Five-Year Outcomes of Bioresorbable Stent Therapy for Coronary Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The efficacy of bioresorbable vascular scaffolds (BVS) compared to metallic stents for the treatment of coronary heart disease remains controversial. The analysis of clinical outcomes at five years following the initial treatment has yet to be reviewed. This study sought to assess the five-year outcomes in randomized controlled trials of BVS in the treatment of coronary heart disease using a systematic review and meta-analysis. Methods: A systematic database search was conducted from their inception to June 30th, 2023 using various Medical Subject Headings (MeSH) terms including: "Coronary Disease", "Bioresorbable stent", "Randomized controlled trials". Results: After a rigorous selection process, a total of five high-quality articles were finally included in this study. Each trial demonstrated a low risk of bias. After 5 years, bioresorbable stents showed outcomes similar to conventional metal stents in terms of cardiac mortality. However, they were inferior in terms of lesion revascularization rates, in-stent thrombosis rates, target lesion failure, target vessel failure, and myocardial infarction. Conclusions: While bioresorbable stents are comparable to metallic stents in terms of cardiac mortality rates, they exhibit significant drawbacks that warrant clinical consideration.

YTHDF3 Regulates the Degradation and Stability of m6A-Enriched Transcripts to Facilitate the Progression of Castration-Resistant Prostate Cancer.

RNA N6-methyladenosine (m6A) readers mediate cancer progression. However, the functional role and potential mechanisms of the m6A readers in prostate cancer tumorigenicity remain to be elucidated. In this study, we demonstrate that YTHDF3 expression is elevated in castration-resistant prostate cancer (CRPC) and positively correlated to high grade, bone metastasis and poor survival. YTHDF3 expression promoted CRPC cell proliferation, epithelial to mesenchymal transition (EMT) and tumour progression. Mechanistically, YTHDF3 promoted the RNA degradation of SPOP and NXK3.1 but stabilized RNA expressions of TWIST1 and SNAI2 dependent on m6A to facilitate cell proliferation and EMT. Additionally, YTHDF3 expression enhanced AKT activity via degrading SPOP in an m6A-dependent manner. Importantly, we found that melatonin can compete with m6A to occupy the m6A-binding cage of YTHDF3, leading to inhibition of YTHFD3 and its target expressions as well as CRPC tumour growth. Our findings uncover an essential role of YTHDF3 in the progression of CRPC and highlight the role of melatonin in anti-CRPC activity.

[Occupational chronic psychological stress and transaminase, HSP70 gene family and its proteins association of the interaction with metabolic syndrome].

OBJECTIVE: To explore the association of Occupational chronic psychological stress with transaminase, heat shock protein70(HSP70)gene family and their protein interaction with metabolic syndrome(MS). METHODS: A case-control study was used. According to the inclusion and exclusion criteria, from March 2015 to March 2016, 583 unrelated MS patients were selected as the case group and 585 unrelated healthy people as the control group among hospitalized and physical examination subjects aged 20-60 in Wuzhong People's Hospital and General Hospital of Ningxia Medical University. Questionnaire survey, physical examination, clinical and biochemical indicators, serum HSP70 level and five-locus polymorphism detection of HSP70 gene were carried out. GMDR 0.7 software was used to analyze the relationship between psychological stress, transaminase, HSP70 gene and its protein interaction and MS. RESULTS: After adjusting for age and sex, the rs1008438, rs1061581, rs539689 and rs222795 locus of HSP70 gene in the Co-dominant model and Dominant model and the rs222795 loci in the Over-dominant model carry wild homozygous genotype and heterozygous genotype were all related to the reduction of MS risk(OR<1, P<0.05). GMDR result: the 2-factor interaction model composed of psychological stress and serum HSP70, the 2-3 factor interaction model composed of transaminase activity, and the 2-6 factor interaction model composed of five locus of HSP70 gene, the 2-9 factor interaction model consisting of psychological stress and transaminase activity, HSP70 gene and its protein were all significantly associated with MS(P<0.01, P<0.05), all each factor interaction models were the best, and the 9-factor optimal interaction model had the highest risk of MS(OR=46.51, 95%CI 27.65-78.26), and the risk of MS in high-risk type was 45.23 times higher than that in low-risk type(95%CI 31.29-65.38, P<0.01). CONCLUSION: HSP70 gene family carrying wild-type alleles is a protective factor for MS. The interaction among Occupational chronic psychological stress interacts with transaminases, HSP70 gene and its serum proteins may be associated with MS. With the increase of involvement interaction factors, the risk of MS increased significantly. The interaction of multiple factors can greatly increase its risk.

Lathyrane diterpenoids with multidrug resistance reversal activity from the tubers of Euphorbia antiquorum.

Nine previously unreported lathyrane diterpenoids named euphorantesters A-I, along with 16 known analogues, have been separated from the tubers of Euphorbia antiquorum. Their structures were established by means of spectroscopic analyses, time-dependent density functional theory based electronic circular dichroism calculation and single crystal X-ray crystallography. Their reversal ability against P-glycoprotein-mediated multidrug resistance (MDR) in MCF-7/ADR cell line was then evaluated, and 15 ones exhibited moderate MDR reversal activity with reversal fold falling in the range of 1.12-13.15. The most active euphorantester B could effectively increase the sensitivity of MCF-7/ADR cell to adriamycin comparably to the reference drug verapamil.

miR-203-3p promotes senescence of mouse bone marrow mesenchymal stem cells via downregulation of Pbk.

The senescence of bone marrow mesenchymal stem cells (BMSCs) contributes to the development of degenerative skeletal conditions. To date, the molecular mechanism resulting in BMSC senescence has not been fully understood. In this study, we identified a small non-coding RNA, miR-203-3p, the expression of which was elevated in BMSCs from aged mice. On the other hand, overexpression of miR-203-3p in BMSCs from young mice reduced cell growth and enhanced their senescence. Mechanistically, PDZ-linked kinase (PBK) is predicted to be the target of miR-203-3p. The binding of miR-203-3p to Pbk mRNA could decrease its expression, which in turn inhibited the ubiquitination-mediated degradation of p53. Furthermore, the intravitreal injection of miR-203-3p-inhibitor into the bone marrow cavity of aged mice attenuated BMSC senescence and osteoporosis in aged mice. Collectively, these findings suggest that targeting miR-203-3p to delay BMSC senescence could be a potential therapeutic strategy to alleviate age-related osteoporosis.

Causal relationship between the gut microbiota, immune cells, and coronary heart disease: a mediated Mendelian randomization analysis.

Background: Recent studies have shown that the gut microbiota (GM), immune cells, and coronary heart disease (CHD) are closely related, but the causal nature of these relationships is largely unknown. This study aimed to investigate this causal relationship and reveal the effect of GM and immune cells on the risk of developing CHD using mediated Mendelian randomization (MR) analysis. Methods: First, we searched for data related to GM, immune cells, and CHD through published genome-wide association studies (GWAS). We filtered the single nucleotide polymorphisms (SNPs) associated with GM and immune cells and then performed the first MR analysis to identify disease-associated intestinal bacteria and disease-associated immune cells. Subsequently, three MR analyses were conducted: from disease-associated GM to disease-associated immune cells, from disease-associated immune cells to CHD, and from disease-associated GM to CHD. Each MR analysis was conducted using inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted models, and simple models. Results: A total of six GM and 25 immune cells were found to be associated with CHD. In the MR analysis using the inverse variance weighting (IVW) method, g__Desulfovibrio.s__Desulfovibrio_piger was associated with EM DN (CD4-CD8-) %T cells (P < 0.05 and OR > 1), EM DN (CD4-CD8-) %T cells was associated with CHD (P < 0.05 and OR < 1), and g__Desulfovibrio.s__Desulfovibrio_piger was associated with CHD (P < 0.05 and OR < 1). Conclusion: An increase in the abundance of g__Desulfovibrio.s__Desulfovibrio_piger leads to an increase in the amount of EM DN (CD4-CD8-) %T cells, and an increase in the amount of EM DN (CD4-CD8-) %T cells reduces the risk of developing CHD. Our study provides some references for reducing the incidence of CHD by regulating GM and immune cells.

Regulating the Scaling Relations in Ammonia Synthesis through a Light-driven Bendable Seesaw Effect on Tailored Iron Catalyst.

Advancing the energy-intensive Haber-Bosch process faces significant challenges due to the intrinsic constraints of scaling relations in heterogeneous catalysis. Herein, we reported an approach of bending the "seesaw effect" to regulate the scaling relations over a tailored α-Fe metallic material (α-Fe-110s), realizing highly efficient light-driven thermal catalytic ammonia synthesis rate of 1260 µmol gcatalyst-1 h-1 without additional heating. Specifically, the thermal catalytic activity of α-Fe-110s was significantly enhanced by the novel stepped {110} surface, exhibiting a 3.8-fold increase compared to the commercial fused-iron catalyst with promoters at 350 °C. The photo-induced hot electron transfer further accelerates the dinitrogen dissociation and hydrogenation simultaneously, effectively overcoming the limitation of scaling relation over identical sites. Consequently, the ammonia production rate of α-Fe-110s was further enhanced by 30 times at the same temperature with irradiation. This work designs an efficient and sustainable system for ammonia synthesis and provides a novel approach for regulating the scaling relations in heterogeneous catalysis.

GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is a highly prevalent degenerative disease worldwide, and tumor necrosis factor (TNF-α) is closely associated with its development. Growth differentiation factor 11 (GDF11) has demonstrated anti-injury and anti-aging abilities in certain tissues; however, its regulatory role in OA remains unclear and requires further investigation. OBJECTIVES: To identify whether GDF11 can attenuate osteoarthritis. To exploring the the potential mechanism of GDF11 in alleviating osteoarthritis. METHODS: In this study, we cultured and stimulated mouse primary chondrocytes with or without TNF-α, analyzing the resulting damage phenotype through microarray analysis. Additionally, we employed GDF11 conditional knockout mice OA model to examine the relationship between GDF11 and OA. To investigate the target of GDF11's function, we utilized NLRP3 knockout mice and its inhibitor to verify the potential involvement of the NLRP3 inflammasome. RESULTS: Our in vitro experiments demonstrated that endogenous overexpression of GDF11 significantly inhibited TNF-α-induced cartilage matrix degradation and inflammatory expression in chondrocytes. Furthermore, loss of GDF11 led to NLRP3 inflammasome activation, inflammation, and metabolic dysfunction. In an in vivo surgically induced mouse model, intraarticular administration of recombinant human GDF11 alleviated OA pathogenesis, whereas GDF11 conditional knockout reversed this effect. Additionally, findings from the NLRP3-knockout DMM mouse model revealed that GDF11 exerted its protective effect by inhibiting NLRP3. CONCLUSION: These findings demonstrate the ability of GDF11 to suppress TNF-α-induced inflammation and cartilage degeneration by preventing mitochondrial dysfunction and inhibiting NLRP3 inflammasome activation, suggesting its potential as a promising therapeutic drug for osteoarthritis.

Mechanism of Autocatalytic Reduction of CO2 over MgCO3 to High Value-Added Chemicals: A DFT & AIMD Study.

Calcination of MgCO3 is an important industrial reaction, but it causes significant and unfavorable CO2 production. Calcination in a reducing green hydrogen atmosphere can substantially reduce CO2 release and produce high value-added products such as CO or hydrocarbons, but the mechanism is still unclear. Here, the in situ transformation process of MgCO3 interacting with hydrogen and the specific formation mechanism of the high value-added products are thoroughly investigated based on reaction thermodynamic, ab initio molecular dynamics (AIMD) simulations, and density functional theory (DFT) calculations. The reaction thermodynamic parameters of MgCO3 coupled with hydrogen to produce CO or methane are calculated, revealing that increasing and decreasing the thermal reductive decomposition temperature favors the production of CO and methane, respectively. Kinetically, the energy barriers of each possible production pathway for the dominant products CO and methane are further calculated in conjunction with the AIMD simulation results of the transformation process. The results suggest that CO is produced via the MgO catalytic-carboxyl pathway (CO2*→ COOH*trans→ COOH*cis→ CO*→ CO), which is autocatalyzed by MgO derived from the thermal reductive decomposition of MgCO3. For the mechanism of methane formation, it prefers to be produced by the stepwise interaction of carbonates in the MgCO3 laminates with hydrogen adsorbed on their surfaces (direct conversion pathway: sur-O-CO → sur-O-HCO → sur-O-HCOH → sur-O-HC → sur-O-CH2 → sur-O-CH3 → sur-O + CH4*).

Effects of tranexamic acid preconditioning on the incidence of postpartum haemorrhage in vaginal deliveries with identified risk factors in China: a prospective, randomized, open-label, blinded endpoint trial.

OBJECTIVE: This study aimed to evaluate the effects of tranexamic acid (TXA) in preventing postpartum haemorrhage (PPH) among women with identified risk factors for PPH undergoing vaginal delivery in China. METHODS: This prospective, randomized, open-label, blinded endpoint (PROBE) trial enrolled 2258 women with one or more risk factors for PPH who underwent vaginal delivery. Participants were randomly assigned in a 1:1 ratio to receive an intravascular infusion of 1 g TXA or a placebo immediately after the delivery of the infant. The primary outcome assessed was the incidence of PPH, defined as blood loss ≥500 mL within 24 h after delivery, while severe PPH was considered as a secondary outcome and defined by total blood loss ≥1000 mL within 24 h. RESULTS: 2245 individuals (99.4%) could be followed up to their primary outcome. PPH occurred in 186 of 1128 women in the TXA group and in 215 of 1117 women in the placebo group (16.5% vs. 19.2%; RR, 0.86; 95% CI, 0.72 to 1.02; p = 0.088). Regarding secondary outcomes related to efficacy, women in the TXA group had a significant lower rate of severe PPH than those in the placebo group (2.7% vs. 5.6%; RR, 0.49; 95% CI, 0.32 to 0.74; p = 0.001; adjusted p = 0.002). Similarly, there was a significant reduction in the use of additional uterotonic agents (7.8% vs. 15.6%; RR, 0.50; 95% CI, 0.39 to 0.63; p < 0.001; adjusted p = 0.001). No occurrence of thromboembolic events and maternal deaths were reported in both groups within 30 days after delivery. CONCLUSIONS: In total population with risk factors for PPH, the administration of TXA following vaginal delivery did not result in a statistically significant reduction in the incidence of PPH compared to placebo; however, it was associated with a significantly lower incidence of severe PPH.

Prophylactic administration of TXA did not yield a statistically significant reduction in the incidence of PPH among women with risk factors in vaginal deliveries.Prophylactic use of TXA may help to reduce the incidence of severe PPH.

A strategy to distinguish similar traditional Chinese medicines by liquid chromatography-mass spectrometry, electronic senses, and gas chromatography-ion mobility spectrometry: Marsdeniae tenacissimae Caulis and Paederiae scandens Caulis as examples.

INTRODUCTION: Marsdeniae tenacissimae Caulis (MTC), a popular traditional Chinese medicine, has been widely used in the treatment of tumor diseases. Paederiae scandens Caulis (PSC), which is similar in appearance to MTC, is a common counterfeit product. It is difficult for traditional methods to effectively distinguish between MTC and PSC. Therefore, there is an urgent need for a rapid and accurate method to identify MTC and PSC. OBJECTIVES: The aim is to distinguish between MTC and PSC by analyzing the differences in nonvolatile organic compounds (NVOCs), taste, odor, and volatile organic compounds (VOCs). METHODS: Liquid chromatography-mass spectrometry (LC-MS) was utilized to analyze the NVOCs of MTC and PSC. Electronic tongue (E-tongue) and electronic nose (E-nose) were used to analyze their taste and odor respectively. Gas chromatography-ion mobility spectrometry (GC-IMS) was applied to analyze VOCs. Finally, multivariate statistical analyses were conducted to further investigate the differences between MTC and PSC, including principal component analysis, orthogonal partial least squares discriminant analysis, discriminant factor analysis, and soft independent modeling of class analysis. RESULTS: The results of this study indicate that the integrated strategy of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis can be effectively applied to distinguish between MTC and PSC. Using LC-MS, 25 NVOCs were identified in MTC, while 18 NVOCs were identified in PSC. The major compounds in MTC are steroids, while the major compounds in PSC are iridoid glycosides. Similarly, the distinct taste difference between MTC and PSC was precisely revealed by the E-tongue. Specifically, the pronounced bitterness in PSC was proven to stem from iridoid glycosides, whereas the bitterness evident in MTC was intimately tied to steroids. The E-nose detected eight odor components in MTC and six in PSC, respectively. The subsequent statistical analysis uncovered notable differences in their odor profiles. GC-IMS provided a visual representation of the differences in VOCs between MTC and PSC. The results indicated a relatively high relative content of 82 VOCs in MTC, contrasted with 32 VOCs exhibiting a similarly high relative content in PSC. CONCLUSION: In this study, for the first time, the combined use of LC-MS, E-tongue, E-nose, GC-IMS, and multivariate statistical analysis has proven to be an effective method for distinguishing between MTC and PSC from multiple perspectives. This approach provides a valuable reference for the identification of other visually similar traditional Chinese medicines.

CORM-3 Inhibits the Inflammatory Response of Human Periodontal Ligament Fibroblasts Stimulated by LPS and High Glucose.

Introduction: Diabetes has been recognized as an independent risk factor for periodontitis. Increasing evidences indicate that hyperglycemia aggravates inflammatory response of human periodontal ligament cells (hPDLCs). Carbon monoxide-releasing molecule-3 (CORM-3) is a water-soluble compound that can release carbon monoxide (CO) in a controllable manner. CORM-3 has been shown the anti-inflammatory effect in different cell lineages. Methods: We stimulated periodontal ligament cells with LPS and high glucose. The expression of inflammatory cytokine was detected by ELISA. RT-qPCR, Western blot and immunofluorescence were used to detect the expression of TLR2, TLR4, RAGE and the activation of NF-κB pathway. We performed silencing and overexpression treatment of RAGE targeting the role of RAGE. We performed the immunostaining of paraffin sections of the periodontitis model in diabetes rats. Results: The results showed that CORM-3 significantly inhibited the expression of inflammatory cytokine in hPDLCs stimulated with LPS and high glucose. CORM-3 also inhibited LPS and high glucose-induced expression of RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway. Silence of RAGE resulted in significantly decreased expression of proteins above. Overexpression of RAGE significantly enhanced the expression of these factors. CORM-3 abrogated the effect of RAGE partially. In animal model, CORM-3 suppressed the inflammatory response of periodontal tissues in experimental periodontitis of diabetic rats. Discussion: Our research proved CORM-3 reduced the inflammatory response via RAGE/NF-κB pathway and TLR2/TLR4/NF-κB pathway in the process of high glucose exacerbated periodontitis. These findings demonstrated the role of RAGE in the process of high glucose exacerbated periodontitis and suggested that CORM3 be a potential therapeutic strategy for the treatment of diabetes patients with periodontitis.

Effect of Flammulina velutipes polysaccharide on mitochondrial apoptosis in lung adenocarcinoma A549 cells.

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells.

Clinical implications of persistent joint pain after gout flare.

OBJECTIVES: A subset of gout patients developed persistent joint pain after flares. Analysis of this clinical phenomenon may shed further light on the factors related to worsening gout and even provide clues to its pathogenesis. METHODS: We analyzed the clinical, laboratory, and ultrasound data of gout patients to explore the associations of these data with persistent joint pain after gout flares. RESULTS: A total of 1029 gout patients were included: 182 (17.7%) patients with persistent joint pain and 847 (82.3%) patients with nonpersistent joint pain. Patients with persistent joint pain had more total involved joints, more gout flares in the past year, and more joints with simultaneous gout flares (P<0.01). Among the ultrasound-detected lesions, patients with persistent joint pain had a higher incidence of tophus (36.4% vs. 21.1%) and bone erosion (18.6% vs. 8.6%) (P<0.05). Higher UA and lower TBil were found in patients with persistent joint pain (P<0.001). Hypertension (54.9% vs. 38.7%) and metabolic syndrome (58.8% vs. 46.4%) were both more frequent in patients with persistent joint pain (P<0.05). TBil was negatively correlated with the incidence of persistent joint pain (P<0.001, r=-0.190), UA values (P<0.001, r=-0.125), and metabolic syndrome scores (P<0.001, r=-0.192). A correlation curve was fitted using LOESS (locally weighted region). CONCLUSION: Persistent joint pain after gout flares is a marker of increased disease burden in gout. The significance of the level of total bilirubin for the exacerbation of gout deserves further study.

Novel biomarkers for prediction of atonic postpartum hemorrhage among 'low-risk' women in labor.

Background: Postpartum hemorrhage (PPH) is the primary cause of maternal mortality globally, with uterine atony being the predominant contributing factor. However, accurate prediction of PPH in the general population remains challenging due to a lack of reliable biomarkers. Methods: Using retrospective cohort data, we quantified 48 cytokines in plasma samples from 40 women diagnosed with PPH caused by uterine atony. We also analyzed previously reported hemogram and coagulation parameters related to inflammatory response. The least absolute shrinkage and selection operator (LASSO) and logistic regression were applied to develop predictive models. Established models were further evaluated and temporally validated in a prospective cohort. Results: Fourteen factors showed significant differences between the two groups, among which IL2Rα, IL9, MIP1ß, TNFß, CTACK, prenatal Hb, Lymph%, PLR, and LnSII were selected by LASSO to construct predictive model A. Further, by logistic regression, model B was constructed using prenatal Hb, PLR, IL2Rα, and IL9. The area under the curve (AUC) values of model A in the training set, internal validation set, and temporal validation set were 0.846 (0.757-0.934), 0.846 (0.749-0.930), and 0.875 (0.789-0.961), respectively. And the corresponding AUC values for model B were 0.805 (0.709-0.901), 0.805 (0.701-0.894), and 0.901 (0.824-0.979). Decision curve analysis results showed that both nomograms had a high net benefit for predicting atonic PPH. Conclusion: We identified novel biomarkers and developed predictive models for atonic PPH in women undergoing "low-risk" vaginal delivery, providing immunological insights for further exploration of the mechanism underlying atonic PPH.

Integration of High-Resolution LC-Q-TOF Mass Spectrometry and Multidimensional Chemical-Biological Analysis to Detect Nanomolar-Level Acetylcholinesterase Inhibitors from Different Parts of Zanthoxylum nitidum.

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer's disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 µM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer's disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

N-Terminal Sequences of Signal Peptides Assuming Critical Roles in Expression of Heterologous Proteins in Bacillus subtilis.

The N-terminal sequences of proteins and their corresponding encoding sequences may play crucial roles in the heterologous expression. In this study, the secretory expression of alkaline pectin lyase APL in B. subtilis was investigated to explore the effects of the N-terminal 5-7 amino acid sequences of different signal peptides on the protein expression and secretion. It was identified for the first time that the first five amino acid sequences of the N-terminal of the signal peptide (SP-LipA) from Bacillus subtilis lipase A play an important role in promoting the expression of APL. Furthermore, it was revealed that SP-LipA resulted in higher secretory expression compared to other signal peptides in this study primarily due to its encoding of N-terminal amino acids with relatively higher transcription levels and its efficient secretion capacity. Based on this foundation, the recombinant strain constructed in this work achieved a new record for the highest extracellular yields of APL in B. subtilis, reaching 12,295 U/mL, which was 1.9-times higher than that expressed in the recombinant Escherichia coli strain previously reported. The novel theories uncovered in this study are expected to play significant roles in enhancing the expression of foreign proteins both inside and outside of cells.

A prominent role of LncRNA H19 in H. pylori CagA induced DNA damage response and cell malignancy.

Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Fabrication and performance evaluation of a design for an extended depth-of-focus intraocular lens based on an improved sinusoidal profile.

This study presents the fabrication and evaluation of a sinusoidal extended depth-of-focus (EDoF) intraocular lens (IOL) based on our previously proposed design approach. The power, through-focus MTF, and surface profile were measured using commercial instruments. Through-focus images of a United States Air Force (USAF) 1951 resolution target formed by the fabricated IOL were compared with Symfony and AR40E under monochromatic and polychromatic light using optical bench testing. Simulations assessed visual acuity (VA) of a pseudophakic model eye with the EDoF IOL, including evaluation of tilt and decentration effects. Results indicate that the base power, add power, and the through-focus MTF@50 lp/mm of the fabricated IOL at a 3 mm pupil size align with the design specifications. The extended-depth-of-focus and imaging performance for the far vision of the fabricated IOL under both monochromatic and polychromatic light conditions at a 3.0 mm pupil diameter is comparable to that of Symfony. In addition, the fabricated IOL exhibits a similar extended-depth-of-focus for three discrete wavelengths. The pseudophakic model eye with the designed EDoF IOL demonstrates a VA exceeding 0.1 logMAR within a defocus range of 2.44 D. The VA is tolerant to both IOL tilt and decentration. These findings demonstrate the promising potential of the sinusoidal EDoF IOL design for future applications in cataract surgery.

Urinary α 1-microglobulin and ß 2-microglobulin as markers of early kidney injury in HIV-positive male patients on tenofovir-based antiretroviral therapy.

BACKGROUND: A retrospective study was conducted to explore the urinary expression of α 1-microglobulin (α1MG) and ß2-microglobulin (ß2MG) in patients with human immunodeficiency virus (HIV) infection, aiming to evaluate their predictive capability for renal injury. METHOD: One hundred and five male HIV-infected patients treated with Tenofovir (TDF) regimen (TDF+3TC or the third drug TDF/FTC+) were selected between March 1, 2021, and March 1, 2022, in Wuhan Jinyintan Hospital. Three months after TDF treatment, the renal function injury was evaluated with the standard creatinine clearance rate. The urinary levels of α1MG and ß2MG were compared between the initiation of TDF treatment and three months thereafter. Spearman correlation was utilized to analyze the correlation between the urinary expression of α1MG and ß2MG and renal injury in HIV patients. The logistic regression was used to analyze the predictive value of urinary α1MG and ß 2-microglobulin expression in renal injury. RESULTS: Up to the first follow-up, 29 (27.6%) cases of the 105 male HIV patients had varying degrees of renal function injury, including 14 (13.3%) mild injury, 9 (8.6%) moderate injury, and 6 (5.7%) severe injury cases. Patients with severe renal injury had the highest levels of urinary α1MG and ß2MG expression while those with mild injury demonstrated higher levels compared to the non-injury group (P < 0.05). Spearman correlation analysis indicated that urinary α1MG and ß2MG were positively correlated with renal impairment in HIV patients (Rho = -0.568, and -0.732; P < 0.001). The ROC curve analysis demonstrated that the area under the curve (AUC) for urine α1MG and ß2MG in predicting kidney damage among HIV patients were 0.928, 0.916, and 0.889, respectively. The sensitivity values were 96.55%, 82.76%, and 89.66% while the specificity values were 84.07%, 94.51%, and 89.29% for urine α1MG and ß2MG, respectively. CONCLUSION: The expression level of urinary α1MG and ß2MG in HIV patients was significantly higher compared to normal people. Detection of these two indexes can enable early determination of renal injury and its severity in HIV patients.