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Abstract Background Hemodialysis patients require a reasonable dietary intake to manage their disease progression effectively. However, there is limited research on these patients’ overall dietary knowledge, attitude, and practice (KAP) status. This study aimed to investigate the dietary KAP status and latent profiles in hemodialysis patients and identify sociodemographic and disease-related factors associated with these profiles and dietary practice. Methods A multicenter cross-sectional study involving 425 hemodialysis patients was conducted. A dietary KAP questionnaire in hemodialysis patients was used to evaluate the dietary KAP of the patients. A structural equation model was employed to analyze the correlations between dietary knowledge, attitude, and practice. Multiple linear regression analysis was used to identify factors associated with dietary practice scores. Latent profile analysis was conducted to determine the latent profiles of dietary KAP, and binary logistic regression was used to explore the sociodemographic and disease-related characteristics associated with each KAP profile in hemodialysis patients. Results The normalized average scores for dietary knowledge, attitude, and practice in hemodialysis patients were 0.58, 0.82, and 0.58, respectively. The structural equation model revealed significant positive correlations between dietary knowledge and attitude, and attitude and practice. Attitude played an indirect effect between knowledge and practice. Gender, cerebrovascular disease, and dietary attitude scores were identified as independent influencing factors for dietary practice scores. Two dietary KAP profiles were developed: a profile with general knowledge and attitude but low practice (40.2%) and a profile with general knowledge and attitude and high practice (59.8%). Binary logistic regression analysis indicated gender and monthly income per household significantly predicted membership in each KAP profile. Conclusions The dietary practice of hemodialysis patients requires improvement. It is necessary to develop more individualized dietary interventions for these patients. Further exploration is needed to understand the motivation of patients to change their dietary behavior.

IntroductionEndophytic fungi can promote secondary metabolite accumulation in medicinal plants. Previously, we observed that the culture filtrate of Fusarium solani CL105 promoted flavonoid production in Scutellaria baicalensis calli. However, the active ingredients and mechanisms associated with this secondary metabolite accumulation remain unclear.MethodsThis study evaluates the effects of different elicitors from the culture filtrate of F. solani CL105 namely, exopolysaccharide (EPS), exoprotein (EP), and other parts (OP), on the flavonoid production in S. baicalensis calli by HPLC. Subsequently, the underlying mechanism of EPS induced flavonoid production in S. baicalensis calli was revealed by transcriptomics and RT-PCR.Results and discussionThe results indicated a significant increase in flavonoid production in S. baicalensis calli following treatment with EPS. Baicalin (1.40 fold), wogonoside (1.91 fold), and wogonin (2.76 fold) were most significantly up-regulated compared with the control. Transcriptome analysis further revealed up-regulation of key enzyme genes (CHS, CHI, FNS, and F6H) involved in flavonoid synthesis after 5 days of EPS treatment. Moreover, the expression of GA2ox and CYP707A—genes involved in gibberellin acid (GA) and abscisic acid biosynthesis (ABA), respectively—were significantly up-regulated. The expression levels of certain transcription factors, including MYB3, MYB8, and MYB13, were also significantly higher than in controls. Our results indicated that EPS was a main active elicitor involved in promoting flavonoid production in S. baicalensis calli. We postulated that EPS might stimulate the expression of MYB3, MYB8, MYB13, GA2ox, and CYP707A, leading to markedly upregulated CHS, CHI, FNS, and F6H expression levels, ultimately promoting flavonoid synthesis. This study provides a novel avenue for large-scale in vitro production of flavonoids in S. baicalensis.

AbstractBackground Decreased dietary protein intake (DPI) may lead to protein-energy malnutrition and may be associated with increased mortality risk. We hypothesized that longitudinal changes in dietary protein intake have independent associations with survival in peritoneal dialysis (PD) patients.Methods 668 stable PD patients were selected in the study from January 2006 to January 2018 and were followed up until December 2019. Their three-day dietary records were collected at the baseline (the sixth month after PD) and thereafter every 3 months for two and a half years. The latent class mixed models (LCMM) were used to identify subgroups of PD patients with similar longitudinal trajectories of DPI. The relation between DPI (baseline and longitudinal data) and survival was examined using Cox model to estimate death hazard ratios. Meanwhile, different formulae were used to assess nitrogen balance.Results The results showed that baseline DPI ≤ 0.60g/kg/day was associated with the worst outcome in PD patients. Patients with DPI 0.80–0.99g/kg/day and DPI ≥ 1.0g/kg/day both presented positive nitrogen balance; patients with DPI 0.61–0.79g/kg/day presented obviously negative nitrogen balance. Longitudinal association between time-dependent DPI and survival was found in PD patients. The consistently low DPI' (0.61–0.79g/kg/d) group was correlated with increased death risk as compared with the 'consistently median DPI' group (0.80–0.99g/kg/d, HR = 1.59, p = 0.008), whereas there was no difference in survival between 'consistently median DPI' group and 'high-level DPI' group (≥1.0 g/kg/d, p > 0.05).Conclusion Our study revealed that DPI ≥ 0.8 g/kg/day was beneficial to the long-term outcome for the PD population.

Abstract Background The objective of this study was to investigate the relationship between P2Y1 and P2Y12 genotypes and the risk of acute myocardial infarction (AMI) in the Quanzhou population and to determine associations between P2Y1 and P2Y12 genotypes and ADP-induced platelet aggregation in this population. Methods All subjects were screened for P2Y1 (c.1622A > G) and P2Y12 (H1/H2, c.34C > T) polymorphisms by direct DNA sequencing. The maximal platelet aggregation rate (MAR) in AMI patients (n = 61) and healthy control subjects (n = 50) was measured by a PL-12 platelet function analyzer, and adenosine diphosphate (ADP) (5 μmol/L) was used as an agonist. Results The haploid H2 allele in the P2Y12 gene was more frequent in patients with AMI than in control subjects (OR 1.887, P = 0.005). The P2Y12 H2 haplotype was significantly associated with AMI in the codominant (P = 0.008), dominant (OR 2.103, P = 0.003), and overdominant models (OR 2.133, P = 0.003). After adjusting for potential confounders, H2 haplotype carriers had a 2.132-fold increased risk for AMI (OR 2.132, P = 0.012) compared with noncarriers. Moreover, we observed that the ADP-induced MAR in the carriers of the H2 haplotype from the control group was somewhat higher than that in noncarriers of this group (P = 0.020). However, we failed to demonstrate that the P2Y1 H1/H2 polymorphism affected ADP-induced MAR in AMI patients. Additionally, P2Y1 c.1622A > and P2Y12 c.34C > T polymorphisms were not associated with the risk of AMI or ADP-induced MAR in either group. Conclusions Therefore, our results suggest that the P2Y12 H2 haplotype was associated with a higher risk of AMI, while its effect on increased ADP-induced platelet aggregation remains to be investigated. Thus, the P2Y12 H2 haplotype may be a potential marker for AMI.

Objective The protein equivalent of total nitrogen appearance (PNA) formula, based on the urea nitrogen appearance (UNA), is popularly used by stable continuous ambulatory peritoneal dialysis (CAPD) patients to estimate dietary daily protein intake (DPI). However, we found that the estimated DPI was higher than that directly evaluated from the dietary records of most of our CAPD patients. Therefore, in the present study, we tried to determine possible bias in PNA estimation by UNA with a nitrogen balance study of our CAPD patients. Methods Thirty-one CAPD patients with stable clinical conditions were included. Their 3-day dietary records were reviewed by a dedicated dietitian to calculate their energy, protein, and nitrogen intake (NI). The nitrogen removal (NR) from urine and dialysate was measured by the Kjeldahl technique. Then, we calculated the proportion of urea nitrogen appearance (UNA) in total nitrogen appearance (TNA) and analyzed the possible factors that could affect this proportion. Results Among these patients, 17 males and 14 females, the mean age was 64.19 ± 12.42, and the dialysate drainage volume was 6700 (2540) ml/day. The percentage of UNA in TNA was 63.22 ± 6.66%. Compared with the other classic nitrogen balance studies in the CAPD population, the protein nitrogen and other nonurea nitrogen losses in this study were all lower. Based on these 31 nitrogen balance studies, we proposed a pair of new equations to estimate PNA by UNA. (1) PNA = 9.3 + 7.73 UNA; (2) PNA = PNPNA + TPL = 6.7 + 7.28 UNA + TPL. Conclusion Our study suggested that the PNA formula generated from previous European studies overestimated DPI in our CAPD patients.

Abstract Chikungunya virus (CHIKV), a highly infectious and rapidly spread viral pathogen, is classified as a pathogenic agent at the biosafety level 3. Operation of live authentic CHIKV needs a specific laboratory with the P3 or above containment, which greatly confines the CHIKV-associated studies. To establish an evaluation system of CHIKV that can be utilized in a BSL2 laboratory, we constructed a pseudovirus (PsV) system of CHIKV containing double reporter genes (ZsGreen1 and luciferase). The fluorescent ZsGreen1 is a convenient and cheap reporter for monitoring the efficiency of transfection and titration of PsV. The enzyme luciferase is a sensitive reporter for the application of PsV to neutralization assay or drug screening. The CHIKV PsV produced in this study, with a titer of up to 3.16 × 106 TU/ml, was confirmed by Western blotting and transmission electronic microscopy (TEM). Finally, we developed a microneutralization assay with the CHIKV PsV produced in this study, which was successfully applied to evaluate neutralizing activities of convalescent sera from CHIKV-infected patients. In summary, we have established a convenient and sensitive double-reporter CHIKV pseudovirus system, which provides a safe and effective platform for screening anti-CHIKV drugs and evaluating vaccines against CHIKV.

Abstract The purpose of this study was to assess the feasibility of machine learning (ML) in predicting the risk of end-stage kidney disease (ESKD) from patients with chronic kidney disease (CKD). Data were obtained from a longitudinal CKD cohort. Predictor variables included patients’ baseline characteristics and routine blood test results. The outcome of interest was the presence or absence of ESKD by the end of 5 years. Missing data were imputed using multiple imputation. Five ML algorithms, including logistic regression, naïve Bayes, random forest, decision tree, and K-nearest neighbors were trained and tested using fivefold cross-validation. The performance of each model was compared to that of the Kidney Failure Risk Equation (KFRE). The dataset contained 748 CKD patients recruited between April 2006 and March 2008, with the follow-up time of 6.3 ± 2.3 years. ESKD was observed in 70 patients (9.4%). Three ML models, including the logistic regression, naïve Bayes and random forest, showed equivalent predictability and greater sensitivity compared to the KFRE. The KFRE had the highest accuracy, specificity, and precision. This study showed the feasibility of ML in evaluating the prognosis of CKD based on easily accessible features. Three ML models with adequate performance and sensitivity scores suggest a potential use for patient screenings. Future studies include external validation and improving the models with additional predictor variables.

Friedreich's ataxia is a rare disorder resulting from deficiency of frataxin, a mitochondrial protein implicated in the synthesis of iron-sulfur clusters. Preclinical studies in mice have shown that gene therapy is a promising approach to treat individuals with Friedreich's ataxia. However, a recent report provided evidence that AAVrh10-mediated overexpression of frataxin could lead to cardiotoxicity associated with mitochondrial dysfunction. While evaluating an AAV9-based frataxin gene therapy using a chicken β-actin promoter, we showed that toxic overexpression of frataxin could be reached in mouse liver and heart with doses between 1 × 1013 and 1 × 1014 vg/kg. In a mouse model of cardiac disease, these doses only corrected cardiac dysfunction partially and transiently and led to adverse findings associated with iron-sulfur cluster deficiency in liver. We demonstrated that toxicity required frataxin's primary function by using a frataxin construct bearing the N146K mutation, which impairs binding to the iron-sulfur cluster core complex. At the lowest tested dose, we observed moderate liver toxicity that was accompanied by progressive loss of transgene expression and liver regeneration. Together, our data provide insights into the toxicity of frataxin overexpression that should be considered in the development of a gene therapy approach for Friedreich's ataxia.

Abstract Trimethylamine-N-oxide (TMAO), a gut-microbiota-dependent metabolite generated from its dietary precursors such as choline, has been identified as an independent risk factor for atherosclerosis. Metformin is the most widely used drug for the treatment of type 2 diabetes (T2D), which has therapeutic effects on hyperglycemia accelerated atherosclerosis. A growing body of evidence suggest that metformin plays a therapeutic role by regulating the structure and metabolic function of gut microbiota. However, whether metformin has an impact on gut-microbiota-mediated TMAO production from choline remains obscure. In this study, the oral administration of metformin significantly reduced choline diet-increased serum TMAO in choline diet-fed C57BL/6J mice. The diversity analysis based on 16S rRNA gene sequencing of C57BL/6J mice fecal samples indicated that metformin markedly changed the gut-microbiota composition. Metformin was positively correlated with the enrichment of different intestinal bacteria such as Bifidobacterium and Akkermansia and a lower cutC (a choline utilization gene) abundance. Furthermore, the ex vivo and in vitro inhibitory effects of metformin on choline metabolism of TMA-producing bacteria were confirmed under anaerobic condition. The results suggested that metformin suppresses serum TMAO level by remodeling gut microbiota involved in TMA generation from choline.

Abstract Trimethylamine-N-oxide (TMAO), a derivative from the gut microbiota metabolite trimethylamine (TMA), has been identified to be an independent risk factor for promoting atherosclerosis. Evidences suggest that berberine (BBR) could be used to treat obesity, diabetes and atherosclerosis, however, its mechanism is not clear mainly because of its poor oral bioavailability. Here, we show that BBR attenuated TMA/TMAO production in the C57BL/6J and ApoE KO mice fed with choline-supplemented chow diet, and mitigated atherosclerotic lesion areas in ApoE KO mice. Inhibition of TMA/TMAO production by BBR-modulated gut microbiota was proved by a single-dose administration of d9-choline in vivo. Metagenomic analysis of cecal contents demonstrated that BBR altered gut microbiota composition, microbiome functionality, and cutC/cntA gene abundance. Furthermore, BBR was shown to inhibit choline-to-TMA conversion in TMA-producing bacteria in vitro and in gut microbial consortium from fecal samples of choline-fed mice and human volunteers, and the result was confirmed by transplantation of TMA-producing bacteria in mice. These results offer new insights into the mechanisms responsible for the anti-atherosclerosis effects of BBR, which inhibits commensal microbial TMA production via gut microbiota remodeling.

Co-infection of chikungunya virus (CHIKV) has been recently reported during dengue fever epidemics. However, the infection of CHIKV is often neglected due to its misdiagnosis as dengue virus (DENV) infection. In the summer of 2019 when dengue fever was epidemic, we collected 697 serum samples from febrile dengue fever–like patients in Xishuangbanna, southwestern part of China. DENV RNA was detectable in 99.42% of these patients. Notably, 88 patients (12.62%) showed the presence of CHIKV RNA, among which 86 patients were co-infected with DENV and CHIKV. We sequenced and analyzed the full genome of CHIKV virus in four out of 88 samples (two CHIKV infected and two co-infected). The results suggested that the four strains were all Asian genotype and had the highest homology (99.4%) with the SZ1239 strain (accession number MG664851) isolated in 2012 and possibly introduced from Indonesia. Further comparison with the conserved sequences in the whole genome of 47 strains of CHIKV showed that there were 13 and 15 amino acid mutants in structural proteins and non-structural proteins, respectively. The previously reported adaptive mutations of E2-W64R, E2-I211T, E2-K233E, E1-A98T, and E1-K211E occurred in the four strains of this study. In conclusion, this study reports a co-infection of CHIKV during the DENV epidemic in the city Xishuangbanna, 2019. Molecular epidemiology revealed that CHIKV identified in this study was indigenous and belongs to Asian lineage with lineage-specific mutations and some reported adaptive mutations, which is distinct from the recently reported CHIKV (East/Central/South African) in Ruili, the city next to Xishuangbanna.

To analyze pesticide residues, GC coupled with quadrupole-Orbitrap MS (GC-Orbitrap-MS) has become a powerful tool because of its unique characteristics of accurate mass full-spectrum acquisition, high resolution, fast acquisition rates, and overcoming matrix interference. This paper presents an efficiency evaluation of GC-Orbitrap-MS for identification and quantitation in the 352 pesticide residues analysis of chrysanthemum flowers in full-scan mode. A streamlined pretreatment approach using one-step extraction and dilution was used, which provided high-throughput processing and excellent recovery. The samples were extracted using acetonitrile. The extracted solution was purified by a Sin-QuEChERS Nano column to suppress the matrix in chrysanthemum flowers and determined by GC-Orbitrap-MS. The calibration curves for the 352 pesticides obtained by GC-Orbitrap-MS were linear in the range of 0.5–200 μg·kg−1, with the correlation coefficients higher than 0.99. The limits of detection (LODs) and the limits of quantification (LOQs) for the 352 pesticide residues were 0.3–3.0 μg·kg−1 and 1.0–10.0 μg·kg−1, respectively. The average recoveries in chrysanthemum flower at three levels were 95.2%, 88.6%, and 95.7%, respectively, with relative standard deviations (RSDs) of 7.1%, 7.5%, and 7.2%, respectively. Lastly, the validated method and retrospective analysis was applied to a total of 200 chrysanthemum flower samples bought in local pharmacies. The proposed method can simultaneously detect multipesticide residues with a good performance in qualitative and quantitative detection.

Background: Though many literatures documented burnout and occupational hazard among healthcare workers and frontliners during pandemic, not many adopted a systemic approach to look at the resilience among this population. Another under-studied population was the large numbers of global healthcare workers who have been deployed to tackle the crisis of COVID-19 pandemic in the less resourceful regions. We investigated both the mental wellbeing risk and protective factors of a deployed healthcare workers (DHWs) team in Wuhan, the epicenter of the virus outbreak during 2020.Method: A consensual qualitative research approach was adopted with 25 DHWs from H province through semi-structured interviews after 3 months of deployment period.Results: Inductive-Deductive thematic coding with self-reflexivity revealed multi-layered risk and protective factors for DHWs at the COVID-19 frontline. Intensive working schedule and high-risk environment, compounded by unfamiliar work setting and colleagues; local culture adaptation; isolation from usual social circle, strained the DHWs. Meanwhile, reciprocal relationships and “familial relatedness” with patients and colleagues; organizational support to the DHWs and their immediate families back home, formed crucial wellbeing resources in sustaining the DHWs. The dynamic and dialectical relationships between risk and protective factors embedded in multiple layers of relational contexts could be mapped into a socio-ecological framework.Conclusion: Our multidisciplinary study highlights the unique social connectedness between patient-DHWs; within DHWs team; between deploying hospital and DHWs; and between DHWs and the local partners. We recommend five organizational strategies as mental health promotion and capacity building for DHWs to build a resilient network and prevent burnout at the disaster frontline.

Objective To explore the roles of human mesenchymal stem cell (hMSC) death-associated protein kinase 1 (DAPK1) in modulating CD4+ T lymphocyte proliferation. Methods Human MSCs and peripheral blood mononuclear cells were isolated and cocultured in vitro for 3 days. Lentiviral-mediated RNA interference (LV-sh-DAPK1) was used to silence DAPK1 expression in hMSCs. Expression of DAPK1 was assessed by western blotting. Transcriptional levels of DAPK1, transforming growth factor-β1, indoleamine 2,3-dioxygenase, inducible nitric oxide synthase, interleukin (IL)-6, suppressor of cytokine signaling 1, IL-10 and cyclooxygenase-2 were investigated by quantitative PCR. Levels of IL-10 were assessed by ELISA. Proliferation of CD4+ T cells was assessed by flow cytometry. Results DAPK1 was abundantly expressed in ex vivo -expanded hMSCs and expression was positively correlated with hMSC suppression of CD4+ T cell proliferation. Silencing of DAPK1 in hMSCs reduced the ability of these cells to inhibit CD4+ T cell proliferation and resulted in decreased IL-10 levels compared with untreated controls. Exogenous supplementation with recombinant human IL-10 in DAPK1-silenced hMSCs restored immunosuppression of CD4+ T cells. Conclusions The DAPK1-IL-10 axis mediates a novel immunoregulatory function of hMSCs toward CD4+ T cells.

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that down-regulates hepatic low-density lipoprotein receptor (LDLR) by binding and shuttling LDLR to lysosomes for degradation. The development of therapy that inhibits PCSK9 has attracted considerable attention for the management of cardiovascular disease risk. However, only monoclonal antibodies of PCSK9 have reached the clinic use. Oral administration of small-molecule transcriptional inhibitors has the potential to become a therapeutic option. Methods: Here, we developed a cell-based small molecule screening platform to identify transcriptional inhibitors of PCSK9. Through high-throughput screening and a series of evaluation, we found several active compounds. After detailed investigation on the pharmacological effect and molecular mechanistic characterization, 7030B-C5 was identified as a potential small-molecule PCSK9 inhibitor. Findings: Our data showed that 7030B-C5 down-regulated PCSK9 expression and increased the total cellular LDLR protein and its mediated LDL-C uptake by HepG2 cells. In both C57BL/6 J and ApoE KO mice, oral administration of 7030B-C5 reduced hepatic and plasma PCSK9 level and increased hepatic LDLR expression. Most importantly, 7030B-C5 inhibited lesions in en face aortas and aortic root in ApoE KO mice with a slight amelioration of lipid profiles. We further provide evidences suggesting that transcriptional regulation of PCSK9 by 7030B-C5 mostly depend on the transcriptional factor HNF1α and FoxO3. Furthermore, FoxO1 was found to play an important role in 7030B-C5 mediated integration of hepatic glucose and lipid metabolism. Interpretation: 7030B-C5 with potential suppressive effect of PCSK9 expression may serve as a promising lead compound for drug development of cholesterol/glucose homeostasis and cardiovascular disease therapy. Fund: This work was supported by grants from the National Natural Science Foundation of China (81473214, 81402929, and 81621064), the Drug Innovation Major Project of China (2018ZX09711001-003-006, 2018ZX09711001-007 and 2018ZX09735001-002), CAMS Innovation Fund for Medical Sciences (2016-I2M-2-002, 2016-I2M-1-011 and 2017-I2M-1-008), Beijing Natural Science Foundation (7162129). Keywords: PCSK9, Small-molecule inhibitor, FoxO1/3, HNF1α, Lipid and glucose metabolism, Atherosclerosis

Myeloperoxidase (MPO) is a highly abundant protein within the neutrophil that is associated with lipoprotein oxidation, and increased plasma MPO levels are correlated with poor prognosis after myocardial infarct. Thus, MPO inhibitors have been developed for the treatment of heart failure and acute coronary syndrome in humans. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide PF-06282999 is a recently described selective small molecule mechanism-based inactivator of MPO. Here, utilizing PF-06282999, we investigated the role of MPO to regulate atherosclerotic lesion formation and composition in the Ldlr-/- mouse model of atherosclerosis. Though MPO inhibition did not affect lesion area in Ldlr-/- mice fed a Western diet, reduced necrotic core area was observed in aortic root sections after MPO inhibitor treatment. MPO inhibition did not alter macrophage content in and leukocyte homing to atherosclerotic plaques. To assess non-invasive monitoring of plaque inflammation, [18F]-Fluoro-deoxy-glucose (FDG) was administered to Ldlr-/- mice with established atherosclerosis that had been treated with clinically relevant doses of PF-06282999, and reduced FDG signal was observed in animals treated with a dose of PF-06282999 that corresponded with reduced necrotic core area. These data suggest that MPO inhibition does not alter atherosclerotic plaque area or leukocyte homing, but rather alters the inflammatory tone of atherosclerotic lesions; thus, MPO inhibition could have utility to promote atherosclerotic lesion stabilization and prevent atherosclerotic plaque rupture.

BackgroundPeritoneal dialysis (PD) is increasingly used for long-term management of Cardiorenal Syndrome (CRS). We compared outcomes in incident PD patients according to their baseline heart failure status.MethodsThis retrospective cohort study evaluated all-cause and cardiovascular mortality in incident PD patients with different heart failure status (non-CRS, acute heart failure [AHF], type II CRS, type IV CRS) who started PD between 2006 and 2016 in the Peking University Third Hospital.ResultsOf 748 patients included in the study, there were 466 (62.3%), 214 (28.6%), 27 (3.6%), and 41 (5.5%) patients in the non-CRS, AHF, type II CRS and type IV CRS groups, respectively. Patients with CRS were older (pConclusionIncident PD patients with different types of CRS had higher rates of both all-cause and cardiovascular mortality compared with patients without CRS. However, these observed adverse outcomes may be related to associated older age and higher prevalence of comorbidities, rather than CRS per se, except for type IV CRS, treatment strategies to reduce high cardiovascular CVD mortality may needed.

Extracellular vesicles (Evs) contain diverse functional proteins, mRNAs, miRNAs, and DNA fragments, are secreted by various types of cells, and play important roles in cellular communication. Here, we show for the first time that plasma Evs inhibited the osteogenic differentiation of mesenchymal stromal cells (MSCs) in vitro and the level of inhibition was positively correlated with the plasma Evs concentration. Plasma Evs downregulated the expression of markers such as osteocalcin (OCN), Runt-related transcription factor 2 (Runx2), and Osterix at mRNA levels required for osteogenic differentiation and reduced pSmad1/5/8 levels in MSCs. Furthermore, pSmad1/5/8 levels increased and MSCs underwent normal osteogenic differentiation after Evs-derived α2-HS glycoprotein (AHSG) function was inhibited with an anti-AHSG neutralizing antibody. However, the levels of pERK1/2, active β-catenin, and HES1 were not significantly altered. Therefore, we propose that as essential components of the extracellular microenvironment of MSCs, plasma Evs are taken up by MSCs and subsequently repress osteogenic differentiation through an AHSG-mediated decrease in pSmad1/5/8 levels. Our work identifies plasma Evs as novel regulators of MSC osteogenic differentiation.

In this work, magnetic In _2 S _3 /ZnFe _2 O _4 nanocomposites were fabricated via a two-step solvothermal process, which In _2 S _3 loading amount on ZnFe _2 O _4 support medium could be controlled by changing reaction mass. Investigation revealed that the photocatalytic activity of In _2 S _3 /ZnFe _2 O _4 nanocomposites was uperior to pure In _2 S _3 and ZnFe _2 O _4 for the degradation of MB driven by visible light. The improved photocatalytic activity may be stemming from the synergy effect of In _2 S _3 and ZnFe _2 O _4 , resulting in the enhanced visible light absorbance and higher separation efficiency of the photo-generated charge carriers. Significantly, this sort of nanocomposites could rapidly be separated through an external magnetic field, and five successive cycle experiments have proved that it was stable and recyclable. Finally, a possible mechanism related to the separation of charge and photocatalytic decomposition of MB was also provided.

AbstractBackground Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.Methods The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software.Results Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81–2.66, p

Abstract Hematological malignancies (HMs) encompass a diverse group of blood neoplasms with significant morbidity and mortality. Immunotherapy has emerged as a validated and crucial treatment modality for patients with HMs. Despite notable advancements having been made in understanding and implementing immunotherapy for HMs over the past decade, several challenges persist. These challenges include immune-related adverse effects, the precise biodistribution and elimination of therapeutic antigens in vivo, immune tolerance of tumors, and immune evasion by tumor cells within the tumor microenvironment (TME). Nanotechnology, with its capacity to manipulate material properties at the nanometer scale, has the potential to tackle these obstacles and revolutionize treatment outcomes by improving various aspects such as drug targeting and stability. The convergence of nanotechnology and immunotherapy has given rise to nano-immunotherapy, a specialized branch of anti-tumor therapy. Nanotechnology has found applications in chimeric antigen receptor T cell (CAR-T) therapy, cancer vaccines, immune checkpoint inhibitors, and other immunotherapeutic strategies for HMs. In this review, we delineate recent developments and discuss current challenges in the field of nano-immunotherapy for HMs, offering novel insights into the potential of nanotechnology-based therapeutic approaches for these diseases.

[Objectives] To optimize the water extraction process of Bawei Shangke Huoxue tablets and determine the best drying method of the extract. [Methods] The orthogonal test method was used to select the optimal water extraction process, with the content of total flavonoids and the yield of dry extract as the test indicators, and the soaking time, the amount of water added, the extraction time and the extraction times as the main test factors. The water content of spray powder was taken as the evaluation indicator, the inlet air temperature, the density of liquid phase and the outlet air temperature were selected as the factors, and the spray drying process of water-extracted concentrated liquid was optimized by orthogonal test. [Results] The optimal water extraction process was no immersion, water decoction and extraction twice, adding 10 times of water each time, extraction for lh, in which the amount of water added was the main factor. The liquid density of spray dried extract powder is 1.05 -1.08 (60 °C), the inlet air temperature is 180°C, the outlet air temperature is 80 °C is the most suitable, and the liquid density is the main factor. [Conclusions] The extraction and drying technology of Bawei Huangke Huoxue tablet is feasible, scientific and reasonable, and can be used for industrial production. [ABSTRACT FROM AUTHOR]