Synthesis of Asp-based lactam cyclic peptides using an amide-bonded diaminodiacid to prevent aspartimide formation.

Asp-based lactam cyclic peptides are considered promising drug candidates. However, using Fmoc solid-phase peptide synthesis (Fmoc-SPPS) for these peptides also causes aspartimide formation, resulting in low yields or even failure to obtain the target peptides. Here, we developed a diaminodiacid containing an amide bond as a ß-carboxyl-protecting group for Asp to avoid aspartimide formation. The practicality of this diaminodiacid has been illustrated by the synthesis of lactam cyclic peptide cyclo[Lys9,Asp13] KIIIA7-14 and 1Y.

Nitrate transformation and source tracking of Yarlung Tsangpo River using a multi-tracer approach combined with Bayesian stable isotope mixing model.

Excessive levels of nitrate nitrogen (NO3--N) could lead to ecological issues, particularly in the Yarlung Tsangpo River (YTR) region located on the Qinghai Tibet Plateau. Therefore, it is crucial to understand the fate and sources of nitrogen to facilitate pollution mitigation efforts. Herein, multiple isotopes and source resolution models were applied to analyze key transformation processes and quantify the sources of NO3-. The δ15N-NO3- and δ18O-NO3- isotopic compositions in the YTR varied between 1.23‰-13.64‰ and -7.98‰-11.19‰, respectively. The NO3--N concentrations varied from 0.08-0.86 mg/L in the dry season and 0.20-1.19 mg/L during the wet season. Nitrification remained the primary process for nitrogen transformation in both seasons. However, the wet season had a widespread effect on increasing nitrate levels, while denitrification had a limited ability to reduce nitrate. The elevated nitrate concentrations during the flood season were caused by increased release of NO3- from manure & sewage (M&S) and chemical fertilizers (CF). Future endeavors should prioritize enhancing management strategies to improve the utilization efficiency of CF and hinder the direct entry of untreated sewage into the water system.

[Optimization of prediction model for personalized water pills based on semantic analysis of traditional Chinese medicine materials].

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

[Composite excipients for preparing concentrated water pills of personalized traditional Chinese medicine prescriptions by extruding-rounding method].

This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrin∶microcrystalline cellulose(MCC)∶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1∶2∶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.

[Research practice and development direction of intelligent manufacturing of presonalized traditional Chinese medicine preparations].

In recent years, as people's living standards continue to improve, and the pace of life accelerates dramatically, the demand and quality of traditional Chinese medicine(TCM) services from patients continue to rise. As an essential supplement to the existing forms of TCM application, such as Chinese patent medicine, decoction, and formulated granules, presonalized TCM preparations is facing an increasing market demand. Currently, manual and semi-mechanized production are the primary production ways in presonalized TCM preparations. However, the production process control level is low, and digitalization and informatization need to be improved, which restricts the automated and intelligent development of presonalized TCM preparations. Presonalized TCM preparations faces a significant opportunity and challenge in integrating with intelligent manufacturing through research and development of intelligent equipment and core technology. This paper overviews the connotation and characteristics of intelligent manufacturing and summarizes the application of intelligent manufacturing technologies such as "Internet of things" "big data", and "artificial intelligence" in the TCM industry. Based on the innovative research and development model of "intelligent classification of TCM materials, intelligent decision making of prescription and process, and online control and intelligent production" of presonalized TCM preparations, the research practice and achievements from our research group in the field of intelligent manufacturing of presonalized TCM preparations are introduced. Ultimately, the paper proposes the direction for developing intelligent manufacturing of presonalized TCM preparations, which will provide a reference for the research and application of automation and intelligence of presonalized TCM preparations.

[Molding law of traditional Chinese medicine gel plaster based on physicochemical properties of raw materials and intermediates].

This paper aims to study the correlation between the physicochemical properties of raw materials and intermediates and the molding quality and law of traditional Chinese medicine(TCM) gel plaster by using TCM slices and powder as raw materials. 48 TCM compounds are selected as model prescriptions to prepare gel plasters. The rotational rheometer is used to determine the rheological parameters of the plaster, including storage modulus(G'), loss modulus(G″), yield stress(τ), and creep compliance [J(t)]. The molding quality of the prepared TCM gel plaster is evaluated by subjective and objective measures. Clustering and principal component analysis are conducted to evaluate the physical properties of the plaster. By measuring the rheological properties of the plaster, the molding quality of the TCM gel plaster can be predicted, with an accuracy of 83.72% after seven days of modeling and 88.37% after 30 days of modeling. When the parameters such as G' and G″ of the plaster are large, and the [J(t)] is small, the molding quality of the plaster is better. When the plaster coating point is no less than 3, it is difficult to be coated. In addition, when the proportion of metal ions in the prescription is higher, the 30-day forming quality of the plaster is mainly affected, and the viscosity of the plaster is poor. If the prescription contains many acidic chemical components, the 7-day forming quality of the plaster is mainly affected, with many residuals. The results suggest that the rheological properties of the plaster can be used to predict the molding quality of TCM slice and powder gel plaster. It can provide a reference for the development of TCM gel plaster prescriptions.

[Intelligent material classification of traditional Chinese medicine based on semantic analysis].

A method for material classification of traditional Chinese medicines based on the physical properties of powder has been established by our research group. This method involves pre-treatment of traditional Chinese medicine decoction pieces, powder preparation, and determination of physical properties, being cumbersome. In this study, the word segmentation logic of semantic analysis was adopted to establish the thesaurus and local standardized semantic word segmentation database with the macroscopic and microscopic characteristics of 36 model traditional Chinese medicines as the basic data. The physical properties of these medicines have been determined and the classification of these medicines is clear in the cluster analysis. A total of 55 keywords for powdery, fibrous, sugary, oily, and brittle materials were screened by association rules and the set inclusion and exclusion criteria, and the weights of the keywords were calculated. Furthermore, the algorithms of the keyword matching scores and the computation rules of the single or multiple material classification were established for building the intelligent model of semantic analysis for the material classification. The semantic classification results of the other 35 TCMs except Pseudostellariae Radix(multi-material medicine) agreed with the clustering results based on the physical properties of the powder, with an agreement rate of 97.22%. In model validation, the prediction results of semantic classification of traditional Chinese medicines were consistent with the clustering results based on the physical properties of powder, with an agreement rate of 83.33%. The results showed that the method of material classification based on semantic analysis was feasible, which laid a foundation for the development of intelligent decision-making technology for personalized traditional Chinese medicine preparations.

[Molding matrix formulation of hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine preparations].

This study aims to optimize the matrix formulation for the hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine(TCM) preparations and verify the applicability of the formulation. The central composite design in JMP Pro 16.1.0 was employed to optimize the dosages of styrene-isoprene-styrene triblock copolymer(SIS), hydrogenated petroleum resin, and lightweight liquid paraffin, with the fine powder of Yipifang as the model drug(drug loading of 10%) and the sensory score and objective evaluation as the comprehensive evaluation indicators. The quality evaluation system of hot-melt pressure-sensitive adhesive plaster of personalized TCM preparations was established. The applicability of the optimized matrix formulation of hot-melt pressure-sensitive adhesive plaster was verified with 16 TCM preparations for external application. Furthermore, the applicability of the matrix formulation was investigated with different drug loadings. The general molding matrix formulation was SIS∶hydrogenated petroleum resin∶lightweight liquid paraffin 3∶3∶5. The optimized matrix formulation showed good molding properties and high quality scores for 16 TCM preparations and were suitable for the plastering of finely powdered decoction pieces with a loading capacity of 10% to 30%. The results suggest that the optimized matrix formulation has good applicability and is suitable for TCM preparations. The findings lay a foundation for the application and promotion of the hot-melt pressure-sensitive adhesive plasters of personalized TCM preparations.

[Preparation process selection of presonalized traditional Chinese medicine concentrated watered pills containing heat-unstable components].

In the process of preparing presonalized concentrated watered pills, the decoction needs to be concentrated by heat and mixed with medicinal slices or powder to prepare a wet mass. However, some of the traditional Chinese medicine(TCM) components are easily decomposed or transformed by heat. In order to optimize the preparation process of presonalized TCM concentrated watered pills and reduce the loss of heat-unstable components in prescriptions, this study uses five compound TCM prescriptions containing heat-unstable components as model prescriptions, namely the Linggui Zhugan Formula, Xiaochengqi Formula, Sanpian Formula, Xiaoer Qixing Formula, and Xiaoyao Formula. Based on the two kinds of preparation process of presonalized concentrated watered pills previously established by our research group, whole extract concentrated watered pills and concentrated watered pills without excipients are prepared, respectively. Characteristic maps are measured and compared with those of the corresponding decoction. The results show that the characteristic maps of the concentrated watered pills without excipients of the five model prescriptions are very close to those of the decoction, and the number of characteristic peaks and peak areas are higher than those of whole extract concentrated watered pills. In addition, the peak area of some peaks is higher than that of the corresponding decoction. Thus, it is recommended to select the preparation process of prescription-based concentrated watered pills without excipients based on the "unification of medicines and excipients" to preserve those heat-unstable components more effectively when the prescription contains a heat-unstable component of TCM. This study provides a basis for the subsequent reasonable development and application of presonalized TCM pills.

The Ideal Proportion of the Auricle Exposure via a Morphometric Analysis in Asian Women.

BACKGROUND: Ears are an important aesthetic feature that is vital to the overall attractiveness of the face. Although there have been many studies on the aesthetics of the auricle, there is currently a lack of consensus on the ideal proportion of auricle exposure for Asian women in frontal view. OBJECTIVES: This study aimed to investigate ideal proportion of auricle exposure in Asian women. METHODS: An observational study was carried out on the photographs of 84 women on the list of the 100 most beautiful faces in Asia (published by TCC Asia in 2020). The proportion of the distance between the outer canthus and the outermost point of auricle to the distance between the inner canthus and the outermost point of auricle was calculated as the auricle exposure proportion. Evaluators were asked to rank a set of photographs of the volunteer with varying auricle exposure proportions from most attractive to least attractive. RESULTS: Measurements of the photographs of the 84 women showed a mean ear exposure proportion of 0.600. With 487 questionnaire responses received, the proportion of auricle exposure that the evaluators considered most attractive was 0.600. People with aesthetic experience considered 0.625 the most attractive proportion, while the general group considered 0.600 the most attractive. CONCLUSIONS: The ideal proportion of the auricle exposure for Asian women is in the range of 0.60-0.625, which may help surgeons reconstruct aesthetically pleasing ears. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A missense mutation in human INSC causes peripheral neuropathy.

PAR3/INSC/LGN form an evolutionarily conserved complex required for asymmetric cell division in the developing brain, but its post-developmental function and disease relevance in the peripheral nervous system (PNS) remains unknown. We mapped a new locus for axonal Charcot-Marie-Tooth disease (CMT2) and identified a missense mutation c.209 T > G (p.Met70Arg) in the INSC gene. Modeling the INSCM70R variant in Drosophila, we showed that it caused proprioceptive defects in adult flies, leading to gait defects resembling those in CMT2 patients. Cellularly, PAR3/INSC/LGN dysfunction caused tubulin aggregation and necrotic neurodegeneration, with microtubule-stabilizing agents rescuing both morphological and functional defects of the INSCM70R mutation in the PNS. Our findings underscore the critical role of the PAR3/INSC/LGN machinery in the adult PNS and highlight a potential therapeutic target for INSC-associated CMT2.

Therapeutic potential of tyrosine-protein kinase MET in osteosarcoma.

Osteosarcoma, the most prevalent primary bone tumor in children and young adults, can often be successfully treated with standard chemotherapy and surgery when diagnosed at an early stage. However, patients presenting with metastases face significant challenges in achieving a cure. Despite advancements in classical therapies over the past few decades, clinical outcomes for osteosarcoma have not substantially improved. Recently, there has been increased understanding of the biology of osteosarcoma, leading to the identification of new therapeutic targets. One such target is MET, a tyrosine kinase receptor for Hepatocyte Growth Factor (HGF) encoded by the MET gene. In vitro and in vivo studies have demonstrated that the HGF/MET pathway plays a crucial role in cancer growth, invasion, metastasis, and drug resistance across various cancers. Clinical trials targeting this pathway are already underway for lung cancer and hepatocellular carcinoma. Moreover, MET has also been implicated in promoting osteosarcoma progression. This review summarizes 3 decades' worth of research on MET's involvement in osteosarcoma and further explores its potential as a therapeutic target for patients with this disease.

Eccrine porocarcinoma in the tempus of an elderly woman: A case report.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin tumor that mainly affects the elderly population. Tumors often present with slow growth and a good prognosis. EPCs are usually distinguished from other skin tumors using histopathology and immunohistochemistry. However, surgical management alone may be inadequate if the tumor has metastasized. However, currently, surgical resection is the most commonly used treatment modality. CASE SUMMARY: A seventy-four-year-old woman presented with a slow-growing nodule in her left temporal area, with no obvious itching or pain, for more than four months. Histopathological examination showed small columnar and short spindle-shaped cells; thus, basal cell carcinoma was suspected. However, immunohistochemical analysis revealed the expression of cytokeratin 5/6, p63 protein, p16 protein, and Ki-67 antigen (40%), and EPC was taken into consideration. The skin biopsy was repeated, and hematoxylin and eosin staining revealed ductal differentiation in some cells. Finally, the patient was diagnosed with EPC, and Mohs micrographic surgery was performed. We adapted follow-up visits in a year and not found any recurrence of nodules. CONCLUSION: This case report emphasizes the diagnosis and differentiation of EPC.

Nutritional support therapy for liver transplantation in an adult-onset type II citrullinemia patient: a case report.

Liver transplantation is an effective measure to treat adult-onset type II citrullinemia (CTLN2). Active and effective perioperative nutrition support is a very important treatment for the prognosis of such patients. In this paper, we analyzed the process, results, and outcome of nutritional support therapy in a case of CTLN2, and concluded that the perioperative nutritional support program for CTLN2 patients should be followed prior to surgery:1.because of the prevalence of severe malnutrition in CTLN2 patients, Enteral nutrition (EN) combined with Parenteral nutrition (PN) should be the first choice for nutritional support; 2. daily energy intake should be 35 ~ 40 kcal/kg; 3. the nutritional formula should be composed of low-carbohydrates and high medium-chain triglyceride (MCT). Postoperative: initiating EN as soon as possible is recommended to restore intestinal function and adjuvant PN might be taken into consideration in the early stage. The purpose of this case was to provide experience for the development and adjustment of the perioperative nutritional support regimen for CTLN2 patients.

Weighted gene co-expression network analysis reveals key biomarkers and immune infiltration characteristics for bronchial epithelial cells from asthmatic patients.

BACKGROUND: Asthma ranks among the most prevalent non-communicable diseases worldwide. Previous studies have elucidated the significant role of the immune system in its pathophysiology. Nevertheless, the immune-related mechanisms underlying asthma are complex and still inadequately understood. Thus, our objective was to investigate novel key biomarkers and immune infiltration characteristics associated with asthma by employing integrated bioinformatics tools. METHODS: In this study, we conducted a weighted gene co-expression network analysis (WGCNA) to identify key modules and genes potentially implicated in asthma. Functional annotation of these key modules and genes was carried out through gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Additionally, we constructed a protein-protein interaction (PPI) network using the STRING database to identify 10 hub genes. Furthermore, we evaluated the relative proportion of immune cells in bronchial epithelial cell samples from 20 healthy individuals and 88 asthmatic patients using CIBERSORT. Finally, we validated the hub genes and explored their correlation with immune infiltration. RESULTS: Furthermore, 20 gene expression modules and 10 hub genes were identified herein. Among them, complement component 3 (C3), prostaglandin I2 receptor (PTGIR), parathyroid hormone-like hormone (PTHLH), and C-X3-C motif chemokine ligand 1 (CX3CL1) were closely correlated with the infiltration of immune cells. They may be novel candidate biomarkers or therapeutic targets for asthma. Furthermore, B cells memory, and plasma cells might play an important role in immune cell infiltration after asthma. CONCLUSIONS: C3, PTGIR, CX3CL1, and PTHLH have important clinical diagnostic values and are correlated with infiltration of multiple immune cell types in asthma. These hub genes, B cells memory, and plasma cells may become important biological targets for therapeutic asthma drug screening and drug design.

Rationally designing of Co-WS2 catalysts with optimized electronic structure to enhance hydrogen evolution reaction.

Designing and developing cost-effective, high-performance catalysts for hydrogen evolution reaction (HER) is crucial for advancing hydrogen production technology. Tungsten-based sulfides (WSx) exhibit great potential as efficient HER catalysts, however, the activity is limited by the larger energy required for water dissociation under alkaline conditions. Herein, we adopt a top-down strategy to construct heterostructure Co-WS2 nanofiber catalysts. The experimental results and theoretical simulations unveil that the work functions-induced built-in electric field at the interface of Co-WS2 catalysts facilitates the electron transfer from Co to WS2, significantly reducing water dissociation energy and optimizing the Gibbs free energy of the entire reaction step for HER. Besides, the self-supported catalysts of Co-WS2 nanoparticles confining 1D nanofibers exhibit an increased number of active sites. As expected, the heterostructure Co-WS2 catalysts exhibit remarkable HER activity with an overpotential of 113 mV to reach 10 mA cm-2 and stability with 30 h catalyzing at 23 mA cm-2. This work can provide an avenue for designing highly efficient catalysts applicable to the field of energy storage and conversion.

Isolation and biomimetic synthesis of phenylpropionyl phenylethylamines from Chloranthus henryi.

In this study, ten phenylpropionyl phenylethylamines, including five previously undescribed ones (1a/b, 2a/b, and 3), five known analogues (4 - 8), and two established phenylpropanoids precursors (9, 10) were isolated from the aerial parts of Chloranthus henryi Hemsl. Their structures, including absolute configurations, were determined by high-resolution mass spectrometry, enantio-separation, electronic circular dichroism calculation, and single crystal diffraction. Compounds 1a and 1b were the first examples of natural hetero-[2 + 2] cycloaddition products between phenylpropionyl phenylethylamine and phenylpropene. The plausible hetero-[2 + 2] biosynthesis pathway was confirmed by a photocatalytic biomimetic synthesis in eight steps, which also led to the production of three other potential natural homo-[2 + 2] adducts (1'a/b, 2', and 3'). Bioactivity screening indicated that these adducts bear medium inhibitory activity on nitric oxide generation, with IC50 values of 6 - 35 µM in RAW 264.7 macrophages.

[Evidence mapping of Chinese patent medicines in treatment of premature ventricular contractions].

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.

Exploring the mechanism of Corbrin capsules in the intervention of AKI-COVID-19 based on network pharmacology combined with GEO dataset.

AIM: of the study: This study used network pharmacology and the Gene Expression Omnibus (GEO) database to investigate the therapeutic effects of Corbrin capsules on acute kidney injury (AKI)-COVID-19 (coronavirus disease 2019). MATERIALS AND METHODS: The active constituents and specific molecular targets of Corbrin capsules were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. The targets related to AKI and COVID-19 disease were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, and GEO databases. A protein-protein interaction (PPI) network was constructed by utilizing Cytoscape. To enhance the analysis of pathways associated with the pathogenesis of AKI-COVID-19, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Furthermore, immune infiltration analysis was performed by using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT. Molecular docking was used to assess interactions between differentially expressed genes and active ingredients. Verification was performed by utilizing GEO databases and in vivo assays. RESULTS: This study revealed an overlap of 18 significantly differentially expressed genes between the Corbrin capsules group and the AKI-COVID-19 target group. Analysis of the PPI network identified TP53, JAK2, PIK3CA, PTGS2, KEAP1, and MCL1 as the top six core protein targets with the highest degrees. The results obtained from GO and KEGG analyses demonstrated that the target genes were primarily enriched in the apoptosis and JAK-STAT signaling pathways. Moreover, the analysis of immune infiltration revealed a notable disparity in the percentage of quiescent memory CD4 + T cells. Western blot analyses provided compelling evidence suggesting that the dysregulation of 6 core protein targets could be effectively reversed by Corbrin capsules. CONCLUSION: This study revealed the key components, targets, and pathways involved in treating AKI-related COVID-19 using Corbrin capsules. This study also provided a new understanding of the molecular mechanisms underlying this treatment.

The causal effect of air pollution on the risk of essential hypertension: a Mendelian randomization study.

Background: Air pollution poses a major threat to human health by causing various illnesses, such as cardiovascular diseases. While plenty of research indicates a correlation between air pollution and hypertension, a definitive answer has yet to be found. Methods: Our analyses were performed using the Genome-wide association study (GWAS) of exposure to air pollutants from UKB (PM2.5, PM10, NO2, and NOX; n = 423,796 to 456,380), essential hypertension from FinnGen (42,857 cases and 162,837 controls) and from UKB (54,358 cases and 408,652 controls) as a validated cohort. Univariable and multivariable Mendelian randomization (MR) were conducted to investigate the causal relationship between air pollutants and essential hypertension. Body mass index (BMI), alcohol intake frequency, and the number of cigarettes previously smoked daily were included in multivariable MRs (MVMRs) as potential mediators/confounders. Results: Our findings suggested that higher levels of both PM2.5 (OR [95%CI] per 1 SD increase in predicted exposure = 1.24 [1.02-1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02-1.06], p = 7.58E-05 from UKB) and PM10 (OR [95%CI] = 1.24 [1.02-1.53], p = 3.46E-02 from Finn; OR [95%CI] = 1.04 [1.02-1.06], p = 7.58E-05 from UKB) were linked to an increased risk for essential hypertension. Even though we used MVMR to adjust for the impacts of smoking and drinking on the relationship between PM2.5 exposure and essential hypertension risks, our findings suggested that although there was a direct positive connection between them, it is not present after adjusting BMI (OR [95%CI] = 1.05 [0.87-1.27], p = 6.17E-01). Based on the study, higher exposure to PM2.5 and PM10 increases the chances of developing essential hypertension, and this influence could occur through mediation by BMI. Conclusion: Exposure to both PM2.5 and PM10 is thought to have a causal relationship with essential hypertension. Those impacted by substantial levels of air pollution require more significant consideration for their cardiovascular health.