Research progress of acupuncture regulating ERK signaling pathway in the treatment of depression. / 针刺调控ERKä¿¡å·é€šè·¯æ²»ç–—æŠ‘éƒç—‡çš„ç ”ç©¶è¿›å±•.

Acupuncture treatment for depression has definite therapeutic efficacy, and its mechanism has been extensively studied. The extracellular regulatory protein kinase(ERK) signaling pathway is involved in the development and progression of depression. This article reviewed and summarized the research progress on the regulation of the ERK signaling pathway by acupuncture in the treatment of depression in recent years, focusing on the physiological activation and regulatory mechanism of the ERK signaling pathway, its association with the occurrence of depression, and the mechanisms through which acupuncture activates the ERK signaling pathway to treat depression (including enhancing neuronal synaptic plasticity, promoting the release of neurotrophic factors, and inhibiting neuronal apoptosis). Future research could explore the relationship between the ERK pathway and other pathways, investigate other brain regions besides the prefrontal cortex and hippocampus, examine differences in regulatory mechanisms between male and female patients, assess the effects of different acupuncture techniques on the ERK pathway, and increase efforts to explore mechanism of synaptic plasticity regulation, so as to provide reference for the clinical application and mechanism sludy of acupuncture in depression treatment.

HCV Reactivation in a Patient with Hepatocellular Carcinoma Due to Sorafenib: A Case Report.

The global prevalence of hepatitis C virus (HCV) infection is approximately 3%, with a post-infection chronicity rate of up to 50%-85%. HCV reactivation can occur when anti-HCV positive individuals receive antineoplastic therapy. In this study, we report a case of an anti-HCV positive patient with negative HCV RNA after 12 weeks of direct antiviral therapy. Two months later, sorafenib was used to treat hepatocellular carcinoma, and HCV reactivation occurred after 8 months of the treatment. HCV RNA was negative after 12 weeks of antiviral treatment with Sofosbuvir-velpatasvir. We also discussed the mechanism of HCV reactivation caused by sorafenib and the antiviral treatment regimen after HCV reactivation with the relevant literature.

Evolutionary characteristics of global offshore carbon emissions network and responsibility allocation of emissions reduction.

Offshore carbon emissions from the international shipping trade are significant contributors to climate change. Based on the complex shipping trade networks, offshore carbon emissions are correlated rather than independent, and allocating responsibility for reducing emissions does not depend solely on the amount but on linkages. We use the global container shipping data covering more than 98% of routes from 2015 to 2020 to calculate the offshore carbon emissions from shipping. Subsequently, we construct an offshore carbon emissions network based on the shipping routes and emissions to identify the evolutionary tendency of network and clarify emissions reduction responsibilities by considering equity and efficiency. We discover that global offshore carbon emissions present a complicated network structure dominated by developed countries and large economies. Countries on the same continent or within the same economic organizations have closer and more frequent carbon correlations. Greater responsibilities should be allocated to countries who are at the center of the network.

Does geopolitical risk matter in carbon and crude oil markets from a multi-timescale perspective?

The ongoing Russia-Ukraine conflict serves as a prime illustration of geopolitical risk, manifesting implications beyond global energy price surges and regional energy deficits; it also resonates within the carbon trading market. This study delves into the non-linear and asymmetric impacts of geopolitical risk on oil-carbon linkages spanning 2013 to 2022. Commencing with an exploration of dynamic correlations within the carbon and crude oil markets, our findings indicate that market movements in carbon or crude oil are subject not only to their respective historical volatility trends but also to reciprocal influences from the alternate market, highlighting the existence of asymmetric spillovers between the carbon and crude oil markets. Subsequently, a threshold vector error correction model (TVECM) sheds light on the long-term transmission dynamics of geopolitical risk to oil-carbon linkages. It is concluded that the oil-carbon linkages have a limited impact on geopolitical risk and are subject to shocks from geopolitical risk. Finally, the maximum overlap discrete wavelet transform (MODWT) method unveils heterogeneity across temporal scales: in the short term, geopolitical risk fluctuations are influenced by oil-carbon linkages, and in the middle and long run it becomes independent. Such insights furnish investors with an enriched comprehension of the interplay between crude oil and carbon markets amid geopolitical disturbances, while also offering policymakers a foundation upon which to sculpt informed responses to geopolitical risk.

Study on the relationship between permeability coefficient and porosity, the confining and osmotic pressure of attapulgite-modified loess.

This study investigated attapulgite-modified loess as an efficient and cost-effective method for creating an impermeable liner for landfills in regions with scarce clay resources. Laboratory permeability tests were conducted using a flexible wall permeameter to determine the permeability of compacted loess and attapulgite mixtures under varying osmotic conditions. The relationship between the permeability coefficient, attapulgite dosage, radial pressure, and osmotic pressure was analyzed. Nuclear magnetic resonance and scanning electron microscopy were also used to observe the microstructure of the modified loess. The results showed that attapulgite dosage significantly reduced the permeability coefficient, but the effect became limited when the content surpassed 10%. The decrease of the permeability coefficient of the modified loess is mainly due to the filling of pores between the loess by attapulgite, which makes the pore size and throat size of the modified loess smaller. The modified loess displayed a sheet structure that contributed to an increased permeability coefficient due to increased radial pressure. This study provides valuable insights into using attapulgite-modified loess as a material for landfill lining in regions with scarce clay resources.

Molecular epidemiology, risk factors, and outcomes of carbapenem-resistant Klebsiella pneumoniae infection in a tertiary hospital in eastern China: for a retrospective study conducted over 4 years.

Objectives: Carbapenem-resistant Klebsiella pneumoniae (CRKP) have been extensively disseminated worldwide, resulting in increased mortality. We performed a retrospective analysis of the epidemiology and risk factors for the outcome of CRKP infection in a general teaching hospital in China. Methods: A molecular and clinical study was conducted for 98 CRKP in a tertiary hospital from January 2013 to December 2016. Carbapenemase gene detection, pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing (MLST) were performed. Logistic regression was also used to identify the risk factors associated with 30-day mortality. Results: The production of KPC carbapenemase was the main resistant mechanism, and KPC carbapenemase increased annually with a significant difference. However, the molecular outcome revealed the dominance and diversity in CRKP with 24 sequence types (STs) and 59 PFGE types (PTs). The ST11 CRKP strains, which showed a significant increasing trend year by year, were documented as predominant in our study. Additionally, the predominant ST11 CRKP corresponding to PT10 and PT15 continued to exhibit their characteristic patterns. Importantly, the newly identified PT09 and PT16 strains, corresponding to the ST11 lineage, were only discovered in 2016. Meanwhile, factors affecting 30-day mortality and ST11 proportionality with CRKP infection were assessed, and ST11, appropriate empirical treatment, and hospital stays were found to be independently associated with 30-day mortality. Conclusion: The ST11 CRKP strains played a dominant role in the process; however, the homology of these strains was polymorphic, and the advantage clusters were subject to changes through evolution. Furthermore, in addition to appropriate empirical treatment and hospital stays, ST11 CRKP was independently associated with 30-day mortality. To the best of our knowledge, this association was reported for the first time.

Genetic analysis of potential biomarkers and therapeutic targets associated with ferroptosis from bronchopulmonary dysplasia.

Ferroptosis is a recently identified form of cell death that is distinct from the conventional modes such as necrosis, apoptosis, and autophagy. Its role in bronchopulmonary dysplasia (BPD) remains inadequately understood. To address this gap, we obtained BPD-related RNA-seq data and ferroptosis-related genes (FRGs) from the GEO database and FerrDb, respectively. A total of 171 BPD-related differentially expressed ferroptosis-related genes (DE-FRGs) linked to the regulation of autophagy and immune response were identified. Least absolute shrinkage and selection operator and SVM-RFE algorithms identified 23 and 14 genes, respectively, as marker genes. The intersection of these 2 sets yielded 9 genes (ALOX12B, NR1D1, LGMN, IFNA21, MEG3, AKR1C1, CA9, ABCC5, and GALNT14) with acceptable diagnostic capacity. The results of the functional enrichment analysis indicated that these identified marker genes may be involved in the pathogenesis of BPD through the regulation of immune response, cell cycle, and BPD-related pathways. Additionally, we identified 29 drugs that target 5 of the marker genes, which could have potential therapeutic implications. The ceRNA network we constructed revealed a complex regulatory network based on the marker genes, further highlighting their potential roles in BPD. Our findings offer diagnostic potential and insight into the mechanism underlying BPD. Further research is needed to assess its clinical utility.

An Analysis of Clinical and Pathologic Features, RecurIndex Genomic Profiles, and Survival Outcomes in HER2-Low Breast Cancer.

BACKGROUND: In recent years, breast cancer has become the most common cancer in the world, increasing women's health risks. Approximately 60% of breast cancers are categorized as human epidermal growth factor receptor 2 (HER2)-low tumors. Recently, antibody-drug conjugates have been found to have positive anticancer efficacy in patients with HER2-low breast cancer, but more studies are required to comprehend their clinical and molecular characteristics. METHODS: In this study, we retrospectively analyzed the data of 165 early breast cancer patients with pT1-2N1M0 who had undergone the RecurIndex testing. To better understand HER2-low tumors, we investigated the RecurIndex genomic profiles, clinicopathologic features, and survival outcomes of breast cancers according to HER2 status. RESULTS: First, there were significantly more hormone receptor (HR)-positive tumors, luminal-type tumors, and low Ki67 levels in the HER2-low than in the HER2-zero. Second, RI-LR (P = .0294) and RI-DR (P = .001) scores for HER2-low and HER2-zero were statistically significant. Third, within HER2-negative disease, HR-positive/HER2-low tumors showed highest ESR1, NFATC2IP, PTI1, ERBB2, and OBSL1 expressions. Fourth, results of the survival analysis showed that lower expression of HER2 was associated with improved relapse-free survival for HR-positive tumors, but not for HR-negative tumors. CONCLUSIONS: The present study highlights the unique features of HER2-low tumors in terms of their clinical characteristics as well as their gene expression profiles. HR status may influence the prognosis of patients with HER2-low expression, and patients with HR-positive/HER2-low expression may have a favorable outcome.

ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion.

ErbB2 is overexpressed in 15-20% of breast cancer, which is associated with malignancy and poor prognosis. We previously reported that ErbB2 supports malignant progression of breast cancer by upregulating lactate dehydrogenase A (LDHA), an important enzyme in glycolysis. However, whether ErbB2 promotes breast cancer progression through other glycolytic enzymes remains unclear. Hexokinase 1 (HK1) and hexokinase 2 (HK2) are the first rate-limiting enzymes of glycolysis and both of them are increased in breast cancer. Here, we aim to investigate whether ErbB2 upregulates HK1 and HK2 and the role of HK1 and HK2 in the malignant progression of ErbB2-overexpressing breast cancer. In current study, we found that the mRNA level of ErbB2 was positively correlated with that of HK1 and HK2, respectively. Moreover, ErbB2 upregulated the protein levels of HK1 and HK2 in breast cancer cells. We also found that both siHK1 and siHK2 significantly inhibited the proliferation, migration and invasion of ErbB2-overexpressing breast cancer cells. Taken together, our findings suggested that ErbB2 promoted the malignant progression of breast cancer cells by upregulating HK1 and HK2, and HK1 and HK2 might serve as promising therapeutic targets for ErbB2-overexpressing breast cancer.

Lorlatinib for ALK-fused, infant-type hemispheric glioma with lung metastasis: a case report.

Infant-type hemispheric glioma, a new subtype of pediatric high-grade glioma, arises in the cerebral hemispheres. Despite better survival outcomes, the treatment of infant-type hemispheric glioma is still facing challenges. Here, we reported a case of QKI-ALK fusion, infant-type hemispheric glioma with lung metastasis who achieved a complete clinical response after lorlatinib treatment. This typical case demonstrated the importance of appropriate molecularly targeted treatments in ALK-fused tumors, and lorlatinib may serve as an effective complement to conventional chemotherapy and radiotherapy in primary glioma harboring ALK fusions and its metastasis.

The effect of miR-155-5p on M1 polarization of Kupffer cells and immune response during liver transplantation through regulating the expression of KDM5D.

BACKGROUND: To explore the effect and its specific mechanism of miR-155-5p on M1 polarization of Kupffer cells (KCs) and immune response in liver transplantation (LT) through KDM5D. METHODS: Primary KCs were isolated from Wistar rats and identified by cell culture, ink-swallowing test and flow cytometry. The cells identified as KCs were induced into LT acute rejection (AR) model cells by LPS/IFN-γ, flow cytometry was used for cell sorting and apoptosis detection. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the levels of inflammatory factors, macrophages and liver function markers. RT-qPCR detected the expression of miR-155-5p and KDM5D mRNA. The protein expression of KDM5D was detected by Western blot. Dual luciferase reporter gene experiment verified the targeting relationship between miR-155-5p and KDM5D. RESULTS: The separated KCs adhered after being cultured for 24 h, had pseudopodia and phagocytosis, and the proportion of F4/80 positive cells was more than 90%. The expression of miR-155-5p was increased in LPS/IFN-γ-induced KCs. And knockdown of miR-155-5p inhibited H3K4me3 and H3K27me3 of TNF-α promoter, M1 polarization of KCs and the immune response of AR model cells by upregulating KDM5D. In animal experiments, knockdown of miR-155-5p was found to inhibit liver damage and immune response in rats with allogeneic orthotopic LT. CONCLUSION: These results confirmed that miR-155-5p inhibited M1 polarization of KCs induced by LPS/IFN-γ, thereby alleviating AR and liver function impairment after LT by upregulating KDM5D.

Preparation of Fe/C-MgCO3 micro-electrolysis fillers and mechanism of phosphorus removal.

Iron-carbon micro-electrolysis is effective for the removal of phosphorus in wastewater; however, meeting the stringent emission standards required for treatment is difficult. To meet these treatment standards, modified micro-electrolytic fillers were prepared from iron dust, powdered activated carbon, clay, and additives using an elevated temperature roasting process under an inert atmosphere. The results show that among several additives, the modified micro-electrolytic (Fe/C-MgCO3) fillers using MgCO3 were the most effective at phosphorus removal. The preparation conditions for the Fe/C-MgCO3 fillers and their effects on phosphorus removal performance were investigated. Under the optimal preparation conditions (calcination temperature: 800 °C, Fe/C = 4:1, clay content 20%, and 5% MgCO3), the filler yielded a high compressive strength of 3.5 MPa, 1 h water absorption rate of 25.7%, and specific surface area and apparent density of 154.2 m2/g and 2689.2 kg/m3, respectively. The iron-carbon micro-electrolysis process removed 97% of phosphorus in the wastewater by using the Fe/C-MgCO3 fillers, which was 14% more than the Fe/C filler. Electrostatic adsorption and surface precipitation were identified as the main phosphorus removal mechanisms, and the surface of the Fe/C-MgCO3 filler was continuously updated. These results demonstrated that Fe/C-MgCO3 is a promising filler for phosphorus removal in water treatment.

Upregulation of SCD1 by ErbB2 via LDHA promotes breast cancer cell migration and invasion.

The incidence of breast cancer ranks at the top of female malignant tumors in China. Metastasis remains the main cause of death among breast cancer patients. The overexpression of ErbB2 is closely related to the metastasis and poor prognosis of breast cancer patients. Therefore, ErbB2 is an important clinical therapeutic target of breast cancer. However, the molecular mechanism of ErbB2 promoting breast cancer metastasis has not been studied clearly. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme in catalyzing the conversion of saturated fatty acids (SFAs) into monounsaturated fatty acids (MUFAs). SCD1 is overexpressed in breast cancer, and its overexpression is an indicator of poor prognosis in breast cancer patients. However, the role of SCD1 in ErbB2-overexpressing breast cancer metastasis has not been reported. In this study, we investigated the role of SCD1 in the migration and invasion of ErbB2-overexpressing breast cancer cells and its molecular mechanism. First, we demonstrated that ErbB2 upregulates the expression of SCD1. Second, we found that SCD1 and its catalytic product oleic acid played crucial roles in migration and invasion of ErbB2-overexpressing breast cancer cells. Finally, we found that in breast cancer cells, ErbB2 upregulated SCD1 through lactate dehydrogenase A (LDHA). To sum up, upregulation of SCD1 by ErbB2 via LDHA promotes the migration and invasion of breast cancer cells.

Measurement and Analysis of Shock Wave Pressure in Moving Charge and Stationary Charge Explosions.

Shock wave pressure is one of the most important parameters in an explosion. However, there have been few experimental and analytical investigations of moving charge explosions. In this article, we present an experimental method to measure the shock wave pressure from a moving charge explosion. Tests of stationary charges and moving charges with speeds of 580 m/s, 703 m/s and 717 m/s were carried out. The shock wave pressure curves and parameters at different measurement points were obtained and analyzed. The theoretical calculation of the shock wave overpressure was studied and compared with the experimental result. The differences between the stationary charge and moving charge explosions were investigated. The results showed that the shock wave pressure distribution of a moving charge had strong directionality. The shock wave pressure parameters (including overpressure, arrival time, duration and impulse) were influenced by the charge's moving velocity, direction angle and distance from the blast point. The shock wave overpressure value was greater than that of a stationary charge explosion at angles between 0° and 90°. The correlation model based on the velocity vector superposition method could describe the relationship of overpressure between the stationary charge and moving charge explosions.

Genomic Features of Solid Tumor Patients Harboring ALK/ROS1/NTRK Gene Fusions.

The fusions of receptor tyrosine kinase (RTK) involving anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), and neurotrophic receptor tyrosine kinase (NTRK) represent the potential targets of therapeutic intervention for various types of solid tumors. Here, the genomic features of 180 Chinese solid tumor patients with ALK, ROS1, and NTRK fusions by next generation sequencing (NGS) were comprehensively characterized, and the data from 121 patients in Memorial Sloan Kettering Cancer Center (MSKCC) database were used to compare. We found that ALK, ROS1, and NTRK fusions were more common in younger female patients (p<0.001) and showed a higher expression of programmed death ligand 1 (PD-L1). The gene-intergenic fusion and the fusion with rare formation directions accounted for a certain proportion in all samples and 62 novel fusions were discovered. Alterations in TP53 and MUC16 were common in patients with RTK fusions. The mutational signatures of patients were mainly distributed in COSMIC signature 1, 2, 3, 15 and 30, while had a higher frequency in copy number variations (CNVs) of individual genes, such as IL-7R. In the MSKCC cohort, patients with fusions and CNVs showed shorter overall survival than those with only fusions. Furthermore, the differentially mutated genes between fusion-positive and -negative patients mainly concentrated on MAPK signaling and FOXO signaling pathways. These results may provide genomic information for the personalized clinical management of solid tumor patients with ALK, ROS1, and NTRK fusions in the era of precision medicine.

The Anti-Virulence Effect of Sub-Minimal Inhibitory Concentrations of Levofloxacin on Hypervirulent Klebsiella pneumoniae.

Background: Hypervirulent Klebsiella pneumoniae (hvKp) is best described as a virulent pathogen and generally associated with the hypermucoviscosity phenotype. Increased capsule and aerobactin production are established important hvKp-specific virulence factors. Although hvKp strains have been relatively susceptible to antimicrobials, given the high morbidity and mortality, there is a critical need for alternative strategies for the treatment of hvKp infections. Thus, the anti-virulence therapy has been targeted for the hvKp development of therapeutics. Materials and Methods: Four hvKp isolates with hypermucoviscous phenotype were used in our experiments. Mucoviscosity of the capsule can be assessed by low-speed centrifugation of cultures. CPS amount was determined by glucuronic acid content. The capsule thickness was measured under microscope after ink staining. The transcriptions of gene were measured by quantitative real-time PCR (qRT-PCR). The effect of levofloxacin on the resistance of K. pneumoniae to phagocytosis by macrophages and mouse lethality assay was observed. Results: Our data revealed that sub-Minimal Inhibitory Concentrations (sub-MIC) of LVX reduce mucoviscosity and CPS production of hvKp. Microscopic observations demonstrated that the capsule of hvkp bacteria became thinned after treatment with LVX. qRT-PCR showed decreased transcript levels of rmpA, wzi, magA, iroN and icuA genes. Down-regulation of these virulence genes occurred leading to increased susceptibility to phagocytosis by macrophages. Mouse lethality assay revealed that the wild strain had the LD50 of 103 CFU, while the sub-MIC LVX-treated bacteria had the LD50 of 105 CFU. Conclusion: Our data suggested that LVX may serve as a potential anti-virulence agent for refractory infection by hvKp.

Role of international network on surveillance and response system leading to malaria elimination: China's engagement in global health.

China has accumulated multiple practices and experiences in building and enhancing malaria surveillance and response system. As China's engagement into global health has gathered stronger momentum than ever, China together with the Swiss Tropical and Public Health Institute and WHO has organised five sessions of the International Forum on Surveillance-Response System Leading to Tropical Diseases Elimination during 2012-2020, in which malaria elimination has always been one of the hottest topics. In this study, the roles of international network on the surveillance and response system were explored to achieve a global malaria-free goal. China's approach to malaria elimination has demonstrated significance of global collaboration on taking joint prevention and control, and building a worldwide institutional-based network.