Molecular epidemiological and clinical infection characteristics analysis of Ralstonia.

PURPOSE: This study was to clarify the molecular epidemiology and clinical infection characteristics of Ralstonia pickettii and establish sequence typing system. METHODS: 48 nonrepetitive Ralstonia pickettii strains were collected from January 2008 to December 2013 at the Chinese People's Liberation Army General Hospital (PLAGH) and were identified through a specific PCR experiment, 16 S rDNA experiment and VITEK 2 system to compare the identification accuracy. The sequence types of the strains were analyzed by multilocus sequence typing (MLST) method. The antibiotic sensitivity of these strains was determined with disc diffusion tests and broth microdilution method. The clinical data of Ralstonia pickettii infected patients were collected. RESULTS: All of the 48 strains were identified as Ralstonia pickettii by VITEK 2 system. 30 and 34 strains were identified as Ralstonia pickettii by PCR and 16 S rDNA experiment respectively. ST9 was the most sequence types (STs) in these 18 STs of 42 strains. 42 strains were divided into 2 groups (A and B) and 18 genotypes. Ralstonia pickettii was sensitive to some cephalosporins, ß-lactam/ß-lactamase inhibitor, levofloxacin and trimethoprim/sulfamethoxazole. Cough, sputum, shortness of breath and pulmonary rales were the common clinical symptoms of most Ralstonia pickettii infected patients. CONCLUSION: We established a sequence typing system with a relatively fine resolution and the PCR assay is a faster and more sensitive method for clinical identification of Ralstonia pickettii. ST9 is the most common sequence types of Ralstonia pickettii. The most common clinical characteristics of Ralstonia pickettii infected patients were cough, sputum, shortness of breath and pulmonary rales.

Proteomics analysis of histone deacetylase inhibitor-resistant solid tumors reveals resistant signatures and potential drug combinations.

Histone deacetylase inhibitors (HDACis) are important drugs for cancer therapy, but the indistinct resistant mechanisms of solid tumor therapy greatly limit their clinical application. In this study we conducted HDACi-perturbated proteomics and phosphoproteomics analyses in HDACi-sensitive and -resistant cell lines using a tandem mass tag (TMT)-based quantitative proteomic strategy. We found that the ribosome biogenesis proteins MRTO4, PES1, WDR74 and NOP16 vital to tumorigenesis might regulate the tumor sensitivity to HDACi. By integrating HDACi-perturbated protein signature with previously reported proteomics and drug sensitivity data, we predicted and validated a series of drug combination pairs potentially to enhance the sensitivity of HDACi in diverse solid tumor. Functional phosphoproteomic analysis further identified the kinase PDK1 and ROCK as potential HDACi-resistant signatures. Overall, this study reveals the potential HDACi-resistant signatures and may provide promising drug combination strategies to attenuate the resistance of solid tumor to HDACi.

Integration of Myrica rubra-based N-doped carbon dots with Fe3S4 as excellent peroxidase mimics for colorimetric assay and smartphone-based intelligent sensing of p-aminophenol in waters.

To realize the reutilization of waste Myrica rubra in the analytical field, we synthesized Myrica rubra-based N-doped carbon dots (MN-CDs) and further anchored them onto the surface of Fe3S4 to fabricate Fe3S4@MN-CD nanocomposites. The as-fabricated nanocomposites possessed higher peroxidase-mimetic activity than its two precursors, resulting from the synergistic effect between them, and could catalyze colorless 3,3',5,5'-tetramethylbenzidine (TMB) into deep blue oxTMB with a strong 652-nm absorption. Under optimized conditions (initial solution pH, 3.5; incubation temperature, 35 ℃; Fe3S4@MN-CD concentration, 50 µg mL-1, and 652-nm absorption), Fe3S4@MN-CDs were employed for colorimetric assay of p-aminophenol (p-AP) with wide linear range (LR, 2.9-100 µM), low detection limit (LOD, 0.87 µM), and satisfactory recoveries (86.3-105%) in environmental waters. Encouragingly, this colorimetric assay provided the relative accuracy of 97.0-99.4% as compared with  conventional HPLC-UV detection. A portable smartphone-based colorimetric application was developed by combining the Fe3S4@MN-CD-based visually chromogenic reaction with a "Thing Identify" APP software. Besides, we engineered an image-capturing device feasible for field use, in which the internal-compact sealing prevented external light source from entering photography chamber, thereby reducing light interference, and also the bottom light source enhanced the intensity of blue imaging. This colorimetric platform exhibited satisfactory LR (1-500 µM), low LOD (0.3 µM), and fortification recoveries (86.6-99.6%). In the chromogenic reaction catalyzed by Fe3S4@MN-CDs, ·O2- played a key role in concomitant with the participation of •OH and h+. Both the colorimetric assay and smartphone-based intelligent sensing show great promising in on-site monitoring of p-AP under field conditions.

Two-dimensional Cu Plates with Steady Fluid Fields for High-rate Nitrate Electroreduction to Ammonia and Efficient Zn-Nitrate Batteries.

Nitrate electroreduction reaction (eNO3 -RR) to ammonia (NH3) provides a promising strategy for nitrogen utilization, while achieving high selectivity and durability at an industrial scale has remained challenging. Herein, we demonstrated that the performance of eNO3 -RR could be significantly boosted by introducing two-dimensional Cu plates as electrocatalysts and eliminating the general carrier gas to construct a steady fluid field. The developed eNO3 -RR setup provided superior NH3 Faradaic efficiency (FE) of 99 %, exceptional long-term electrolysis for 120 h at 200 mA cm-2, and a record-high yield rate of 3.14 mmol cm-2 h-1. Furthermore, the proposed strategy was successfully extended to the Zn-nitrate battery system, providing a power density of 12.09 mW cm-2 and NH3 FE of 85.4 %, outperforming the state-of-the-art eNO3 -RR catalysts. Coupled with the COMSOL multiphysics simulations and in situ infrared spectroscopy, the main contributor for the high-efficiency NH3 production could be the steady fluid field to timely rejuvenate the electrocatalyst surface during the electrocatalysis.

Ephrin receptor A10 monoclonal antibodies and the derived chimeric antigen receptor T cells exert an antitumor response in mouse models of triple-negative breast cancer.

Expression of the receptor tyrosine kinase ephrin receptor A10 (EphA10), which is undetectable in most normal tissues except for the male testis, has been shown to correlate with tumor progression and poor prognosis in several malignancies, including triple-negative breast cancer (TNBC). Therefore, EphA10 could be a potential therapeutic target, likely with minimal adverse effects. However, no effective clinical drugs against EphA10 are currently available. Here, we report high expression levels of EphA10 in tumor regions of breast, lung, and ovarian cancers as well as in immunosuppressive myeloid cells in the tumor microenvironment. Furthermore, we developed anti-EphA10 monoclonal antibodies (mAbs) that specifically recognize cell surface EphA10, but not other EphA family isoforms, and target tumor regions precisely in vivo with no apparent accumulation in other organs. In syngeneic TNBC mouse models, we found that anti-EphA10 mAb clone #4 enhanced tumor regression, therapeutic response rate, and T cell-mediated antitumor immunity. Notably, the chimeric antigen receptor T cells derived from clone #4 significantly inhibited TNBC cell viability in vitro and tumor growth in vivo. Together, our findings suggest that targeting EphA10 via EphA10 mAbs and EphA10-specific chimeric antigen receptor-T cell therapy may represent a promising strategy for patients with EphA10-positive tumors.

Early antidepressant treatment response prediction in major depression using clinical and TPH2 DNA methylation features based on machine learning approaches.

OBJECTIVE: To identify DNA methylation and clinical features, and to construct machine learning classifiers to assign the patients with major depressive disorder (MDD) into responders and non-responders after a 2-week treatment into responders and non-responders. METHOD: Han Chinese patients (291 in total) with MDD comprised the study population. Datasets contained demographic information, environment stress factors, and the methylation levels of 38 methylated sites of tryptophan hydroxylase 2 (TPH2) genes in peripheral blood samples. Recursive Feature Elimination (RFE) was employed to select features. Five classification algorithms (logistic regression, classification and regression trees, support vector machine, logitboost and random forests) were used to establish the models. Performance metrics (AUC, F-Measure, G-Mean, accuracy, sensitivity, specificity, positive predictive value and negative predictive value) were computed with 5-fold-cross-validation. Variable importance was evaluated by random forest algorithm. RESULT: RF with RFE outperformed the other models in our samples based on the demographic information and clinical features (AUC = 61.2%, 95%CI: 60.1-62.4%) / TPH2 CpGs features (AUC = 66.6%, 95%CI: 65.4-67.8%) / both clinical and TPH2 CpGs features (AUC = 72.9%, 95%CI: 71.8-74.0%). CONCLUSION: The effects of TPH2 on the early-stage antidepressant response were explored by machine learning algorithms. On the basis of the baseline depression severity and TPH2 CpG sites, machine learning approaches can enhance our ability to predict the early-stage antidepressant response. Some potentially important predictors (e.g., TPH2-10-60 (rs2129575), TPH2-2-163 (rs11178998), age of first onset, age) in early-stage treatment response could be utilized in future fundamental research, drug development and clinical practice.

NOS2/miR-493-5p Signaling Regulates in the LPS-Induced Inflammatory Response in the RAW264.7 Cells.

Tuberculosis (TB) is a fatal infectious disease; however, the molecular mechanisms underlying the pathogenicity of TB remain elusive. The present study aims to identify potential biomarkers associated with Mycobacterium tuberculosis (M.tb) infection by using integrated bioinformatics and in vitro validation studies. GSE50050, GSE78706, and GSE108844 data from the gene expression omnibus (GEO) database were downloaded to identify differentially expressed genes (DEGs). The functions of DEGs were further subjected to gene ontology (GO) and KEGG pathway analysis. The hub genes from the DEGs were determined based on the protein-protein interaction (PPI) network analysis. Finally, the hub genes were experimentally validated using the in vitro functional studies. A total of 26 common DEGs were identified among GSE50050, GSE78706, and GSE108844. The functional enrichment analysis showed that the common DEGs were associated with cytokines response and TB pathways. The PPI network analysis identified nine hub genes. Further in vitro studies showed that nitric oxide synthase 2 (NOS2) was up-regulated in RAW264.7 cells upon lipopolysaccharides (LPS) stimulation, which was accompanied by increased inflammatory cytokines release. Furthermore, NOS2 was found to be a target of miR-493-5p, which was confirmed by luciferase reporter assay. NOS2 was repressed by miR-493-5p overexpression and was up-regulated after miR-493-5p inhibition in RAW264.7 cells. The rescue experiments showed that LPS-induced increase in the inflammatory cytokines of the RAW264.7 cells was significantly attenuated by NOS2 knockdown and miR-493-5p overexpression. Collectively, our results for the first time demonstrated that NOS2/miR-493-5p signaling pathway may potentially involve in the inflammatory response during bacterial infection such as M. tb infection.

Rethinking personal carbon trading (PCT) mechanism: A comprehensive review.

The implementation of Personal Carbon Trading (PCT) holds promise in facilitating a noteworthy contribution towards the attainment of emissions reduction predicated on consumption patterns and consequently motivating lifestyle modifications. As individual consumption behaviors usually lead to continuous changes in carbon emissions, it is crucial to rethink PCT from a systematic perspective. This review employed a bibliometric analysis of 1423 papers related to PCT, highlighting the key themes of carbon emissions from energy consumption, climate change, and public opinion on policies in the context of PCT. Most of the existing PCT researches focus on theoretical assumptions and public attitudes, while the quantification of carbon emissions and simulation of PCT require further investigation. Furthermore, the concept of Tan Pu Hui is seldom addressed in PCT studies and case analyses. Moreover, there are limited PCT schemes worldwide that can be directly implemented in practice, leading to a scarcity of large-scale, high-participation case studies. To address these gaps, this review proposes a framework to clarify how PCT can stimulate individual emission reductions on the consumption side, comprising two phases, from motivation to behavior and behavior to target. Future endeavors should prioritize the enhancement of the systematic study of the theoretical foundation of PCT, encompassing carbon emissions accounting and policy design, the incorporation of cutting-edge technology, and the reinforcement of integrated policy practice. This review serves as a valuable reference for future research endeavors and policymaking efforts.

Determination of estrogens in human serum using a novel chemical derivatization-assisted liquid chromatography-electrospray ionization-tandem mass spectrometry method.

RATIONALE: Assessing estrogen concentrations in biological systems can provide valuable information on physiological processes, which is crucial for the early diagnosis of many diseases. Because estrogens are present in the human body in low concentrations and in a wide dynamic range, analytical methods with high sensitivity and specificity are required for their determination in complex biological matrices. METHODS: To discover an appropriate derivatization reagent for estrogen mass spectrometry (MS) analysis, we compared five sulfonyl chloride derivatization reagents, namely 3-methyl-8-quinolinesulfonyl chloride (MQSCl) and 8-quinolinesulfonyl chloride (QSCl), 1-methyl-1H-pyrazole-4-sulfonyl chloride, 1,2-methyl-imidazole-5-sulfonyl chloride, and dansyl chloride. By selecting the derivatization reagent with the best performance, we developed and validated a novel chemical derivatization-assisted-liquid chromatography-electrospray ionization-tandem mass spectrometry (CD-LC-ESI-MS/MS) method to simultaneously determine the concentrations of estrone, estradiol, and estriol (E1, E2, and E3) in human serum. RESULTS: It was found that among the five investigated reagents, MQSCl-derivatized estrogens presented the highest sensitivity using LC-ESI-MS/MS. Based on this discovery, MQSCl was chosen to derivatize the analyzed estrogens to assist LC-ESI-MS/MS analysis. The limit of quantification of E1, E2, and E3 was measured as 2.7, 4.6, and 5.1 pg/mL, respectively. Inter- and intra-day precision, expressed as the coefficient of variation, was shown to be lower than 13.2% for all concentrations. The mean recovery was 72.4% overall, with good reproducibility at low, medium, and high concentrations in the calibration range. CONCLUSIONS: The developed method was successfully applied to the quantitative determination of estrogens in clinical human serum from pediatric and adult women, demonstrating the suitability of estrogen analysis in the biological matrix at low concentration (pg/mL).

Reuse of waste Myrica rubra for green synthesis of nitrogen-doped carbon dots as an "on-off-on" fluorescent probe for Fe3+ and ascorbic acid detection.

As one kind of high nutrition fruits, abandoned Myrica rubra causes great waste due to short storage period. For resource utilization, we herein fabricated the Myrica rubra-based N-doped carbon dots (MN-CDs) by a facile/green hydrothermal method. MN-CDs, fabricated from four regions of China, displayed significant differences in their corresponding fluorescence intensities (FIs). Interestingly, different batches of waxberry samples from the same region (Wenzhou, China) exhibited slight differences in their FIs, and also an excellent anti-photobleaching and anti-salt capacity. Based on Fe3+-triggered quenching effect and fluorescent recovery by redox reaction of AA and Fe3+, MN-CDs were employed to construct an "on-off-on" switch probe for sequential detection of Fe3+ and ascorbic acid (AA). Through Zeta potential, UV spectrum, Stern-Volmer equation, and valence-conduction band theory, the Fe3+-triggered quenching belonged to a static quenching process, which resulted from the synergistic contribution of inner filtering effect and photo-induced electron transfer mechanisms. The linear ranges for Fe3+ and AA detections were 1-1000 and 0.1-1000 mM. The limits of detection were 0.3 µM for Fe3+ in environmental waters, and 0.03 µM for AA in pharmaceutical tablets and fruit juice samples. Under 365-nm UV lamp, the color changes of test papers were easily observed from dark blue and bright blue in the presence of Fe3+ and AA, and thus the MN-CDs-based switch probe could be satisfactorily used for visually qualitative detection of Fe3+ and AA outdoor with our naked eyes. To sum up, MN-CDs not only realize resource reutilization of abandoned Myrica rubra, but also offer an convenient outdoor approach for qualitative detection of Fe3+ and AA in complex matrices.

Sensitive colorimetric assay of hydrogen peroxide and glucose in humoral samples based on the enhanced peroxidase-mimetic activity of NH2-MIL-88-derived FeS2@CN nanocomposites compared to its precursors.

By employing NH2-MIL-88 as a template, we synthesized the intermediate Fe@CN under high-temperature calcination and further fabricated the FeS2@CN nanocomposites in the presence of sulfur powder. Under varying temperatures (300-600 °C) and Fe@CN-to-S ratios (1:3-6), FeS2@CN500-5 nanocomposites had the highest peroxidase-mimetic activity. Under optimized conditions (incubation temperature 40 °C; solution pH 4.0 and nanocomposite concentration 10 µg/mL; 652-nm absorption), the Michaelis-Menten constant (Km) of FeS2@CN was much lower than that of horseradish peroxidase (HRP), therefore demonstrating that it had a higher affinity for both chromogenic substrates than conventional HRP. The limits of detection for H2O2 and glucose were 0.15 and 0.30 µmol/L, respectively, and the recoveries for glucose were 91.8-103% with RSDs <5.2%. The novelty of this study lies in (1) the FeS2@CN was confirmed to possess stronger enzyme-mimetic activity than its precursors (NH2-MIL-88 and Fe@CN); (2) the enhanced activity resulted from the unsaturated sites of N and S doping and the plentiful defects on the porous carbon surface; and (3) free radical trapping experiments evidenced that •OH played a major role in the catalytic reaction, while h+ and •O2- simultaneously participated in the catalytic process. These convincing performance metrics lead us to postulate that the FeS2@CN-based colorimetric biosensor provides a promising approach for several real-world applications, such as point-of-care diagnosis and workplace health evaluations.

Controllable Fibrillization Reinforces Genetically Engineered Rubberlike Protein Hydrogels.

Rubberlike protein hydrogels are unique in their remarkable stretchability and resilience but are usually low in strength due to the largely unstructured nature of the constitutive protein chains, which limits their applications. Thus, reinforcing protein hydrogels while retaining their rubberlike properties is of great interest and has remained difficult to achieve. Here, we propose a fibrillization strategy to reinforce hydrogels from engineered protein copolymers with photo-cross-linkable resilin-like blocks and fibrillizable silklike blocks. First, the designer copolymers with an increased ratio of the silk to resilin blocks were photochemically cross-linked into rubberlike hydrogels with reinforced mechanical properties. The increased silk-to-resilin ratio also enabled self-assembly of the resulting copolymers into fibrils in a time-dependent manner. This allowed controllable fibrillization of the copolymer solutions at the supramolecular level for subsequent photo-cross-linking into reinforced hydrogels. Alternatively, the as-prepared chemically cross-linked hydrogels could be reinforced at the material level by inducing fibrillization of the constitutive protein chains. Finally, we demonstrated the advantage of reinforcing these hydrogels for use as piezoresistive sensors to achieve an expanded pressure detection range. We anticipate that this strategy may provide intriguing opportunities to generate robust rubberlike biomaterials for broad applications.

Magnetic amino-functionalized metal-organic frameworks as a novel solid support in ionic liquids-based effervescent tablets for efficient extraction of polycyclic aromatic hydrocarbons in milks.

Herein, a kind of novel multi-layer core-shell nanocomposites (NSPN) was prepared by employing SiO2 and polyvinylpyrrolidone (PVP) polymers as modifiers and amino-functionalized metal-organic frameworks (NH2-MIL101(Fe)) as coating. It was referred to as the NSPN and ILs-based effervescence-assisted dispersive solid-phase microextraction, hereafter abbreviated as NIE-DSM. In terms of extraction efficiency, SiO2 and PVP as modifiers and NH2-MIL(Fe) as coating onto the surface of NiFe2O4 cores played a synergistically enhancing effect on adsorption/extraction. Effervescent tablets were prepared by integrating the NSPN magnetic nanoparticles as adsorbents with imidazolium-based ionic liquids (ILs) as extractants as well as acidic and alkaline sources. Under vigorous dispersion of CO2 bubbles, the NIE-DSM method realized the goal of rapidly diffusing and separating the adsorbent/extractant (~3 min) without needing conventional vortexing or centrifugation step. Consequently, the NIE-DSM approach combined dispersion and adsorption/extractant in a synchronous way. Under optimized conditions, the NIE-DSM/HPLC-FLD method gave low limits of detection (0.008-0.034 µg kg-1) and satisfactory extraction recoveries (74.1-101.6%) for five polycyclic aromatic hydrocarbons (PAHs; fluorene, anthracene, pyrene, chrysene and benzo(a)pyrene) in milk samples. The intra-day and inter-day precision, expressed as relative standard deviations, was < 5.9% and 6.5%, respectively, demonstrating a high precision. Owing to no requirement for electrical power, this method shows great potential for outdoor monitoring of trace-level PAHs in food matrices.

miR-188-5p inhibits apoptosis of neuronal cells during oxygen-glucose deprivation (OGD)-induced stroke by suppressing PTEN.

The miRNAs and mRNAs are found to play a crucial role in modulating different diseases including stroke, according to the recent evidence. The current study is aimed at assessing the functional role played by miR-188-5p in the regulation of cell apoptosis and viability in OGD-induced human neural cell line HNC. With the help of RT-qPCR, the authors determined miR-188-5p as well as its putative target PTEN among OGD-treated cells in different treatment times. The cell viability was assessed through CCK-8 assay while the cell transfection either upregulated or may have silenced the genes. Both Western Blot as well as RT-qPCR found the proliferation biomarkers such as Ki87 and PCNA in addition to apoptosis biomarkers such as caspase-8 and caspase-3. The luciferase activity was tracked by conducting luciferase assay. The researchers observed an elevation in the expression of miR-188-5p while the PTEN got downregulated in Human Neural Cell line HNC with increase in the time span. The expressions of miR-188-5p and PTEN got increased with increasing OGD treatment time while the Luciferase reassured the binding site. The cell viability was suppressed by the overexpression of miR-188-5p which further inhibited the apoptosis biomarkers too. Meanwhile, it was understood that the results could be reversed to some extent with the inhibition of PTEN. The study findings from in vitro investigations yielded promising results and provided excellent insights about the fundamental molecular mechanisms of miR-188-5p involved in stroke via PTEN. This could be considered as a potential therapeutic axis among stroke patients in the near future.

Evaluation of a combined cognitive-behavioural and exercise intervention to manage fear of falling among elderly residents in nursing homes.

OBJECTIVES: Although the fear of falling is common among elderly residents in long-term care facilities, interventions developed for fear of falling management is very rare. Of these limited interventions, most were exercise interventions with only limited testing. The cognitive-behavioural intervention can decrease the fear of falling; however no intervention of the kind was developed and assessed to decrease fear of falling among the elderly in long-term care facilities. The purpose of this study was to examine the effectiveness of cognitive-behavioural strategies either with or without exercise in reducing fear of falling among elderly residents in nursing homes. METHOD: A prospective randomized control trial was conducted in six nursing homes in northern Taiwan. Seventy-five elderly participants were randomly assigned to one of the three groups: the comparison group, the cognitive-behavioural strategies with or without exercise group. The fear of falling, falls, depressive inclination, mobility, and muscle strength of extremities were collected at the two-month and five-month follow-up sessions, in which the progress of the patients were assessed. RESULTS: The mixed model analysis revealed that elderly adults in the combination experimental group had significant improvements compared with the other two groups on fear of falling, depressive inclination, mobility, and muscle strength at five months. The incidences of falls, post intervention, in both experimental groups were significantly lower than those in the comparison group. CONCLUSIONS: The results suggest that the combination intervention helped elderly residents manage their fear of falling and falls, decrease their depressive inclination, and enhance their mobility and muscle strength.

ASK1 promotes apoptosis of normal and malignant plasma cells.

Although the overproduction of immunoglobulins by short-lived plasma cells accompanying an immune response links with their apoptosis, how long-lived plasma cells adapt to ensure their longevity in this context is obscure. Here, we show that apoptosis signal-regulating kinase 1 (ASK1) contributes to apoptosis of plasma cells because ASK1 activity was induced during differentiation of short-lived plasma cells, and, when produced by ASK1-deficient mice, these cells survived better than those of control mice. Moreover, antigen-specific long-lived plasma cells generated by immunization accumulated in ASK1-deficient mice, suggesting ASK1 also plays a negative role in survival of long-lived plasma cells. In malignant plasma cells, ASK1 transcription was directly suppressed by B lymphocyte-induced maturation protein-1 (Blimp-1). The expression of ASK1 and Blimp-1 showed an inverse correlation between normal human mature B cells and bone marrow plasma cells from patients with multiple myeloma (MM). Suppression of ASK1 is crucial for cell survival because its enforced expression in MM cells caused apoptosis in vitro and lowered MM load in a xenograft animal model; furthermore, alteration of ASK1 activity affected MM cell survival. Our findings indicate a novel mechanism underlying the regulation of survival in normal and malignant plasma cells by ASK1.

Immune response of COVID-19 vaccines in solid cancer patients: A meta-analysis.

Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after COVID-19 infections. They also have different immune responses after doses of COVID-19 vaccination, but limited evidence is available to reveal the effectiveness and help to guide immunization programs for this subpopulation; MEDLINE, Embase, Web of Science, Cochrane Library databases, and clinicaltrials.gov were used to search literature. The pooled seroconversion rate was calculated using a random-effects model and reported with a 95% confidence interval (CI); The review includes 66 studies containing serological responses after COVID-19 vaccination in 13,050 solid cancer patients and 8550 healthy controls. The pooled seropositive rates after the first dose in patients with solid cancer and healthy controls are 55.2% (95% CI 45.9%-64.5% N = 18) and 90.2% (95% CI 80.9%-96.6% N = 13), respectively. The seropositive rates after the second dose in patients with solid cancer and healthy controls are 87.6% (95% CI 84.1%-90.7% N = 50) and 98.9% (95% CI 97.6%-99.7% N = 35), respectively. The seropositive rates after the third dose in patients with solid cancer and healthy controls are 91.4% (95% CI 85.4%-95.9% N = 21) and 99.8% (95% CI 98.1%-100.0% N = 4), respectively. Subgroup analysis finds that study sample size, timing of antibody testing, and vaccine type have influence on the results; Seroconversion rates after COVID-19 vaccination are significantly lower in patients with solid malignancies, especially after the first dose, then shrinking gradually after the following two vaccinations, indicating that subsequent doses or a booster dose should be considered for the effectiveness of this subpopulation.

Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells.

OBJECTIVES: We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE. METHODS: Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network. RESULTS: There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = - 0.7225, p = 0.0279), AC124248.1 (r = - 0.7653, p = 0.0163), LINC00482 (r = - 0.8317, p = 0.0054), and MIR503HG (r = - 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = - 0.7348, p < 0.05) and MIR503 HG (r = - 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell. CONCLUSIONS: The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism. Key points • Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE. • This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms. • It is possible to target epigenetic therapy for SLE.

Indirubin-3'-monoxime exhibits potent antiviral and anti-inflammatory effects against human adenoviruses in vitro and in vivo.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

Clinical efficacy of plasma exchange in systemic lupus erythematosus during pregnancy.

OBJECTIVE: To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. METHODS: The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non-PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. RESULTS: Three patients in the non-PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non-PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non-PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. CONCLUSIONS: The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.