Quantitative determination of prothioconazole in wheat grain, soybean, and pond water based on a polyclonal antibody.

Prothioconazole and its metabolite are considered a potential threat to human health and environmental safety. Thus, the development of a sensitive and rapid detection method for prothioconazole is crucial to ensure the safety of agricultural products. In this study, a new hapten of prothioconazole was designed and synthesized, and a selective polyclonal antibody with high affinity against prothioconazole was produced, which was obtained from immunized New Zealand white rabbits. Based on the polyclonal antibody, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and indirect competitive chemiluminescence enzyme immunoassay (ic-CLEIA) were developed for detecting prothioconazole pesticides. Under optimized experimental conditions, the limit of quantification (LOQ) values for ic-CLEIA and ic-ELISA were 1.8 and 10.7 ng mL-1, respectively. The results demonstrated that the sensitivity (LOQ) achieved by ic-CLEIA was more than five times higher compared to that obtained with ic-ELISA. In addition, the recoveries obtained by adding standard prothioconazole to wheat grain, soybean, and pond water samples were in the range of 81.9 to 104.7% for ic-ELISA and 89.0 to 118.0% for ic-CLEIA.

Prognostic value of the Naples prognostic score in patients with intrahepatic cholangiocarcinoma after hepatectomy.

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Reducing economic burden through split-shared care model for people living with uncontrolled type 2 diabetes and polypharmacy: a multi-center randomized controlled trial.

BACKGROUND: Interprofessional collaborative care such as a split-shared care model involving family physicians and community pharmacists can reduce the economic burden of diabetes management. This study aimed to evaluate the economic outcome of a split-shared care model between family physicians and community pharmacists within a pharmacy chain in managing people with uncontrolled type 2 diabetes and polypharmacy. METHOD: This was a multi-center, parallel arm, open label, randomized controlled trial comparing the direct and indirect economic outcomes of people who received collaborative care involving community pharmacists (intervention) versus those who received usual care without community pharmacist involvement (control). People with uncontrolled type 2 diabetes, defined as HbA1c > 7.0% and taking ≥ 5 chronic medications were included while people with missing baseline economic data (such as consultation costs, medication costs) were excluded. Direct medical costs were extracted from the institution's financial database while indirect costs were calculated from self-reported gross income and productivity loss, using Work Productivity Activity Impairment Global Health questionnaire. Separate generalized linear models with log link function and gamma distribution were used to analyze changes in direct and indirect medical costs. RESULTS: A total of 175 patients (intervention = 70, control = 105) completed the trial and were included for analysis. The mean age of the participants was 66.9 (9.2) years, with majority being male and Chinese. The direct medical costs were significantly lower in the intervention than the control group over 6 months (intervention: -US$70.51, control: -US$47.66, p < 0.001). Medication cost was the main driver in both groups. There were no significant changes in productivity loss and indirect costs in both groups. CONCLUSION: Implementation of split-shared visits with frontline community partners may reduce economic burden for patient with uncontrolled type 2 diabetes and polypharmacy. TRIAL REGISTRATION: Clinicaltrials.gov Reference Number: NCT03531944 (Date of registration: June 6, 2018).

Effects of nitrogen regulation on heavy metal phytoextraction efficiency (Leucaena leucocephala): Application of a nitrogen fertilizer and a fungal agent.

Lead (Pb) and cadmium (Cd) have been identified as the primary contaminants in soil, posing potential health threats. This study aimed to examine the effects of applying a nitrogen fertilizer and a fungal agent Trichoderma harzianum J2 (nitrogen alone, fungi alone, and combined use) on the phytoremediation of soils co-contaminated with Pb and Cd. The growth of Leucaena leucocephala was monitored in the seedling, differentiation, and maturity stages to fully comprehend the remediation mechanisms. In the maturity stage, the biomass of L. leucocephala significantly increased by 18% and 29% under nitrogen-alone (NCK+) and fungal agent-alone treatments (J2), respectively, compared with the control in contaminated soil (CK+). The remediation factors of Pb and Cd with NCK+ treatment significantly increased by 50% and 125%, respectively, while those with J2 treatment increased by 73% and 145%, respectively. The partial least squares path model suggested that the nitrogen-related soil properties were prominent factors affecting phytoextraction compared with biotic factors (microbial diversity and plant growth). This model explained 2.56 of the variation in Cd concentration under J2 treatment, and 2.97 and 2.82 of the variation in Pb concentration under NCK+ and J2 treatments, respectively. The redundancy analysis showed that the samples under NCK+ and J2 treatments were clustered similarly in all growth stages. Also, Chytridiomycota, Mucoromucota, and Ciliophora were the key bioindicators for coping with heavy metals. Overall, a similar remediation mechanism allowed T. harzianum J2 to replace the nitrogen fertilizer to avoid secondary pollution. In addition, their combined use further increased the remediation efficiency.

Identification of Mycobacterium tuberculosis Resistance to Common Antibiotics: An Overview of Current Methods and Techniques.

Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication.

Novel drug-drug salt crystals of metformin with ibuprofen or naproxen: Improved solubility, dissolution rate, and synergistic antinociceptive effects.

As the monotherapy of available analgesics is usually accompanied by serious side effects or limited efficacy in the management of chronic pain, multimodal analgesia is widely used to achieve improved benefit-to-risk ratios in clinic. Drug-drug salts are extensively researched to optimize the physicochemical properties of active pharmaceutical ingredients (APIs) and achieve clinical benefits compared with individual APIs or their combination. New drug-drug salt crystals metformin-ibuprofen (MET-IBU) and metformin-naproxen (MET-NAP) were prepared from metformin (MET) and two poorly water-soluble anti-inflammatory drugs (IBU and NAP) by the solvent evaporation method. The structures of these crystals were confirmed by single crystal and powder X-ray diffraction, Hirshfeld surface, Fourier transform infrared spectroscopy and thermal analysis. Both MET-IBU and MET-NAP showed significantly improved solubility and intrinsic dissolution rate than the pure IBU or NAP. The stability test indicated that MET-IBU and MET-NAP have excellent physical stability under stressing test (10 days) and accelerated conditions (3 months). Moreover, isobolographic analysis suggested that MET-IBU and MET-NAP exerted potent and synergistic antinociceptive effects in λ-Carrageenan-induced inflammatory pain in mice, and both of them had an advantage in rapid pain relief. These results demonstrated the potential of MET-IBU and MET-NAP to achieve synergistic antinociceptive effects by developing drug-drug salt crystals.

Lifetime prevalence and associated factors of itch with skin conditions: Atopic dermatitis, psoriasis and dry skin in individuals aged over 50.

BACKGROUND: Itch, common in dermatological conditions, is often accompanied by psychological distress and reduced quality of life. However, research on the prevalence and associated factors of itch with skin conditions in general populations is limited. OBJECTIVES: This cross-sectional study aimed to determine the lifetime prevalence of itch with skin conditions and identify its associated factors in middle-aged and elderly individuals. METHODS: Participants from the Rotterdam Study, a population-based cohort, were interviewed to assess whether they had ever had an itchy skin condition, defining lifetime itch with skin conditions. Over 20 demographic, lifestyle, dermatological, and non-dermatological factors were collected. Multivariable logistic regression analysis explored associations between these factors and itch with skin conditions, reported as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: 5,246 eligible participants (age range: 51-100, median age: 67, female: 56.0%) revealed a lifetime prevalence of 33.7% for itch with skin conditions. Female sex (OR (95% CI): 1.26 (1.11-1.43)), body mass index (1.02 (1.01-1.03)), self-reported and presence of atopic dermatitis (4.29 (3.74-4.92), and 1.97 (1.60-2.43)), self-reported and presence of psoriasis (2.31 (1.77-3.01), and 2.11 (1.55-2.87)), self-reported dry skin (1.95 (1.73-2.29)), self-reported asthma (1.40 (1.08-1.83)), renal impairment (1.45 (1.17-1.79)), and clinically relevant depressive and anxiety symptoms (1.85 (1.52-2.25), and 1.36 (1.11-1.66)) were significantly associated with it. CONCLUSIONS: This study reveals a substantial one-third lifetime prevalence of itch with skin conditions in individuals aged over 50. Significant associations with diverse lifestyle, demographic, dermatological and, intriguingly, non-dermatological factors including renal impairment, imply additional contributors to itch induction or persistence in individuals with skin conditions.

Accumulation of Iron Oxide-Based Contrast Agents in Rabbit Atherosclerotic Plaques in Relation to Plaque Age and Vulnerability Features.

Purpose: In this study, a detailed characterization of a rabbit model of atherosclerosis was performed to assess the optimal time frame for evaluating plaque vulnerability using superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI). Methods: The progression of atherosclerosis induced by ballooning and a high-cholesterol diet was monitored using angiography, and the resulting plaques were characterized using immunohistochemistry and histology. Morphometric analyses were performed to evaluate plaque size and vulnerability features. The accumulation of SPIONs (novel dextran-coated SPIONDex and ferumoxytol) in atherosclerotic plaques was investigated by histology and MRI and correlated with plaque age and vulnerability. Toxicity of SPIONDex was evaluated in rats. Results: Weak positive correlations were detected between plaque age and intima thickness, and total macrophage load. A strong negative correlation was observed between the minimum fibrous cap thickness and plaque age as well as the mean macrophage load. The accumulation of SPION in the atherosclerotic plaques was detected by MRI 24 h after administration and was subsequently confirmed by Prussian blue staining of histological specimens. Positive correlations between Prussian blue signal in atherosclerotic plaques, plaque age, and macrophage load were detected. Very little iron was observed in the histological sections of the heart and kidney, whereas strong staining of SPIONDex and ferumoxytol was detected in the spleen and liver. In contrast to ferumoxytol, SPIONDex administration in rabbits was well tolerated without inducing hypersensitivity. The maximum tolerated dose in rat model was higher than 100 mg Fe/kg. Conclusion: Older atherosclerotic plaques with vulnerable features in rabbits are a useful tool for investigating iron oxide-based contrast agents for MRI. Based on the experimental data, SPIONDex particles constitute a promising candidate for further clinical translation as a safe formulation that offers the possibility of repeated administration free from the risks associated with other types of magnetic contrast agents.

Triglyceride-glucose index (TyG index) and endometrial carcinoma risk: A retrospective cohort study.

OBJECTIVE: We analyzed the association between the triglyceride-glucose index (TyG index) and incident endometrial carcinogenesis, aiming to determine whether the TyG index is a promising predictive biomarker for endometrial carcinoma (EC). METHODS: In this retrospective cohort study, multiple logistic regression analysis was performed to evaluate the relationship between TyG index and EC incidence and progression. The receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC), as well as the cut-off value of the TyG index for EC incidence. RESULTS: The TyG index was significantly higher in patients with EC or endometrial atypical hyperplasia (EAH) than in those with normal endometrium (P < 0.001). A continuous rise was observed in the incidence of EC and EAH among the tertiles of the TyG index (P < 0.001). The multiple logistic regression analysis revealed that the TyG index was associated with EC and EAH risk after adjusting for potential confounding factors (EAH: odds ratio [OR] 2.54, 95% confidence interval [CI] 1.33-4.85, P = 0.005; EC: OR 2.65, 95% CI 1.60-4.41, P < 0.001). Moreover, high TyG index was positively associated with advanced pathological stage (OR 2.14, 95% CI 1.32-3.47, P = 0.002) and poorer differentiation (OR 2.53, 95% CI 1.36-4.72, P = 0.004). CONCLUSION: The TyG index might be a promising biomarker for endometrial carcinogenesis. Subjects with a higher TyG index should be aware of the risk of EC incidence and progression.

Major Facilitator Superfamily Domain Containing 5 Inhibition Reduces Lipoprotein(a) Uptake and Calcification in Valvular Heart Disease.

BACKGROUND: High circulating levels of Lp(a) (lipoprotein[a]) increase the risk of atherosclerosis and calcific aortic valve disease, affecting millions of patients worldwide. Although atherosclerosis is commonly treated with low-density lipoprotein-targeting therapies, these do not reduce Lp(a) or risk of calcific aortic valve disease, which has no available drug therapies. Targeting Lp(a) production and catabolism may provide therapeutic benefit, but little is known about Lp(a) cellular uptake. METHODS: Here, unbiased ligand-receptor capture mass spectrometry was used to identify MFSD5 (major facilitator superfamily domain containing 5) as a novel receptor/cofactor involved in Lp(a) uptake. RESULTS: Reducing MFSD5 expression by a computationally identified small molecule or small interfering RNA suppressed Lp(a) uptake and calcification in primary human valvular endothelial and interstitial cells. MFSD5 variants were associated with aortic stenosis (P=0.027 after multiple hypothesis testing) with evidence suggestive of an interaction with plasma Lp(a) levels. CONCLUSIONS: MFSD5 knockdown suppressing human valvular cell Lp(a) uptake and calcification, along with meta-analysis of MFSD5 variants associating with aortic stenosis, supports further preclinical assessment of MFSD5 in cardiovascular diseases, the leading cause of death worldwide.

Residue Behavior of Chiral Fungicide Prothioconazole and Its Major Chiral Metabolite in Flour Product Processing.

This study systematically investigates the stereoselective metabolism and residue behavior of chiral pesticide prothioconazole enantiomers during the steaming, baking, and frying of steamed buns, bread, and deep-fried dough sticks. The results show that steaming, baking, and frying can significantly promote the degradation of the prothioconazole enantiomers. In low- and high-concentration treatments, the degradation rates of prothioconazole enantiomers were over 96.0% and 45.4%, respectively, and the residual concentration of prothioconazole-desthio enantiomers was less than 32.7 µg/kg (excluding fried processing). During the processing of steamed buns, bread, and deep-fried dough sticks, the enantiomer fraction (EF) value of the prothioconazole enantiomer was close to 0.5, and the stereoselectivity was not significant. During the processing of steamed buns (low concentration), bread (low and high concentrations), and deep-fried dough sticks (low concentration), the stereoselectivity of prothioconazole-desthio was significant, and preferential enantiomer degradation occurred. Following the analysis of 120 flour product samples, the residual risk.

The Potential Relationship Between Cardiovascular Diseases and Monkeypox.

Mpox, a novel epidemic disease, has broken out the period of coronavirus disease 2019 since May 2022, which was caused by the mpox virus. Up to 12 September 2023, there are more than 90,439 confirmed mpox cases in over 115 countries all over the world. Moreover, the outbreak of mpox in 2022 was verified to be Clade II rather than Clade I. Highlighting the significance of this finding, a growing body of literature suggests that mpox may lead to a series of cardiovascular complications, including myocarditis and pericarditis. It is indeed crucial to acquire more knowledge about mpox from a perspective from the clinical cardiologist. In this review, we would discuss the epidemiological characteristics and primary treatments of mpox to attempt to provide a framework for cardiovascular physicians.

A new perspective on the current and future development potential of ABCG1.

ABCG1 is an essential protein involved in the efflux of intracellular cholesterol to the extracellular space, thus playing a critical role in reducing cholesterol accumulation in neighboring tissues. Bibliometric analysis pertains to the interdisciplinary field of quantitative examination of diverse documents using mathematical and statistical techniques. It integrates the investigation of structural and temporal patterns in academic publications with an exploration of subject focus and forms of uncertainty. This research paper examines the historical evolution, current areas of interest, and future development trends of ABCG1 through bibliometric analysis. This study aims to offer readers insights into the research status and emerging trends of ABCG1, thereby assisting researchers in the exciting field to explore novel research avenues. Following rigorous selection, research on ABCG1 has remained highly active over the past two decades. ABCG1 has even started to emerge in previously unrelated fields, such as the field of cancer research. According to the analysis conducted by Citespace, a lot of keywords and influential citations were identified. ABCG1 has been found to establish a connection between cancer and cardiovascular disease, highlighting their interrelationship. This review aims to assist readers who have limited familiarity with ABCG1 research in gaining a rapid understanding of its developmental trajectory. Additionally, it aims to offer researchers potential areas of focus for future studies related to ABCG1.

Calpain-2 protein influences chikungunya virus replication and regulates vimentin rearrangement caused by chikungunya virus infection.

Chikungunya fever (CHIF), a vector-borne disease transmitted mainly by Aedes albopictus and Aedes aegypti, is caused by Chikungunya virus (CHIKV) infection. To date, it is estimated that 39% of the world's population is at risk of infection for living in countries and regions where CHIKV is endemic. However, at present, the cellular receptors of CHIKV remains not clear, and there are no specific drugs and vaccines for CHIF. Here, the cytotoxicity of calpain-2 protein activity inhibitor III and specific siRNA was detected by MTT assays. The replication of CHIKV was detected by qPCR amplification and plaque assay. Western blot was used to determine the level of the calpain-2 protein and vimentin protein. Immunofluorescence was also operated for detecting the rearrangement of vimentin protein. Our results indicated that calpain-2 protein activity inhibitor III and specific siRNA might suppress CHIKV replication. Furthermore, CHIKV infection led to vimentin remodeling and formation of cage-like structures, which could be inhibited by the inhibitor III. In summary, we confirmed that calpain-2 protein influenced chikungunya virus replication and regulated vimentin rearrangement caused by chikungunya virus infection, which could be important for understanding the biological significance of CHIKV replication and the future development of antiviral strategies.

Differential response of the soil nutrients, soil bacterial community structure and metabolic functions to different risk areas in Lead-Zine tailings.

Rapid growth in the mining industry has brought about a large formation of tailings, which result in serious destruction of the ecological environment and severe soil pollution problems. This study assesses soil nutrients, soil bacterial community and soil microbes' metabolic function in heavily polluted areas (W1), moderately polluted areas (W2), lightly polluted areas (W3) and clean areas (CK) using 16S Illumina sequencing. The results of this study showed that compared with CK, a severe loss of soil nutrients and richness of OTUs (Chao1 and ACE indices) were observed with the aggravated pollution of tailings. The Chao1 and ACE indices in the W1 group decreased significantly by 15.53 and 16.03%, respectively, (p < 0.01). Besides, the relative abundance of Actinobacteria and Proteobacteria was high whereas and relative abundance of Chloroflexi in the polluted areas. Among them, W1 groups increased significantly the relative abundance of Actinobacteria and decreased significantly the relative abundance of Chloroflexi, these can be used as indicator phyla for changes in soil community structures under polluted stress. Tax4 Fun analysis showed that W1 groups affected the soil bacterial community and altered the primary types of biological metabolism in polluted areas. Tailings have adverse impacts on soil bacterial community and metabolic functions, and the deterioration in soil quality is dependent on the levels of tailings pollution. Cumulatively, this study provides valuable information on the bacterial community structure and metabolic functions in the tailing polluted soil.

Research progress on the mechanism of Treponema pallidum breaking through placental barrier.

Congenital syphilis, a significant cause of fetal mortality worldwide, is a congenital infectious disease instigated by the vertical transmission of Treponema pallidum during pregnancy. Clinical manifestations include preterm delivery, stillbirth, neonatal skin lesions, skeletal abnormalities, and central nervous system aberrations. The ongoing increase in the incidence of congenital syphilis, coupled with complexities in diagnosis, necessitates a detailed understanding of its pathogenesis for the development of improved diagnostic approaches, and to interrupt the route of vertical transmission. Drawing from the broader body of research associated with vertical transmission pathogens, we aim to clarify the potential mechanisms by which Treponema pallidum breaches the placental barrier to infect the fetus.

Enhancing remediation potential of heavy metal contaminated soils through synergistic application of microbial inoculants and legumes.

Soil microorganisms play a crucial role in remediating contaminated soils in modern ecosystems. However, the potential of combining microorganisms with legumes to enhance the remediation of heavy metal-contaminated soils remains unexplored. To investigate this, we isolated and purified a highly efficient cadmium and lead-tolerant strain. Through soil-cultivated pot experiments with two leguminous plants (Robinia pseudoacacia L. and Sophora xanthantha), we studied the effects of applying this microbial agent on plant nutrient uptake of soil nutrients, heavy metal accumulation, and the dynamics of heavy metal content. Additionally, we examined the response characteristics of inter-root microbial and bacterial communities. The results demonstrated that microorganisms screened from heavy metal-contaminated soil environments exhibited strong survival and adaptability in heavy metal solutions. The use of the Serratia marcescens WZ14 strain-phytoremediation significantly increased the soil's ammonium nitrogen (AN) and organic carbon (OC) contents compared to monoculture. In addition, the lead (Pb) and cadmium (Cd) contents of the soil significantly decreased after combined remediation than those of the soil before potting. However, the remediation effects on Pb- and Cd-contaminated soils differed between the two legumes following the Serratia marcescens WZ14 inoculation. The combined restoration altered the composition of the plant inter-rhizosphere bacterial community, with the increase in the relative abundance of both Proteobacteria and Firmicutes. Overall, the combined remediation using the tolerant strain WZ14 with legumes proved advantageous. It effectively reduced the heavy metal content of the soil, minimized the risk of heavy metal migration, and enhanced heavy metal uptake, accumulation, and translocation in the legumes of S. xanthantha and R. pseudoacacia. Additionally, it improved the adaptability and resistance of both legumes, leading to an overall improvement in the soil's environmental quality. These studies can offer primary data and technical support for remediating and treating Cd and Pb in soils, as well as rehabilitating mining sites.

Preparation of astrocytes by directed differentiation of pluripotent stem cells and somatic cell transdifferentiation.

Astrocytes (ACs) are the most widely distributed cells in the mammalian central nervous system, which are essential for the function and homeostasis of nervous system. Increasing evidence indicates that ACs also participate in the development of many neurological diseases and repair after nerve injury. ACs cultured in vitro provide a cellular model for studying astrocytic development, function, and the pathogenesis of associated diseases. The preparation of primary ACs (pACs) faces many limitations, so it is important to obtain high-quality ACs by the differentiation of pluripotent stem cell (PSC) or somatic cell transdifferentiation. Initially, researchers mainly tried to induce embryonic stem cells to differentiate into ACs via embryoid body (EB) and then turned to employ induced PSCs as seed cells to explore more simple and efficient directed differentiation strategies, and serum-free culture was delved to improve the quality of induced ACs. While exploring the induction of ACs by the overexpression of AC-specific transcription factors, researchers also began to investigate small molecule-mediated somatic cell transdifferentiation. Here, we provide an updated review on the research progresses in this field.

[Preparation of porous organic cage and its use as chiral stationary phase for capillary electrochromatography].

Porous organic cages (POCs) are a unique type of microporous materials composed of discrete molecules with internal cavities that are accessible to various compounds. In this study, a prismatic chiral POC with good thermochemical stability was synthesized by condensing (1R,2R)-diaminocyclohexane and 3,3',5,5'-teturonic-4,4'-biphenediol via the Schiff base reaction and characterized by proton nuclear magnetic resonance spectroscopy, infrared (IR) spectroscopy, thermogravimetric analysis (TGA), and scanning electron microscopy. The IR spectrum of the POC revealed a strong characteristic absorption peak at 1635 cm-1, indicating that it formed imine bonds (C=N). The absorption peak at 3425 cm-1 was attributed to the stretching vibrations of -OH, the absorption peaks at 2925 and 2858 cm-1 were attributed to the stretching vibrations of N=C-H and C-H, and the absorption peaks at 1446 and 1383 cm-1 were attributed to the stretching vibrations of C=C-H and C=C in the benzene ring. High-resolution mass spectral analysis of the POC showed a molecular ion peak at m/z 1363.7228, indicating its successful synthesis. TGA was performed from 25 to 800 ℃ at a rate of 10 ℃/min, and the results of this analysis showed that the POC was stable up to approximately 300 ℃. The POC was dissolved in dichloromethane and uniformly coated on the inner wall of a quartz capillary via the dynamic coating method to prepare a capillary electrochromatographic column. The experimental results revealed that the chiral electrochromatographic column could not only resolve ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-amyl alcohol but also separate the isomers of o-, m-, and p-toluidine and o-, m-, and p-chloroaniline, indicating its good chiral separation ability. Investigation of the optimal separation conditions for ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-amyl alcohol revealed that the voltage, buffer solution concentration, and pH significantly affected their separation degree. In particular, the optimal separation voltage for ofloxacin, Troger's base, and 2-amino-1-butanol was 15 kV, while that for 1-phenyl-1-amyl alcohol was 17 kV. The optimal buffer concentration and pH for ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-amyl alcohol were 0.100 mol/L and 7.5. Under optimal chromatographic conditions, the resolution values for ofloxacin, Troger's base, 2-amino-1-butanol, and 1-phenyl-1-pentanol were 1.80, 3.33, 1.69, and 1.18, respectively. The results collectively demonstrate that the prepared POC may serve as a good chiral stationary phase for capillary electrochromatography with a certain chiral resolution ability and has good application prospects in chromatographic separation.

The outer membrane protein Tp92 of Treponema pallidum delays human neutrophil apoptosis via the ERK, PI3K/Akt, and NF-κB pathways.

Syphilis is a persistent sexually transmitted disease caused by infiltration of the elusive pathogen Treponema pallidum. Despite the prevalence of human polymorphonuclear neutrophils (hPMNs) within cutaneous lesions, which are characteristic of incipient syphilis, their role in T. pallidum infection remains unclear. Tp92 is the only T. pallidum helical outer membrane protein that exhibits structural features similar to those of outer membrane proteins in other gram-negative bacteria. However, the functional mechanism of this protein in immune cells remains unclear. Neutrophils are short-lived cells that undergo innate apoptosis in response to external stimuli that typically influence this process. In this study, we determined that Tp92 impedes the activation of procaspase-3 via the ERK MAPK, PI3K/Akt, and NF-κB signaling pathways, consequently suppressing caspase-3 activity within hPMNs, and thereby preventing hPMNs apoptosis. Furthermore, Tp92 could also modulate hPMNs apoptosis by enhancing the expression of the anti-apoptotic protein Mcl-1, stimulating IL-8 secretion, and preserving the mitochondrial membrane potential. These findings provide valuable insights into the molecular mechanisms underlying T. pallidum infection and suggest potential therapeutic targets for syphilis treatment.