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BACKGROUND:HIV-related opportunistic infections (OIs) and malignancies continued to cause morbidity and mortality in Chinese HIV-infected individuals. The objective for this study is to elucidate the prevalence and spectrums of OIs and malignancies in HIV-infected patients in the Beijing Ditan Hospital. METHODS:The evaluation of the prevalence and spectrums of OIs and malignancies was conducted by using the clinical data of 834 HIV-infected patients admitted in the Beijing Ditan hospital from January 1, 2009, to November 30, 2012. RESULTS:The prevalence and spectrums of OIs and malignancies varied contingent on geographic region, transmission routes, and CD4 levels. We found that tuberculosis was most common OI and prevalence was 32.5%, followed by candidiasis(29.3%), Pneumocystis pneumonia(PCP)(22.4%), cytomegalovirus(CMV) infection(21.7%), other fungal infections(16.2%), mycobacterium avium complex(MAC)(11.3%), cryptococcosis(8.0%), progressive multifocal leukoencephalopathy(PML)(4.4%), Cerebral Toxoplasmosis(3.5%) and Penicillium marneffei infection(1.4%); while Lymphoma(2.9%), Kaposi's sarcoma(0.8%) and cervix carcinoma(0.3%) were emerged as common AIDS-defining malignancies. Pulmonary OI infections were the most prevalent morbidity and mortality in patients in the AIDS stage including pulmonary tuberculosis (26.6%) and PCP (22.4%). CMV infection(21.7%) was most common viral infection; Fungal OIs were one of most prevalent morbidity in patients in the AIDS stage, including oral candidiasis (29.3%), other fungal infection (16.2%), Cryptococcosis (8.0%) and Penicillium marneffei infection (1.4%). We found the low prevalence of AIDS-defining illnesses in central neural system in this study, including progressive multifocal leukoencephalopathy (4.4%), cerebral toxoplasmosis (3.5%), tuberculosis meningitis (3.2%), cryptococcal meningitis (2.4%) and CMV encephalitis (1.1%). In-hospital mortality rate was 4.3 per 100 person-years due to severe OIs, malignancies, and medical cost constraints. CONCLUSIONS:The prevalence and spectrums of OIs, malignancies and co-infections were discussed in this study. It would help increase the awareness for physicians to make a diagnosis and empirical treatment sooner and plan good management strategies, especially in resource limited regions.

Small and medium-sized enterprises (SMEs) were an important part of China's economy, but they faced challenges to growth due to financing difficulties. Government subsidies are considered as a potential way to address this problem. This study aims to assess the effectiveness of the Chinese government's subsidy program aimed at improving the accessibility of financing for SMEs. We analyze a comprehensive dataset of Chinese firms' subsidy programs from 2011 to 2020. We classify subsidies into unconditional and conditional categories and use fixed-effects regression models to control for the effects of time and between-group variation to more accurately assess the effectiveness of government subsidies. In addition, we use a PSM-DID model to reduce the effect of selectivity bias to more accurately estimate the causal effect of subsidies on financing strategies. We also use a mediated effects model to help understand the mechanisms by which different types of subsidies affect financing strategies. The results show that government subsidies can significantly improve SMEs' financing ability, but different types of subsidies produce subtle differences. Conditional subsidies support debt financing mainly through incentives, while unconditional subsidies help SMEs improve their equity financing ability through information effects. Furthermore, we find that over-reliance on a single subsidy type may reduce its effectiveness, suggesting a complex relationship between government intervention and SME financing. Thus, well-designed policies are crucial for promoting SMEs and fostering economic growth.

In this paper, we introduce the mixed-frequency data model (MIDAS) to China's insurance demand forecasting. We select the monthly indicators Consumer Confidence Index (CCI), China Economic Policy Uncertainty Index (EPU), Consumer Price Index (PPI), and quarterly indicator Depth of Insurance (TID) to construct a Mixed Data Sampling (MIDAS) regression model, which is used to study the impact and forecasting effect of CCI, EPU, and PPI on China's insurance demand. To ensure forecasting accuracy, we investigate the forecasting effects of the MIDAS models with different weighting functions, forecasting windows, and a combination of forecasting methods, and use the selected optimal MIDAS models to forecast the short-term insurance demand in China. The experimental results show that the MIDAS model has good forecasting performance, especially in short-term forecasting. Rolling window and recursive identification prediction can improve the prediction accuracy, and the combination prediction makes the results more robust. Consumer confidence is the main factor influencing the demand for insurance during the COVID-19 period, and the demand for insurance is most sensitive to changes in consumer confidence. Shortly, China's insurance demand is expected to return to the pre-COVID-19 level by 2023Q2, showing positive development. The findings of the study provide new ideas for China's insurance policymaking.

With the rapid development of technologies such as cloud computing and big data, various levels of government departments in the country have successively introduced digital subsidy policies to promote enterprises' digital transformation. However, the effectiveness of these policies and their ability to truly achieve policy objectives have become pressing concerns across society. Against this backdrop, this paper employs a moderated mediation effects model to empirically analyze the incentive effects of financial subsidies on the digital transformation of A-share listed manufacturing companies in the Shanghai and Shenzhen stock markets from 2013 to 2022. The research findings indicate a significant promotion effect of financial subsidies on the digital transformation of manufacturing enterprises, especially demonstrating a notable incentive impact on the digital transformation of large enterprises, non-asset-intensive enterprises, technology-intensive enterprises, and non-labor-intensive enterprises. However, the incentive effect on the digital transformation of small and medium-sized enterprises (SMEs), asset-intensive enterprises, non-technology-intensive enterprises, and labor-intensive enterprises is not significant. Notably, the expansion of financial subsidies positively influences the augmentation of R&D investment within manufacturing enterprises, subsequently providing indirect encouragement for their digital transformation. Additionally, the incorporation of the degree of marketization implies its potential to moderate both the direct and indirect impacts of financial subsidies on enterprise digital transformation. This study enriches the research on the mechanism of the role of financial subsidies in digital transformation and provides empirical evidence on how market participation influences the effects of financial subsidies, thereby assisting policymakers in comprehensively understanding the impact of financial subsidy policies on different types of enterprises.

BackgroundThoracic aortic aneurysm (TAA) occurs due to pathological aortal dilation, and both individuals with normal tricuspid aortic valves (TAV) or abnormal bicuspid aortic valves (BAV), the latter being a congenital condition, are at risk. However, some differences are present between TAA/BAV and TAA/TAV with respect to their pathophysiological processes and molecular mechanisms, but their exact nature is still mostly unknown. Therefore, it is necessary to elucidate TAA developmental differences among BAV vs. TAV patients.MethodsPublically-available gene expression datasets, aortic tissue derived from TAA/BAV and TAA/TAV individuals, were analyzed by weighted gene co-expression network analysis (WGCNA) to identify gene modules associated with those conditions. Gene Ontology (GO) enrichment analysis was performed on those modules to identify the enriched genes within those modules, which were verified by Gene Set Variation Analysis (GSVA) on a dataset derived from aortic smooth muscle cell gene expression between TAA/TAV and TAV/BAV patients. Immune cell infiltration patterns were then analyzed by CIBERSORT, and a protein-protein interaction (PPI) network was constructed based on WGCNA and enrichment analysis results to identify hub genes, followed by validation via stepwise regression analysis. Three signatures most strongly associated with TAA/TAV were confirmed by receiver operating characteristic (ROC) and decision curve analyses (DCA) between prior-established training and testing gene sets.ResultsWGCNA delineated 2 gene modules being associated with TAA/TAV vs. TAA/BAV; both were enriched for immune-associated genes, such as those relating to immune responses, etc., under enrichment analysis. TAA/TAV and TAA/BAV tissues also had differing infiltrating immune cell proportions, particularly with respect to dendritic, mast and CD4 memory T cells. Identified three signatures, CD86, integrin beta 2 (ITGB2) and alpha M (ITGAM), as yielding the strongest associations with TAA/TAV onset, which was verified by areas under the curve (AUC) at levels approximating 0.8 or above under ROC analysis, indicating their predictive value for TAA/TAV onset. However, we did not examine possible confounding variables, so there are many alternative explanations for this association.ConclusionsTAA/TAV pathogenesis was found to be more associated with immune-related gene expression compared to TAA/BAV, and the identification of three strongly-associated genes could facilitate their usage as future biomarkers for diagnosing the likelihood of TAA/TAV onset vs. TAA/BAV, as well as for developing future treatments.

Employees, as the most valuable assets and critical sources of competitive advantage in enterprises, are among the important stakeholders in enterprises. Employee social responsibility (ESR) has been a continually important research interest in the field of enterprise social responsibility. However, in the literature, few studies explore how personal features affect employee social responsibility. Thus, sampling China's listed companies from 2006 to 2019, we investigate how the home bias of senior executives influences enterprises' employee social responsibility. We identify home bias based on whether a chairperson's or CEO's hometown matches the firm's registration place. Three main results are obtained. First, the home bias of both CEOs and chairpersons can improve the corporate fulfillment of employee social responsibility. Second, further cost-benefit analysis shows that this result is due to not only identification but also benefit exchange. Although senior executives' home bias significantly decreases employee turnover rate, enterprises absorb more employment, which significantly increases their redundant personnel costs. Therefore, firms should balance the potential benefits and costs incurred by home bias via trade-off. Third, in firms facing less market competition, firms with more governmental subsidies or state-owned firms, senior executives' home bias has a more significant promoting effect on the fulfillment of ESR, supporting the view of benefit exchange. Accordingly, by extending theories on the effects of senior executives' home bias and enriching the ESR literature, this paper has important practical value, our findings can guide and promote firms to perform ESR while actively complying with a national policy for stabilizing employment and ensuring people's well-being.

Sensing and responding to endogenous electrical fields are important abilities for cells engaged in processes such as embryogenesis, regeneration and wound healing. Many types of cultured cells have been induced to migrate directionally within electrical fields in vitro using a process known as galvanotaxis. The underlying mechanism by which cells sense electrical fields is unknown. In this study, we assembled a polydimethylsiloxane (PDMS) galvanotaxis system and found that mouse fibroblasts and human prostate cancer PC3 cells migrated to the cathode. By comparing the effects of a pulsed direct current, a constant direct current and an anion-exchange membrane on the directed migration of mouse fibroblasts, we found that these cells responded to the ionic flow in the electrical fields. Taken together, the observed effects of the calcium content of the medium, the function of the store-operated calcium channels (SOCs) and the intracellular calcium content on galvanotaxis indicated that calcium ionic flow from the anode to the cathode within the culture medium permeated the cells through SOCs at the drift velocity, promoting migration toward the cathode. The RTK-PI3K pathway was involved in this process, but the ROCK and MAPK pathways were not. PC3 cells and mouse fibroblasts utilized the same mechanism of galvanotaxis. Together, these results indicated that the signaling pathway responsible for cathode-directed cellular galvanotaxis involved calcium ionic flow from the anode to the cathode within the culture medium, which permeated the cells through SOCs, causing cytoskeletal reorganization via PI3K signaling.

Double minute chromosomes (DMs) have important implications for cancer progression because oncogenes frequently amplified on them. We previously detected a functionally undefined gene amplified on DMs, Ribosomal L22-like1 (RPL22L1). The relationship between RPL22L1 and cancer progression is unknown. Here, RPL22L1 was characterized for its role in ovarian cancer (OC) metastasis and its underlying mechanism was examined. DNA copy number and mRNA expression of RPL22L1 in OC cells was analyzed using data obtained from The Cancer Genome Atlas and the Gene Expression Omnibus database. An immunohistochemical analysis of clinical OC specimens was performed and the relationships between expression level and clinicopathological factors were evaluated. Additionally, in vivo and in vitro assays were performed to understand the role of RPL22L1 in OC. RPL22L1 expression was higher in OC specimens than in normal tissues, and its expression level was highly positively correlated with invasion and lymph node metastasis (P < 0.05). RPL22L1 over-expression significantly enhanced intraperitoneal xenograft tumor development in nude mice and promoted invasion and migration in vitro. Additionally, RPL22L1 knockdown remarkably inhibited UACC-1598 cells invasion and migration. Further, RPL22L1 over-expression up-regulated the mesenchymal markers vimentin, fibronectin, and α-SMA, reduced expression of the epithelial markers E-cadherin, α-catenin, and β-catenin. RPL22L1 inhibition reduced expression of vimentin and N-cadherin. These results suggest that RPL22L1 induces epithelial-to-mesenchymal transition (EMT). Our data showed that the DMs amplified gene RPL22L1 is critical in maintaining the aggressive phenotype of OC and in triggering cell metastasis by inducing EMT. It could be employed as a novel prognostic marker and/or effective therapeutic target for OC.

Double minute chromosomes are cytogenetic manifestations of gene amplification frequently seen in cancer cells. Genes amplified on double minute chromosomes include oncogenes and multi-drug resistant genes. These genes encode proteins which contribute to cancer formation, cancer progression, and development of resistance to drugs used in cancer treatment. Elimination of double minute chromosomes, and therefore genes amplified on them, is an effective way to decrease the malignancy of cancer cells. We investigated the effectiveness of a cancer drug, gemcitabine, on the loss of double minute chromosomes from the ovarian cancer cell line UACC-1598. Gemcitabine is able to decrease the number of double minute chromosomes in cells at a 7500X lower concentration than the commonly used cancer drug hydroxyurea. Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment. Gemcitabine, even at a low nanomolar concentration, is able to cause DNA damage. The selective incorporation of double minutes chromatin and γ-H2AX signals into micronuclei provides a strong link between DNA damage and the loss of double minute chromosomes from gemcitabine treated cells. Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion. Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.

Mycoplasma bovis is the causative agent of Mycoplasma bovis-associated disease (MbAD). Although the mechanisms underlying M. bovis adherence to host cells is not clear, recent studies have shown that the cell surface protein α-enolase facilitates bacterial invasion and dissemination in the infected host. In this study, we cloned, expressed and purified recombinant M. bovis α-enolase and induced polyclonal anti-α-enolase antibodies in rabbits. M. bovis α-enolase was detected in the cytoplasmic and membrane protein fractions by these antibodies. Triple immunofluorescence labeling combined with confocal laser scanning microscopy (CLSM) revealed that the plasminogen (Plg) enhanced the adherence of M. bovis to embryonic bovine lung (EBL) cells; the values obtained for adherence and inhibition are consistent with this finding. Interestingly, we found that trace amounts of trypsin acted as a more effective enhancer of cell adherence than Plg. Hence, our data indicate that surface-associated M. bovis α-enolase is an adhesion-related factor of M. bovis that contributes to adherence by binding Plg.

High-frequency electrical stimulation is becoming a promising therapy for neurological disorders, however the response of the central nervous system to stimulation remains poorly understood. The current work investigates the response of myelin to electrical stimulation by laser-scanning coherent anti-Stokes Raman scattering (CARS) imaging of myelin in live spinal tissues in real time. Paranodal myelin retraction at the nodes of Ranvier was observed during 200 Hz electrical stimulation. Retraction was seen to begin minutes after the onset of stimulation and continue for up to 10 min after stimulation was ceased, but was found to reverse after a 2 h recovery period. The myelin retraction resulted in exposure of Kv 1.2 potassium channels visualized by immunofluorescence. Accordingly, treating the stimulated tissue with a potassium channel blocker, 4-aminopyridine, led to the appearance of a shoulder peak in the compound action potential curve. Label-free CARS imaging of myelin coupled with multiphoton fluorescence imaging of immuno-labeled proteins at the nodes of Ranvier revealed that high-frequency stimulation induced paranodal myelin retraction via pathologic calcium influx into axons, calpain activation, and cytoskeleton degradation through spectrin break-down.

Paranodal myelin damage is observed in white matter injury. However the culprit for such damage remains unknown. By coherent anti-Stokes Raman scattering imaging of myelin sheath in fresh tissues with sub-micron resolution, we observed significant paranodal myelin splitting and retraction following glutamate application both ex vivo and in vivo. Multimodal multiphoton imaging further showed that glutamate application broke axo-glial junctions and exposed juxtaparanodal K+ channels, resulting in axonal conduction deficit that was demonstrated by compound action potential measurements. The use of 4-aminopyridine, a broad-spectrum K+ channel blocker, effectively recovered both the amplitude and width of compound action potentials. Using CARS imaging as a quantitative readout of nodal length to diameter ratio, the same kind of paranodal myelin retraction was observed with applications of Ca2+ ionophore A23187. Moreover, exclusion of Ca2+ from the medium or application of calpain inhibitor abolished paranodal myelin retraction during glutamate exposure. Examinations of glutamate receptor agonists and antagonists further showed that the paranodal myelin damage was mediated by NMDA and kainate receptors. These results suggest that an increased level of glutamate in diseased white matter could impair paranodal myelin through receptor-mediated Ca2+ overloading and subsequent calpain activation.