Influence of storage solution, temperature, assay time and concentration on RT-qPCR nucleic acid detection for SARS-CoV-2 detection of SARS-CoV-2 by the RT-qPCR.

Real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is an important method for the early diagnosis of coronavirus disease 2019 (COVID-19). This study investigated the effects of storage solution, temperature and detection time on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid detection by RT-qPCR. Various concentrations of SARS-CoV-2 were added to inactive and non-inactive storage solution and the viral suspensions were stored at various temperatures (room temperature, 4, -20 and -80 °C). Then, at five different detection time points, the Ct values were determined by RT-qPCR. Active and inactive storage solutions and storage temperature have a great impact on the detection of N gene of SARS-CoV-2 at different concentration corridors but have little impact on the ORF gene. The storage time has a greater impact on the N gene and ORF gene at high concentrations but has no effect on the two genes at low concentrations. In conclusion, storage temperature, storage time and storage status (inactivated, non-inactivated) have no effect on the nucleic acid detection of SARS-CoV-2 at the same concentration. For different concentrations of SARS-CoV-2, the detection of N gene is mainly affected.

2D Film-Like Magnetic SERS Tag with Enhanced Capture and Detection Abilities for Immunochromatographic Diagnosis of Multiple Bacteria.

Here, a multiplex surface-enhanced Raman scattering (SERS)-immunochromatography (ICA) platform is presented using a graphene oxide (GO)-based film-like magnetic tag (GFe-DAu-D/M) that effectively captures and detects multiple bacteria in complex specimens. The 2D GFe-DAu-D/M tag with universal bacterial capture ability is fabricated through the layer-by-layer assembly of one layer of small Fe3O4 nanoparticles (NPs) and two layers of 30 nm AuNPs with a 0.5 nm built-in nanogap on monolayer GO nanosheets followed by co-modification with 4-mercaptophenylboronic acid (MPBA) and 5,5'-dithiobis-(2-nitrobenzoic acid).The GFe-DAu-D/M enabled the rapid enrichment of multiple bacteria by MPBA and quantitative analysis of target bacteria on test lines by specific antibodies, thus achieving multiple signal amplification of magnetic enrichment effect and multilayer dense hotspots and eliminating matrix interference in real-world applications. The developed technology can directly and simultaneously diagnose three major pathogens (Staphylococcus aureus, Pseudomonas aeruginosa, and Salmonella typhimurium) with detection limits down to the level of 10 cells mL-1. The good performance of the proposed method in the detection of real urinary tract infection specimens is also demonstrated, suggesting the great potential of the GFe-DAu-D/M-ICA platform for the highly sensitive monitoring of bacterial infections or contamination.

Ultra-Strong Janus Covalent Organic Framework Membrane with Smart Response to Organic Vapor.

Vapor-driven smart Janus materials have made significant advancements in intelligent monitoring, control, and interaction, etc. Nevertheless, the development of ultrafast response single-layer Janus membrane, along with a deep exploration of the smart response mechanisms, remains a long-term endeavor. Here, the successful synthesis of a high-crystallinity single-layer Covalent organic framework (COF) Janus membrane is reported by morphology control. This kind of membrane displays superior mechanical properties and specific surface area, along with excellent responsiveness to CH2Cl2 vapor. The analysis of the underlying mechanisms reveals that the vapor-induced breathing effect of the COF and the stress mismatch of the Janus structure play a crucial role in its smart deformation performance. It is believed that this COF Janus membrane holds promise for complex tasks in various fields.

Porcine epidemic diarrhea virus strain CH/HLJ/18 isolated in China: characterization and phylogenetic analysis.

BACKGROUND: Porcine epidemic diarrhea (PED) is an infectious disease of the digestive tract caused by the porcine epidemic diarrhea virus (PEDV), characterized by vomiting, severe diarrhea, and high mortality rates in piglets. In recent years, the distribution of this disease in China has remarkably increased, and its pathogenicity has also increased. PEDV has been identified as the main cause of viral diarrhea in piglets. This study aimed to understand the genetic evolution and diversity of PEDV to provide a theoretical basis for the development of new vaccines and the prevention and treatment of PED. METHODS: A PEDV strain was isolated from the small intestine of a diarrheal piglet using Vero cells. The virus was identified using reverse transcription-polymerase chain reaction (RT-PCR), indirect immunofluorescence assay (IFA), and transmission electron microscopy. The whole genome sequence was sequenced, phylogenetic analysis was conducted using MEGA (version 7.0), and recombination analysis was performed using RDP4 and SimPlot. The S protein amino acid sequence was aligned using Cluster X (version 2.0), and the S protein was modeled using SWISS-MODEL to compare differences in structure and antigenicity. Finally, the piglets were inoculated with PEDV to evaluate its pathogenicity in newborn piglets. RESULT: PEDV strain CH/HLJ/18 was isolated. CH/HLJ/18 shared 89.4-99.2% homology with 52 reference strains of PEDV belonging to the GII-a subgroup. It was a recombinant strain of PEDV BJ-2011-1 and PEDV CH_hubei_2016 with a breakpoint located in ORF1b. Unique amino acid deletions and mutations were observed in the CH/HLJ/18 S protein. The piglets then developed severe watery diarrhea and died within 7 d of inoculation with CH/HLJ/18, suggesting that CH/HLJ/18 was highly pathogenic to newborn piglets. CONCLUSION: A highly pathogenic recombinant PEDV GII-a strain, CH/HLJ/18, was identified in China, with unique deletion and mutation of amino acids in the S protein that may lead to changes in protein structure and antigenicity. These results will be crucial for understanding the prevalence and variation of PEDV and for preventing and controlling PED.

Advancing mRNA Therapeutics: The Role and Future of Nanoparticle Delivery Systems.

The coronavirus (COVID-19) pandemic has underscored the critical role of mRNA-based vaccines as powerful, adaptable, readily manufacturable, and safe methodologies for prophylaxis. mRNA-based treatments are emerging as a hopeful avenue for a plethora of conditions, encompassing infectious diseases, cancer, autoimmune diseases, genetic diseases, and rare disorders. Nonetheless, the in vivo delivery of mRNA faces challenges due to its instability, suboptimal delivery, and potential for triggering undesired immune reactions. In this context, the development of effective drug delivery systems, particularly nanoparticles (NPs), is paramount. Tailored with biophysical and chemical properties and susceptible to surface customization, these NPs have demonstrated enhanced mRNA delivery in vivo and led to the approval of several NPs-based formulations for clinical use. Despite these advancements, the necessity for developing a refined, targeted NP delivery system remains imperative. This review comprehensively surveys the biological, translational, and clinical progress in NPs-mediated mRNA therapeutics for both the prevention and treatment of diverse diseases. By addressing critical factors for enhancing existing methodologies, it aims to inform the future development of precise and efficacious mRNA-based therapeutic interventions.

Exploring the Alternative Conformation of a Known Protein Structure Based on Contact Map Prediction.

The rapid development of deep learning-based methods has considerably advanced the field of protein structure prediction. The accuracy of predicting the 3D structures of simple proteins is comparable to that of experimentally determined structures, providing broad possibilities for structure-based biological studies. Another critical question is whether and how multistate structures can be predicted from a given protein sequence. In this study, analysis of tens of two-state proteins demonstrated that deep learning-based contact map predictions contain structural information on both states, which suggests that it is probably appropriate to change the target of deep learning-based protein structure prediction from one specific structure to multiple likely structures. Furthermore, by combining deep learning- and physics-based computational methods, we developed a protocol for exploring alternative conformations from a known structure of a given protein, by which we successfully approached the holo-state conformations of multiple representative proteins from their apo-state structures.

Assessing nicotine pharmacokinetics of new generation tobacco products and conventional cigarettes: a systematic review and meta-analysis.

INTRODUCTION: New generation tobacco products (NGPs) hold promises as modified-risk alternatives to conventional cigarettes (CCs), given their comparable characteristics. This study investigated the nicotine pharmacokinetics (PK) of NGPs, encompassing closed pod systems, refillable e-cigarettes (ECs), and heated tobacco products (HTPs), in comparison to CCs through systematic review and meta-analysis. METHODS: A comprehensive search was conducted on PubMed, Embase, and Web of Science for articles published between January 2013 and July 2023. Maximum nicotine concentration (Cmax), time to the peak concentration (Tmax), and total nicotine exposure (area under the concentration-time curve, AUC) were extracted to evaluate nicotine delivery PK. Random effects meta-analyses were performed to determine pooled standardized mean differences (SMD), facilitating a comparison of PK profiles between NGPs and CCs. Subgroup analyses exploring flavors and nicotine concentrations across NGPs, and CCs were also conducted. RESULTS: The meta-analysis incorporated 30 articles with 2728 participants. Cmax and AUC were significantly lower for NGPs, while Tmax demonstrated statistical similarity compared to CCs. Among three NGPs, Cmax and AUC were lower for closed pod systems and refillable ECs. In HTPs, Cmax was statistically similar while AUC was lower compared to CCs. Tmax was statistically similar in closed pod systems and HTPs compared to that of CCs. No significant difference was observed in the comparisons of PK between each type of NGPs versus CCs. CONCLUSIONS: NGPs delivered less nicotine than CCs but reached Cmax over a similar timeframe, indicating that NGPs may serve as modified-risk alternatives with lower nicotine delivery to CCs for craving relief and smoking cessation. IMPLICATION: This study suggested that NGPs, such as the closed pod systems, the refillable ECs, and the HTPs, delivered either lower or comparable nicotine levels and achieved peak nicotine concentration at a similar rate as CCs. Our findings carry implications that NGPs can serve as modified-risk nicotine alternative to CCs in helping smokers to manage cravings and potentially quit smoking, thereby highlighting their value in the field of tobacco harm reduction.

Analysis of PANoptosis-related ceRNA network reveals lncRNA MIR17HG involved in osteogenic differentiation inhibition impaired by tumor necrosis factor-α.

BACKGROUND: Inflammatory cytokines such as Interleukin 1ß(IL1ß), IL6,Tumor Necrosis Factor-α (TNF-α) can inhibit osteoblast differentiation and induce osteoblast apoptosis. PANoptosis, a newly identified type of programmed cell death (PCD), may be influenced by long noncoding RNA (lncRNAs) which play important roles in regulating inflammation. However, the potential role of lncRNAs in inflammation and PANoptosis during osteogenic differentiation remains unclear. This study aimed to investigate the regulatory functions of lncRNAs in inflammation and apoptosis during osteogenic differentiation. METHODS AND RESULTS: High-throughput sequencing was used to identify differentially expressed genes involved in osteoblast differentiation under inflammatory conditions. Two lncRNAs associated with inflammation and PANoptosis during osteogenic differentiation were identified from sequencing data and Gene Expression Omnibus (GEO) databases. Their functionalities were analyzed using diverse bioinformatics methodologies, resulting in the construction of the lncRNA-miRNA-mRNA network. Among these, lncRNA (MIR17HG) showed a high correlation with PANoptosis. Bibliometric methods were employed to collect literature data on PANoptosis, and its components were inferred. PCR and Western Blotting experiments confirmed that lncRNA MIR17HG is related to PANoptosis in osteoblasts during inflammation. CONCLUSIONS: Our data suggest that TNF-α-induced inhibition of osteogenic differentiation and PANoptosis in MC3T3-E1 osteoblasts is associated with MIR17HG. These findings highlight the critical role of MIR17HG in the interplay between inflammation, PANoptosis, and osteogenic differentiation, suggesting potential therapeutic targets for conditions involving impaired bone formation and inflammatory responses.

Hypothesis Tests for Continuous Audiometric Threshold Data.

OBJECTIVES: Hypothesis tests for hearing threshold data may be challenging due to the special structure of the response variable, which consists of the measurements from the participant's two ears at multiple frequencies. The commonly-used methods may have inflated type I error rates for the global test that examines whether exposure-hearing threshold associations exist in at least one of the frequencies. We propose using both-ear methods, including all frequencies in the same model for hypothesis testing. DESIGN: We compared the both-ear method to commonly used single-ear methods, such as the worse-ear, better-ear, left/right-ear, average-ear methods, and both-ear methods that evaluate individual audiometric frequencies in separate models, through both theoretical consideration and a simulation study. Differences between the methods were illustrated using hypothesis tests for the associations between the Dietary Approaches to Stop Hypertension adherence score and 3-year change in hearing thresholds among participants in the Conservation of Hearing Study. RESULTS: We found that (1) in the absence of ear-level confounders, the better-ear, worse-ear and left/right-ear methods have less power for frequency-specific tests and for the global test; (2) in the presence of ear-level confounders, the better-ear and worse-ear methods are invalid, and the left/right-ear and average-ear methods have less power, with the power loss in the left/right-ear much greater than the average-ear method, for frequency-specific tests and for the global test; and (3) the both-ear method with separate analyses for individual frequencies is invalid for the global test. CONCLUSIONS: For hypothesis testing to evaluate whether there are significant associations between an exposure of interest and audiometric hearing threshold measurements, the both-ear method that includes all frequencies in the same model is the recommended analytic approach.

Assessing immunogenicity of CRISPR-NCas9 engineered strain against porcine epidemic diarrhea virus.

Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV), is an acute and highly infectious disease, resulting in substantial economic losses in the pig industry. Given that PEDV primarily infects the mucosal surfaces of the intestinal tract, it is crucial to improve the mucosal immunity to prevent viral invasion. Lactic acid bacteria (LAB) oral vaccines offer unique advantages and potential applications in combatting mucosal infectious diseases, making them an ideal approach for controlling PED outbreaks. However, traditional LAB oral vaccines use plasmids for exogenous protein expression and antibiotic genes as selection markers. Antibiotic genes can be diffused through transposition, transfer, or homologous recombination, resulting in the generation of drug-resistant strains. To overcome these issues, genome-editing technology has been developed to achieve gene expression in LAB genomes. In this study, we used the CRISPR-NCas9 system to integrate the PEDV S1 gene into the genome of alanine racemase-deficient Lactobacillus paracasei △Alr HLJ-27 (L. paracasei △Alr HLJ-27) at the thymidylate synthase (thyA) site, generating a strain, S1/△Alr HLJ-27. We conducted immunization assays in mice and piglets to evaluate the level of immune response and evaluated its protective effect against PEDV through challenge tests in piglets. Oral administration of the strain S1/△Alr HLJ-27 in mice and piglets elicited mucosal, humoral, and cellular immune responses. The strain also exhibited a certain level of resistance against PEDV infection in piglets. These results demonstrate the potential of S1/△Alr HLJ-27 as an oral vaccine candidate for PEDV control. KEY POINTS: • A strain S1/△Alr HLJ-27 was constructed as the candidate for an oral vaccine. • Immunogenicity response and challenge test was carried out to analyze the ability of the strain. • The strain S1/△Alr HLJ-27 could provide protection for piglets to a certain extent.

Inducible Fgf13 ablation alleviates cardiac fibrosis via regulation of microtubule stability.

Fibroblast growth factor (FGF) isoform 13, a distinct type of FGF, boasts significant potential for therapeutic intervention in cardiovascular dysfunctions. However, its impact on regulating fibrosis remains unexplored. This study aims to elucidate the role and mechanism of FGF13 on cardiac fibrosis. Here, we show that following transverse aortic constriction (TAC) surgery, interstitial fibrosis and collagen content increase in mice, along with reduced ejection fraction and fractional shortening, augmented heart mass. However, following Fgf13 deletion, interstitial fibrosis is decreased, ejection fraction and fractional shortening are increased, and heart mass is decreased, compared with those in the TAC group. Mechanistically, incubation of cardiac fibroblasts with transforming growth factor ß (TGFß) increases the expressions of types I and III collagen proteins, as well as α-smooth muscle actin (α-SMA) proteins, and enhances fibroblast proliferation and migration. In the absence of Fgf13, the expressions of these proteins are decreased, and fibroblast proliferation and migration are suppressed, compared with those in the TGFß-stimulated group. Overexpression of FGF13, but not FGF13 mutants defective in microtubule binding and stabilization, rescues the decrease in collagen and α-SMA protein and weakens the proliferation and migration function of the Fgf13 knockdown group. Furthermore, Fgf13 knockdown decreases ROCK protein expression via microtubule disruption. Collectively, cardiac Fgf13 knockdown protects the heart from fibrosis in response to haemodynamic stress by modulating microtubule stabilization and ROCK signaling pathway.

Diabetes and osteoporosis: a two-sample mendelian randomization study.

BACKGROUND: The effects on bone mineral density (BMD)/fracture between type 1 (T1D) and type 2 (T2D) diabetes are unknown. Therefore, we aimed to investigate the causal relationship between the two types of diabetes and BMD/fracture using a Mendelian randomization (MR) design. METHODS: A two-sample MR study was conducted to examine the causal relationship between diabetes and BMD/fracture, with three phenotypes (T1D, T2D, and glycosylated hemoglobin [HbA1c]) of diabetes as exposures and five phenotypes (femoral neck BMD [FN-BMD], lumbar spine BMD [LS-BMD], heel-BMD, total body BMD [TB-BMD], and fracture) as outcomes, combining MR-Egger, weighted median, simple mode, and inverse variance weighted (IVW) sensitivity assessments. Additionally, horizontal pleiotropy was evaluated and corrected using the residual sum and outlier approaches. RESULTS: The IVW method showed that genetically predicted T1D was negatively associated with TB-BMD (ß = -0.018, 95% CI: -0.030, -0.006), while T2D was positively associated with FN-BMD (ß = 0.033, 95% CI: 0.003, 0.062), heel-BMD (ß = 0.018, 95% CI: 0.006, 0.031), and TB-BMD (ß = 0.050, 95% CI: 0.022, 0.079). Further, HbA1c was not associated with the five outcomes (ß ranged from - 0.012 to 0.075). CONCLUSIONS: Our results showed that T1D and T2D have different effects on BMD at the genetic level. BMD decreased in patients with T1D and increased in those with T2D. These findings highlight the complex interplay between diabetes and bone health, suggesting potential age-specific effects and genetic influences. To better understand the mechanisms of bone metabolism in patients with diabetes, further longitudinal studies are required to explain BMD changes in different types of diabetes.

Interventions to Support the Return to Work for Individuals with Stroke: A Systematic Review and Meta-analysis.

PURPOSE: An increasing number of individuals with stroke are having difficulties in returning to work, having a significant impact on both individuals and society. The aims of this meta-analysis were to summarize the interventions to support the return to work (RTW) for individuals with stroke and to quantitatively evaluate the efficacy of each type of intervention. METHODS: A systematic review and meta-analysis were conducted according to PRISMA guidelines. PubMed, Embase, Cochrane Library, CINAHL, and PsycINFO were searched until 26 June 2023, and the list of references of the initially included articles was also searched. Two researchers independently performed the search, screening, selection, and data extraction. The primary outcome was RTW rate (the RTW rate was defined as the proportion of individuals who returned to work in each group (intervention and control) at the endpoint). Pooled risk ratio (RR) was estimated using a random-effects model with 95% confidence intervals (CIs). RESULTS: A total of 13 studies representing 4,282 individuals with stroke were included in our study. Results showed that physiological interventions could improve the RTW rate of individuals with stroke (RR: 1.19, 95% CI: 1.01 to 1.42, I2 = 72%). And receiving intravenous thrombolytic therapy was beneficial in promoting the RTW in individuals with stroke. Subgroup analysis and meta-regression analysis showed that the individuals' functional status during hospitalization was the only source of heterogeneity. Psychological interventions had little or no effect on the RTW rate of individuals with stroke (RR: 1.20, 95% CI: 0.58 to 2.51, I2 = 30%). Work-related interventions had little or no effect on the RTW rate of the individuals with stroke (RR:1.36,95%CI: 0.99 to 1.88, I2 = 73%). The subgroup analysis showed that country, age, and follow-up method were the sources of heterogeneity. CONCLUSION: Physiological intervention promoted the RTW of individuals with stroke. But, the effect of psychological and work-related interventions in promoting the RTW of individuals with stroke was not significant. We anticipate that these findings may inform the design of future interventions. For future research, we recommend that more high-quality randomized controlled trials be conducted to further promote the RTW of individuals with stroke. SYSTEMATIC REVIEW REGISTRATION: PROSPERO Registration Number, CRD42023443668.

Artificial Intelligence-Based Microfluidic Platform for Detecting Contaminants in Water: A Review.

Water pollution greatly impacts humans and ecosystems, so a series of policies have been enacted to control it. The first step in performing pollution control is to detect contaminants in the water. Various methods have been proposed for water quality testing, such as spectroscopy, chromatography, and electrochemical techniques. However, traditional testing methods require the utilization of laboratory equipment, which is large and not suitable for real-time testing in the field. Microfluidic devices can overcome the limitations of traditional testing instruments and have become an efficient and convenient tool for water quality analysis. At the same time, artificial intelligence is an ideal means of recognizing, classifying, and predicting data obtained from microfluidic systems. Microfluidic devices based on artificial intelligence and machine learning are being developed with great significance for the next generation of water quality monitoring systems. This review begins with a brief introduction to the algorithms involved in artificial intelligence and the materials used in the fabrication and detection techniques of microfluidic platforms. Then, the latest research development of combining the two for pollutant detection in water bodies, including heavy metals, pesticides, micro- and nanoplastics, and microalgae, is mainly introduced. Finally, the challenges encountered and the future directions of detection methods based on industrial intelligence and microfluidic chips are discussed.

Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function.

Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs. In vitro cell experiments have demonstrated that CDC23 promotes the proliferation of myoblasts, as well as significantly positively regulating the differentiation of skeletal muscle satellite cells. In addition, Gene Set Enrichment Analysis (GSEA) revealed a significant downregulation of the cell cycle pathway during the differentiation process of skeletal muscle satellite cells. The protein-protein interaction (PPI) network showed a high degree of interaction between genes related to the cell cycle pathway and CDC23. Subsequently, in differentiated myocytes induced after overexpression of CDC23, the level of CDC23 exhibited a significant negative correlation with the expression of key factors in the cell cycle pathway, suggesting that CDC23 may be involved in the inhibition of the cell cycle signaling pathway in order to promote the differentiation process. In summary, we preliminarily determined the function of CDC23 with the aim of providing new insights into molecular regulation during porcine skeletal muscle development.

Construction of self-cleaning g-C3N4/Bi2MoO6/PVDF membrane and coupling with photo-Fenton-like reaction for sustainable removal of antibiotics in wastewater.

Constructing a photocatalytic membrane and photo-Fenton reaction coupling system is a novel strategy to enhance the photocatalytic activity of the membrane and eliminate the problem of membrane contamination. Herein, a g-C3N4/Bi2MoO6/PVDF photocatalytic membrane was prepared using a tannic acid-assisted in-situ deposition method. The membrane was characterized by three advantages of photocatalytic, self-cleaning, and antibacterial properties. Under the photo-Fenton-like conditions, the membrane had superior photodegradation efficiency of 90.7% for tetracycline, one of the main antibiotic contaminants in the China's aquatic system. Moreover, the membrane had excellent photo-Fenton self-cleaning ability, its flux recovery rate was up to 96%-98% after the self-cleaning process. Photoluminescence spectra, diffuse UV-visible spectrum, transient photocurrent responses, and electrochemical AC impedance spectrum results show that the heterojunction structure formed by g-C3N4 and Bi2MoO6 could improve the separation efficiency of photogenerated electrons-hole pairs. Electron spin resonance spectroscopy confirmed the photo-electrons facilitated the formation of hydroxyl radical (·OH) in the existence of H2O2, which enhanced tetracycline degradation. Moreover, the superior photo-Fenton self-cleaning performance, which mainly relied on the active free radicals produced by the photo-Fenton-like membrane to remove dirt on the membrane surface or in the membrane pore channel. Our results may shed new light on the development of promising photocatalytic membrane systems by coupling with photo-Fenton-like processes, and facilitate their applications for wastewater treatment.

Exploring the causal relationship between inflammatory cytokines and immunoinflammatory dermatoses: a Mendelian randomization study.

Objectives: Previous studies have shown that the onset and progression of several immunoinflammatory dermatoses are closely related to specific immune-inflammatory responses. To further assess the causal relationship between 41 inflammatory cytokines and immunoinflammatory dermatoses, we used a Mendelian randomization method. Methods: Mendelian two-sample randomization utilized inflammatory cytokines from a GWAS abstract containing 8,293 healthy participants as well as psoriasis (4,510 cases and 212,242 controls), atopic dermatitis (7,024 cases and 198,740 controls), and vitiligo (131 cases and 207,482 controls). The causal relationship between exposure and outcome was explored primarily using inverse variance weighting. In addition, multiple sensitivity analyses, including MR-Egger, weighted median, simple model, weighted model, and MR-PRESSO, were simultaneously applied to enhance the final results. Results: The results showed that in clinical practice, IL-4 and IL-1RA were suggestive indicators of atopic dermatitis risk (OR = 0.878, 95% CI = 0.78-0.99, p = 0.036; OR = 0.902, 95% CI = 0.82-1.00, p = 0.045). SCGF-b was a suggestive indicator of psoriasis risk (OR = 1.095, 95% CI = 1.01-1.18, p = 0.023). IL-4 is a suggestive indicator of vitiligo risk (OR = 2.948, 95% CI = 1.28-6.79, p = 0.011). Conclusion: Our findings suggest that circulating inflammatory cytokines may play a crucial role in the pathogenesis of chronic skin inflammation. IL-4 and IL-1RA may have inhibitory roles in the risk of developing atopic dermatitis, while SCGF-b may have a promoting role in the risk of developing psoriasis. Furthermore, IL-4 may contribute to the risk of developing vitiligo. These results provide insights into further understanding the mechanisms of chronic skin inflammation and offer new targets and strategies for the prevention and treatment of related diseases.

Recent advancements in hydrogels as novel tissue engineering scaffolds for dental pulp regeneration.

Although conventional root canal treatment offers an effective therapeutic solution, it negatively affects the viability of the affected tooth. In recent years, pulp regeneration technology has emerged as a novel method for treating irreversible pulpitis due to its ability to maintain tooth vitality. The successful implementation of this technique depends on scaffolds and transplantation of exogenous stem cells or recruitment of endogenous stem cells. Accordingly, the three-dimensional structure and viscoelastic characteristics of hydrogel scaffolds, which parallel those of the extracellular matrix, have generated considerable interest. Furthermore, hydrogels support the controlled release of regenerative drugs and to load a wide variety of bioactive molecules. By integrating antibacterial agents into the hydrogel matrix and stimulating an immune response, root canal disinfection can be significantly improved and the rate of pulp regeneration can be accelerated. This review aims to provide an overview of the clinical applications of hydrogels that have been reported in the last 5 years, and offer a comprehensive summary of the different approaches that have been utilized for the optimization of hydrogel scaffolds for pulp regeneration. Advancements and challenges in pulp regeneration using hydrogels treating aged teeth are discussed.