Synthesis of alkenylphosphine oxides via Tf2O promoted addition-elimination of ketones and secondary phosphine oxides.

Herein, we describe an efficient method for the synthesis of alkenylphosphine oxides via a Tf2O promoted addition-elimination process. Various diarylphosphine oxides and alkylarylphosphine oxides react with ketones smoothly and produce alkenylphosphine oxides in moderate to excellent yields with abundant functional group compatibility. In addition, several transformations and applications of the product also demonstrate the potential value of the methodology.

A novel fluorescent probe with a large Stokes shift for colorimetric and selective detection of cysteine in water, milk, cucumber, pear and tomato.

Cysteine is an important amino acid that is related to human health and food safety. How to effectively detect Cys in food has received widespread attention. Compared with other methods, fluorescent probes have the advantages of simple operation, high sensitivity, and good selectivity. Therefore, a selective fluorescence probe 2 for Cys in food was designed and synthesized. Probe 2 employed the acrylate group as a thiol-recognition site for Cys, which endowed probe 2 with better selectivity for Cys over Hcy and GSH. The recognition pathway underwent Michael addition, intramolecular cyclization, and concomitant release of the piperideine-based fluorophore, along with a chromogenic change from yellow to orange. This pathway was supported by 1H NMR analysis and DFT calculations. In addition, probe 2 displays a linear response to Cys concentrations (0-30 µM), low detection limit (0.89 µM), and large Stokes shift (125 nm). Overall, probe 2 showed great application potential for the quantitative determination of Cys in water, milk, cucumber, pear and tomato.

The impact of long-term care insurance pilot on the mental health of older adults: Quasi-experimental evidence from China.

The Chinese government launched pilot programs for a long-term care insurance system in response to the ongoing increase in the aging population. This study uses the difference-in-differences (DID) model to analyze the impact of long-term care insurance on older adults' mental health based on China Health and Retirement Longitudinal Study (CHARLS) four-period panel data from 2011 to 2018. This study found that long-term care insurance reduced Center for Epidemiological Studies Depression Scale (CES-D) scores among older adults by 1.059 points. Moreover, there was an improvement of 0.181 and 0.870 points in mental status and scenario memory scores, respectively. The impact of the long-term care insurance pilot program on improving the mental health of older adults was more pronounced, especially for those with chronic diseases or disabilities as well as those living in rural and western regions. This study also revealed that long-term care insurance enhances mental health by reducing medical expenses and increasing daily companionship and social interaction. Therefore, a pilot study of long-term care insurance showed a significant improvement in the mental health of older adults. To provide a comprehensive care service system for older adults, the government should expand the scope of the pilot program and increase the accessibility of mental health services for older adults.

Economic growth effects of public health expenditure in OECD countries: An empirical study using the dynamic panel threshold model.

Background: Member countries of the Organization for Economic Co-operation and Development (OECD) have experienced a downward trend in capital and macro investment returns. Countries rely on investments in healthcare and health-related sectors to ensure continuous input and an efficient labor market. Public healthcare coverage is a social welfare policy implemented by governments, which contributes to improving human capital quality and ensuring stable economic growth. Methods: This study employs a method that combines theoretical modeling and empirical testing examining 33 OECD countries from 2001 to 2017. We first construct a nonlinear dynamic panel threshold model to examine the impact of public health spending on economic growth. We then employ the model to empirically analyze the threshold effect of public health expenditure on economic growth, validating the effectiveness of our theoretical model. Results: When the level of household consumption is below the 9.63 threshold, the effect of public health expenditure on economic growth is significantly negative (p < 0.1); however, when consumption exceeds the 9.63 threshold, the effect becomes significantly positive (p < 0.05). Similarly, when employee wages are below the 10.57 threshold, the effect of public health expenditure on economic growth is significantly negative (p > 0.1), and it becomes significantly positive when it exceeds 10.57 (p < 0.5). Finally, when the level of physical capital investment falls below the 8.73 threshold, the effect of public health expenditure on economic growth is significantly negative (p < 0.5), and it becomes significantly positive when it exceeds 8.73 (p < 0.5). The positive impact of public health expenditure on economic growth gradually strengthens as household consumption, employee wages, and per capita physical capital investment continue to rise. Conclusions: In an economic environment with higher household consumption, employee wages, and physical capital investment, public health expenditure will significantly promote economic growth.

The effect of urban-rural health insurance integration on consumption of middle-aged and older adult households in rural areas: evidence from China.

Introduction: Rural consumption is crucial in promoting economic and social development in China's economic slowdown. Integrating urban-rural residents' health insurance has alleviated the financial burden of medical expenses for rural households and boosted rural household consumption. This study examines the effect of integrating urban-rural residents' health insurance on the consumption patterns of middle-aged and older adult households in rural China. Our research provides a reference basis for improving rural healthcare security and enhancing the sustainable consumption capacity in rural areas. Methods: We employed a Propensity Score Matching Difference-in-Differences model (PSM-DID) to estimate the association between health insurance integration and household consumption using panel data from the China Health and Retirement Longitudinal Study (CHARLS) from 2013 to 2018. Furthermore, we employed a mediation model to analyze the influencing mechanisms. Results: Our findings suggested a positive association between health insurance integration and survival consumption as well as total consumption among rural middle-aged and older adult households. The conclusion remained valid after endogeneity treatment, robustness and placebo tests. Furthermore, we found that the impact of health insurance integration is more pronounced for middle-aged, female, and high-income rural residents' households. Integrating urban-rural residents' health insurance raised consumption by reducing medical expenses and increasing health and life expectancy. Discussion: Policymakers should deepen the rural medical and health system reform, improve the convenience of medical services for middle-aged and older adult families in rural areas, and improve the medical and life assistance mechanism for vulnerable groups in rural areas. Additionally, the local government should continuously broaden rural household income channels to promote upgrading consumption structure while improving overall consumption levels.

Effect of intraoperative muscle relaxation reversal on the success rate of motor evoked potential recording in patients undergoing spinal surgery: a randomized controlled trial.

BACKGROUND: Partial neuromuscular blockade (NMB) has been applied for some surgeries to reduce bleeding and prevent patient movement for spinal surgery. Sugammadex selectively binds to rocuronium in the plasma and consequently lowers the rocuronium concentration at the neuromuscular junction. In this study, we aimed to observe whether the success rate of transcranial motor-evoked potential (TceMEP) can be increased by sugammadex compared with partial NMB during spinal surgery. METHODS: Patients who underwent elective spinal surgery with TceMEP monitoring were randomly assigned to the sugammadex group and control group. Rocuronium was continuously infused to maintain the train of four counts (TOFc) = 2. The sugammadex group discontinued rocuronium infusion at the time of TceMEP monitoring and was infused with 2 mg/kg sugammadex; the control group was infused with the same dose of saline. RESULTS: A total of 171 patients were included. The success rate of TceMEP monitoring in the sugammadex group was significantly higher than that in the control group. TceMEP amplitudes were greater in the sugammadex group than in the control group at 5 min, 10 min, and 20 min after the start of motor-evoked potential monitoring. The latencies of upper extremity TceMEPs monitoring showed no difference between groups. TOF ratios were greater in the sugammadex group at 5 min, 10 min, and 20 min after the start of motor-evoked potential monitoring. There were no adverse effects caused by sugammadex. CONCLUSIONS: Sugammadex can improve the success rate of motor-evoked potential monitoring compared with moderate neuromuscular blockade induced by continuous infusion of rocuronium in spinal surgery. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov.cn on 29/10/2020 (trial registration number: NCT04608682).

Hot and cold tumors: Immunological features and the therapeutic strategies.

The "hotness" or "coldness" of the tumors are determined by the information of the cancer cells themselves, tumor immune characteristics, tumor microenvironment, and signaling mechanisms, which are key factors affecting cancer patients' clinical efficacy. The switch mechanism of "hotness" and "coldness" and its corresponding pathological characteristics and treatment strategies are the frontier and hot spot of tumor treatment. How to distinguish the "hotness" or "coldness" effectively and clarify the causes, microenvironment state, and characteristics are very important for the tumor response and efficacy treatments. Starting from the concept of hot and cold tumor, this review systematically summarized the molecular characteristics, influencing factors, and therapeutic strategies of "hot and cold tumors," and analyzed the immunophenotypes, the tumor microenvironment, the signaling pathways, and the molecular markers that contribute to "hot and cold tumors" in details. Different therapeutic strategies for "cold and hot tumors" based on clinical efficacy were analyzed with drug targets and proteins for "cold and hot tumors." Furthermore, this review combines the therapeutic strategies of different "hot and cold tumors" with traditional medicine and modern medicine, to provide a basis and guidance for clinical decision-making of cancer treatment.

Efficacy and Safety Analysis of VRD-PDCE in Treatment-Native Patients with Multiple Extramedullary Plasmacytomas or Plasma Cell Leukemia.

The prognosis of multiple extramedullary plasmacytomas (MEP) and plasma cell leukemia (PCL) is extremely poor, with the median overall survival (OS) of only 8 months with standard chemotherapy. Innovative treatment approaches incorporating various strategies are required to improve outcome. From November 2019 to September 2021, a total of 12 newly diagnosed MEP or PCL patients were enrolled in our department. An intensive chemotherapy treatment as VRD-PDCE consisted of bortezomib, lenalidomide, dexamethasone plus cisplatin, pegylated liposomal doxorubicin, cyclophosphamide and etoposide was first proposed. Disease activity and toxicity were evaluated after each cycle. Of the patients receiving therapy achieved a rapid and sustained response, and the overall response rate (ORR) was up to 75%. Nine patients achieved partial response (PR) or better, the response was the best response and the median time to best response was 4 cycles. Median overall survival (OS) and progression-free survival (PFS) were 24 (5-30) months and 18 (2-23) months. The toxicities were acceptable and there was no treatment related mortality. Our intensive treatment showed encouraging results in terms of disease control and improving survival, VRD-PDCE may be a novel regimen which is feasible and generally well-tolerated in MEP or PCL patients.

Study on autonomic neuropathy of the digestive system caused by bortezomib in the treatment of multiple myeloma.

OBJECTIVE: To research the effects of autonomic neuropathy of the digestive system induced by bortezomib on clinical efficacy and quality of life. METHODS: A total of 150 patients with newly diagnosed multiple myeloma (MM) were hospitalized in our department from January 2018 to December 2021, and treated with bortezomib-based combination regimens. To observe the incidence of autonomic neuropathy of the digestive system and analyse the correlations between the severity of autonomic neuropathy and the efficacy, survival, age, underlying diseases and personal history. RESULTS: The incidence of autonomic neuropathy of the digestive system was 60.0%. The overall response rate (ORR), 2-year progression-free survival (PFS) rate and 2-year overall survival (OS) rate in the grade 3 group of autonomic neuropathy were significantly lower than those in the grade 1-2 group, and the differences were statistically significant (P < 0.05). Age, constipation, diabetes, fracture/spinal cord compression in bed and history of alcoholism were positively correlated with the risk of autonomic neuropathy of the digestive system (P < 0.05). The autonomic neuropathy of the digestive system was significantly alleviated in most patients after the timely adjustment of the treatment regimen, and bortezomib could continue to be administered. CONCLUSIONS: The incidence of autonomic neuropathy of the digestive system induced by bortezomib is high, and its severity is closely related to efficacy, advanced age, constipation, diabetes, fracture/spinal cord compression in bed and history of alcoholism. Early detection and early treatment are necessary to better treat the disease and reverse the autonomic neuropathy.

Effects of Ketamine on Chronic Postsurgical Pain in Patients Undergoing Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: Chronic postsurgical pain (CPSP) has become a common complication during the perioperative period. The efficacy of one of the most potent strategies, ketamine, remains unclear. OBJECTIVES: The aim of this meta-analysis was to evaluate the effect of ketamine on CPSP in patients undergoing common surgeries.. STUDY DESIGN: Systematic review and meta-analysis. METHODS: English-language randomized controlled trials (RCTs) published in MEDLINE, Cochrane Library, and EMBASE from 1990 through 2022 were screened. RCTs with a placebo control group that evaluated the effect of intravenous ketamine on CPSP in patients undergoing common surgeries were included. The primary outcome was the proportion of patients who experienced CPSP 3 - 6 months postsurgery. The secondary outcomes included adverse events, emotional evaluation, and 48 hour postoperative opioid consumption. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pooled effect sizes were measured using the common-effects model or random-effects model, and several subgroup analyses were conducted. RESULTS: Twenty RCTs were included with 1,561 patients. Our pooled meta-analysis showed a significant difference between ketamine and placebo in the treatment of CPSP (Relative Risk [RR] = 0.86; 95% CI, 0.77 - 0.95; P = 0.02; I2 = 44%). In the subgroup analyses, our results indicated that compared with placebo, intravenous ketamine might decrease the prevalence of CPSP 3 - 6 months postsurgery (RR = 0.82; 95% CI, 0.72 - 0.94; P = 0.03; I2 = 45%). For adverse events, we observed that intravenous ketamine might lead to hallucinations (RR = 1.61; 95% CI, 1.09 - 2.39; P = 0.27; I2 = 20%) but did not increase the incidence of postoperative nausea and vomiting (RR = 0.98; 95% CI, 0.86 - 1.12; P = 0.66; I2 = 0%). LIMITATIONS: Inconsistent assessment tools and follow-up for chronic pain may contribute to the high heterogeneity and limitation of this analysis. CONCLUSIONS: We discovered that intravenous ketamine may reduce the incidence of CPSP in patients undergoing surgery, especially 3 - 6 months postsurgery. Because of the small sample size and high heterogeneity of the included studies, the effect of ketamine in the treatment of CPSP still needs to be explored in future large-sample, standardized-assessment studies.

The effect of city size on the disability rate of the older adults: empirical evidence from CHARLS data.

Background: Exploring the value orientation of city development from the perspective of people's well-being is key to clarifying the current debate on city size strategies. Methods: Based on the survey data of the China Health and Retirement Longitudinal Study in two phases, and by using the unbalanced panel-ordered logit model, stepwise analysis method, and KHB method, among others, we discuss the impact of city size on the disability rate of older adults. Results: The study finds that city size significantly and positively affects the activities of daily living (ADL) of older adults, with odd ratios of 1.3286 (95% CI = [1.082243, 1.631089]), and exhibits significant group heterogeneity in terms of age, registered residence, income, and education level. City size has indeed played an mediation role through the health improvement effect, disease mitigation effect, emotional effect, and employment structure optimization effect, with a cumulative contribution rate of the mediation effect of 35.17%. In addition, the urban sprawl index has a significant moderation role. Discussion: Robust urban sprawl is conducive to promoting the improvement of the regional health environment, the improvement of the medical security policy, the optimization of the family support policy, and the employment structure, thus helping to reduce the disability rate of older adults.

Association Between Some Different Obesity Anthropometric Indices and Type 2 Diabetes Mellitus in Middle-Aged and Elderly Chinese Men and Women in Beijing, China: A Cross-Sectional Study.

Background: Obesity can lead to the development of type 2 diabetes mellitus (T2DM). However, the predictive power of different obesity anthropometric indices (ObAIs) for T2DM varies with race and geographical area. Therefore, the study aimed to investigate the association between different ObAIs and T2DM and determine the best index for screening T2DM in middle-aged and elderly men and women in Beijing, China. Methods: A cross-sectional study was conducted in Shijingshan district (Beijing, China) from November 2011 to August 2012, involving a total of 14,558 subjects aged ≥40 years. Data on demographic information, lifestyle, history of T2DM, hypertension and dyslipidemia were collected. Body height, body weight, waist circumference (WC), hip circumference, and blood pressure were recorded. The oral glucose tolerance test or a standard meal test and blood lipid test were performed. The relationship between different ObAIs and T2DM was analyzed using multiple logistic regression. Results: After adjustment for age, smoking status, alcohol intake, occupation and education degree, diabetes family history, hypertension and dyslipidemia, body mass index (BMI), WC, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were positively associated with T2DM in both men and women. Compared with the lowest BMI, WC, WHR, and WHtR quartiles, ORs of the highest quartiles were 2.131 (95% CI: 1.465-3.099), 1.752 (95% CI: 1.270-2.417), 1.342 (95% CI: 1.072-1.678), 2.739 (95% CI: 2.293-3.271) in men and 1.837 (95% CI: 1.584-2.130), 3.122 (95% CI: 1.980-4.924), 3.781 (95% CI: 2.855-5.007), 2.379 (85% CI: 2.040-2.775), respectively, in women. The areas under ROC curve of BMI, WC, WHR, and WHtR for men were 0.584 (95% CI: 0.568-0.600), 0.509 (95% CI: 0.492-0.525), 0.501 (95% CI: 0.485-0.518), and 0.642 (95% CI: 0.627-0.658) and 0.619 (95% CI: 0.607-0.632), 0.709 (95% CI: 0.697-0.720), 0.741 (95% CI: 0.730-0.752), and 0.654 (95% CI: 0.642-0.666), respectively, for women. Conclusion: WHtR and WHR have been found to perform better as predictors of T2DM in middle-aged and elderly Chinese men and women, respectively.

Difunctionalization of gem-Difluoroalkenes via Photoredox Catalysis: Synthesis of Diverse α,α-Difluoromethyl-ß-alkoxysulfones.

Visible-light-promoted alkoxysulfonylation of gem-difluoroalkenes using sulfonyl chlorides and alcohols has been developed. The reaction exhibits a relatively broad substrate scope with excellent functional group compatibility. This synthesis method includes an atom transfer radical addition-like process. The products can be used as platform molecules for further modification.

Regulation of the formation and structure of biofilms by quorum sensing signal molecules packaged in outer membrane vesicles.

Quorum sensing signal molecules can be used to regulate the formation of biofilm, but it has not been reported that outer membrane vesicles (OMVs) can package and mediate signal molecules to regulate biofilm. We isolated and purified OMVs packaged with Pseudomonas quinolone signal (PQS) released by Pseudomonas aeruginosa and studied the effects of OMV-mediated PQS on the formation and structure of biofilms. OMV-mediated PQS promoted the growth of biofilm, and the cells in the biofilm were stretched, deformed and "bridged" with the surrounding cells. Raman spectrometry showed that the structure and components of the extracellular polymeric substances of P. aeruginosa changed; moreover extracellular proteins rather than polysaccharides played the dominant role in the formation of P. aeruginosa biofilms when regulated by OMV-mediated PQS. In the combination biofilm formed by P. aeruginosa and Staphylococcus aureus, the mediation of OMVs enhanced the inhibitory effect of PQS to the growth of S. aureus, resulting a decrease in EPS produced by the two bacteria. OMV-mediated PQS led to changes in the biodiversity, richness and structure of the microbial community in biofilms formed by active sludge. This work reveals the mechanism of OMVs mediated signal molecules regulating biofilm, which lays a new theoretical and practical foundation for guiding the operation of low-level of biofouling MBRs.

Hsa_circ_0015278 Regulates FLT3-ITD AML Progression via Ferroptosis-Related Genes.

AML with the FLT3-ITD mutation seriously threatens human health. The mechanism by which circRNAs regulate the pathogenesis of FLT3-ITD mutant-type AML through ferroptosis-related genes (FerRGs) remains unclear. Differentially expressed circRNAs and mRNAs were identified from multiple integrated data sources. The target miRNAs and mRNAs of the circRNAs were predicted using various databases. The PPI network, ceRNA regulatory network, GO, and KEGG enrichment analyses were performed. The "survival" and the "pROC" R packages were used for K-M and ROC analysis, respectively. GSEA, immune infiltration analysis, and clinical subgroup analysis were performed. Finally, circRNAs were validated by Sanger sequencing and qRT-PCR. In our study, 77 DECircs-1 and 690 DECircs-2 were identified. Subsequently, 11 co-up-regulated DECircs were obtained by intersecting DECircs-1 and DECircs-2. The target miRNAs of the circRNAs were screened by CircInteractome, circbank, and circAtlas. Utilizing TargetScan, ENCORI, and miRWalk, the target mRNAs of the miRNAs were uncovered. Ultimately, 73 FerRGs were obtained, and the ceRNA regulatory network was constructed. Furthermore, MAPK3 and CD44 were significantly associated with prognosis. qRT-PCR results confirmed that has_circ_0015278 was significantly overexpressed in FLT3-ITD mutant-type AML. In summary, we constructed the hsa_circ_0015278/miRNAs/FerRGs signaling axis, which provides new insight into the pathogenesis and therapeutic targets of AML with FLT3-ITD mutation.

Identification of key miRNA signature and pathways involved in multiple myeloma by integrated bioinformatics analysis.

Multiple myeloma (MM) is one of the most common types of hematologic malignancy for which the underlying molecular mechanisms remain largely unclear. Dysregulated miRNA expression has been shown to be involved in MM tumorigenesis, progression and drug response. Therefore, a comprehensive analysis based on miRNA-level integrated strategy was performed.This study aimed to elucidate key miRNA signatures and pathways in MM by integrated bioinformatics analysis. Expression profiles GSE24371, GSE49261 and GSE54156 were obtained from the Gene Expression Omnibus database, and differentially expressed miRNAs (DEMirs) with p < 0.05 were identified. The target genes of these DEMirs were obtained from ENCORI database, and functional enrichment, subpathway enrichment and protein-protein interaction network construction were performed. The key target genes were identified by random walk algorithm and survival verification was performed.and discussion: First, six up-regulated and four down-regulated DEMirs shared between any two GSE data sets were identified. Second, target genes (DEMirTGs) by up-regulated and down-regulated DEMirs were obtained. Functional and subpathway enrichment analysis showed that these up-regulated DEMirs are consistently involved in the Wnt signaling pathway. Moreover, enrichment of the down-regulated DEMirs is mainly in the MAPK signaling pathway. Finally, a protein-protein interaction sub-network for these DEMirTGs was constructed, the correlations between the two key genes were identified and survival in MM was evaluated using multiple independent data sets.We identified miRNA signatures and key target genes that were closely related to MM biology, and these genes might serve as potential therapeutic targets for MM patients.

Dynamic monitoring of serum ferritin as an adverse prognostic biomarker in patients with multiple myeloma.

Aim: Increased serum ferritin (SF) indicates an adverse prognosis in patients with hematologic malignancies. However, its prognostic significance in multiple myeloma (MM) remains unknown. Patients & methods: The impact of SF levels on outcomes in patients with MM was retrospectively analyzed and dynamically assessed. Results: At initial diagnosis, 188 out of 295 patients (63.7%) had high SF that correlated with poor prognosis factors including adverse overall survival and progression-free survival. SF expression was dynamically observed at different time points and SF levels significantly decreased after treatment induction. In addition, SF expression significantly increased at disease progression or relapse. Conclusion: SF can be used as a prognostic factor at initial diagnosis and relapse in patients with MM.

The Health Status Transition and Medical Expenditure Evaluation of Elderly Population in China.

(1) Background: Because of the rapid expansion of the aging population in China, their health status transition and future medical expenditure have received increasing attention. This paper analyzes the health transition of the elderly and how their health transition impacts medical expenditures. At the same time, feasible policy suggestions are provided to respond to the rising medical expenditure and the demand for social care. (2) Methods: The data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2015 and analyzed using the Markov model and the Two-Part model (TPM) to forecast the size of the elderly population and their medical expenditures for the period 2020-2060. (3) Results: The study indicates that: (1) for the elderly with a mild disability, the probability of their health improvement is high; in contrast, for the elderly with a moderate or severe disability, their health deterioration is almost certain; (2) the frequency of the diagnosis and treatments of the elderly is closely related to their health status and medical expenditure; alternatively, as the health status deteriorates, the intensity of the elderly individuals' acceptance of their diagnosis and treatment increases, and so does the medical expense; (3) the population of the elderly with mild and moderate disability demonstrates an inverted "U"-shape, which reaches a peak around 2048, whereas the elderly with severe disability show linear growth, being the target group for health care; (4) with the population increase of the elderly who have severe disability, the medical expenditure increases significantly and poses a huge threat to medical service supply. Conclusions: It is necessary to provide classified and targeted health care according to the health status of the elderly. In addition, improving the level of medical insurance, establishing a mechanism for sharing medical expenditure, and adjusting the basic demographic structure are all important policy choices.

Outer membrane vesicles mediated horizontal transfer of an aerobic denitrification gene between Escherichia coli.

Bacterial genetic material can be horizontally transferred between microorganisms via outer membrane vesicles (OMVs) released by bacteria. Up to now, the application of vesicle-mediated horizontal transfer of "degrading genes" in environmental remediation has not been reported. In this study, the nirS gene from an aerobic denitrification bacterium, Pseudomonas stutzeri, was enclosed in a pET28a plasmid, transformed into Escherichia coli (E. coli) DH5α and expressed in E. coli BL21. The E. coli DH5α released OMVs containing the recombination plasmid pET28a-nirS-EGFP. When compared with the free pET28a-nirS-EGFP plasmid's inability to transform, nirS in OMVs could be transferred into E. coli BL21 with the transformation frequency of 2.76 × 106 CFU/g when the dosage of OMVs was 200 µg under natural conditions, and nirS could express successfully in recipient bacteria. Furthermore, the recipient bacteria that received OMVs containing pET28a-nirS-EGFP could produce 18.16 U/mL activity of nitrite reductase.

Downregulation of microRNA-155-5p prevents immune thrombocytopenia by promoting macrophage M2 polarization via the SOCS1-dependent PD1/PDL1 pathway.

AIMS: We set about to investigate the potential role of microRNA-155-5p (miR-155-5p) in the development of immune thrombocytopenia (ITP), an idiopathic deficiency of blood platelets. MAIN METHODS: Initially, RT-qPCR and Western blot analyses were carried out to determine the expression of miR-155-5p and SOCS1 in peripheral blood mononuclear cells (PBMCs) and macrophages from ITP patients. We undertook gain- and loss- function methods by transfection of macrophages and PBMCs with treated plasmids. The expression patterns of platelet-related factors were measured by ELISA, and the expressions of PD1, PDL1, and macrophage M2 marker CD206 and CD86 were also measured. The relationship between miR-155-5p and SOCS1 was determined using the dual-luciferase reporter gene assay. We also established an ITP mouse model to explore the roles of miR-155-5p and SOCS1 in vivo. KEY FINDINGS: miR-155-5p was up-regulated, while SOCS1 was down-regulated in PBMCs and macrophages from ITP patients. SOCS1 was indicated as a target of miR-155-5p. Inhibition of miR-155-5p or up-regulation of SOCS1 facilitated macrophage M2 polarization as demonstrated by an increased M2/M1 ratio and suppressed expression of platelet-related factors. Furthermore, silencing of SOCS1 promoted ITP progression through blocking the PD1/PDL1 pathway, whilst upregulation of miR-155-5p remarkably increased the platelet abundance and suppressed SOCS1 expression in ITP model mice. SIGNIFICANCE: Silencing of miR-155-5p could promote PD1/PDL1 pathway-mediated macrophage M2 polarization and prevent ITP via up-regulation of SOCS1, thus relieving ITP.