Lactylation Modification in Cardiometabolic Disorders: Function and Mechanism.

Cardiovascular disease (CVD) is recognized as the primary cause of mortality and morbidity on a global scale, and developing a clear treatment is an important tool for improving it. Cardiometabolic disorder (CMD) is a syndrome resulting from the combination of cardiovascular, endocrine, pro-thrombotic, and inflammatory health hazards. Due to their complex pathological mechanisms, there is a lack of effective diagnostic and treatment methods for cardiac metabolic disorders. Lactylation is a type of post-translational modification (PTM) that plays a regulatory role in various cellular physiological processes by inducing changes in the spatial conformation of proteins. Numerous studies have reported that lactylation modification plays a crucial role in post-translational modifications and is closely related to cardiac metabolic diseases. This article discusses the molecular biology of lactylation modifications and outlines the roles and mechanisms of lactylation modifications in cardiometabolic disorders, offering valuable insights for the diagnosis and treatment of such conditions.

The Roles of Exosome-Derived microRNAs in Cardiac Fibrosis.

Cardiovascular disease (CVD) stands as the foremost cause of patient mortality, and the lack of early diagnosis and defined treatment targets significantly contributes to the suboptimal prevention and management of CVD. Myocardial fibrosis (MF) is not only a complex pathogenic process with no effective treatment currently available but also exerts detrimental effects on the progression of various cardiovascular diseases, thereby escalating their mortality rates. Exosomes are nanoscale biocommunication vehicles that facilitate intercellular communication by transporting bioactive substances, such as nucleic acids and proteins, from specific cell types. Numerous studies have firmly established that microRNAs (miRNAs), as non-coding RNAs, wield post-transcriptional regulatory mechanisms and exhibit close associations with various CVDs, including coronary heart disease (CHD), atrial fibrillation (AF), and heart failure (HF). MiRNAs hold significant promise in the diagnosis and treatment of cardiovascular diseases. In this review, we provide a concise introduction to the biological attributes of exosomes and exosomal miRNAs. We also explore the roles and mechanisms of distinct cell-derived exosomal miRNAs in the context of myocardial fibrosis. These findings underscore the pivotal role of exosomes in the diagnosis and treatment of cardiac fibrosis and emphasize their potential as biotherapies and drug delivery vectors for cardiac fibrosis treatment.

Observation of the validity of the upper lip bite test in predicting difficult intubation.

The upper lip bite test (ULBT) is considered an effective method for predicting difficult airways, but data on the ULBT for predicting difficult tracheal intubation are lacking. This study aimed to examine the clinical utility of the ULBT in predicting difficult endotracheal intubation. We conducted an observational case-cohort study of adult patients undergoing elective surgery and requiring endotracheal intubation for general anesthesia. Difficult airway assessment was performed on the recruited patients before the operation, including the ULBT, mouth opening, thyromental distance, modified Mallampati test, and body mass index. The primary outcome was the incidence of difficult tracheal intubation. The receiver operating characteristic curve analysis was used to compare the performance of variables in predicting difficult tracheal intubation. We successfully recruited 2522 patients for analysis and observed 64 patients with difficult tracheal intubation. When predicting difficult tracheal intubation, grade 2 ULBT had a sensitivity of 0.75 and a specificity of 0.54, and grade 3 had a sensitivity of 0.28 and a specificity of 0.75. Compared with mouth opening, the area under the receiver operating characteristic curve of the ULBT was lower in predicting difficult tracheal intubation (0.69 [95% confidence interval: 0.67-0.71] vs. 0.84 [95% confidence interval: 0.82-0.87], P < 0.05).Clinical Trials Registry: ChiCTR-ROC-16009050, principal investigator: Weidong Yao.

Development and validation of a screening method for difficult tracheal intubation based on geometric simulation and computer technology.

BACKGROUND: The anatomical characteristics of difficult airways can be analysed geometrically. This study aims to develop and validate a geometry-assisted difficult airway screening method (GADAS method) for difficult tracheal intubation. METHODS: In the GADAS method, a geometric simulated model was established based on computer graphics. According to the law of deformation of the upper airway on laryngoscopy, the expected visibility of the glottis was calculated to simulate the real visibility on laryngoscopy. Validation of the new method: Approved by the Ethics Committee of Yijishan Hospital of Wannan Medical College. Adult patients who needed tracheal intubation under general anaesthesia for elective surgery were enrolled. The data of patients were input into the computer software to calculate the expected visibility of the glottis. The results of tracheal intubation were recorded by anaesthesiologists. The primary observation outcome was the screening performance of the expected visibility of the glottis for difficult tracheal intubation. RESULTS: The geometric model and software of the GADAS method were successfully developed and are available for use. We successfully observed 2068 patients, of whom 56 patients had difficult intubation. The area under the receiver operating characteristic curve of low expected glottis visibility for predicting difficult laryngoscopy was 0.96 (95% confidence interval [CI]: 0.95-0.96). The sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 94.3% (95% CI: 93.2%-95.3), respectively. CONCLUSIONS: It is feasible to screen difficult-airway patients by applying computer techniques to simulate geometric changes in the upper airway.

n-Type doping of BiVO4 with different F-doped concentrations for improving the electronic character of BiVO4 as a photoanode nanomaterial for solar water splitting: a first-principles study.

Atom doping has been realized as an effective way to improve the photocatalytic performance of the most promising photoanode material, BiVO4, but the effects of doping mass concentration still need to be explored. In this work, the effects of F-doping with different doping mass concentrations (1%, 2%, 5%, 10%, 15%, and 20%) on the electronic character of BiVO4 were examined theoretically using density functional theory (DFT) calculations. The thermal stability of BiVO4 with different F-doped mass concentrations was confirmed using formation energy (Ef) calculations though F-doped BiVO4 becomes harder as the mass concentration of induced dopants increases. n-Type doping effects on the electronic character of BiVO4 were observed upon F-doping, leading to the energy level of CBM shifting far away from the Fermi level and giving F-doped BiVO4 metallic character. Moreover, a linear relationship between the frontier energy level shifts and the total charge transfer amounts from doped F atoms to other atoms involved in F-doped BiVO4 was observed, which means the oxidizing capacity of the VBM is increased and the reducing capacity of the CBM is decreased upon increased F-doped mass concentration. Moreover, the recombination of photogenerated electron-hole pairs is suppressed by F-doping strategies, which will not change a lot with the increased F-doped mass concentration. This means atom doping is an effective strategy to improve the photocatalytic efficiency of the BiVO4, but the number of atoms introduced into BiVO4 should be appropriate.

Fufang Zhenzhu Tiaozhi (FTZ) capsule ameliorates diabetes-accelerated atherosclerosis via suppressing YTHDF2-mediated m6A modification of SIRT3 mRNA.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu TiaoZhi (FTZ), a Chinese medicinal decoction, has continuously been used to treat metabolic syndrome. Atherosclerosis is the main pathological basis of cardiovascular disease. The N6 methyladenosine (m6A) modification is a highly dynamic and reversible process involving a variety of important biological processes. AIM OF THE STUDY: Here, we investigated the therapeutic effects and mechanism of FTZ in diabetes-accelerated atherosclerosis. MATERIALS AND METHODS: Doppler ultrasonography was used to examine the carotid intima-media thickness and plaque area in diabetic atherosclerosis patients. HFD mice were injected with streptozotocin to induce diabetes. HE and Oil red O staining were used to assess the effect of FTZ on lipid deposition. HUVECs were induced with HG/ox-LDL as a model of diabetic atherosclerosis. Furthermore, application of m6A methylation level kit, qRT-PCR, Western blot, tunel staining, reactive oxygen species staining and mPTP staining were performed to analyze the detailed mechanism. RESULTS: Clinical trials of FTZ have shown obvious effect of lowering blood glucose and blood lipids. These effects were reversed after FTZ intervention. Compared with the control, lipid deposition decreased significantly after FTZ administration. FTZ reduced endothelial cell apoptosis. At the same time, we found that FTZ reversed the increase of methylation reader YTHDF2 caused by ox-LDL treatment. Subsequently, we discovered that YTHDF2 degraded SIRT3 mRNA, leading to endothelial cell apoptosis and oxidative stress. CONCLUSION: FTZ attenuated diabetes-accelerated atherosclerosis by decreasing blood glucose and serum lipids levels, and increased endothelial cell antioxidant capacity, inhibited endothelial cell apoptosis via inhibiting YTHDF2-mediated m6A modification of SIRT3 mRNA, which reduced mRNA degradation.

Molecular modification effects on the electrochromic and photochromic properties of diarylethene with intramolecular isomerization behavior.

Diarylethene (DAE) is one of the most widely used functional units for electrochromic or photochromic materials. To better understand the molecular modification effects on the electrochromic and photochromic properties of DAE, two modification strategies, substitution with functional groups or heteroatoms, were investigated theoretically by density functional theory calculations. It is found that red-shifted absorption spectra caused by a decreased highest occupied molecular orbital-lowest unoccupied molecular orbital energy gap and S0 → S1 transition energy during the ring-closing reaction become more significant by adding different functional substituents. In addition, for two isomers, the energy gap and S0 → S1 transition energy decreased by heteroatom substitution of S atoms with O or NH, while they increased by replacing two S atoms with CH2. For intramolecular isomerization, one-electron excitation is the most effective way to trigger the closed-ring (O → C) reaction, while the open-ring (C → O) reaction occurs most readily in the presence of one-electron reduction. Moreover, it is confirmed that substitution with strong electron donating groups (-OCH3/-NH2) or with one O/two CH2 heteroatoms leads to a more favorable closed-ring (O → C) reaction. Functionalized with strong electron-withdrawing groups (-NO2 and -COOH) or one/two NH heteroatom substitutions, the open-ring (C → O) reaction is easier. Our results confirmed that the photochromic and electrochromic properties of DAE can be tuned effectively by molecular modifications, which provides theoretical guidance for the design of new DAE-based photochromic/electrochromic materials.

Catalytic Asymmetric Hydroalkoxylation and Formal Hydration and Hydroaminoxylation of Conjugated Dienes.

The straightforward construction of stereogenic centers bearing unprotected functional groups, as in nature, has been a persistent pursuit in synthetic chemistry. Abundant applications of free enantioenriched allyl alcohol and allyl hydroxylamine motifs have made the asymmetric hydration and hydroaminoxylation of conjugated dienes from water and hydroxylamine, respectively, intriguing and efficient routes that have, however, been unachievable thus far. A fundamental challenge is the failure to realize transition-metal-catalyzed enantioselective C-O bond constructions via hydrofunctionalization of conjugated dienes. Here, we perform a comprehensive study toward the stereoselective formal hydration and hydroaminoxylation of conjugated dienes by synthesizing a set of new P,N-ligands and identifying an aryl-derived oxime as a surrogate for both water and hydroxylamine. Asymmetric hydroalkoxylation with new P,N-ligands is also elucidated. Furthermore, versatile derivatizations following hydration provide indirect but concise routes to formal hydrophenoxylation, hydrofluoroalkoxylation, and hydrocarboxylation of conjugated dienes that have been unreported thus far. Finally, a ligand-to-ligand hydrogen transfer process is proposed based on the results of preliminary mechanistic experiments.

Evaluation of a culturally adapted cognitive behavior therapy-based, third-wave therapy manual.

BACKGROUND: Recommendations for psychotherapy have evolved over the years, with cognitive behavioral therapy (CBT) taking precedence since its inception within clinical guidelines in the United Kingdom and United States. The use of CBT for severe mental illness is now more common globally. AIM: To investigate the feasibility and acceptability of a culturally adapted, CBT-based, third-wave therapy manual using the Comprehend, Cope, and Connect approach with individuals from a diverse population presenting to primary and secondary healthcare services. METHODS: A pilot study was used to assess the feasibility and acceptability of the manualised intervention. Outcome measures were evaluated at baseline, post-intervention and 12 wk-follow up. 32 participants with mental health conditions aged 20-53 years were recruited. Assessments were completed at three time points, using Clinical Outcomes in Routine Evaluation (CORE), Hospital Anxiety and Depression Scale (HADS), Bradford Somatic Inventory and World Health Organization Disability Assessment Schedule 2.0 (WHODAS). The Patient Experience Ques-tionnaire was completed post-treatment. RESULTS: Repeated measures of analysis of variance associated with HADS depression, F (2, 36) = 12.81, P < 0.001, partial η2 = 0.42 and HADS anxiety scores, F (2, 26) = 9.93, P < 0.001, partial η2 = 0.36; CORE total score and WHODAS both showed significant effect F (1.25, 18.72) = 14.98, P < 0.001, partial η2 = 0.5. and F (1.29, 14.18) = 6.73, P < 0.001, partial η2 = 0.38 respectively. CONCLUSION: These results indicate the effectiveness and acceptability of the culturally adapted, CBT-based, third-wave therapy manual intervention among minoritized groups with moderate effect sizes. Satisfaction levels and acceptability were highly rated. The viability and cost-effectiveness of this approach should be explored further to support universal implementation across healthcare systems.

BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation.

Atherosclerosis is a chronic systemic inflammatory disease that causes severe cardiovascular events. B cell lymphoma 2-associated athanogene (BAG3) was proven to participate in the regulation of tumor angiogenesis, neurodegenerative diseases, and cardiac diseases, but its role in atherosclerosis remains unclear. Here, we aim to investigate the role of BAG3 in atherosclerosis and elucidate the potential molecular mechanism. In this study, ApoE-/- mice were given a tail-vein injection of BAG3-overexpressing lentivirus and fed a 12-week high-fat diet (HFD) to investigate the role of BAG3 in atherosclerosis. The overexpression of BAG3 reduced plaque areas and improved atherosclerosis in ApoE-/- mice. Our research proves that BAG3 promotes autophagy in vitro, contributing to the suppression of EndMT in human umbilical vein endothelial cells (HUVECs). Mechanically, autophagy activation is mediated by BAG3 via the interaction between BAG3 and its chaperones HSP70 and HSPB8. In conclusion, BAG3 facilitates autophagy activation via the formation of the chaperone-assisted selective autophagy (CASA) complex interacting with HSP70 and HSPB8, leading to the inhibition of EndMT during the progression of atherosclerosis and indicating that BAG3 is a potential therapeutic target for atherosclerosis.

The Traditional Chinese Medicine Formula FTZ Protects against Cardiac Fibrosis by Suppressing the TGFß1-Smad2/3 Pathway.

Background: Fu fang Zhen Zhu Tiao Zhi (FTZ) is a patented preparation of Chinese herbal medicine that has been used as a natural medicine to treat several chronic diseases including cardiovascular disease. However, its effects on cardiac fibrosis remain unclear. Therefore, this study was designed to investigate the effects and potential mechanisms of FTZ in treating cardiac fibrosis. Methods: FTZ was administered to mice by oral gavage daily at a dosage of 1.2 g/kg or 2.4 g/kg of body weight for 7 weeks after a transverse aorta constriction (TAC) surgery. Doppler echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining were used to assess the effect of FTZ on the cardiac structure and function of mice that had undergone TAC. EdU and wound-healing assays were performed to measure the proliferative and migratory abilities of cardiac fibroblasts. Western blotting and qRT-PCR were used to determine the expression of TGFß1, Col1A2, Col3, and α-SMA proteins and mRNA levels. Results: FTZ treatment reduced collagen synthesis, attenuated cardiac fibrosis, and improved cardiac function in mice subjected to TAC. Moreover, FTZ treatment prevented the proliferation and migration of cardiac fibroblasts and reduced Ang-II-induced collagen synthesis. Furthermore, FTZ downregulated the expression of TGFß1, p-smad2, and p-smad3 and inhibited the TGFß1-Smad2/3 pathway in the setting of cardiac fibrosis. Conclusion: FTZ alleviated the proliferation and migration of cardiac fibroblasts and suppressed collagen synthesis via the TGFß1-Smad2/3 pathway during the progression of cardiac fibrosis. These findings indicated the therapeutic potential of FTZ in treating cardiac fibrosis.

Antibacterial Properties Enhancement of Layer-by-Layer Self-Assembled Nanofiltration Membranes.

Membrane technology is now being widely used in the field of water treatment for its unique advantages. Layer-by-layer (LbL) self-assembly technique is a convenient and versatile method of modified nanofiltration (NF) membranes fabrication, which can be used to control the thickness and the surface properties of membranes by chemical deposition of polyelectrolytes. Herein, a new kind of composite NF membrane with enhanced antibacterial properties was successfully fabricated through LbL self-assembly method, having polyether sulfone (PES) ultrafiltration (UF) membrane as support layer, N-[(2-hydroxy-3-trimethylammonium)propyl] chloride chitosan (HTCC) and polyacrylic acid (PAA) as active layer, and epichlorohydrin (ECH) as crosslinking reagent. Subsequently, nanosilver was finally loaded on the membrane surface by photoreduction technique. Our results revealed that the positively charged four semi-assembled membranes prepared using 5 g/L HTCC aqueous solution, 1 g/L PAA solution (pH = 6-8), and 0.5 g/L NaCl as supporting salt exhibited optimum performance. Atomic force microscopy and contact angle tests showed that the prepared membranes improved the surface roughness and hydrophilicity as compared to those of the polyether sulfone (PES) membranes. The retention test indicated that the (HTCC/PAA)4HTCC membranes exhibited highly-efficient removal of pharmaceuticals and personal care products in the order of Amlodipine > Atenolol > Carbamazepine > Ibuprofen. The X-ray Diffraction results confirmed the presence of nano-silver on the membrane surface. In addition, the prepared membranes exhibited excellent antibacterial activity, especially against gram-negative bacteria.

Shiga Toxin-Producing Escherichia coli in Plateau Pika (Ochotona curzoniae) on the Qinghai-Tibetan Plateau, China.

Shiga toxin-producing Escherichia coli (STEC) are an emerging group of zoonotic pathogens. Ruminants are the natural reservoir of STEC. In this study we determined the prevalence and characteristics of the STEC in plateau pika (Ochotona curzoniae) on the Qinghai-Tibetan Plateau, China. A total of 1116 pika samples, including 294 intestinal contents samples, 317 fecal samples, and 505 intestinal contents samples, were collected from May to August in the years 2012, 2013, and 2015, respectively. Twenty-one samples (1.88%) yielded at least one STEC isolate; in total, 22 STEC isolates were recovered. Thirteen different O serogroups and 14 serotypes were identified. One stx 1 subtype (stx 1a) and three stx 2 subtypes (stx 2a, stx 2b, and stx 2d) were present in the STEC isolates. Fifteen, fourteen, and three STEC isolates harbored the virulence genes ehxA, subA, and astA, respectively. Adherence-associated genes iha and saa were, respectively, present in 72.73 and 68.18% of the STEC isolates. Twenty antibiotics were active against all the STEC isolates; all strains were resistant to penicillin G, and some to cephalothin or streptomycin. The 22 STEC isolates were divided into 16 pulsed-field gel electrophoresis patterns and 12 sequence types. Plateau pikas may play a role in the ongoing circulation of STEC in the Qinghai-Tibetan plateau. This study provides the first report on STEC in plateau pikas and new information about STEC reservoirs in wildlife. Based on the serotypes, virulence gene profiles and multi-locus sequence typing (MLST) analysis, the majority of these pika STECs may pose a low public health risk.

[PCR-derived technology in gene identification and typing of Yersinia pestis].

Application of the PCR-derived technology in gene identification and genotypes of different ecotype Yersinia pestis to make the high-throughput experimental results can reflect the epidemic history and compare the diversity in genome, pathogenicity, so that results from these experiments provide an important basis for clinical diagnosis, treatment and origin. But the experiment should be considered typing ability, practicality, budget and other experimental factors or conditions, because each PCR-derivative technology has advantages and disadvantages.

Prevalence and characteristics of Shiga toxin-producing Escherichia coli isolated from retail raw meats in China.

Shiga toxin-producing Escherichia coli (STEC) causes diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome in humans. Most human infections are attributed to consumption of STEC-contaminated foodstuffs of animal origin. In this study, we evaluated the prevalence of STEC from retail raw meats collected from two geographical regions in China. The results revealed that 166 out of 853 samples were stx-positive; 63 STEC isolates were recovered from 58 stx-positive samples including pork (4.4%, 14/318), beef (11.0%, 21/191), mutton (20.6%, 26/126), chicken (0.5%, 1/205), and duck (7.7%, 1/13). Twenty-six O serogroups and 33 O:H serotypes were identified. All three stx1 subtypes and five stx2 subtypes (2a to 2e) were found in the 63 STEC isolates, among which stx2e-positive STEC isolates were the most predominant (39.7%), followed by stx1c only (20.6%), stx1c+stx2b (14.3%), and stx1a only (9.5%). STEC isolates carried virulence genes eae (6.3%), ehxA (36.5%), katP (4.8%), astA (11.1%), and subA (36.5%). Of the four adherence-associated genes tested, toxB was absent, whereas saa, paa, and efa1 were present in 28, three, and one STEC isolates respectively. The STEC isolates were divided into 50 PFGE patterns and 33 sequence types. STEC from different sources and geographical regions were separated by PFGE and MLST. Our results revealed that there is a high genetic diversity of STEC in retail raw meats, some of which have potential to cause human diseases.

Chromosomal rearrangement features of Yersinia pestis strains from natural plague foci in China.

The Yersinia pestis chromosome contains a large variety and number of insert sequences that have resulted in frequent chromosome rearrangement events. To identify the chromosomal rearrangement features of Y. pestis strains from five typical plague foci in China and study spontaneous DNA rearrangements potentially stabilized in certain lineages of Y. pestis genomes, we examined the linking mode of locally collinear blocks (LCBs) in 30 Y. pestis strains by a polymerase chain reaction-based method. Our results suggest most strains have relatively stable chromosomal arrangement patterns, and these rearrangement characteristics also have a very close relationship with the geographical origin. In addition, some LCB linking modes are only present in specific strains. We conclude Y. pestis chromosome rearrangement patterns may reflect the genetic features of specific geographical areas and can be applied to distinguish Y. pestis isolates; furthermore, most of the rearrangement events are stable in certain lineages of Y. pestis genomes.