroma manipulates the immune microenvironment could help improve cancer treatment. Here, we aimed to elucidate potential approaches for stromal reprogramming and improved cancer immunotherapy. Platelet-derived growth factor C (PDGFC) and D expression were significantly associated with a poor prognosis in patients with gastric cancer, and PDGF receptor beta (PDGFRβ) was predominantly expressed in diffuse-type gastric cancer stroma. CAFs stimulated with PDGFs exhibited markedly increased expression of CXCL1, CXCL3, CXCL5, and CXCL8, which are involved in polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) recruitment. Fibrotic gastric cancer xenograft tumors exhibited increased PMN-MDSC accumulation and decreased lymphocyte infiltration, as well as resistance to anti–PD-1. Single-cell RNA sequencing and spatial transcriptomics revealed that PDGFRα/β blockade reversed the immunosuppressive microenvironment through stromal modification. Finally, combining PDGFRα/β blockade and anti–PD-1 treatment synergistically suppressed the growth of fibrotic tumors. These findings highlight the impact of stromal reprogramming on immune reactivation and the potential for combined immunotherapy for patients with fibrotic cancer.Significance:Stromal targeting with PDGFRα/β dual blockade reverses the immunosuppressive microenvironment and enhances the efficacy of immune checkpoint inhibitors in fibrotic cancer.See related commentary by Tauriello, p. 655

Abstract: A series of functional biomaterials with different sizes and morphologies can be constructed through self-assembly, among which amphiphilic peptide-based materials have received intense attention. One main possible reason is that the short amphiphilic peptides can facilitate the formation of versatile materials and promote their further applications in different fields. Another reason is that the simple structure of amphiphilic peptides can help establish the structure-function relationship. This review highlights the recent advances in the self-assembly of two typical peptide species, surfactant-like peptides (SLPs) and peptides amphiphiles (PAs). These peptides can self-assemble into diverse nanostructures. The formation of these different nanostructures resulted from the delicate balance of varied non-covalent interactions. This review embraced each non-covalent interaction and then listed the typical routes for regulating these non-covalent interactions, then realized the morphologies modulation of the self-assemblies. Finally, their applications in some biomedical fields, such as the stabilization of membrane proteins, templating for nanofabrication and biomineralization, acting as the antibacterial and antitumor agents, hemostasis, and synthesis of melanin have been summarized. Further advances in the self-assembly of SLPs and PAs may focus on the design of functional materials with targeted properties and exploring their improved properties.

The DArk Matter Particle Explorer (DAMPE) is well suitable for searching for monochromatic and sharp $\gamma$-ray structures in the GeV$-$TeV range thanks to its unprecedented high energy resolution. In this work, we search for $\gamma$-ray line structures using five years of DAMPE data. To improve the sensitivity, we develop two types of dedicated data sets (including the BgoOnly data which is the first time to be used in the data analysis for the calorimeter-based gamma-ray observatories) and adopt the signal-to-noise ratio optimized regions of interest (ROIs) for different DM density profiles. No line signals or candidates are found between 10 and 300 GeV in the Galaxy. The constraints on the velocity-averaged cross section for $\chi\chi \to \gamma\gamma$ and the decay lifetime for $\chi \to \gamma\nu$, both at 95% confidence level, have been calculated and the systematic uncertainties have been taken into account. Comparing to the previous Fermi-LAT results, though DAMPE has an acceptance smaller by a factor of $\sim 10$, similar constraints on the DM parameters are achieved and below 100 GeV the lower limits on the decay lifetime are even stronger by a factor of a few. Our results demonstrate the potential of high-energy-resolution observations on dark matter detection., Comment: 14 pages, 8 figures. Update the content to keep up with the published version

Accumulating evidences confirm that epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement have coexisted in lung adenocarcinoma (LUAD). However, Its biological mechanism, clinicopathological features, and optimization of targeted drugs have not yet been completely elucidated.To explore the clinical profile of LUAD patients with co-mutations ofTwo hundred and thirty-seven LUAD patients were enrolled. EGFR mutations were detected by the amplification refractory mutation system-peptide nucleic acid technique, while the expression of ALK rearrangement was screened by the 5'/3' imbalance strategy for reverse transcription followed by quantitative polymerase chain reaction analysis. The clinicopathological features of these patients were analysed retrospectively, and the follow-up data were collected.There were six cases with co-mutations ofIn Gannan region, the positive rate of co-mutations of

Purpose To compare total en bloc spondylectomy with marginal margins against piecemeal spondylectomy with intralesional margins in the surgical treatment of Enneking stage III spinal giant cell tumor (GCT) in terms of local recurrence. Methods A retrospective survival analysis of patients with Enneking stage III GCT who underwent TES with marginal margins or total piecemeal spondylectomy with intralesional margins was performed between January 2006 and April 2020. Local recurrence-free survival (LRFS) was the time between the date of surgery and recurrence. Factors with p-values Results Sixty patients (25 men and 35 women) with a mean age of 35.6 (range 11–71) years were included. The mean follow-up duration was 93 (range 24–198) months. Two patients were lost to follow-up 6 and 14 years after the procedure. Over a 10-year period, the recurrence rate was 13.3%. The 2-, 5-, and 10-year LRFS rates were 95%, 88%, and 78%, respectively. Univariate analysis identified total piecemeal spondylectomy and no adjuvant radiotherapy as prognostic factors for LRFS. Multivariate Cox‐regression models showed a significant association between local recurrence and total piecemeal spondylectomy and no adjuvant radiotherapy. Conclusion TES with marginal margins is better than total piecemeal spondylectomy with intralesional margins owing to its lower postoperative recurrence rate. Adjuvant radiotherapy should be administered to reduce postoperative recurrence rates.

Mechanism-driven models based on transmission dynamics and statistic models driven by public health data are two main methods for simulating and predicting emerging infectious diseases. In this paper, we intend to combine these two methods to develop a more comprehensive model for the simulation and prediction of emerging infectious diseases. First, we combine a standard epidemic dynamic, the susceptible–exposed–infected–recovered (SEIR) model with population migration. This model can provide a biological spread process for emerging infectious diseases. Second, to determine suitable parameters for the model, we propose a data-driven approach, in which the public health data and population migration data are assembled. Moreover, an objective function is defined to minimize the error based on these data. Third, based on the proposed model, we further develop a swarm-optimizer-assisted simulation and prediction method, which contains two modules. In the first module, we use a level-based learning swarm optimizer to optimize the parameters required in the epidemic mechanism. In the second module, the optimized parameters are used to predicate the spread of emerging infectious diseases. Finally, various experiments are conducted to validate the effectiveness of the proposed model and method.

Dual-hereditary jaundice (Dubin–Johnson syndrome (DJS) and Gilbert’s syndrome (GS)) is a rare clinical entity resulting from defects of the ATP binding cassette subfamily C member 2 (ABCC2) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genes with autosomal recessive inheritance. In this study, we aimed to investigate the mutation profiles and characterize the phenotypes in a Han Chinese family with DJS and GS. Genetic screening for variants in the ABCC2 and UGT1A1, immunohistochemistry for expression of ABCC2, and histopathological examination were carried out. The proband and his brother had unconjugated and conjugated hyperbilirubinemia after birth. The proband’s sister had only conjugated hyperbilirubinemia after birth. The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. Hepatocellular carcinoma occurred in the proband’s brother at age 46. Seven compound defects of the ABCC2 gene [c.2414delG, p.(Ile1489Gly), p.(Thr1490Pro), and p.(Ile1491Gln)] and the UGT1A1 gene (c.-3279T>G, p.(Gly71Arg), and p.(Pro451Leu)) were identified in family members. Accumulation of pigment in hepatocytes characteristic of that in DJS was present in the proband and his brother. Expression of ABCC2 protein was markedly diminished in the patient’s liver. Our results show a different genetic profile of DJS and GS in a Han Chinese family, indicating a more complex pattern of dual-hereditary jaundice among different populations. The present study illuminates the underpinnings of DJS and GS and extends the mutation profiles and phenotypes of these two syndromes in dual-hereditary jaundice.

Aging results in progressive decline of renal function as well as histological alterations including glomerulosclerosis and interstitial fibrosis. The objective of current study was to test the benefits of moderate swimming exercise in aged rats on renal function and structure and investigate its molecular mechanisms. Aged rats of 21-months old were given moderate swimming exercise for 12 weeks. Swimming exercise in aged rats led to reduced plasma levels of creatinine and blood urea nitrogen. Periodic acid-Schiff staining results revealed reduced renal injury scores in aged rats after swimming exercise. Swimming exercise in aged rats mitigated renal fibrosis and downregulated the mRNA expression of Acta2, Fn, Col1a, Col4a, and Tgfb1 in kidneys. Swimming exercise in aged rats attenuated lipid accumulation and reduced levels of triglyceride in kidneys. Swimming exercise in aged rats abated oxidative stress, evidenced by reduced MDA levels and increased MnSOD activities in kidneys. Swimming exercise in aged rats inhibited NF-κB activities and reduced renal expression of pro-inflammatory cytokines including MCP-1, IL-1β and IL-6. Mechanistically, swimming exercise restored mRNA and protein expression of PPAR-α in kidney of aged rats. Furthermore, swimming exercise in aged rats increased expression of PPAR-α-targeting microRNAs including miR-21 and miR-34a. Collectively, swimming exercise activated PPAR-α, which partly explained the benefits of moderate swimming exercise in aging kidneys.

Legumes in the inverted repeat-lacking clade (IRLC) each produce a unique set of nodule-specific cysteine-rich (NCR) peptides, which act in concert to determine the terminal differentiation of nitrogen-fixing bacteroid. IRLC legumes differ greatly in their numbers of NCR and sequence diversity. This raises the significant question how bacteroid differentiation is collectively controlled by the specific NCR repertoire of an IRLC legume. Astragalus sinicus is an IRLC legume that forms indeterminate nodules with its microsymbiont Mesorhizobium huakuii 7653R. Here, we performed transcriptome analysis of root and nodule samples at 3, 7, 14, 28 days postinoculation with M. huakuii 7653R and its isogenic ∆ bacA mutant. BacA is a broad-specificity peptide transporter required for the host-derived NCRs to target rhizobial cells. A total of 167 NCRs were identified in the RNA transcripts. Comparative sequence and electrochemical analysis revealed that A. sinicus NCRs (AsNCRs) are dominated by a unique cationic group (termed subgroup C), whose mature portion is relatively long (>60 amino acids) and phylogenetically distinct and possessing six highly conserved cysteine residues. Subsequent functional characterization showed that a 7653R variant harboring AsNCR083 (a representative of subgroup C AsNCR) displayed significant growth inhibition in laboratory media and formed ineffective white nodules on A. sinicus with irregular symbiosomes. Finally, bacterial two-hybrid analysis led to the identification of GroEL1 and GroEL3 as the molecular targets of AsNCR067 and AsNCR076. Together, our data contribute to a systematic understanding of the NCR repertoire associated with the A. sinicus and M. huakuii symbiosis. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

To further determine how BHE affected the growth of HCC cells, the proportion of each cell cycle phase was explored in HCC cells by flow cytometry. Blue honeysuckle (Lonicera caerulea L.) is a species of bush that grows in eastern Russia. Blue honeysuckle extract (BHE) is rich in bioactive phytochemicals which can inhibit the proliferation of tumor cells. The mechanism underlying the anticancer activity of BHE in primary liver cancer is poorly understood. The purpose of this study was to evaluate the growth inhibition mechanism of bioactive substances from blue honeysuckle on hepatocellular carcinoma (HCC) cells and to explore its protein and gene targets. The compounds in BHE were determined by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). Cell counting kit-8 (CCK8) assay was used to evaluate the effects of BHE on HCC cell proliferation, and flow cytometry assay (FCA) was used to determine how BHE arrested the proportion of each cell cycle phase in HCC cells. Western blot (WB) was performed to determine the expression of cell cycle-related proteins in HCC cells treated with different concentrations of BHE. The xenograft tumor animal models were established by HCC cell implantation. The results showed that cyanidin-3-o-glucoside and cyanidin-3-o-sophoroside which are the main biologically active components were detected in BHE. BHE is highly effective in inhibiting the proliferation of HCC cells by arresting the HCC cell cycle in the G2/M phase. BHE also downregulated the expression of conventional or classical dendritic cells-2 (cDC2) and cyclin B1 by promoting the expression of myelin transcription factor 1 (MyT1) in HCC cells. The weight and volume of xenografts were significantly decreased in the BHE treated groups when compared to the control group. BHE increased the expression of MyT1 in xenograft tissues. These findings showed that blue honeysuckle extract inhibits proliferation in vivo and in vitro by downregulating the expression of cDC2 and cyclin B1 and upregulating the expression of MyT1 in HCC cells.

Abstract: A new β-dihydroagarofuran-type sesquiterpenoid named 1α,2α,5α,11-tetraacetoxy-8α- (trans-p-coumaroyl)-β-dihydroagarofuran (1), together with five known compounds (2-6), was isolated from the CHCl3-soluble extract of the stems of Celastrus orbiculatus. The structure of the new compound was elucidated with spectroscopic physicochemical analyses. All isolates were evaluated for in vitro cytotoxic activity against four human cancer lines, including HepG2, MCF-7, A549, and HCT-116 cells. Among them, compounds 1 and 6 showed potent cytotoxic activities against HepG2 cells with IC50 values of 8.78 ± 2.31 and 10.28 ± 1.15 μM, respectively. In addition, compound 6 exhibited significant cytotoxic activity against HCT-116 cells with an IC50 value of 6.37 ± 2.52 μM.