Systematic assessment of source identification and ecological and probabilistic health risks of potentially toxic elements (PTEs) in soils of a typical coal mining area in Guanzhong region.

Mining activities may cause the accumulation of potentially toxic elements (PTEs) in surrounding soils, posing ecological threats and health dangers to the local population. Therefore, a comprehensive assessment using multiple indicators was used to quantify the level of risk in the region. The results showed that the mean values of the nine potentially toxic elements in the study area were lower than the background values only for Cr, and the lowest coefficient of variation was 17.1 % for As, and the spatial distribution characteristics of the elements indicate that they are enriched by different factors. The elements Hg and Cd, which have substantial cumulative features, are the key contributors to ecological risk in the study region, which is overall at moderate risk. APCS-MLR model parses out 4 possible sources: mixed industrial, mining and transportation sources (53.98 %), natural sources (24.56 %), atmospheric deposition sources (12.60 %), and agricultural production sources (8.76 %). The probabilistic health risks show that children are more susceptible to health risks than adults; among children, the safety criteria (HI < 1 and CR < 10-4) were surpassed by 29.29 % of THI and 8.58 % of TCR. According to source-orientated health hazards, the element Ni significantly increases the risk of cancer. Mixed sources from industry, mining, and transportation are important sources of health risks. The results of this research provide some scientific references for the management and decrease of regional ecological and health risks.

Unveiling novel insights into human IL-6 - IL-6R interaction sites through 3D computer-guided docking and systematic site mutagenesis.

The cytokine interleukin-6 (IL-6) plays a crucial role in autoimmune and inflammatory diseases. Understanding the precise mechanism of IL-6 interaction at the amino acid level is essential to develop IL-6-inhibiting compounds. In this study, we employed computer-guided drug design tools to predict the key residues that are involved in the interaction between IL-6 and its receptor IL-6R. Subsequently, we generated IL-6 mutants and evaluated their binding affinity to IL-6R and the IL-6R - gp130 complex, as well as monitoring their biological activities. Our findings revealed that the R167A mutant exhibited increased affinity for IL-6R, leading to enhanced binding to IL-6R - gp130 complex and subsequently elevated intracellular phosphorylation of STAT3 in effector cells. On the other hand, although E171A reduced its affinity for IL-6R, it displayed stronger binding to the IL-6R - gp130 complex, thereby enhancing its biological activity. Furthermore, we identified the importance of R178 and R181 for the precise recognition of IL-6 by IL-6R. Mutants R181A/V failed to bind to IL-6R, while maintaining an affinity for the IL-6 - gp130 complex. Additionally, deletion of the D helix resulted in complete loss of IL-6 binding affinity for IL-6R. Overall, this study provides valuable insights into the binding mechanism of IL-6 and establishes a solid foundation for future design of novel IL-6 inhibitors.

Development of novel monoclonal antibodies for blocking NF-κB activation induced by CD2v protein in African swine fever virus.

Background: CD2v, a critical outer envelope glycoprotein of the African swine fever virus (ASFV), plays a central role in the hemadsorption phenomenon during ASFV infection and is recognized as an essential immunoprotective protein. Monoclonal antibodies (mAbs) targeting CD2v have demonstrated promise in both diagnosing and combating African swine fever (ASF). The objective of this study was to develop specific monoclonal antibodies against CD2v. Methods: In this investigation, Recombinant CD2v was expressed in eukaryotic cells, and murine mAbs were generated through meticulous screening and hybridoma cloning. Various techniques, including indirect enzyme-linked immunosorbent assay (ELISA), western blotting, immunofluorescence assay (IFA), and bio-layer interferometry (BLI), were employed to characterize the mAbs. Epitope mapping was conducted using truncation mutants and epitope peptide mapping. Results: An optimal antibody pair for a highly sensitive sandwich ELISA was identified, and the antigenic structures recognized by the mAbs were elucidated. Two linear epitopes highly conserved in ASFV genotype II strains, particularly in Chinese endemic strains, were identified, along with a unique glycosylated epitope. Three mAbs, 2B25, 3G25, and 8G1, effectively blocked CD2v-induced NF-κB activation. Conclusions: This study provides valuable insights into the antigenic structure of ASFV CD2v. The mAbs obtained in this study hold great potential for use in the development of ASF diagnostic strategies, and the identified epitopes may contribute to vaccine development against ASFV.

Mechanisms of the novel pesticide sodium dodecyl benzene sulfonate in the mitigation of protozoan ciliated pathogens during microalgal cultivation.

Protozoan ciliates represent a common biological contaminant during microalgae cultivation, which will lead to a decline in microalgae productivity. This study investigated the effectiveness of sodium dodecyl benzene sulfonate (SDBS) in controlling ciliate populations within microalgae cultures. SDBS concentrations of 160 mg/L and 100 mg/L were found to effectively manage the representative species of ciliates contamination by Euplotes vannus and Uronema marinum during the cultivation of Synechococcus and Chlorella, and the growth vitality of microalgae has been restored. Additionally, SDBS at these concentrations reduced oxidative stress resistance and induced membrane damage to remove biological pollutants by modulating enzyme activity, affecting lipid, energy, amino acid metabolism pathways, and processes such as translation and protein folding. This research provides insights into the mechanisms through which SDBS effectively combats protozoan ciliates during the microalgal cultivation. This contributes to reduce biological pollution, ensure the overall productivity and healthy and sustainable management of microalgae ecosystems.

Spatial distribution, ecological risk and health risk assessment of heavy metals in agricultural soil from Ankang basin, Shaanxi Province.

In order to assess the heavy metal pollution features, ecological dangers, and health risk status posed to human beings by soils in the Ankang Basin, a study was conducted. This involved the collection of 38 surface soil samples, followed by the determination of elemental levels of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc. The concentrations of arsenic, mercury, copper, cadmium, lead, chromium, nickel, and zinc were quantified through the collection of 38 surface soil samples. The data obtained from the study was subjected to analysis and evaluation utilizing various academic methodologies, including the geo-accumulation index method, potential ecological risk assessment method, human health risk assessment model, and Monte Carlo simulation method. The findings indicated that the concentrations of the eight heavy metals in the soil above the background levels, with only Cadmium (Cd) marginally surpassing the threshold set for controlling soil pollution risks. The ground accumulation index revealed a higher degree of soil pollution with mercury, cadmium, copper, and zinc components. According to the possible ecological risk index, the presence of mercury and cadmium elements poses significant ecological hazards. The geographical distribution analysis suggests that these risks mostly stem from the combined impacts of human activities and the topographical and geomorphological characteristics of the river valley. The findings of the human health risk assessment indicated that the non-carcinogenic risk fell within acceptable limits. Additionally, it was observed that the carcinogenic risk associated with arsenic, mercury, cadmium, and nickel was comparatively greater for children as compared to adults. The results of the Monte Carlo simulations indicate that the non-carcinogenic hazards have a negligible effect on human health. However, it was seen that arsenic and nickel have a greater likelihood of presenting a substantial carcinogenic risk to humans, particularly in relation to the pediatric population, hence exerting a more pronounced impact on their health. In general, it is observed that conventional deterministic risk assessments tend to overstate the potential health risks associated with a given situation. Conversely, the utilization of Monte Carlo simulations has been found to effectively mitigate uncertainties in health risk assessments. It has been observed that children exhibit a higher vulnerability to both carcinogenic and non-carcinogenic health impacts resulting from exposure to heavy metals present in soil, in comparison to adults. It is recommended that residents prioritize the surveillance of soil heavy metals in relation to potential impacts on human health.

NEUROD1 predicts better prognosis in pancreatic cancer revealed by a TILs-based prognostic signature.

It has been well-defined that tumor-infiltrating lymphocytes (TILs) play critical roles in pancreatic cancer (PaCa) progression. This research aimed to comprehensively explore the composition of TILs in PaCa and their potential clinical significance. A total of 178 samples from the TCGA and 63 samples from the GSE57495 dataset were enrolled in our study. ImmuCellAI was applied to calculate the infiltrating abundance of 24 immune cell types in PaCa and further survival analysis revealed the prognostic values of TILs in PaCa. Moreover, the Hallmark enticement analysis of differentially expressed genes (DEGs) between low- and high-risk groups was performed as well. Immunohistochemistry staining was used to evaluate NEUROD1 expression. As result, different kinds of TILs had distinct infiltrating features. In addition, Specific TILs subsets had notable prognostic values in PaCa. We further established a 6-TILs signature to assess the prognosis of PaCa patients. Kaplan-Meier and Cox regression analyses both suggested the significant prognostic value of the signature in PaCa. Based on the prognostic signature, we screened a great deal of potential prognostic biomarkers and successfully validated NEUROD1 as a novel prognostic biomarker in PaCa. Overall, the current study illuminated the immune cells infiltrating the landscape in PaCa and identified a TILs-dependent signature and NEUROD1 for prognostic prediction in PaCa patients.

Case report: Conversion therapy for advanced intrahepatic cholangiocarcinoma using PD-1 inhibitor plus S-1 and nab-paclitaxel.

Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant hepatobiliary tumor with a high rate of advanced disease at initial presentation. Conversion into resectable iCCA is important for improving the prognosis. Immunotherapy-based regimens are being increasingly used for treating advanced iCCA in recent years. However, the use of combined chemotherapy and immunotherapy for conversion has rarely been reported. The aim of this report was to present the outcomes of a 52-year-old female patient with IIIB iCCA. The patient was treated with a programmed cell death protein-1 inhibitor plus S-1 and nab-paclitaxel. The postoperative histopathological results indicated pathologic complete response after six cycles of systematic treatment. The patient is currently disease-free for one year.

Computer tomography-guided negative pressure drainage treatment of intrathoracic esophagojejunal anastomotic leakage: A case report.

BACKGROUND: Esophagojejunal anastomotic leakage (EJAL) is a serious and potentially crucial complication of total gastrectomy and represents the major cause of postoperative death, with a mortality rate of up to 50%. However, treatment remains challenging and controversial. We report here the case of a patient whose intrathoracic EJAL was successfully treated with computer tomography (CT)-guided negative pressure drainage treatment. CASE SUMMARY: A 69-year-old male patient complained of difficulty swallowing within the last six months. He was diagnosed with esophagogastric junction carcinoma, Siewert II, cT3N0M0 stage II. Total gastrectomy and Roux-en-Y esophagojejunostomy were performed. High fever, left chest pain and dyspnea appeared on postoperative day 5, and EJAL was confirmed by CT, gastroscopy and oral blue-dimethylene tests. Conservative treatment measures were applied immediately, including antibiotics, nasojejunal tubes, and repeated thoracic puncture and drainage under ultrasound guidance. However, without sufficient and effective drainage, the thoracic infection and systemic condition continued to deteriorate. With the cooperation of multiple departments, percutaneous CT-guided drainage (24 Fr 7 mm) in the thoracic cavity was successfully placed near the anastomotic leakage. Because of continuous negative pressure suction, the infection symptoms were effectively controlled and the general situation gradually recovered. Subsequent follow-up examination showed that the patient was in good condition. CONCLUSION: Negative pressure drainage via CT may represent an effective minimally invasive approach to treating intrathoracic EJAL.

Effects of climatic and social factors on dispersal strategies of alien species across China.

Determination of dispersal strategies of alien species and its relationship with social and climatic factors are essential to understand the mechanisms of species invasion and adaption. Based on morphological trait, dispersal mode, and dispersal agent of diaspore of 562 alien species across China, we determined: (i) the proportions of five dispersal strategies (i.e., autochory, anemochory, hydrochory, zoochory, and anthropochory), (ii) the relationships between the dispersal strategies and socio-climatic factors in 34 administrative regions across China, and (iii) the correlations between different dispersal strategies. Anthropochory, zoochory, and anemochory account for nearly 90.0% of all the dispersal strategies of alien species. Mean frost days (MFD), mean annual humidity (MAH), and gross domestic product (GDP) were the main climatic and social factors that were correlated to different dispersal strategies. Zoochory was positively related to MFD, but negatively related to the autochory and anthropochory. MAH negatively influenced the anemochory, while GDP positively influenced the hydrochory. We classified the six dispersal strategies into two groups based on the correlations among dispersal strategies, group I included autochory and anthropochory, and group II included anemochory, hydrochory, and zoochory. Within a group, dispersal strategies were positively correlated, while between groups, dispersal strategies were negatively correlated. Positive correlation between different strategies might be co-owned while negative correlation between different strategies might not be co-owned by one alien species. Understanding the characteristics of the dispersal strategies of alien species is important for policy makers when controlling the dispersal of malignant invasive alien species, predicting the distribution, and decreasing or cutting off the dispersal pathways of invasive alien species.

Heterogeneous iron-nickel compound/RGO composites with tunable microwave absorption frequency and ultralow filler loading.

We fabricated heterogeneous iron-nickel compound/reduced graphene oxide (RGO) composites to obtain lightweight and high-efficiency microwave absorption materials with tunable absorption frequency. Using a facile hydrothermal route in combination with calcination at varying temperatures of 500-700 °C, the magnetic components Fe0.64Ni0.36, Fe0.64Ni0.36@Fe2Ni2N, and Fe2Ni2N were obtained. Due to strong interfacial polarization and dipole polarization as well as the conductive network formed by the substantial number of interfaces, all the magnetic RGO hybrids presented remarkable electromagnetic wave attenuation ability even when the filler content was only 5.2 wt%. More importantly, the optimization of reflection loss and tunable absorption frequency could be successfully realized by tuning the hybrid architecture and electromagnetic properties. This work reveals the mechanism of polarization-related dielectric relaxation of RGO, which provides new opportunities for designing lightweight and highly efficient microwave-absorbing materials by fully utilizing the hetero-interfacial effects.

Association between mitogen-activated protein kinase kinase kinase 1 rs889312 polymorphism and breast cancer risk: evidence from 59,977 subjects.

Published data on the association between mitogen-activated protein kinase kinase kinase 1 (MAP3K1) gene rs889312 polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association between them. A total of seven eligible articles including 26,015 cases and 33,962 controls based on the search criteria were involved in this meta-analysis. We observed that the MAP3K1 rs889312 polymorphism was significantly correlated with breast cancer risk from the fixed effects model when all studies were pooled into the meta-analysis (the allele contrast model: OR 1.09, 95% CI 1.07-1.12; the homozygote codominant: OR 1.22, 95% CI 1.15-1.29; the heterozygote codominant: OR 1.07, 95% CI 1.04-1.11; the dominant model: OR 1.10, 95% CI 1.06-1.13; the recessive model: OR 1.18, 95% CI 1.12-1.25). No significant association was found in the BRCA1 mutation carriers in all genetic models. When stratified by BRCA2 mutation carriers status, statistically significantly elevated risk was found in this meta-analysis (C vs. A: OR 1.12, 95% CI 1.01-1.23; CC vs. AA: OR 1.35, 95% CI 1.06-1.71; the recessive model: OR 1.31, 95% CI 1.05-1.65). There was no evidence for significant association between MAP3K1 rs889312 polymorphism and breast cancer risk in BRCA1 and BRCA2 positive cohort for all comparison models. In conclusion, this meta-analysis suggests that the MAP3K1 rs889312 C allele is a low-penetrant risk factor for developing breast cancer, and there is limited evidence to indicate that MAP3K1 rs889312 polymorphism is associated with increased risk of breast cancer in BRCA1 mutation carriers.

Surgery for rare aneurysm associated with colorectal cancer.

The occurrence of concomitant aortic aneurysm and colorectal cancer is a rare medical entity, and controversy surrounds its optimal treatment. We report a case of rectal cancer and concomitant aneurysm from the ascending aorta to the common iliac artery. As with DeBakey type I aortic dissecting aneurysm, our patient was treated by rectal cancer resection, with preservation of the anus (Dixon operation) under controlled hypotension. Blood pressure was maintained at 80-90/50-60 mmHg and the pulse at 70-90 beats/min. The pathological examination of the surgical specimen showed a poorly differentiated T3N0 tumor. The patient had an uneventful recovery without aneurysm rupture, and was discharged from hospital on postoperative day 15 after 3 d adjuvant chemotherapy with oxaliplatin combined with calcium folinate and fluorouracil. The patient was given six courses of adjuvant chemotherapy in 6 mo, without recurrence or metastasis, and the aneurysm was still stable after 2 years follow-up.

[The application of p53 gene mutation status in fecal specimen in the diagnosis of colorectal carcinoma].

OBJECTIVE: To explore the value of analysis of p53 gene mutation in fecal specimen in the diagnosis of colorectal carcinoma (CRC) in order to establish a non-invasive method for the screening of CRC. METHODS: The status of p53 gene mutation of the tumor tissues and corresponding fecal specimens was analyzed by polymerase chain reaction-single strand configuration polymorphism with EB staining in 40 CRC, 20 colorectal adenoma and 15 gastrocarcinoma. RESULTS: Amplification rates of fecal p53 gene were 90%, 85% and 93% in 40 CRC, 20 colorectal adenoma and 15 gastrocarcinoma, respectively. Total amplification rate was 89%. p53 gene mutation in tumor tissue was detected in 29 of 40 cases of CRC, 23 cases of which had p53 mutation in fecal specimens with the diagnostic sensitivity rate of 57.5%. Analysis of fecal p53 gene mutation had relatively higher diagnostic sensitivity rate than the detection of serum carcinoembryonic antigen and fecal occult blood (P < 0.05) for the diagnosis of CRC. 3 of 20 colorectal adenoma had p53 mutation both in tumor tissues and fecal specimens. 10 of 15 gastrocarcinoma had p53 mutation in tumor tissues but none in fecal specimens. CONCLUSIONS: Analysis of fecal p53 gene mutation has relatively higher diagnostic sensitivity rate for diagnosis of CRC and is expected to be a relatively sensitive, specific and effective method for early diagnosis of CRC, especially for CRC screening in large scale of the population.