Shared insights for heat health risk adaptation in metropolitan areas of developing countries.

Global warming has led to a surge in heat health risks (HHRs), the impacts of which are particularly pronounced in metropolitan areas of developing countries. In the current study, six metropolitan areas - Beijing, China; Cairo, Egypt; Jakarta, Indonesia; Mumbai, India; Rio de Janeiro, Brazil; and Tehran, Iran - were selected as the study area to further differentiate the built-up landscapes by utilizing the concept of local climate zones. Moreover, we assessed the similarities and differences in HHR associated with the landscape. Results revealed a 30.67% higher HHR in compact built-up landscapes than in the open built-up type. Urban green spaces played an effective but differentiated role in mitigating HHR. That is, low vegetation in urbanized areas and trees in suburban areas significantly mitigated HHR. Collectively, our findings emphasize the role of effective planning and management in addressing HHR and provide empirical support for implementing HHR mitigation and adaptation strategies.

Clinical features, treatment, and outcomes of patients with carfilzomib induced thrombotic microangiopathy.

BACKGROUND: Thrombotic microangiopathy (TMA) is associated with carfilzomib, and knowledge of carfilzomib-induced TMA is based mainly on case reports. This study investigated the clinical characteristics of patients with carfilzomib-induced TMA and provided a reference for the rational use of carfilzomib. METHODS: Reports of carfilzomib-induced TMA were collected for retrospective analysis by searching the Chinese and English databases from inception to January 31, 2024. RESULTS: Sixty-six patients were included, with a median age of 63 years (range 39, 85). The median time to onset of TMA was 42 days (range 1, 1825) from initial administration, and the median number of cycles was 3 cycles (range 1, 15). Hemolytic anemia was recorded in 64 patients, with a median of 8.3 g/dL (range 4.6, 13). Sixty-three patients had thrombocytopenia with a median of 18 × 109/L (range 1, 139). The median value of increased LDH was 1192 IU/L (range 141, 5378). ADAMTS13 activity was normal in 41 (62.1 %) of the 42 patients. Mutations were found in 9 (13.6 %) of the 15 patients. Fifty-seven patients achieved a clinical response after discontinuing carfilzomib and receiving therapeutic plasma exchange (53.0 %), eculizumab (24.2 %), or hemodialysis (39.4 %). CONCLUSION: Carfilzomib-induced TMA is an important adverse event that should be considered in patients receiving carfilzomib for multiple myeloma with anemia, thrombocytopenia, and acute kidney injury. Withdrawal of carfilzomib and treatment with eculizumab have proven successful in some patients.

Structural characterization of squash polysaccharide and its effect on STZ-induced diabetes mellitus model in MIN6 cells.

A novel natural water-soluble acidic polysaccharide (PWESP-3) was isolated from squash with a molecular mass of 140.519 kDa, which was composed of arabinose (Ara, 35.30 mol%), galactose (Gal, 61.20 mol%), glucose (Glc, 1.80 mol%), and Mannuronic acid (ManA, 1.70 mol%) and contained Araf-(1→, →3)-Araf-(1→, →5)-Araf-(1→, Glcp-(1→, Galp-(1→, →3,5)-Araf-(1→, →2)-Glcp-(1→, →2)-Manp-(1→, →3)-Glcp-(1→, →4)-Galp-(1→, →3)-Galp-(1→, →6)-Galp-(1→, →3,4)-Galp-(1→, →4,6)-Galp-(1→ residues in the backbone. Moreover, the structure of PWESP-3 was identified by NMR spectra. The branch chain was connected to the main chain by the O-3 and O-4 atom of Gal. In addition, the effect of PWESP-3 on STZ-induced type I diabetes mellitus model in MIN6 cells was investigated. The results showed that PWESP-3 can increase the viability and insulin secretion of MIN6 cells and reduce the oxidative stress caused by ROS and NO. Meanwhile, PWESP-3 can also reduce the content of ATP, Ca2+, mitochondrial membrane potential and Caspase-3 activity in MIN6 cells. Furthermore, treatment with PWESP-3 can prevent single or double stranded DNA breaking to form DNA fragments and improve DNA damage in MIN6 cells, thereby avoiding apoptosis. Therefore, the above data highlight that PWESP-3 can improve the function of insulin secretion in STZ-induced MIN6 cells in vitro and can be used as an alternative food supplement to diabetes drugs.

TRPV1 signaling of perirenal adipose tissue promotes DOCA-Salt-induced hypertension and kidney injury.

BACKGROUND: Denervation of renal or perirenal adipose tissue (PRAT) can reduce arterial blood pressure in various hypertensive experimental models. Trpv1 (transient receptor potential vanillin 1) channel is highly expressed in the renal sensory nerves and the dorsal root ganglias (DRGs) projected by PRAT. However, it is currently unclear whether Trpv1 in DRGs projected from PRAT can regulate renal hypertension. METHODS: We used resintoxin (RTX) to block the afferent sensory nerves of rat PRAT. We also constructed Trpv1-/- mice and Trpv1+/- mice or used the injection of AAV2-retro-shTrpv1 to detect the effects of Trpv1 knockout or knockdown of PRAT-projected DRGs on deoxycorticosterone acetate (DOCA)-Salt-induced hypertension and kidney injury. RESULTS: Blocking the afferent sensory nerves of PRAT with RTX can alleviate DOCA-Salt-induced hypertension and renal injury in rats. And this blockade reduces the expression of Trpv1 in the DRGs projected by PRAT. Injecting AAV2-retro-shTrpv1 into the PRAT of DOCA-Salt mice also achieved the same therapeutic effect. However, DOCA-Salt-induced hypertension and renal injury can be treated in Trpv1+/- mice but not alleviated or even worsened in Trpv1-/- mice, possibly because of compensatory increase of Trpv5 in DRG of Trpv1-/- mice. CONCLUSION: Reducing, rather than eliminating, Trpv1 in DRG from PRAT-projection can reduce blood pressure and kidney damage in DOCA-Salt in rats or mice. Trpv1 in PRAT-DRGs may serve as a therapeutic target for salt-sensitive hypertension and its renal complications.

Clinical features, treatment, and outcome of pembrolizumab induced cholangitis.

Pembrolizumab induced hepatitis has received increasing attention, while pembrolizumab induced cholangitis is poorly understood. This study investigated the clinical features, treatment, and outcome of pembrolizumab induced cholangitis. Case reports, case series and clinical studies of pembrolizumab induced cholangitis were collected by retrieving English and Chinese database from inception until October 30, 2023. Fifty patients with cholecystitis entered our study with a median age of 68 years (range 48, 89). The median time to onset of cholecystitis was 1.1 months (range 0.3, 24), and the median number of cycles was 5 cycles (range 1, 27) after initial administration. Most of the patients had no clinical symptoms and only showed elevated biliary enzymes (24 cases, 48.0%), while some patients showed jaundice (12 cases, 24.0%), abdominal pain (10 cases, 20.0%) and fever (7 cases, 14.0%). The median alkaline phosphatase value was 1111 IU(range 130, 3515) and the median glutamyltransferase value was 649.5 IU(range 159, 3475). The imaging features of gallbladder were bile duct dilatation, stenosis and bile duct wall thickening and irregularity. Bile duct biopsy showed inflammatory infiltration, mainly CD8 + T cell infiltration. Immunosuppression treatment resulted in complete response in 4 cases (8.0%), partial response in 28 cases (56.0%), and poor response in 15 cases (30.0%). Cholangitis is a rare and serious adverse effect of pembrolizumab. Clinicians should be aware of the possibility of cholangitis when administering pembrolizumab. Steroids may not be effective in most patients with cholecystitis, and ursodeoxycholic acid may be an option.

Dose-Dependent Association Between Body Mass Index and Mental Health and Changes Over Time.

Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods. Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018. Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023. Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity. Results: Our analysis of 1 036 869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527 585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized ß, 0.14; 95% CI, 0.08 to 0.19; unstandardized ß, 0.27; 95% CI, 0.24 to 0.30; and unstandardized ß, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized ß, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized ß, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized ß, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized ß, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized ß, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized ß, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized ß, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized ß, 2.12; 95% CI, 2.09 to 2.15). Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.

Prediction of Postoperative Pneumonia after SICU Surgery: A Retrospective Single Center Study.

Objective: Postoperative pneumonia in critically ill patients is becoming an important cause for adverse clinical outcomes. It is very important to predict postoperative pneumonia. Surgical Intensive Care Unit(SICU), is an intensive care unit that deals with post-surgical patients, and is usually staffed by a team of surgeons, critical care specialists, and nurses to provide close monitoring and care. The purpose of this study is to investigate the risk factors of postoperative pneumonia in patients in SICU after surgery, establish a risk prediction model, and help surgeons and SICU doctors to early identify patients with high-risk postoperative pneumonia. Methods: To explore risk factors for postoperative pneumonia, Patients in the SICU from January 1, 2019, to December 31, 2019, were collected and retrospectively analyzed. The data were randomly divided into a derivation set (n=533) and a validation set (n=277). Patients were divided into postoperative pneumonia (PP) group and non-postoperative pneumonia (NPP) group. t test and Chi-square test were used to compare the differences between the PP and NPP groups before and after surgery. The risk factors of postoperative pneumonia in SICU patients were identified using univariate and multivariate logistic regression. A derivation set was used to build the model, and a validation set was used for model evaluation. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were used to evaluate the model performance. The model was validated by AUC using a validation set. Results: With this model, a total of 8 independent risk factors were identified to be associated with postoperative pneumonia in SICU patients after surgery. Patients with the 8 risk factors were assigned the following scores: recorded aspiration: 8, preoperative disturbance of consciousness: 4, thoracic and abdominal surgery: 3, contaminated wound: 10, abnormal choking cough on SICU admission: 9, abnormal pulmonary auscultation on SICU admission: 5, postoperative sedation, 4 points, and postoperative analgesia >1 day: 3. Eight risk factors were significantly correlated with postoperative pneumonia. Based on the scoring standard above, a risk factor table was created using the 8 predictors with a total score of 46. The AUC was 0.933 and 0.908 in derivation set and validation set. A cumulative score > 12 indicates high risk of postoperative pneumonia. Conclusions: This study identified 8 risk factors that are significantly associated with postoperative pneumonia in SICU patients after surgery and provides operable clinical tools for early prevention and intervention of postoperative pneumonia. The implementation of this model has significant potential to enhance patient outcomes in the SICU by enabling early identification and stratification of patients at elevated risk of developing postoperative pneumonia. This model allows for the timely initiation of targeted preventative and therapeutic interventions, potentially reducing the incidence of pneumonia, shortening hospital stays, and improving overall patient survival rates. Furthermore, the use of a cumulative scoring system, simplifies clinical decision-making, making it accessible and actionable for surgeons and SICU staff.

Label-free OIRD detection of protein microarrays on high dielectric constant substrate with enhanced intrinsic sensitivity.

Oblique-incidence reflectivity difference (OIRD) is a dielectric constant-sensitive technique and exhibits intriguing applications in label-free and high-throughput detection of protein microarrays. With the outstanding advantage of being compatible with arbitrary substrates, however, the effect of the substrate, particularly its dielectric constant on the OIRD sensitivity has not been fully disclosed. In this paper, for the first time we investigated the dependence of OIRD sensitivity on the dielectric constant of the substrate under top-incident OIRD configuration by combining theoretical modeling and experimental evaluation. Optical modeling suggested that the higher dielectric constant substrate exhibits a higher intrinsic sensitivity. Experimentally, three substrates including glass, fluorine-doped tin oxide (FTO) and silicon (Si) with different dielectric constants were selected as microarray substrates and their detection performances were evaluated. In good agreement with the modeling, high dielectric constant Si-based microarray exhibited the highest sensitivity among three chips, reaching a detection limit of as low as 5 ng mL-1 with streptavidin as the model target. Quantification of captured targets on three chips with on-chip enzyme-linked immunosorbent assay (ELISA) further confirmed that the enhanced performance originates from the high dielectric constant enhanced intrinsic OIRD sensitivity. This work thus provides a new way to OIRD-based label-free microarrays with improved sensitivity.

Neuromuscular Electrical Stimulation of Peroneal Longus on Balance Control Ability in Young Adults with Chronic Ankle Instability: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate the effects of six weeks of peroneal longus neuromuscular electrical stimulation (NMES) on the balance control ability in young adults with chronic ankle instability (CAI). DESIGN: This study is a double blind randomized controlled trial. Six weeks of NMES and placebo intervention were conducted in the NMES and control groups for 20 minutes, three times a week, respectively. Thirty-eight participants successfully completed the whole intervention and single-leg standing tests. The kinetics data of the center of pressure (COP) trajectory during static single-leg stance were measured using a Kistler force platform. Two-way repeated measures ANOVA was used to analyze the electrical stimulation effects. RESULTS: Significant interactions were detected in CAIT scores and all balance parameters including Displacement X (Dx), Displacement Y(Dy), 95% confidence ellipse area (95%AREA), root-mean-square (RMS) and COP mean displacement velocity (MV) (p < 0.05, 0.103 ≤ η2 ≤ 0.201). Significant between-group differences were found in CAIT scores (p = 0.003, Cohen's d = 0.215), Dx (p = 0.045, Cohen's d = 0.107), RMS-ml (p = 0.019, Cohen's d = 0.143) and 95%AREA (p = 0.031, Cohen's d = 0.123) after the six weeks interventions. CONCLUSION: Six weeks of NMES on the peroneus longus can improve static balance control ability in young adults with CAI, especially the stability of ankle frontal plane.

Co(II)-N4 Catalysts for the Coupling of CO2 with Epoxides into Cyclic Carbonates: Catalytic Activity, Computational and Kinetic Studies.

In this study, we synthesized and characterized a series of cobalt(II) complexes bearing linear tetradentate N4 ligands. These Co(II)-N4 complexes proved to be efficient catalysts for the cycloaddition reaction between carbon dioxide and epoxides even at room temperature and 1 bar pressure of carbon dioxide without the need for solvents or cocatalysts. Furthermore, when combined with (triphenylphosphoranylidene)ammonium chloride (PPNCl) as a cocatalyst, the Co-N4 catalysts exhibited an impressive turnover frequency of up to 41,000 h-1 for coupling of epichlorohydrin/CO2. These Co(II)-N4 catalysts were found to have excellent stability and reusability, retaining their catalytic activity after they were recycled seven times. Density functional theory (DFT) calculations provided a comprehensive mechanism for the cycloaddition reaction, indicating that the rate-determining step is the epoxide ring opening, in both the presence and absence of PPNCl. Further kinetic studies allow us to determine the activation parameters (ΔH‡, ΔS‡, and ΔG‡ at 25 °C) of the coupling reaction using the Eyring equation. The Gibbs free activation energy obtained from the kinetic studies was in close agreement with that of the DFT calculations. The substituent effect on the cycloaddition reaction of CO2 with various substituted styrene oxides was also examined for the first time.

Pd-Catalyzed Three-Component Coupling of Cyclopropenones via Sequential C-C Bond Activation and Allylation.

A novel Pd-catalyzed three-component domino reaction for the stereoselective synthesis of highly functionalized allyl cinnamates has been developed. In this protocol, a sequential process of C-C bond activation and intermolecular allylic substitution was well-organized. The key for this transformation is the in situ generated hydrolysis product of cyclopropenone, which triggered a new reaction with vinylethylene carbonates. The reaction mechanism was investigated, demonstrating the high stereoselectivity and excellent atomic economy in this process.

Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS-STING Pathway.

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.

Correlation of NAT10 expression with clinical data and survival profiles in esophageal squamous cell carcinoma patients, and its impact on cell proliferation and apoptosis.

BACKGROUND: This study investigates the association between NAT10 expression and clinical parameters while assessing prognostic outcomes in esophageal squamous cell carcinoma (ESCC) patients. Furthermore, the study seeks to elucidate the functional role of NAT10 in neoplastic cell proliferation and apoptosis. MATERIALS AND METHODS: NAT10 expression was assessed in ESCC tissue microarrays through immunohistochemistry (IHC) tests. We employed SPSS software to analyze the correlation between NAT10 staining data, clinical indicators, and their implications for patient prognosis. Small interference RNA (siRNA) was utilized to inhibit NAT10 expression in two esophageal cancer cell lines, TE-1 and KYSE150. Subsequently, we meticulously quantified and compared cellular proliferation and apoptotic ratios among experimental groups. NAT10, Ki67, and Caspase3 expression levels in different groups were evaluated using quantitative polymerase chain reaction (qPCR) and Western blot (WB) assays. Statistical analyses were conducted using GraphPad Prism software, with significance at p<0.05. RESULTS: Our findings indicate that NAT10 is overexpressed in ESCC tissues and exhibits a significant correlation with tumor diameter and overall patient survival. Decreasing NAT10 expression led to the inhibition of tumor cell proliferation and the promotion of apoptosis. Furthermore, siRNA-mediated NAT10 inhibition resulted in the downregulation of Ki67 expression and the concomitant upregulation of Caspase3. CONCLUSION: The observed overexpression of NAT10 in ESCC tissues is associated with larger tumor diameters and reduced patient survival. NAT10 appears to play a pivotal role in the progression of esophageal cancer by influencing cell proliferation and apoptosis. These findings suggest potential clinical implications, with Ki67 and Caspase3 potentially participating in this intricate molecular biological process.

Non-coding RNAs as regulators of the Hippo pathway in cardiac development and cardiovascular disease.

Cardiovascular diseases pose a serious threat to human health. The onset of cardiovascular diseases involves the comprehensive effects of multiple genes and environmental factors, and multiple signaling pathways are involved in regulating the occurrence and development of cardiovascular diseases. The Hippo pathway is a highly conserved signaling pathway involved in the regulation of cell proliferation, apoptosis, and differentiation. Recently, it has been widely studied in the fields of cardiovascular disease, cancer, and cell regeneration. Non-coding RNA (ncRNAs), which are important small molecules for the regulation of gene expression in cells, can directly target genes and have diverse regulatory functions. Recent studies have found that ncRNAs interact with Hippo pathway components to regulate myocardial fibrosis, cardiomyocyte proliferation, apoptosis, and hypertrophy and play an important role in cardiovascular disease. In this review, we describe the mode of action of ncRNAs in regulating the Hippo pathway, provide new ideas for further research, and identify molecules involved in the mechanism of action of ncRNAs and the Hippo pathway as potential therapeutic targets, with the aim of finding new modes of action for the treatment and prevention of cardiovascular diseases.

The clinical significance of sarcopenia in patients with hepatocellular carcinoma treated with lenvatinib and PD-1 inhibitors.

Background and aim: Sarcopenia has gained considerable attention in the context of hepatocellular carcinoma, as it has been correlated with a poorer prognosis among patients undergoing sorafenib or lenvatinib treatment for hepatocellular carcinoma (HCC). The clinical significance of sarcopenia in first-line advanced HCC patients treated with lenvatinib and programmed death-1 (PD-1) inhibitors needs to be clarified. Methods: Sarcopenia was diagnosed using CT (Computed tomography) or MRI (Magnetic Resonance Imaging), with the psoas muscle index (PMI) as the surrogate marker. Patients were grouped based on sarcopenia presences, and a comparative analysis examined characteristics, adverse events, and prognosis. The Cox regression analysis was applied to identify independent prognostic factors for survival, while nomograms were constructed to predict 1-year survival. Results: Among 180 patients, 46 had sarcopenia. Patients with baseline sarcopenia demonstrated significantly inferior median progression-free survival (mPFS) (3.0 vs. 8.3 months) and median overall survival (mOS) (7.3 vs. 21.6 months). The same results for mPFS (3.3 vs. 9.2 months) and mOS (9.4 vs. 24.2 months) were observed in patients who developed sarcopenia after treatment. Furthermore, significantly higher grade 3 or higher adverse events (AEs) (73.91% vs 41.79%, p<0.001) were recorded in the sarcopenia group compared to the non-sarcopenia group. In the multivariate analysis, distant metastasis, elevated PLR and CRP levels, and low PMI remained independent predictive factors for poor OS. Additionally, skeletal muscle loss remained a significant independent risk factor for PFS. We developed a nomogram incorporating these four indicators, which predicted 12-month survival with a C-index of 0.853 (95% CI, 0.791 - 0.915), aligning well with actual observations. Conclusion: The prognosis of patients with HCC and sarcopenia is significantly worse when treated with lenvatinib and PD-1 inhibitors. The combination regimen of lenvatinib plus PD-1 inhibitors should be cautiously recommended due to the inferior prognosis and higher AEs.

TMV-CP based rational design and discovery of α-Amide phosphate derivatives as anti plant viral agents.

The tobacco mosaic virus coat protein (TMV-CP) is indispensable for the virus's replication, movement and transmission, as well as for the host plant's immune system to recognize it. It constitutes the outermost layer of the virus particle, and serves as an essential component of the virus structure. TMV-CP is essential for initiating and extending viral assembly, playing a crucial role in the self-assembly process of Tobacco Mosaic Virus (TMV). This research employed TMV-CP as a primary target for virtual screening, from which a library of 43,417 compounds was sourced and SH-05 was chosen as the lead compound. Consequently, a series of α-amide phosphate derivatives were designed and synthesized, exhibiting remarkable anti-TMV efficacy. The synthesized compounds were found to be beneficial in treating TMV, with compound 3g displaying a slightly better curative effect than Ningnanmycin (NNM) (EC50 = 304.54 µg/mL) at an EC50 of 291.9 µg/mL. Additionally, 3g exhibited comparable inactivation activity (EC50 = 63.2 µg/mL) to NNM (EC50 = 67.5 µg/mL) and similar protective activity (EC50 = 228.9 µg/mL) to NNM (EC50 = 219.7 µg/mL). Microscale thermal analysis revealed that the binding of 3g (Kd = 4.5 ± 1.9 µM) to TMV-CP showed the same level with NNM (Kd = 5.5 ± 2.6 µM). Results from transmission electron microscopy indicated that 3g could disrupt the structure of TMV virus particles. The toxicity prediction indicated that 3g was low toxicity. Molecular docking showed that 3g interacted with TMV-CP through hydrogen bond, attractive charge interaction and π-Cation interaction. This research provided a novel α-amide phosphate structure target TMV-CP, which may help the discovery of new anti-TMV agents in the future.

Gold nanoparticle-decorated fluorine-doped tin oxide substrate for sensitive label-free OIRD microarray chips.

Oblique incidence reflectance difference (OIRD) is an emerging technique enabling real-time and label-free detection of bio-affinity binding events on microarrays. The interfacial architecture of the microarray chip is critical to the performance of OIRD detection. In this work, a sensitive label-free OIRD microarray chip was developed by using gold nanoparticle-decorated fluorine-doped tin oxide (AuNPs-FTO) slides as a chip substrate. This AuNPs-FTO chip demonstrates a higher signal-to-noise ratio and improved sensitivity compared to that built on FTO glass, showing a detection limit of as low as 10 ng mL-1 for the model target, HRP-conjugated streptavidin. On-chip ELISA experiments and optical calculations suggest that the enhanced performance is not only due to the higher probe density enabling a high capture efficiency toward the target, but most importantly, the AuNP layer arouses optical interference to improve the intrinsic sensitivity of OIRD. This work provides an effective strategy for constructing OIRD-based microarray chips with enhanced sensitivity, and may help extend their practical applications in various fields.

Molecular mechanisms and potential therapeutic targets in the pathogenesis of hypertension in visceral adipose tissue induced by a high-fat diet.

Background: Hypertension (HTN) presents a significant global public health challenge with diverse causative factors. The accumulation of visceral adipose tissue (VAT) due to a high-fat diet (HFD) is an independent risk factor for HTN. While various studies have explored pathogenic mechanisms, a comprehensive understanding of impact of VAT on blood pressure necessitates bioinformatics analysis. Methods: Datasets GSE214618 and GSE188336 were acquired from the Gene Expression Omnibus and analyzed to identify shared differentially expressed genes between HFD-VAT and HTN-VAT. Gene Ontology enrichment and protein-protein interaction analyses were conducted, leading to the identification of hub genes. We performed molecular validation of hub genes using RT-qPCR, Western-blotting and immunofluorescence staining. Furthermore, immune infiltration analysis using CIBERSORTx was performed. Results: This study indicated that the predominant characteristic of VAT in HTN was related to energy metabolism. The red functional module was enriched in pathways associated with mitochondrial oxidative respiration and ATP metabolism processes. Spp1, Postn, and Gpnmb in VAT were identified as hub genes on the pathogenic mechanism of HTN. Proteins encoded by these hub genes were closely associated with the target organs-specifically, the resistance artery, aorta, and heart tissue. After treatment with empagliflozin, there was a tendency for Spp1, Postn, and Gpnmb to decrease in VAT. Immune infiltration analysis confirmed that inflammation and immune response may not be the main mechanisms by which visceral adiposity contributes to HTN. Conclusions: Our study pinpointed the crucial causative factor of HTN in VAT following HFD. Spp1, Postn, and Gpnmb in VAT acted as hub genes that promote elevated blood pressure and can be targets for HTN treatment. These findings contributed to therapeutic strategies and prognostic markers for HTN.