The whole-cell proteome shows the characteristics of macrolides-resistant Bordetella pertussis in China linked to the biofilm formation.

The macrolides-resistant Bordetella pertussis (MR-Bp) isolates in China evolved from the ptxP1/fhaB3 allele and rapidly became predominant, suggestive of an adaptive transmission ability. This was different from the global prevalent ptxP3 strains, in which MR-Bp was rarely reported. The study aimed to determine the underlying mechanism responsible for fitness and resistance in these two strains. We identify proteomic differences between ptxP1/fhaB3 and ptxP3/fhaB1 strains using tandem mass tag (TMT)-based proteomics. We then performed in-depth bioinformatic analysis to determine differentially expressed genes (DEGs), followed by gene ontology (GO), and protein-protein interaction (PPI) network analysis. Further parallel reaction monitoring (PRM) analysis confirmed the expression of four target proteins. Finally, the crystal violet method was used to determine biofilm-forming ability. The results showed that the main significantly different proteins between the two represent isolates were related to biofilm formation. Furthermore, we have confirmed that ptxP1/fhaB3 showed hyperbiofilm formation in comparison with ptxP3/fhaB1. It is suggested that the resistance and adaptability of ptxP1/fhaB3 strains may be related to the formation of biofilm through proteomics. In a word, we determined the significantly different proteins between the ptxP1/fhaB3 and ptxP3/fhaB1 strains through whole-cell proteome, which were related to biofilm formation.

Accumulation of DNA damage alters microRNA gene transcription in Arabidopsis thaliana.

BACKGROUND: MicroRNAs (miRNAs) and other epigenetic modifications play fundamental roles in all eukaryotic biological processes. DNA damage repair is a key process for maintaining the genomic integrity of different organisms exposed to diverse stresses. However, the reaction of miRNAs in the DNA damage repair process is unclear. RESULTS: In this study, we found that the simultaneous mutation of zinc finger DNA 3'-phosphoesterase (ZDP) and AP endonuclease 2 (APE2), two genes that play overlapping roles in active DNA demethylation and base excision repair (BER), led to genome-wide alteration of miRNAs. The transcripts of newly transcribed miRNA-encoding genes (MIRs) decreased significantly in zdp/ape2, indicating that the mutation of ZDP and APE2 affected the accumulation of miRNAs at the transcriptional level. In addition, the introduction of base damage with the DNA-alkylating reagent methyl methanesulfonate (MMS) accelerated the reduction of miRNAs in zdp/ape2. Further mutation of FORMAMIDOPYRIMIDINE DNA GLYCOSYLASE (FPG), a bifunctional DNA glycosylase/lyase, rescued the accumulation of miRNAs in zdp/ape2, suggesting that the accumulation of DNA damage repair intermediates induced the transcriptional repression of miRNAs. CONCLUSIONS: Our investigation indicates that the accumulation of DNA damage repair intermediates inhibit miRNAs accumulation by inhibiting MIR transcriptions.

Prognosis of hepatocellular carcinoma and its association with immune cells using systemic inflammatory response index.

Aim: To explore the prognostic value of the systemic inflammatory response index (SIRI) and peripheral blood T-cell subsets in patients with hepatocellular carcinoma (HCC) and the relationship between them. Materials & methods: We treated 352 patients with HCC with sorafenib and/or immune checkpoint inhibitors (ICIs) and analyzed SIRI and peripheral blood T cells. Results: SIRI was an independent prognostic factor for patients with HCC receiving systemic therapy. Patients with high SIRI and low baseline peripheral blood T-cell counts showed a poor response to ICIs. SIRI was significantly and negatively correlated with CD3+, CD4+ and CD8+ T-cell counts. Conclusion: SIRI markers can be employed to noninvasively assess the presence of cancer-promoting inflammation in the tumor microenvironment and predict the efficacy of targeted therapy and immunotherapy.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The change of immune microenvironment plays an important role in the occurrence and development of HCC. Recently, targeted therapy and immunotherapy have brought new hope to patients with advanced HCC. However, owing to the complexity of the immune microenvironment, not all patients can benefit from it. This study explores a simple, non-invasive method based on blood cell count to assess the immune microenvironment of HCC and predict the efficacy of treatment.

Rapid detection of cellulose and hemicellulose contents of corn stover based on near-infrared spectroscopy combined with chemometrics.

The feasibility of near-infrared spectroscopy (NIRS) combined with chemometrics for the rapid detection of the cellulose and hemicellulose contents in corn stover is discussed. Competitive adaptive reweighted sampling (CARS) and genetic simulated annealing algorithm (GSA) were combined (CARS-GSA) to select the characteristic wavelengths of cellulose and hemicellulose and to reduce the dimensionality and multicollinearity of the NIRS data. The whole spectra contained 1845 wavelength variables. After CARS-GSA optimization, the number of characteristic wavelengths of cellulose (hemicellulose) was reduced to 152 (260), accounting for 8.24% (14.09%) of all wavelengths. The coefficients of determination of the regression models for predicting the cellulose and hemicellulose contents were 0.968 and 0.996, the root mean square errors of prediction (RMSEPs) were 0.683 and 0.648, and the residual predictive deviations (RPDs) were 5.213 and 16.499, respectively. The RMSEP of the cellulose and hemicellulose regression models was 0.152 and 0.190 lower for CARS-GSA than for the full-spectrum, and the RPD was increased by 0.949 and 3.47, respectively. The results showed that the CARS-GSA model substantially reduced the number of characteristic wavelengths and significantly improved the predictive ability of the regression model.

Effects of tumor distance from anal verge on survival outcomes for rectal NENs and lymphatic metastasis risk score for colorectal NENs.

OBJECTIVE: To explore whether the distance of rectal neuroendocrine neoplasms from the anal margin has an impact on the prognosis of patients and evaluate lymphatic metastases risk score for colorectal neuroendocrine neoplasms (NENs). METHODS: Clinical pathological and follow-up data of 71 patients identified as colorectal neuroendocrine neoplasms by pathology from July 2011 to July 2019 were carefully collected. RESULTS: Among 71 patients with colorectal NENs, most of the tumors were rectal NENs (62 cases). A total of 26 patients were in the presence of lymph node metastasis, and 44 patients had negative lymph nodes. Patients with lesions from the anal margin > 5 cm in rectum have a better prognosis (P = 0.022). Tumor stage (P = 0.034) and grade (P = 0.001) were independent risk predictors of lymphatic metastases. We developed a lymphatic metastasis risk score for rectal NENs, and patients with the score ≥ 7.5 were more likely to develop lymph node metastases (area 0.958, 95% CI 0.903-1.000, P = 0.000) with a sensitivity of 72.2% and a specificity of 97.3%. CONCLUSION: Patients with lesions from the anal margin > 5 cm and lymphatic metastasis risk score ≥ 7.5 should be treated actively.

Clinical efficacy and safety of paclitaxel liposomes as first-line chemotherapy in advanced gastric cancer.

Aim: To compare the performance of first-line paclitaxel liposome + oxaliplatin and SOX (tegafur/gimeracil/oteracil + oxaliplatin) in advanced gastric cancer patients. Materials & methods: Stage IIb-IV gastric cancer patients underwent either first-line paclitaxel liposome + oxaliplatin (n = 52) or SOX (n = 69) between 2010-2013, and followed up until 2015 or death. Results: Both groups had similar objective response rate (p = 0.48) and disease control rate (p = 0.992) after two chemotherapy cycles, median progression-free survival (p = 0.495) and median overall survival (p = 0.208). Liposome group had significantly lower rate of grade I-II platelet decline and liver function damage (p = 0.04 and 0.019). Multivariate COX regression identified pre-treatment neutrophil-to-lymphocyte ratio as an independent prognostic factor. Conclusion: First-line paclitaxel liposome + oxaliplatin has comparable efficacy, but causes reduced adverse reactions in advanced gastric cancer as compared with SOX.

Altered fecal microbiota composition in patients with major depressive disorder.

Studies using animal models have shown that depression affects the stability of the microbiota, but the actual structure and composition in patients with major depressive disorder (MDD) are not well understood. Here, we analyzed fecal samples from 46 patients with depression (29 active-MDD and 17 responded-MDD) and 30 healthy controls (HCs). High-throughput pyrosequencing showed that, according to the Shannon index, increased fecal bacterial α-diversity was found in the active-MDD (A-MDD) vs. the HC group but not in the responded-MDD (R-MDD) vs. the HC group. Bacteroidetes, Proteobacteria, and Actinobacteria strongly increased in level, whereas that of Firmicutes was significantly reduced in the A-MDD and R-MDD groups compared with the HC group. Despite profound interindividual variability, levels of several predominant genera were significantly different between the MDD and HC groups. Most notably, the MDD groups had increased levels of Enterobacteriaceae and Alistipes but reduced levels of Faecalibacterium. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. These findings enable a better understanding of changes in the fecal microbiota composition in such patients, showing either a predominance of some potentially harmful bacterial groups or a reduction in beneficial bacterial genera. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and depression and to evaluate the suitability of the microbiome as a biomarker.

Impairment of CD4+ cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma.

UNLABELLED: The role of CD4(+) cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD4(+) CTLs in HCC patients and further elucidated the associations between CD4(+) CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study. CD4(+) CTLs were defined by flow cytometry, immunohistochemistry, and lytic granule exocytosis assays. A multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Circulating and liver-infiltrating CD4(+) CTLs were found to be significantly increased in HCC patients during early stage disease, but decreased in progressive stages of HCC. This loss of CD4(+) CTLs was significantly correlated with high mortality rates and reduced survival time of HCC patients. In addition, the proliferation, degranulation, and production of granzyme A, granzyme B, and perforin of CD4(+) CTLs were inhibited by the increased forkhead/winged helix transcription factor (FoxP3(+) ) regulatory T cells in these HCC patients. Further analysis showed that both circulating and tumor-infiltrating CD4(+) CTLs were independent predictors of disease-free survival and overall survival after the resection of the HCC. CONCLUSION: The progressive deficit in CD4(+) CTLs induced by increased FoxP3(+) regulatory T cells was correlated with poor survival and high recurrence rates in HCC patients. These data suggest that CD4(+) CTLs may represent both a potential prognostic marker and a therapeutic target for the treatment of HCC.

[Expression of ß-catenin and HNF-1α and their influence on prognosis in human hepatocellular carcinoma].

OBJECTIVE: To study the expressions of ß-catenin in hepatocellular carcinoma (HCC) tissue, adjacent cirrhotic liver tissue and hemangioma-surrounding liver tissue to understand whether their difference in expression will influence on the prognosis and to study the relationship between Wnt/ß-catenin signaling pathway and HNF-1α expression. METHODS: 50 specimens of HCC, 50 specimens of adjacent cirrhotic liver tissue and 7 specimens of hemangioma-surrounding liver tissue were used to detect the differences in the expression of ß-catenin and HNF-1α in them by immunohistochemistry. RESULTS: The expression rate of ß-catenin was 74.0% (37/50) in the HCC tissue, 18.0% (9/50) in cirrhotic liver tissue, and 14.3% (1/7) in hemangioma-surrounding liver tissue. The expression rate of ß-catenin in HCC tissue was significantly higher than that in the hemangioma-surrounding liver tissue (P = 0.002) and cirrhotic liver tissue (P < 0.001). The patients with abnormal expression had worse prognosis. Among the 50 HCC cases, the expression of HNF-1α was negative in 20.0% (10/50), weak positive in 40.0% (20/50), moderately positive in 26.0% (13/50), and strong positive in 14.0% (7/50). Among the 50 adjacent cirrhotic liver tissues, the expression of HNF-1α was negative in 12.0% (6/50), weak positive in 20.0% (10/50), moderately positive in 52.0% (26/50) and strong positive in 16.0% (8/50). In the 7 cases of hemangioma-surrounding liver tissue, the expression of HNF-1α was negative in 0(0/7), weak positive in 14.3% (1/7), moderately positive in 28.6% (2/7) and strong positive in 57.1% (4/7). The positive expression rate of HNF-1α in the HCC tissue was significantly lower than that in the hemangioma-surrounding liver tissues (P = 0.029) and adjacent cirrhotic liver tissues (P = 0.008). The patients with positive HNF-1α expression had a better prognosis. The abnormal expression of ß-catenin was negatively correlated with positive HNF-1α expression (r = -0.673, P < 0.001). CONCLUSIONS: The occurrence and development of HCC is related to the abnormal ß-catenin expression. There is a negative correlation between Wnt/ß-catenin signaling pathway and HNF-1α expression.

Effects of acid mine drainage and sediment contamination on soil bacterial communities, interaction patterns, and functions in alkaline desert grassland.

Acid mine drainage and sediments (AMD-Sed) contamination pose serious ecological and environmental problems. This study investigated the geochemical parameters and bacterial communities in the sediment layer (A) and buried soil layer (B) of desert grassland contaminated with AMD-Sed and compared them to an uncontaminated control soil layer (CK). The results showed that soil pH was significantly lower and iron, sulfur, and electroconductivity levels were significantly higher in the B layer compared to CK. A and B were dominated by Proteobacteria and Actinobacteriota, while CK was dominated by Firmicutes and Bacteroidota. The pH, Fe, S, and potentially toxic elements (PTEs) gradients were key influences on bacterial community variability, with AMD contamination characterization factors (pH, Fe, and S) explaining 48.6 % of bacterial community variation. A bacterial co-occurrence network analysis showed that AMD-Sed contamination significantly affected topological properties, reduced network complexity and stability, and increased the vulnerability of desert grassland soil ecosystems. In addition, AMD-Sed contamination reduced C/N-cycle functioning in B, but increased S-cycle functioning. The results highlight the effects of AMD-Sed contamination on soil bacterial communities and ecological functions in desert grassland and provide a reference basis for the management and restoration of desert grassland ecosystems in their later stages.

Ythdf2-mediated STK11 mRNA decay supports myogenesis by inhibiting the AMPK/mTOR pathway.

An emerging research focus is the role of m6A modifications in mediating the post-transcriptional regulation of mRNA during mammalian development. Recent evidence suggests that m6A methyltransferases and demethylases play critical roles in skeletal muscle development. Ythdf2 is a m6A "reader" protein that mediates mRNA degradation in an m6A-dependent manner. However, the specific function of Ythdf2 in skeletal muscle development and the underlying mechanisms remain unclear. Here, we observed that Ythdf2 expression was significantly upregulated during myogenic differentiation, whereas Ythdf2 knockdown markedly inhibited myoblast proliferation and differentiation. Combined analysis of high-throughput sequencing, Co-IP, and RIP assay revealed that Ythdf2 could bind to m6A sites in STK11 mRNA and form an Ago2 silencing complex to promote its degradation, thereby regulating its expression and consequently, the AMPK/mTOR pathway. Furthermore, STK11 downregulation partially rescued Ythdf2 knockdown-induced impairment of proliferation and myogenic differentiation by inhibiting the AMPK/mTOR pathway. Collectively, our results indicate that Ythdf2 mediates the decay of STK11 mRNA, an AMPK activator, in an Ago2 system-dependent manner, thereby driving skeletal myogenesis by suppressing the AMPK/mTOR pathway. These findings further enhance our understanding of the molecular mechanisms underlying RNA methylation in the regulation of myogenesis and provide valuable insights for conducting in-depth studies on myogenesis.

Evaluation of soil heavy metals pollution and the phytoremediation potential of copper-nickel mine tailings ponds.

Heavy metal pollution in soils caused by mining has led to major environmental problems around the globe and seriously threatens the ecological environment. The assessment of heavy metal pollution and the local phytoremediation potential of contaminated sites is an important prerequisite for phytoremediation. Therefore, the purpose of this study was to understand the characteristics of heavy metal pollution around a copper-nickel mine tailings pond and screen local plant species that could be potentially suitable for phytoremediation. The results showed that Cd, Cu, Ni, and Cr in the soil around the tailings pond were at the heavy pollution level, Mn and Pb pollution was moderate, and Zn and As pollution was light; The positive matrix factorization (PMF) model results showed that the contributions made by industrial pollution to Cu and Ni were 62.5% and 66.5%, respectively, atmospheric sedimentation and agricultural pollution contributions to Cr and Cd were 44.6% and 42.8%, respectively, the traffic pollution contribution to Pb was 41.2%, and the contributions made by natural pollution sources to Mn, Zn, and As were 54.5%, 47.9%, and 40.0% respectively. The maximum accumulation values for Cu, Ni, Cr, Cd, and As in 10 plants were 53.77, 102.67, 91.10, 1.16 and 7.23 mg/kg, respectively, which exceeded the normal content of heavy metals in plants. Ammophila breviligulata Fernald had the highest comprehensive extraction coefficient (CEI) and comprehensive stability coefficient (CSI) at 0.81 and 0.83, respectively. These results indicate that the heavy metal pollution in the soil around the copper nickel mine tailings pond investigated in this study is serious and may affect the normal growth of plants. Ammophila breviligulata Fernald has a strong comprehensive remediation capacity and can be used as a remediation plant species for multiple metal compound pollution sites.

Dicer Suppresses Hepatocellular Carcinoma via Interleukin-8 Pathway.

Background: Elevated level of interleukin-8 (IL-8) promotes hepatocellular carcinoma (HCC) development and contributes to poor prognosis. Previously, we have proved that Dicer inhibits HCC progression. In this study, we evaluated the potential interaction between IL-8 and Dicer as well as their influence on HCC. Methods: Hepatocellular carcinoma cells of SMMC-7721 were divided into 2 groups for subsequent analysis: pCMV-Dicer group for Dicer-overexpressing lentivirus transfected cells (pCMV-Dicer cells) and pCMV-NC group for empty lentivirus transfected cells (pCMV-NC cells). Cell Counting kit-8 (CCK8), wound healing, and transwell were used to evaluate the inhibitory effect of Dicer overexpression on proliferation, migration, and invasion of HCC cells. The level of IL-8 was measured by flow cytometry bead-based immunoassays. Male nude BALB/c mice injected with pCMV-Dicer or pCMV-NC cell suspensions was used for transplant of HCC tumor. Results: We found that the secretion of IL-8 was reduced in the medium of pCMV-Dicer cells (P = .027). Recombinant human IL-8 (rhIL-8) reversed the inhibitory effect of Dicer on proliferation (P < .01), migration (P = .003), and invasion (P = .001), whereas IL-8 inhibitor of reparixin enhanced inhibitory effect of Dicer on proliferation (P < .05), migration (P = .008), and invasion (P = .000). Lenvatinib downregulated the IL-8 level of HCC cells (P = .000) as well as promote Dicer-induced inhibition for HCC cells referring to proliferation (P < .05), migration (P = .000), and invasion (P = .000). Animal experiments also demonstrated that Dicer cooperated with lenvatinib to inhibit the growth of HCC tumors (P < .05). Conclusions: Dicer cooperated with lenvatinib to inhibit HCC growth via downregulating IL-8, and Dicer displayed its potential capability to enhance the anti-tumor effect of lenvatinib.

Transarterial Chemoembolization Combined With PD-1 Inhibitors Plus Lenvatinib Showed Improved Efficacy for Treatment of Unresectable Hepatocellular Carcinoma Compared With PD-1 Inhibitors Plus Lenvatinib.

Background: Programmed cell death protein-1 inhibitors combined with lenvatinib have become a popular treatment option for patients with unresectable hepatocellular carcinoma. Transarterial chemoembolization combined with programmed cell death protein-1 inhibitors and lenvatinib has also shown preliminary efficacy in the unresectable hepatocellular carcinoma. We conducted this observational, retrospective, cohort study to compare the clinical outcomes and safety of transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib versus programmed cell death protein-1 inhibitors plus lenvatinib in patients with unresectable hepatocellular carcinoma. Methods: Between November 2019 and November 2021, patients who were diagnosed with unresectable hepatocellular carcinoma and received transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib or programmed cell death protein-1 inhibitors plus lenvatinib treatment were reviewed for eligibility. The primary endpoints included objective response rate, overall survival, and progression-free survival. The secondary endpoint was the frequency of key adverse events. Results: In total, 105 patients were eligible for the present study, and they were divided into the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group (n = 46) and the programmed cell death protein-1 inhibitors plus lenvatinib group (n = 59). The patient cohort after a one-to-one propensity score matching (n = 86) was also analyzed. The transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had a higher objective response rate both in the patient cohort before propensity score matching (54.3% vs 25.4%, P = .002) and after propensity score matching (55.8% vs 30.2%, P = .017). The patients in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group had prolonged overall survival (median, 20.5 vs 12.6 months, P = .015) and progression-free survival (median, 10.2 vs 7.4 months, P = .035). For patient cohort- propensity score matching, the overall survival (20.5 vs 12.8 months, P = .013) and progression-free survival (12.1 vs 7.8 months, P = .030) were also significantly better in the transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib group than in the programmed cell death protein-1 inhibitors plus lenvatinib group. There were no significant differences between the 2 groups concerning adverse reactions caused by immunotherapy and lenvatinib. The adverse reactions caused by transarterial chemoembolization were transient and were quickly reversed. Conclusions: Compared to programmed cell death protein-1 inhibitors plus lenvatinib, transarterial chemoembolization combined with programmed cell death protein-1 inhibitors plus lenvatinib may provide better treatment response and survival benefits for patients with unresectable hepatocellular carcinoma, and the adverse events were manageable.

Molecular typing and mutational characterization of rectal neuroendocrine neoplasms.

BACKGROUND: Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing. METHODS: The paraffin-embedded tissue specimens of 38 patients with rectal NENs after surgery were subjected to whole gene sequencing (WGS), and mutation profilings were drawn to identify high-frequency mutation genes, copy-number variations (CNVs), tumor mutation burden (TMB), signal pathways, mutation signatures, DNA damage repair (DDR) genes, and molecular types. The differences of mutated genes and signaling pathways in different pathological grades and metastatic/non-metastatic groups were compared. It helped to search for potential targets. RESULTS: C > T and T > C transitions are the most common base substitutions in rectal NENs. DNA mismatch repair deficiency, DNA base modifications, smoking and exposure to ultraviolet light might play a role in the occurrence of rectal NENs. DAXX, KMT2C, BCL2L1, LTK, MERTK, SPEN, PKN1, FAT3, and LRP2 mutations were found in only low-grade rectal NETs, whereas APC, TP53, NF1, SOX9, and BRCA1 mutations were common in high-grade rectal NECs/MiNENs. These genes helped in distinguishing poorly-differentiated or well-differentiated rectal NENs. Alterations in P53, Wnt and TGFß signaling pathways were more pronounced in rectal NECs and MiNENs. Alterations in Wnt, MAPK and PI3K/AKT signaling pathways promoted metastases. Rectal NENs were classified into two molecular subtypes by cluster analysis based on the mutant genes and signaling pathways combined with clinicopathological features. Patients with mutations in the LRP2, DAXX, and PKN1 gene showed a trend of well-differentiated and early-stage tumors with less metastasis (p = 0.000). CONCLUSIONS: This study evaluated risk factors for regional lymphatic and/or distant metastases, identified high-frequency mutated genes, mutation signatures, altered signaling pathways through NGS. Rectal NENs were divided into two molecular types. This helps to evaluate the likelihood of metastasis, formulate follow-up strategies for patients and provide a target for future research on precision treatment of rectal NENs. PARP inhibitors, MEK inhibitors, mTOR/AKT/PI3K and Wnt signaling pathway inhibitors may be effective drugs for the treatment of metastatic rectal NENs.

Matrine improves the hepatic microenvironment and reverses epithelial-mesenchymal transition in hepatocellular carcinoma by inhibiting the Wnt-1/ß-catenin signaling pathway.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Despite rapid progress in targeted therapy and immunotherapy for HCC over the past 10 years, the overall efficacy remains unsatisfactory. This is mainly due to the presence of an intrahepatic microenvironment of cirrhosis in HCC patients, leading to cancer recurrence and drug resistance. METHODS: In this study, we investigated the correlations between the Wnt-1/ß-catenin signaling pathway and the prognosis as well as liver function of HCC patients. Additionally, we conducted in vitro experiments using different concentrations of matrine on HuH-7 cells. Furthermore, we verified the associations between the Wnt-1/ß-catenin signaling pathway, inflammation, and epithelial-mesenchymal transition (EMT) in a rat model of pre-hepatocellular carcinoma. Finally, matrine was employed to treat pre-hepatocellular carcinoma in rats and patients with advanced hepatocellular carcinoma. RESULTS: The results demonstrated the activation of the Wnt-1/ß-catenin signaling pathway, the occurrence of EMT, and exacerbated inflammation in human HCC tissues. In HuH-7 cell experiments, matrine effectively downregulated the Wnt-1/ß-catenin pathway, reversed EMT, and suppressed migration and invasion of HCC cells. In the rat model of pre-hepatocellular carcinoma, matrine dose-dependently inhibited the activation of the Wnt-1/ß-catenin signaling pathway, reversed the occurrence of EMT, and alleviated liver inflammation. Matrine analogues exhibited promising hepatoprotective effects in patients with advanced HCC. CONCLUSIONS: Matrine can reverse EMT, alleviate intrahepatic inflammation, and counteract immune depletion by inhibiting the Wnt-1/ß-catenin signaling pathway in HCC.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study.

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

Hypercytolytic activity of hepatic natural killer cells correlates with liver injury in chronic hepatitis B patients.

UNLABELLED: Natural killer (NK) cells are abundant in the liver and serve as a major innate immune component against microbial infection. Although NK cells have been implicated in inducing hepatocellular damage in patients with chronic hepatitis virus infections, the roles that hepatic NK cells play in chronic hepatitis B virus (HBV) infections remain obscure. In this study, we comprehensively characterized intrahepatic and peripheral NK cells and investigated their impact on liver pathology in a cohort of HBV-infected individuals; this cohort included 51 immune-activated (IA) patients, 27 immune-tolerant (IT) carriers, and 26 healthy subjects. We found that NK cells expressing NK receptors (activation receptors) preferentially accumulated in the livers of IA patients, in which they were activated and skewed toward cytolytic activity but without a concomitant increase in interferon-γ production, in comparison with those of IT carriers and healthy subjects. Further analysis showed that the livers of IA patients, in comparison with those of IT and healthy subjects, expressed higher levels of interleukin-12 (IL-12), IL-15, and IL-18 in situ and lower levels of IL-10, which in vitro can induce the activation and degranulation of NK cells from healthy individuals. Finally, hepatic NK cells displayed more cytolytic activity than peripheral NK cells, and this was found to be positively correlated with the liver histological activity index and serum alanine aminotransferase levels in these IA patients. CONCLUSION: In IA patients, hepatic NK cells are activated and preferentially skew toward cytolytic activity, which depends on an imbalanced cytokine milieu and correlates with liver injury during chronic HBV infection.

Passivation of heavy metals in copper-nickel tailings by in-situ bio-mineralization: A pilot trial and mechanistic analysis.

Metal tailings contain a variety of toxic heavy metals and have potential environmental risks owing to long-term open piling. In the present study, a strain of ureolytic bacteria with bio-mineralization ability, Lysinibacillus fusiformis strain Lf, was isolated from copper-nickel mine tailings in Xinjiang and applied to a pilot trial of tailings solidification under field conditions. The results of the pilot trial (0.5 m3 in scale) showed that strain Lf effectively solidified the tailings. The compressive strength of the solidified tailings increased by 121 ± 9 % and the permeability coefficient decreased by 68 ± 3 %. Compared to the control, the leaching reduction of the solidified tailings of Cu and Ni was >98 %, and that of As was 92.5 ± 1.7 %. Two mechanisms of tailings solidification and heavy metal passivation were proposed based on the findings of Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM), and energy-dispersive X-ray spectroscopy (EDS) mapping. Biogenic calcite filled the interstices of the tailings particles and cemented the adjacent particles. This improved the mechanical properties and reduced permeability. Moreover, heavy metal colloids were incorporated into large-sized calcite crystals, and heavy metal ions were sequestered within the calcite lattice. This method of using indigenous ureolytic bacteria to solidify tailings was successful in this work and may be replicated to remediate other tailings.

[Establishment of a Mouse Model of Acquired Aplastic Anemia Mediated by Cyclophosphamide Combined with Cyclosporine].

OBJECTIVE: To establish a stable mouse model of acquired aplastic anemia. METHODS: Female BALB/C mice aged 6 months were intraperitoneally injected with cyclophosphamide and cyclosporine for 14 days. The number of peripheral blood cells, the concentration of hemoglobin, the number of bone marrow nucleated cells, bone marrow smear, bone marrow pathological sections and other indexes were observed. RESULTS: In BALB/C mice injected intraperitoneally with cyclophosphamide and cyclosporine, the number of peripheral blood cells and the concentration of hemoglobin were significantly decreased, especially the white blood cells and platelets. Bone marrow smear showed a significant decrease in the number of nucleated cells and bone marrow hyperplasia. Bone marrow pathology showed decreased hematopoietic cells and increased non-hematopoietic cells such as adipocytes. CONCLUSION: The mouse model with intraperitoneal injection of cyclophosphamide and cyclosporine can meet the diagnostic criteria of acquired aplastic anemia, which can be used as a mouse model for the study of the pathogenesis and treatment of acquired aplastic anemia.