Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Genetically determined type 1 diabetes mellitus and risk of osteoporosis.

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.

Optimization of Ti-PA efficiently catalytic the alcoholysis of waste PET using response surface methodology.

A new type of titanium phthalate (Ti-PA) catalyst was prepared by exchange method of phthalic acid and isopropyl titanate, which is never been reported before. The Ti-PA catalyst was characterized by FT-IR, TG, Uv-vis, BET, SEM, and EDS. The Ti-PA catalyst shows good catalytic activity in the alcoholysis reaction of polyethylene terephthalate (PET) and optimal experimental conditions for the alcoholysis process were optimized by response surface methodology; the Ti-PA catalyst provided a BHET yield of 81.98% for reaction lasting 3.98 h at 191 °C of 0.86% catalyst and 13.7 ml ethylene glycol; the model has good reliability. The kinetics and reaction mechanism of the process were explored and apparent activation energy is 75.52 kJ/mol. Finally, the good catalytic activity of Ti-PA was illustrated by comparing it with currently reported catalysts.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

Integrated analysis of diverse cancer types reveals a breast cancer-specific serum miRNA biomarker through relative expression orderings analysis.

PURPOSE: Serum microRNA (miRNA) holds great potential as a non-invasive biomarker for diagnosing breast cancer (BrC). However, most diagnostic models rely on the absolute expression levels of miRNAs, which are susceptible to batch effects and challenging for clinical transformation. Furthermore, current studies on liquid biopsy diagnostic biomarkers for BrC mainly focus on distinguishing BrC patients from healthy controls, needing more specificity assessment. METHODS: We collected a large number of miRNA expression data involving 8465 samples from GEO, including 13 different cancer types and non-cancer controls. Based on the relative expression orderings (REOs) of miRNAs within each sample, we applied the greedy, LASSO multiple linear regression, and random forest algorithms to identify a qualitative biomarker specific to BrC by comparing BrC samples to samples of other cancers as controls. RESULTS: We developed a BrC-specific biomarker called 7-miRPairs, consisting of seven miRNA pairs. It demonstrated comparable classification performance in our analyzed machine learning algorithms while requiring fewer miRNA pairs, accurately distinguishing BrC from 12 other cancer types. The diagnostic performance of 7-miRPairs was favorable in the training set (accuracy = 98.47%, specificity = 98.14%, sensitivity = 99.25%), and similar results were obtained in the test set (accuracy = 97.22%, specificity = 96.87%, sensitivity = 98.02%). KEGG pathway enrichment analysis of the 11 miRNAs within the 7-miRPairs revealed significant enrichment of target mRNAs in pathways associated with BrC. CONCLUSION: Our study provides evidence that utilizing serum miRNA pairs can offer significant advantages for BrC-specific diagnosis in clinical practice by directly comparing serum samples with BrC to other cancer types.

REDH: A database of RNA editome in hematopoietic differentiation and malignancy.

BACKGROUND: The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. METHODS: We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. RESULTS: We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. CONCLUSIONS: REDH is accessible at http://www.redhdatabase.com/ . This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.

Risk-based detection as a cost-effective strategy to reduce foodborne illness due to salmonella.

Background: Salmonella, a widespread pathogen, poses a significant threat to global food safety, leading to foodborne diseases and substantial economic losses. The timely and accurate detection of foodborne pathogens is pivotal for averting food contamination and outbreaks across the food production chain. This study assesses the cost-effectiveness of traditional culture-based methods versus risk-based approaches, incorporating polymerase chain reaction (PCR) for Salmonella detection. Methods: We employed a stochastic scenario tree model to simulate scenarios based on the sampling inspection plan for raw aquatic products conducted by the Guangzhou Center for Disease Control and Prevention from 2018 to 2020. Various detection methods (culture or PCR) were applied to these aquatic products based on their categorized risk level. Sensitivity values were derived from published data, and incremental cost-effectiveness ratios were used to compare the different scenarios against the traditional culture method. Results: A total of 360 samples were collected for analysis. The cost of culture-based detection alone amounted to 125,423.20 Chinese Yuan (CNY) and yielded nine instances of positive Salmonella detections. The risk-based detection strategy, which combined the more sensitive PCR method with high-risk sample characteristics, while employing the culture method for the remaining combinations, imposed a total cost of 128,775.83 CNY and yielded ten positive detections. This approach cost approximately 3391.74 CNY per additional positive sample detected compared to the culture method alone. Meanwhile, PCR-only detection imposed a total cost of 62,960.03 CNY. Conclusions: In comparison to traditional culture-based methods, both the risk-based detection strategy and the PCR-only approach demonstrated superior capabilities with respect to detecting contaminated aquatic products. Implementing risk-based detection strategies can enhance cost-effectiveness, not only ensuring food safety but also reducing the incidence and economic burden of foodborne diseases.

Ti-Si composite glycol salts: depolymerization and repolymerization studies of PET.

In this study, a Ti-Si-ethylene glycol salt (Ti/Si-EG) was synthesized and used as a catalyst for the depolymerization of PET-ethylene glycol to produce bis(hydroxyethyl)terephthalate (BHET), and the optimum conditions for the depolymerization were determined by response surface analysis: w(EG) : w(PET) was 4 : 1, the catalyst mass dosage was 0.56% (in terms of the mass of PET), the depolymerization temperature was 203 °C, the depolymerization time was 3.8 h, and the highest yield of the product (BHET) was 90.10%. Furthermore, the depolymerization product BHET was used as the raw material and Ti/Si-EG was used as the catalyst for the polycondensation reaction to synthesize PET, and the amount of the catalyst added was 0.015% by mass (in terms of BHET). The performance of the synthesized PET was tested to be the same as that of PET synthesized by the PTA method under the same conditions, thus achieving the resourceful treatment and high-value recycling of waste PET. The introduction of Si in the catalyst reduced the catalytic activity of Ti and avoided the problem of yellowing of polyester products, and the use of the glycol salt as a catalyst in the depolymerization and polycondensation reaction process did not introduce impurity groups.

Order transfer in a hybrid Raman-laser-optomechanical resonator.

Order is one of the most important concepts to interpret various phenomena such as the emergence of turbulence and the life-evolution process. The generation of laser can also be treated as an ordering process in which the interaction between the laser beam and the gain medium leads to the correlation between photons in the output optical field. Here, we demonstrate experimentally in a hybrid Raman-laser-optomechanical system that an ordered Raman laser can be generated from an entropy-absorption process by a chaotic optomechanical resonator. When the optomechanical resonator is chaotic or disordered enough, the Raman-laser field is in an ordered lasing mode. This can be interpreted by the entropy transfer from the Raman-laser mode to the chaotic motion mediated by optomechanics. Different order parameters, such as the box-counting dimension, the maximal Lyapunov exponent, and the Kolmogorov entropy, are introduced to quantitatively analyze this entropy transfer process, by which we can observe the order transfer between the Raman-laser mode and the optomechanical resonator. Our study presents a new mechanism of laser generation and opens up new dimensions of research such as the modulation of laser by optomechanics.

Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389-2.681, p = 1.30 × 10-7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

Deciphering the Functional Long Non-Coding RNAs Derived from MicroRNA Loci.

Albeit the majority of eukaryotic genomes can be pervasively transcribed to a diverse population of lncRNAs and various subtypes of lncRNA are discovered. However, the genome-wide study of miRNA-derived lncRNAs is still lacking. Here, it is reported that over 800 miRNA gene-originated lncRNAs (molncRNAs) are generated from miRNA loci. One of them, molnc-301b from miR-301b and miR-130b, functions as an "RNA decoy" to facilitate dissociation of the chromatin remodeling protein SMARCA5 from chromatin and thereby sequester transcription and mRNA translation. Specifically, molnc-301b attenuates erythropoiesis by mitigating the transcription of erythropoietic and translation-associated genes, such as GATA1 and FOS. In addition, a useful and powerful CRISPR screen platform to characterize the biological functions of molncRNAs at large-scale and single-cell levels is established and 29 functional molncRNAs in hematopoietic cells are identified. Collectively, the focus is on miRNA-derived lncRNAs, deciphering their landscape during normal hematopoiesis, and comprehensively evaluating their potential roles.

Optimization of Ti-BA efficiently for the catalytic alcoholysis of waste PET using response surface methodology.

A titanium benzoate (Ti-BA) catalyst was prepared by hydrothermal method, which has an ordered eight-face structure, and was used for polyethylene terephthalate (PET) depolymerization. With bis(2-hydroxyethyl)terephthalate (BHET) as the target molecule and ethylene glycol (EG) as the solvent, the best reaction conditions for catalytic alcoholysis via a PET alcoholic solution were investigated via response surface experiments and found to be a EG/PET mass ratio of 3.59, temperature of 217 °C and reaction time of 3.3 h. Under these conditions, the amount of the catalyst required was only 2% of the mass of the PET, and the yield of BHET reached 90.01% and under the same conditions, the yield of BHET could still reach 80.1%. Based on the experimental results, the mechanism of alcoholysis, Ti-BA catalyst activated ethylene glycol deprotonation to achieve the progressive degradation of polymers. This experiment provides a reference for the degradation of polymer waste and other transesterification reactions.

The SWGEDWGEIW from Soybean Peptides Reduces Insulin Resistance in 3T3-L1 Adipocytes by Activating p-Akt/GLUT4 Signaling Pathway.

Diabetes mellitus, a group of metabolic disorders characterized by persistent hyperglycemia, affects millions of people worldwide and is on the rise. Dietary proteins, from a wide range of food sources, are rich in bioactive peptides with anti-diabetic properties. Notably, the protective mechanism of the single peptide SWGEDWGEIW (TSP) from soybean peptides (SBPs) on insulin resistance of adipocytes in an inflammatory state was investigated by detecting the lipolysis and glucose absorption and utilization of adipocytes. The results showed that different concentrations of TSP (5, 10, 20 µg/mL) intervention can reduce 3T3-L1 adipocytes' insulin resistance induced by inflammatory factors in a dose-dependent manner and increase glucose utilization by 34.2 ± 4.6%, 74.5 ± 5.2%, and 86.7 ± 6.1%, respectively. Thus, TSP can significantly alleviate the lipolysis of adipocytes caused by inflammatory factors. Further mechanism analysis found that inflammatory factors significantly reduced the phosphorylation (p-Akt) of Akt, two critical proteins of glucose metabolism in adipocytes, and the expression of GLUT4 protein downstream, resulting in impaired glucose utilization, while TSP intervention significantly increased the expression of these two proteins. After pretreatment of adipocytes with PI3K inhibitor (LY294002), TSP failed to reduce the inhibition of p-Akt and GLUT4 expression in adipocytes. Meanwhile, the corresponding significant decrease in glucose absorption and the increase in the fat decomposition of adipocytes indicated that TSP reduced 3T3-L1 adipocytes' insulin resistance by specifically activating the p-Akt/GLUT4 signal pathway. Therefore, TSP has the potential to prevent obesity-induced adipose inflammation and insulin resistance.

m6 A Reader YTHDF1-Targeting Engineered Small Extracellular Vesicles for Gastric Cancer Therapy via Epigenetic and Immune Regulation.

N6 -methyladenosine (m6 A) modulators decide the fate of m6 A-modified transcripts and drive cancer development. RNA interference targeting m6 A modulators promise to be an emerging cancer therapy but is challenging due to its poor tumor targeting and high systematic toxicity. Here engineered small extracellular vesicles (sEVs) with high CD47 expression and cyclic arginine-glycine-aspartic (c(RGDyC)) modification are developed for effective delivery of short interfering RNA against m6 A reader YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) to treat gastric cancer via epigenetic and immune regulation. This nanosystem efficiently depletes YTHDF1 expression and suppresses gastric cancer progression and metastasis through hampering frizzled7 translation and inactivating Wnt/ß-catenin pathway in an m6 A dependent manner. Loss of YTHDF1 mediates overexpression of interferon (IFN)-γ receptor 1 and enhances IFN-γ response, promoting expression of major histocompatibility complex class I on tumor cells to achieve self-presentation of the immunogenic tumor cells to stimulate strong cytotoxic T lymphocytes responses. CD47 expression on the engineered sEVs can competitively bind with signal regulatory protein α to enhance phagocytosis of the tumor cells by tumor-associated macrophages. This versatile nanoplatform provides an efficient and low toxic strategy to inhibit epigenetic regulators and holds great potential in promoting immunotherapy.

KHSRP combines transcriptional and posttranscriptional mechanisms to regulate monocytic differentiation.

RNA-binding proteins (RBPs) are widely involved in the transcriptional and posttranscriptional regulation of multiple biological processes. The transcriptional regulatory ability of RBPs was indicated by the identification of chromatin-enriched RBPs (Che-RBPs). One of these proteins, KH-type splicing regulatory protein (KHSRP), is a multifunctional RBP that has been implicated in mRNA decay, alternative splicing, and miRNA biogenesis and plays an essential role in myeloid differentiation by facilitating the maturation of miR-129. In this study, we revealed that KHSRP regulates monocytic differentiation by regulating gene transcription and RNA splicing. KHSRP-occupied specific genomic sites in promoter and enhancer regions to regulate the expression of several hematopoietic genes through transcriptional activation and bound to pre-mRNA intronic regions to modulate alternative splicing during monocytic differentiation. Of note, KHSRP had co-regulatory effects at both the transcriptional and posttranscriptional levels on MOGOH and ADARB1. Taken together, our analyses revealed the dual DNA- and RNA-binding activities of KHSRP and have provided a paradigm to guide the analysis of other functional Che-RBPs in different biological systems.

METTL3 preferentially enhances non-m6A translation of epigenetic factors and promotes tumourigenesis.

METTL3 encodes the predominant catalytic enzyme to promote m6A methylation in nucleus. Recently, accumulating evidence has shown the expression of METTL3 in cytoplasm, but its function is not fully understood. Here we demonstrated an m6A-independent mechanism for METTL3 to promote tumour progression. In gastric cancer, METTL3 could not only facilitate cancer progression via m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3. Mechanistically, cytoplasm-anchored METTL3 interacted with PABPC1 to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded to prostate cancer. Therefore, the cytoplasmic METTL3 enhances the translation of epigenetic mRNAs, thus serving as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnosis and predict prognosis for patients with cancer.

On Imported and Domestic Human Papillomavirus Vaccines: Cognition, Attitude, and Willingness to Pay in Chinese Medical Students.

This study aimed to analyze the cognition, attitude, and willingness to pay (WTP) for imported and domestic human papillomavirus (HPV) vaccines in Chinese medical students. Methods: Medical students in Eastern, Central and Western China were investigated. We used the HPV cognitive list to measure the cognition of participants and implemented contingent valuation method (CVM) to value WTP. Tobit model was used to analyze the factors associated with WTP. Results: The participants' average score for the 21 cognitive questions was 13.05 (±5.09). Among the participants, 60.82 and 88.01% reported that they would wish to be vaccinated and support the partners to be vaccinated. In addition, 92.54% (670) of the participants were willing to pay for HPV vaccines, at mean values (in RMB) of 1,689.80 (±926.13), 2,216.61 (±1190.62), and 3,252.43 (±2064.71) for imported bivalent, quadrivalent, and 9-valent vaccines, respectively, and at 910.63 (±647.03), 1,861.69 (±1147.80), and 2,866.96 (±1784.41) for their domestic counterparts, respectively. The increase in cognitive score has a positive effect on the WTP for imported vaccines (P < 0.05). Conclusions: Most of the participants were likewise willing to receive the HPV vaccines. Their perceptions of the HPV vaccines valent and origin may affect their willingness to be vaccinated and pay for the vaccines. Increasing awareness of the HPV vaccines and the inclusion of the HPV vaccines in a Medicare reimbursement policy or immunization program could increase the coverage of the HPV vaccine.

Economic Burden and Influencing Factors of Acute Gastroenteritis in China: A Population-Based Face to Face Survey in 2018.

Background: Acute gastroenteritis is an important and highly prevalent public health problem worldwide. The purpose of this study was to assess the economic burden of disease and its influencing factors in patients with acute gastroenteritis in Heilongjiang Province, China. Methods: A multi-stage stratified random sampling method was used in a face-to-face household survey in 2018. Demographic and socioeconomic characteristics, clinical symptoms, suspicious dietary history, and disease treatment information were collected from 19,647 respondents. One-way analysis of variance and multiple stepwise regression analysis were used to investigate the factors associated with the economic burden of acute gastroenteritis. Quantitative risk analysis and sensitivity analysis were performed to estimate the uncertainty and risk factors of the economic burden of acute gastroenteritis. Results: The total economic burden of patients with acute gastroenteritis was 63,969.22 CNY (Chinese Yuan), of which the direct economic burden accounted for 63.82%; the per capita economic burden was 131.35 CNY per month. Age, region, disease duration, and disease treatment were the main factors significantly associated with the economic burden of acute gastroenteritis (P < 0.05). The average economic burden of patients with acute gastroenteritis was approximately 571.84 CNY/person (95% CI: 227-1,459). Sensitivity analysis showed that the greatest impact was from the indirect economic burden. Conclusions: Acute gastroenteritis brings a substantial health burden to patients due to its high incidence. The economic burden of self-purchased drugs and the indirect economic burden of patients cannot be ignored. To better estimate the economic burden of acute gastroenteritis in China, further studies on the pathogen-specific economic burden of acute gastroenteritis are required.

Single-cell architecture and functional requirement of alternative splicing during hematopoietic stem cell formation.

Single-cell transcriptional profiling has rapidly advanced our understanding of the embryonic hematopoiesis; however, whether and what role RNA alternative splicing (AS) plays remains an enigma. This is important for understanding the mechanisms underlying splicing-associated hematopoietic diseases and for the derivation of therapeutic stem cells. Here, we used single-cell full-length transcriptome data to construct an isoform-based transcriptional atlas of the murine endothelial-to-hematopoietic stem cell (HSC) transition, which enables the identification of hemogenic signature isoforms and stage-specific AS events. We showed that the inclusion of these hemogenic-specific AS events was essential for hemogenic function in vitro. Expression data and knockout mouse studies highlighted the critical role of Srsf2: Early Srsf2 deficiency from endothelial cells affected the splicing pattern of several master hematopoietic regulators and significantly impaired HSC generation. These results redefine our understanding of the dynamic HSC developmental transcriptome and demonstrate that elaborately controlled RNA splicing governs cell fate in HSC formation.

Whitening and inhibiting NF-κB-mediated inflammation properties of the biotransformed green ginseng berry of new cultivar K1, ginsenoside Rg2 enriched, on B16 and LPS-stimulated RAW 264.7 cells.

BACKGROUND: Main bioactive constituents and pharmacological functions of ripened red ginseng berry (Panax ginseng Meyer) have been frequently reported. Yet, the research gap targeting the beneficial activities of transformed green ginseng berries has not reported elsewhere. METHODS: Ginsenosides of new green berry cultivar K-1 (GK-1) were identified by HPLC-QTOF/MS. Ginsenosides bioconversion in GK-1 by bgp1 enzyme was confirmed with HPLC and TLC. Then, mechanisms of GK-1 and ß-glucosidase (bgp1) biotransformed GK-1 (BGK-1) were determined by Quantitative Reverse Transcription-Polymerase Chain Reaction and Western blot. RESULTS: GK-1 possesses highest ginsenosides especially ginsenoside-Re amongst seven ginseng cultivars including (Chunpoong, Huangsuk, Kumpoong, K-1, Honkaejong, Gopoong, and Yunpoong). Ginseng root's biomass is not affected with the harvest of GK-1 at 3 weeks after flowering period. Then, Re is bio-converted into a promising pharmaceutical effect of Rg2 via bgp1. According to the results of cell assays, BGK-1 shows decrease of tyrosinase and melanin content in α-melanocyte-stimulating hormone challenged-murine melanoma B16 cells. BGK-1 which is comparatively more effective than GK-1 extract shows significant suppression of the nuclear factor (NF)-κB activation and inflammatory target genes, in LPS-stimulated RAW 264.7 cells. CONCLUSION: These results reported effective whitening and anti-inflammatory of BGK-1 as compared to GK-1.