Dynamic changes of peripheral inflammatory markers link with disease severity and predict short-term poor outcome of myasthenia gravis.

The relationship between peripheral inflammatory markers, their dynamic changes, and the disease severity of myasthenia gravis (MG) is still not fully understood. Besides, the possibility of using it to predict the short-term poor outcome of MG patients have not been demonstrated. This study aims to investigate the relationship between peripheral inflammatory markers and their dynamic changes with Myasthenia Gravis Foundation of America (MGFA) classification (primary outcome) and predict the short-term poor outcome (secondary outcome) in MG patients. The study retrospectively enrolled 154 MG patients from June 2016 to December 2021. The logistic regression was used to investigate the relationship of inflammatory markers with MGFA classification and determine the factors for model construction presented in a nomogram. Finally, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were utilized to evaluate the incremental capacity. Logistic regression revealed significant associations between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI) and MGFA classification (p = 0.013, p = 0.032, p = 0.017, respectively). Incorporating dynamic changes of inflammatory markers into multivariable models improved their discriminatory capacity of disease severity, with significant improvements observed for NLR, systemic immune-inflammation index (SII) and AISI in NRI and IDI. Additionally, AISI was statistically associated with short-term poor outcome and a prediction model incorporating dynamic changes of inflammatory markers was constructed with the area under curve (AUC) of 0.953, presented in a nomograph. The inflammatory markers demonstrate significant associations with disease severity and AISI could be regarded as a possible and easily available predictive biomarker for short-term poor outcome in MG patients.

Development of multi-epitope mRNA vaccine against Clostridioides difficile using reverse vaccinology and immunoinformatics approaches.

Clostridioides difficile (C. difficile), as the major pathogen of diarrhea in healthcare settings, has become increasingly prevalent within community populations, resulting in significant morbidity and mortality. However, the therapeutic options for Clostridioides difficile infection (CDI) remain limited, and as of now, no authorized vaccine is available to combat this disease. Therefore, the development of a novel vaccine against C. difficile is of paramount importance. In our study, the complete proteome sequences of 118 strains of C. difficile were downloaded and analyzed. We found four antigenic proteins that were highly conserved and can be used for epitope identification. We designed two vaccines, WLcd1 and WLcd2, that contain the ideal T-cell and B-cell epitopes, adjuvants, and the pan HLA DR-binding epitope (PADRE) sequences. The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications. Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors (TLRs) than WLcd2. Furthermore, molecular dynamics (MD) simulations, performed using Gmx_MMPBSA v1.56, confirmed the binding stability of WLcd1 with TLR2 and TLR4. The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI; however, experimental studies are necessary to confirm these predictions.

The role of serum chloride ion in the prognosis of COPD.

BACKGROUND: As exacerbations of chronic obstructive pulmonary disease (COPD) are one of the leading causes of hospitalization and are associated with significant mortality, it is particularly important to accurately assess the risk of exacerbations in COPD. Most of the current clinical biomarkers are related to inflammation and few consider how ion levels affect COPD. Chloride ion, the second most abundant serum electrolyte, has been shown to be associated with poor prognoses in several diseases, but their relationship with COPD remains unclear. METHODS: In total, 105 patients with acute exacerbations of COPD were recruited. Data on clinical characteristics, lung function, blood count, blood biochemistry, relevant scales including the Clinical COPD Questionnaire (CCQ), BODE (BMI, airflow obstruction, dyspnea, exercise capacity) index and the St. George's Respiratory Questionnaire (SGRQ) were collected from all patients for statistical analysis. RESULT: There were significant differences in lung function indicators and disease severity in the low chloride ion subgroup compared with the high chloride ion subgroup. On multiple logistic regression analysis, chloride ion was an independent factor affecting lung function in COPD patients (OR = 0.808, 95% CI: 0.708 - 0.922, p = 0.002). The sensitivity of chloride ion in predicting COPD severity was 78%, the specificity was 63%, and the area under the curve was 0.734 (p < 0.001). Subgroup analysis showed that chloride ion was a stronger predictor in male and smoking patients. CONCLUSIONS: Chloride ion was a novel prognostic biomarker for COPD, and low levels of chloride ion were independently associated with exacerbations in COPD patients.

Small-Molecule Allosteric Inhibitors of Human Aspartate Transcarbamoylase Suppress Proliferation of Bone Osteosarcoma Epithelial Cells.

Aspartate transcarbamoylase (ATC) is the first committed step in de novo pyrimidine biosynthesis in eukaryotes and plants. A potent transition state analog of human ATCase (PALA) has previously been assessed in clinical trials for the treatment of cancer, but was ultimately unsuccessful. Additionally, inhibition of this pathway has been proposed to be a target to suppress cell proliferation in E. coli, the malarial parasite and tuberculosis. In this manuscript we screened a 70-member library of ATC inhibitors developed against the malarial and tubercular ATCases for inhibitors of the human ATC. Four compounds showed low nanomolar inhibition (IC50 30-120 nM) in an in vitro activity assay. These compounds significantly outperform PALA, which has a triphasic inhibition response under identical conditions, in which significant activity remains at PALA concentrations above 10 µM. Evidence for a druggable allosteric pocket in human ATC is provided by both in vitro enzyme kinetic, homology modeling and in silico docking. These compounds also suppress the proliferation of U2OS osteoblastoma cells by promoting cell cycle arrest in G0/G1 phase. This report provides the first evidence for an allosteric pocket in human ATC, which greatly enhances its druggability and demonstrates the potential of this series in cancer therapy.

Systemic Inflammatory Response Index, a Potential Inflammatory Biomarker in Disease Severity of Myasthenia Gravis: A Pilot Retrospective Study.

Purpose: Myasthenia gravis (MG) is a chronic autoimmune disease caused by neuromuscular junction (NMJ) dysfunction. Our current understanding of MG's inflammatory component remains poor. The systemic inflammatory response index (SIRI) presents a promising yet unexplored biomarker for assessing MG severity. This study aimed to investigate the potential relationship between SIRI and MG disease severity. Patients and Methods: We conducted a retrospective analysis of clinical data from 171 MG patients admitted between January 2016 and June 2021. Patients with incomplete data, other autoimmune diseases, or comorbidities were excluded. Disease severity was evaluated using the Myasthenia Gravis Foundation of America (MGFA) classification and Myasthenia Gravis Activities of Daily Living (MG-ADL) on admission. The association between SIRI and disease severity was assessed through logistic regression analysis, along with receiver operating characteristic (ROC) curve and decision curve analysis (DCA) comparisons with established inflammation indicators. Results: After exclusion, 143 patients were analyzed in our study. SIRI levels significantly differed between patients with higher and lower disease severity (p < 0.001). Univariate logistic regression showed that SIRI had a significant effect on high disease severity (OR = 1.376, 95% CI 1.138-1.664, p = 0.001). This association remained significant even after adjusting for age, sex, disease duration, history of MG medication and thymoma (OR = 1.308, 95% CI 1.072-1.597, p = 0.008). Additionally, a positive correlation between SIRI and MG-ADL was observed (r = 0.232, p = 0.008). Significant interactions were observed between SIRI and immunosuppressor (p interaction = 0.001) and intravenous immunoglobulin (p interaction = 0.005). DCA demonstrated the superior net clinical benefit of SIRI compared to other markers when the threshold probability was around 0.2. Conclusion: Our findings indicate a strong independent association between SIRI and disease severity in MG, suggesting SIRI's potential as a valuable biomarker for MG with superior clinical benefit to currently utilized markers.

Neuronal Intranuclear Inclusion Disease with NOTCH2NLC GGC Repeat Expansion: A Systematic Review and Challenges of Phenotypic Characterization.

Neuronal intranuclear inclusion disease (NIID) is a highly clinically heterogeneous neurodegenerative disorder primarily attributed to abnormal GGC repeat expansions in the NOTCH2NLC gene. This study aims to comprehensively explore its phenotypic characteristics and genotype-phenotype correlation. A literature search was conducted in PubMed, Embase, and the Cochrane Library from September 1, 2019, to December 31, 2022, encompassing reported NIID cases confirmed by pathogenic NOTCH2NLC mutations. Linear regressions and trend analyses were performed. Analyzing 635 cases from 85 included studies revealed that familial cases exhibited significantly larger GGC repeat expansions than sporadic cases (p < 0.001), and this frequency significantly increased with expanding GGC repeats (p trend < 0.001). Age at onset (AAO) showed a negative correlation with GGC repeat expansions (p < 0.001). The predominant initial symptoms included tremor (31.70%), cognitive impairment (14.12%), and muscle weakness (10.66%). The decreased or absent tendon reflex (DTR/ATR) emerged as a notable clinical indicator of NIID due to its high prevalence. U-fiber was observed in 79.11% of patients, particularly prominent in paroxysmal disease-dominant (87.50%) and dementia-dominant cases (81.08%). Peripheral neuropathy-dominant cases exhibited larger GGC repeat expansions (median = 123.00) and an earlier AAO (median = 33.00) than other phenotypes. Moreover, a significant genetic anticipation of 3.5 years was observed (p = 0.039). This study provides a comprehensive and up-to-date compilation of genotypic and phenotypic information on NIID since the identification of the causative gene NOTCH2NLC. We contribute a novel diagnostic framework for NIID to support clinical practice.

CAV1 Protein Encapsulated in Mouse BMSC-Derived Extracellular Vesicles Alleviates Myocardial Fibrosis Following Myocardial Infarction by Blocking the TGF-ß1/SMAD2/c-JUN Axis.

Extracellular vesicles (EVs) derived from mouse bone marrow mesenchymal stem cells (mBMSCs) convey the CAV1 protein, influencing the TGF-ß1/SMAD2/c-JUN pathway and thus the molecular mechanisms underlying myocardial fibrosis (MF) post-myocardial infarction (MI). Through various experimental methods, including transmission electron microscopy, Nanosight analysis, Western blot, ELISA, and qRT-PCR, we isolated, purified, and identified EVs originating from mBMSCs. Bioinformatics and experimental findings show a reduced expression of CAV1 in myocardial fibrosis tissue. Furthermore, our findings suggest that mBMSC-EVs can deliver CAV1 to cardiac fibroblasts (CFs) and that silencing CAV1 in mBMSC-EVs promotes CF fibrosis. In vivo studies further corroborated these findings. In conclusion, mBMSC-EVs mitigate myocardial fibrosis in MI mice by delivering the CAV1 protein, inhibiting the TGF-ß1/SMAD2/c-JUN pathway. Molecular mechanism of mBMSC-EVs-CAV1-mediated TGF-ß1/SMAD2/c-JUN axis in inhibiting cardiac fibroblast differentiation to improve MF after MI. mBMSC-EVs deliver CAV1 protein to CFs where the protein expression of CAV1 is upregulated upon hypoxia conditions. The TGF-ß1/SMAD2 signaling pathway downstream of CAV1 is consequently inactivated, the transcription of c-JUN is inhibited, and transcription of SMAD2/c-JUN transcription complex target genes α-SMA and Collagen I is reduced. By this mechanism, CF fibrosis and apoptosis are suppressed in vitro and MF is ameliorated in MI mice.

Prediction of non-perfusion volume ratio for uterine fibroids treated with ultrasound-guided high-intensity focused ultrasound based on MRI radiomics combined with clinical parameters.

BACKGROUND: Prediction of non-perfusion volume ratio (NPVR) is critical in selecting patients with uterine fibroids who will potentially benefit from ultrasound-guided high-intensity focused ultrasound (HIFU) treatment, as it reduces the risk of treatment failure. The purpose of this study is to construct an optimal model for predicting NPVR based on T2-weighted magnetic resonance imaging (T2MRI) radiomics features combined with clinical parameters by machine learning. MATERIALS AND METHODS: This retrospective study was conducted among 223 patients diagnosed with uterine fibroids from two centers. The patients from one center were allocated to a training cohort (n = 122) and an internal test cohort (n = 46), and the data from the other center (n = 55) was used as an external test cohort. The least absolute shrinkage and selection operator (LASSO) algorithm was employed for feature selection in the training cohort. The support vector machine (SVM) was adopted to construct a radiomics model, a clinical model, and a radiomics-clinical model for NPVR prediction, respectively. The area under the curve (AUC) and the decision curve analysis (DCA) were performed to evaluate the predictive validity and the clinical usefulness of the model, respectively. RESULTS: A total of 851 radiomic features were extracted from T2MRI, of which seven radiomics features were screened for NPVR prediction-related radiomics features. The radiomics-clinical model combining radiomics features and clinical parameters showed the best predictive performance in both the internal (AUC = 0.824, 95% CI 0.693-0.954) and external (AUC = 0.773, 95% CI 0.647-0.902) test cohorts, and the DCA also suggested the radiomics-clinical model had the highest net benefit. CONCLUSIONS: The radiomics-clinical model could be applied to the NPVR prediction of patients with uterine fibroids treated by HIFU to provide an objective and effective method for selecting potential patients who would benefit from the treatment mostly.

Decision tool of medical endoscope maintenance service in Chinese hospitals: a conjoint analysis.

BACKGROUND: Medical devices are instruments, apparatus, appliances, software, implants, reagents, materials or other articles that are intended for use in the treatment or diagnosis of disease or injury in humans. Concerning medical endoscope devices, which enable doctors to observe and manipulate the area under examination through a puncture hole in the body cavity or organ, hospitals predominantly consider the quality and cost of maintenance services when making their selection. The effective and efficient provision of maintenance services plays a crucial role in ensuring cost-effective and high-quality management of medical devices. In this study, we have developed an innovative decision tool that analyzed key factors impacting the choice of medical devices' maintenance service. This tool assists hospitals in evaluating and selecting appropriate maintenance services for medical device, specifically endoscopy devices. Moreover, it also serves as a valuable resource for manufacturers and suppliers to enhance their after-sales service offerings. METHODS: A cross-sectional survey was undertaken in 50 Chinese hospitals, including primary and tertiary hospitals. Moreover, 56 medical staff and 65 medical engineers were recruited from 50 Chinese hospitals to participate the survey. A comprehensive set of factors were defined and investigated. Conjoint analysis and orthogonal design were used for survey design and statistical analysis. RESULTS: Factors importance and utility values of decision-making factors were analyzed at the aggregate, occupation, and medical institution levels. (1) At the aggregate level, the most critical factor is "maintenance response" and the least important one is "maintenance efficiency". (2) At the occupation level, medical staff paid more attention to "maintenance response" while medical engineers paid more attention to "maintenance quality". (3) At the medical institution level, Primary hospitals paid more attention to "maintenance price", while tertiary hospitals paid more attention to "maintenance quality". CONCLUSIONS: In general, this study provides a more scientific decision-making tool to both hospitals in choosing maintenance service for medical device such as endoscopy, and it also helps manufacturers and suppliers improve the after-sales service.

Nanocarrier-based targeting of metabolic pathways for endometrial cancer: Status and future perspectives.

Cancer is the second-most lethal global disease, as per health reports, and is responsible for around 70% of deaths in low- and middle-income countries. Endometrial cancer is one of the emerging malignancies and has been predicted as a public health challenge for the future. Insulin resistance, obesity, and diabetes mellitus are the key metabolic factors that promote risks for the development of endometrial cancer. Various signaling pathways and associated genes are involved in the genesis of endometrial cancer, and any mutation or deletion in such related factors leads to the induction of endometrial cancer. The conventional way of drug delivery has been used for ages but is associated with poor management of cancer due to non-targeting of the endometrial cancer cells, low efficacy of the therapy, and toxicity issues as well. In this context, nanocarrier-based therapy for the management of endometrial cancer is an effective alternate choice that overcomes the problems associated with conventional therapy. In this review article, we highlighted the nanocarrier-based targeting of endometrial cancer, with a special focus on targeting various metabolic signaling pathways. Furthermore, the future perspectives of nanocarrier-based targeting of metabolic pathways in endometrial cancer were also underpinned. It is concluded that targeting metabolic signaling pathways in endometrial cancer via nanocarrier scaffolds is the future of pharmaceutical design for the significant management and treatment of endometrial cancer.

Three-Dimensional (3D) Ordered Macroporous Bimetallic (Mn,Fe) Selenide/Carbon Composite with Heterojunction Interface for High-Performance Sodium Ion Batteries.

Transition-metal selenides have captured significant research attention as anode materials for sodium ion batteries (SIBs) due to their high theoretical specific capacities and excellent electronic conductivity. However, volumetric expansion and inferior cycle life still hinder their practical application. Herein, a three-dimensional (3D) ordered macroporous bimetallic (Mn,Fe) selenide modified by a carbon layer (denoted as 3DOM-MnFeSex@C) composite containing a heterojunction interface is fabricated through selenizing a 3D ordered macroporous Mn-based Prussian Blue analogue single crystal. The 3DOM-MnFeSex@C exhibits hierarchically porous architecture with enhanced mass-transfer efficiency; MnSe and FeSe2 particles are encapsulated into macroporous carbon framework, which can significantly promote the electronic conductivity and maintain the structural integrity. The density functional theory calculation indicates that the heterojunction interface between MnSe and FeSe2 has been successfully engineered so that Na+ can be readily adsorbed and rapidly converted, thus promoting the reaction kinetics and extending the cyclic life. As expected, the 3DOM-MnFeSex@C composite delivers excellent rate performance (277.6 mA h g-1 at 10 A g-1), and prolonged cycling life (191.6 mA h g-1 even after 1000 cycles at 2 A g-1) as a sodium storage anode. The sodium storage mechanism of the composite was further investigated by in situ X-ray diffraction and ex situ high-resolution transmission electron microscopy characterization techniques.

Determining changes in crystallinity of rice starch after heat-moisture treatment using terahertz spectroscopy.

To investigate the potential of Fourier-transform terahertz (FT-THz) spectroscopy to follow crystalline structure changes in rice starch after heat-moisture treatment (HMT), we measured the crystallinity by X-ray diffraction (XRD) spectra and found its correlation with THz spectra. According to A-type crystal structure and Vh-type crystalline structure of amylose-lipid complex (ALC) in rice starch, crystallinity is divided into A-type and Vh-type. The intensity of second derivative spectra peak at 9.0 THz was highly correlated with both A-type and Vh-type crystallinity. Additionally, other three peaks at 10.5 THz, 12.2 THz, and 13.1 THz were also sensitive to Vh-type crystalline structure. These results indicate that after HMT, the crystallinity of ALC (Vh-type) and A-type starch can be quantified using THz peaks.

Pickering emulsions stabilized by homogenized ball-milled eggshell particles in combination with sodium alginate.

Eggshells, by-products of egg processing, were ball-milled and homogenized into particles (eggshell particles, ESPs) and then were used as the stabilizer with a two-step oil addition method to produce Pickering emulsions. Meanwhile, sodium alginate (SA) was used to modify the emulsifying ability of ESPs. The results indicated that SA addition helped to improve the dispersion performance and increase the negative charge of ESPs. Pickering emulsions stabilized by ESPs/SA showed much smaller particle size than those stabilized by ESPs. The maximum oil fraction in the ESPs/SA-stabilized emulsions reached up to 0.8, while that was only 0.75 in ESPs-stabilized emulsions. The presence of SA significantly enhanced the freeze-thaw, thermal, dilution, and centrifuge stability of ESPs-stabilized Pickering emulsions. The findings demonstrate the potential of eggshell particles as a kind of natural Pickering stabilizer, which will increase the high value-added utilization of poultry egg industry by-products.

Dissolution of harmful trace elements from coal and the environmental risk to mine water utilization.

Under the pressure of water shortages, coal mine water has been allocated as a national water resource in China. However, the existence of harmful trace elements (HTEs) in coal mine water causes environmental risks and health concerns over its reuse. Through a lixiviation experiment, the dominant factors affecting the dissolution of HTEs in coal were simulated and analyzed, and the environmental risks of HTEs in coal mine water in China were evaluated for the first time. The average dissolved content levels of HTEs from coal were Mn > Cu > Zn > Ni > Ba > Cr > Co > V > Mo > Se > U > Pb > Cd, and the average maximum dissolution rates were Ni > Co > Mo > Zn > Cu > Cd > Mn > Se > Ba > Cr > U > Pb > V. Oxidation-reduction potential (Eh) and pH are the dominant factors controlling HTE dissolution. Higher oxygen exposure levels induce Eh and pH development, resulting in more HTE dissolution. This study constructed the dissolution potential index (FC) of HTEs from coal. Based on the results of the FC model, the areas with the highest migration potential and environmental risk of HTEs from coal seams to mine water are located in southern China, especially in the southwest, followed by areas of eastern Inner Mongolia and Shanxi and Shaanxi provinces. The corresponding risks in other regions are relatively low; thus, mine water utilization remains an effective option. This study provides an effective reference for the analysis of HTE enrichment in coal mine water and an evaluation of its safe utilization.

Postoperative Alanine Aminotransferase Levels Are Associated with Outcomes in Pediatric Patients Undergoing Total Cavopulmonary Connection.

BACKGROUND: This single-center, retrospective study aims to determine the association between alanine aminotransferase (ALT) and outcomes in pediatric patients undergoing total cavopulmonary connection (TCPC). METHODS: In total, 256 pediatric patients undergoing TCPC were included and divided into a normal-ALT group and a high-ALT group. Clinical data were collected for comparisons between groups, and risk factors of high postoperative ALT were identified by univariate and multivariate analysis. A ROC analysis of the predictive value of postoperative ALT was conducted. RESULTS: Compared to the normal-ALT group, the members of the high-ALT group were 1.6 years older and had significantly higher preoperative creatinine and direct bilirubin levels. The high-ALT group had increased fluid overload, higher vasoactive inotropic drug scores, and inferior central venous pressure. The short-term outcomes in the high-ALT group were markedly worse: they suffered a longer duration of mechanical ventilation (MV), had a higher ICU and hospital length of stay (LOS), and higher rates of mortality, infection, and reintubation. Prolonged ICU and hospital LOS, longer MV, and reintubation were identified as independent risk factors for high postoperative ALT. Postoperative ALT was of high value in predicting reintubation, MV, ICU LOS, and mortality. CONCLUSIONS: Elevated postoperative ALT levels are associated with poor short-term outcomes in pediatric patients undergoing TCPC.

Evaluation of the potential of ultrasound-mediated drug delivery for the treatment of ovarian cancer through preclinical studies.

Ovarian cancer (OC) has the greatest mortality rate among gynecological cancers, with a five-year survival rate of <50%. Contemporary adjuvant chemotherapy mostly fails in the case of OCs that are refractory, metastatic, recurrent, and drug-resistant. Emerging ultrasound (US)-mediated technologies show remarkable promise in overcoming these challenges. Absorption of US waves by the tissue results in the generation of heat due to its thermal effect causing increased diffusion of drugs from the carriers and triggering sonoporation by increasing the permeability of the cancer cells. Certain frequencies of US waves could also produce a cavitation effect on drug-filled microbubbles (MBs, phospholipid bilayers) thereby generating shear force and acoustic streaming that could assist drug release from the MBs, and promote the permeability of the cell membrane. A new class of nanoparticles that carry therapeutic agents and are guided by US contrast agents for precision delivery to the site of the ovarian tumor has been developed. Phase-shifting of nanoparticles by US sonication has also been engineered to enhance the drug delivery to the ovarian tumor site. These technologies have been used for targeting the ovarian cancer stem cells and protein moieties that are particularly elevated in OCs including luteinizing hormone-releasing hormone, folic acid receptor, and vascular endothelial growth factor. When compared to healthy ovarian tissue, the homeostatic parameters at the tissue microenvironment including pH, oxygen levels, and glucose metabolism differ significantly in ovarian tumors. US-based technologies have been developed to take advantage of these tumor-specific alterations for precision drug delivery. Preclinical efficacy of US-based targeting of currently used clinical chemotherapies presented in this review has the potential for rapid human translation, especially for formulations that use all substances that are deemed to be generally safe by the U.S. Food and Drug Administration.

Corrigendum: Immunoinformatics approach toward the introduction of a novel multi-epitope vaccine against Clostridium difficile.

[This corrects the article DOI: 10.3389/fimmu.2022.887061.].

Immunoinformatics Approach Toward the Introduction of a Novel Multi-Epitope Vaccine Against Clostridium difficile.

Clostridium difficile (C.difficile) is an exclusively anaerobic, spore-forming, and Gram-positive pathogen that is the most common cause of nosocomial diarrhea and is becoming increasingly prevalent in the community. Because C. difficile is strictly anaerobic, spores that can survive for months in the external environment contribute to the persistence and diffusion of C. difficile within the healthcare environment and community. Antimicrobial therapy disrupts the natural intestinal flora, allowing spores to develop into propagules that colonize the colon and produce toxins, thus leading to antibiotic-associated diarrhea and pseudomembranous enteritis. However, there is no licensed vaccine to prevent Clostridium difficile infection (CDI). In this study, a multi-epitope vaccine was designed using modern computer methods. Two target proteins, CdeC, affecting spore germination, and fliD, affecting propagule colonization, were chosen to construct the vaccine so that it could simultaneously induce the immune response against two different forms (spore and propagule) of C. difficile. We obtained the protein sequences from the National Center for Biotechnology Information (NCBI) database. After the layers of filtration, 5 cytotoxic T-cell lymphocyte (CTL) epitopes, 5 helper T lymphocyte (HTL) epitopes, and 7 B-cell linear epitopes were finally selected for vaccine construction. Then, to enhance the immunogenicity of the designed vaccine, an adjuvant was added to construct the vaccine. The Prabi and RaptorX servers were used to predict the vaccine's two- and three-dimensional (3D) structures, respectively. Additionally, we refined and validated the structures of the vaccine construct. Molecular docking and molecular dynamics (MD) simulation were performed to check the interaction model of the vaccine-Toll-like receptor (TLR) complexes, vaccine-major histocompatibility complex (MHC) complexes, and vaccine-B-cell receptor (BCR) complex. Furthermore, immune stimulation, population coverage, and in silico molecular cloning were also conducted. The foregoing findings suggest that the final formulated vaccine is promising against the pathogen, but more researchers are needed to verify it.

New insights of epigenetics in vascular and cellular senescence.

Vascular senescence plays a vital role in cardiovascular diseases and it is closely related to cellular senescence. At the molecular level, aging begins with a single cell, and it is characterized by telomere shortening, mitochondrial dysfunction, stem cell exhaustion, epigenetic changes, and so on. Epigenetics is an independent discipline that modifies DNA activity without altering the DNA sequence. The application of epigenetics helps to alleviate the occurrence of human diseases, inhibit senescence, and even inhibit tumor occurrence. Epigenetics mainly includes the modification of DNA, histone, and noncoding RNA. Herein, the application of epigenetics in vascular senescence and aging has been reviewed to provide the prospects and innovative inspirations for future research.

Predictive Roles of Thinking Styles in Coping Strategies Among Mainland Postgraduate Students in Hong Kong.

The primary objective of the present research was to explore the statistical predictive power of thinking styles in coping strategies beyond demographic factors. One hundred and forty-eight mainland postgraduate students were administered to the Thinking Styles Inventory-Revised II (TSI-R2) and the Coping Orientation to Problems Experienced (COPE) Revised. Results indicated that Type I thinking styles primarily predicted adaptive coping strategies, while Type II thinking styles positively contributed to maladaptive coping strategies. Results in the present research were largely in the expected directions beyond the influence of demographic factors. Furthermore, thinking styles varied as a function of age, gender, gender-role orientation, and marital status. Implications for postgraduate students, academics, university administrators, and the limitations of the research, are discussed.