The impact of dipeptidyl peptidase 4 inhibitors on health-related quality of life in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: To evaluate the impact of dipeptidyl peptidase 4 (DPP-4) inhibitors on Health-related quality of life (HRQOL) in patients with type 2 diabetes mellitus (T2DM) compared with other hypoglycemic agents. METHODS: A systematic review and meta-analysis based on randomized controlled trials was conducted following the Cochrane Handbook and PRISMA. Studies were identified by searching PubMed (MEDLINE), EMBASE, Web of Science, CNKI, WANGFANG DATA, VIP DATABASE, Google Scholar, and Cochrane Central Register of Controlled Trials from database inception to Dec 30, 2023. The main result was HRQOL scores. The outcomes were extracted using the mean difference (MD) from each study. Sensitivity analysis and subgroup analysis were also performed. RESULTS: Forty studies (4,579 participants) were included, with 32 pooled for meta-analysis. DPP-4 inhibitors alongside conventional treatment significantly enhanced HRQOL compared to conventional treatment alone (MD = 9.85, 95% CI [7.98-11.71], P < 0.001; heterogeneity, I2 = 94%, P < 0.001), as assessed by SF-36 using a random-effects model. No additional benefit was found when measured by DTR-QOL using a fixed-effects model (MD = 2.29, 95% CI [-0.06-4.64], P = 0.06; heterogeneity, I2 = 49%, P = 0.1) and compared to SGLT-2 inhibitors. Subgroup analysis indicated that DPP-4 inhibitors favored patients ≥ 60 years old on medication for ≥ 6 months. CONCLUSIONS: DPP-4 inhibitors were superior for T2DM HRQOL improvement. More long-term, multicenter evidence is needed to generalize findings and compare them with newer hypoglycemic agents. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42023440134.

SARC-UNet: A coronary artery segmentation method based on spatial attention and residual convolution.

BACKGROUND AND OBJECTIVE: Coronary artery segmentation is a pivotal field that has received increasing attention in recent years. However, this task remains challenging because of the inhomogeneous distributions of the contrast agent and dim light, resulting in noise, vascular breakages and small vessel losses in the obtained segmentation results. METHODS: To acquire better automatic blood vessel segmentation results for coronary angiography images, a UNet-based segmentation network (SARC-UNet) is constructed for coronary artery segmentation; this approach is based on residual convolution and spatial attention. First, we use the low-light image enhancement (LIME) approach to increase the contrast and clarity levels of coronary angiography images. Then, we design two residual convolution fusion modules (RCFM1 and RCFM2) that can successfully fuse the local and global information of coronary images while also capturing the characteristics of finer-grained blood vessels, hence preventing the loss of tiny blood vessels in the segmentation findings. Finally, using a cascaded waterfall structure, we create a new location-enhanced spatial attention (LESA) mechanism that can efficiently improve the long-distance dependencies between coronary vascular pixel features, eradicating vascular ruptures and noise in the segmentation results. RESULTS: This article subjectively and objectively evaluates the experimental results. This method has performed well on five general indicators. Furthermore, it outperforms the connectivity indicators proposed in this article. This method can effectively segment blood vessels and obtain higher accuracy results. CONCLUSIONS: Numerous experiments have shown that the suggested method outperforms the state-of-the-art approaches, particularly in terms of vessel connectivity and small blood vessel segmentation.

CD33 Ameliorates Surgery-Induced Spatial Learning and Memory Impairments Through TREM2.

Neuroinflammation is implicated in the onset of postoperative cognitive dysfunction (POCD), with CD33 and triggering receptor expressed on myeloid cells 2 (TREM2) playing crucial roles in immune response modulation and neuroinflammatory processes. A total of 96 aged male C57/BL6 mice (9-12 months) were randomly assigned to one of four groups, each receiving an siRNA injection into the lateral ventricle. Subsequently, the mice underwent partial hepatectomy under general anesthesia. To assess cognitive function, the Morris water maze tests were conducted both pre- and post-surgery. Following behavioral assessments, hippocampal tissues were swiftly harvested. The regulation of CD33 and TREM2 expression was achieved through siRNA in the BV2 microglia cell line. Expression levels of CD33 and TREM2 were evaluated both in vitro and in vivo using quantitative RT-PCR and western blot analyses. This study explored the impact of CD33 and TREM2 on POCD in aged mice and revealed that surgery and anesthesia increased CD33 expression, leading to spatial learning and memory impairments. Inhibiting CD33 expression via siRNA administration ameliorated cognitive deficits and mitigated the neuroinflammatory response triggered by surgery. Additionally, CD33 inhibition reversed the surgery-induced decrease in synaptic-related proteins, highlighting its role in preserving synaptic integrity. Moreover, our experiments suggest that CD33 may influence neuroinflammation and cognitive function through mechanisms involving TREM2. This is evidenced by the suppression of pro-inflammatory cytokines following CD33 knockdown in microglia and the reversal of these effects when both CD33 and TREM2 are concurrently knocked down. These findings imply that CD33 might promote neuroinflammation by inhibiting TREM2. This study highlights the potential of targeting CD33 as a promising therapeutic strategy for preventing and treating POCD. It provides valuable insights into the intricate mechanisms underlying cognitive dysfunction following surgical procedures.

Ag2Se as a tougher alternative to n-type Bi2Te3 thermoelectrics.

For half a century, only Bi2Te3-based thermoelectrics have been commercialized for near room temperature applications including both power generation and refrigeration. Because of the strong layered structure, Bi2Te3 in particular for n-type conduction has to be texturized to utilize its high in-plane thermoelectric performance, leaving a substantial challenge in toughness. This work presents the fabrication and performance evaluation of thermoelectric modules based on n-type Ag2Se paring with commercial p-Bi2Te3. Ag2Se mechanically allows an order of magnitude larger fracture strain and thermoelectrically secures the module efficiency quite competitive to that of commercial one for both refrigeration and power generation within ± 50 K of room temperature, enabling a demonstration of a significantly tougher alternative to n-type Bi2Te3 for practical applications.

Isolation of an α-glucosidase Inhibitor from Houttuynia cordata Thunb. and Its In vitro and In vivo Hypoglycemic Bioactivity.

The Houttuynia cordata Thunb. belongs to the Saururaceae family and is a well-known medicine and food homologous plant. Herein, the isolation of an α-glucosidase inhibitor from Houttuynia cordata Thunb. and characterization of its in vitro and in vivo hypoglycemic bioactivities are reported. We optimized the extraction conditions and isolated neochlorogenic acid (nCGA), which has α-glucosidase inhibitory activity from Houttuynia cordata Thunb. for the first time. nCGA competed with glucose for the α-glucosidase binding site, with a 50% inhibitory concentration (IC50) of 0.711 mg/mL. In vivo experiments in zebrafish showed that effects of nCGA on blood glucose varied by its concentrations. In particular, 4 mg/L nCGA significantly decreased the blood glucose level and inhibited effects of α-glucosidase in zebrafish. This work provides a theoretical basis for the extraction of hypoglycemic active ingredients from Houttuynia cordata Thunb. and a foundation for the development of natural and effective α-glucosidase inhibitors.

Mendelian randomization implicates causal association between epigenetic age acceleration and age-related eye diseases or glaucoma endophenotypes.

BACKGROUND: Age-related eye diseases (AREDs) have become increasingly prevalent with the aging population, serving as the leading causes of visual impairment worldwide. Epigenetic clocks are generated based on DNA methylation (DNAm) levels and are considered one of the most promising predictors of biological age. This study aimed to investigate the bidirectional causal association between epigenetic clocks and common AREDs or glaucoma endophenotypes. METHODS: Instrumental variables for epigenetic clocks, AREDs, and glaucoma endophenotypes were obtained from corresponding genome-wide association study data of European descent. Bidirectional two-sample Mendelian randomization (MR) was employed to explore the causal relationship between epigenetic clocks and AREDs or glaucoma endophenotypes. Multivariable MR (MVMR) was used to determine whether glaucoma endophenotypes mediated the association of epigenetic clocks with glaucoma. Multiple sensitivity analyses were conducted to confirm the robustness of MR estimates. RESULTS: The results showed that an increased intrinsic epigenetic age acceleration (HorvathAge) was significantly associated with an increased risk of primary open-angle glaucoma (OR = 1.04, 95% CI 1.02 to 1.06, P = 6.1E-04). The epigenetic age acceleration (EEA) of HannumAge was related to a decreased risk of primary angle-closure glaucoma (OR = 0.92, 95% CI 0.86 to 0.99, P = 0.035). Reverse MR analysis showed that age-related cataract was linked to decreased HannumAge (ß = -0.190 year, 95% CI -0.374 to -0.008, P = 0.041). The EEA of HannumAge (ß = -0.85 µm, 95% CI -1.57 to -0.14, P = 0.019) and HorvathAge (ß = -0.63 µm, 95% CI -1.18 to -0.08, P = 0.024) were associated with decreased central corneal thickness (CCT). PhenoAge was related to an increased retinal nerve fiber layer thickness (ß = 0.06 µm, 95% CI 0.01 to 0.11, P = 0.027). MVMR analysis found no mediation effect of CCT in the association of HannumAge and HorvathAge with glaucoma. DNAm-based granulocyte proportions were significantly associated with presbyopia, rhegmatogenous retinal detachment, and intraocular pressure (P < 0.05). DNAm-based plasminogen activator inhibitor-1 levels were significantly related to age-related macular degeneration and intraocular pressure (P < 0.05). CONCLUSION: The present study revealed a causal association between epigenetic clocks and AREDs. More research is warranted to clarify the potential mechanisms of the biological aging process in AREDs.

A novel NIR-II fluorescent probe for hydrogen peroxide detection in drug-induced liver injury.

The synthesis of H2O2-activatable small molecules in the second near-infrared (NIR-II) window remains challenging. We present the NIR-II probe Z-1065 for real-time detection of H2O2. Z-1065 demonstrates high sensitivity and selectivity towards H2O2in vitro and effectively monitors H2O2 generation in drug-induced liver injury (DILI) mouse models.

Contact-Electro-Catalysis Through Electret Behavior to Facilitate Electron Transfer.

Contact-electro-catalysis (CEC) usually uses polymer dielectrics as its catalysts under mechanical stimulation conditions, which although has a decent catalytic dye degradation effect still warrants performance improvement. A carrier separation promotion strategy based on an internal electric field by polarization can effectively improve ferroelectric material performance in photocatalysis and piezocatalysis. Therefore, carrier separation as a necessary process of CEC also can be promoted and is largely expected to improve CEC performance theoretically. However, the carrier separation enhancement by the internal electric field strategy has not been achieved in the CEC experiment yet, because of the difficulty of building an internal electric field in an inert polymer dielectric. Herein, a polytetrafluoroethylene (PTFE) dielectric was charged through an electret process, which was believed to establish an internal electric field for CEC catalysts proved by KPFM, XPS, and triboelectric nanogenerator voltage output analysis. The fastest degradation rate of methyl orange reached over 90% at 1.5 h, while the hydroxyl free radical (•OH) yield of the PTFE electret was nearly three times that of the original PTFE. Density functional theory (DFT) calculations verified that the potential barrier of interatomic electron transfer between PTFE and H2O was reduced by 37% under the internal electric field. The electret strategy used herein to optimize the PTFE catalyst provides a base for the use of other general plastics in CEC and facilitates the production of easily prepared, easily recyclable, and inexpensive polymer dielectric catalysts that can promote large-scale pollutant degradation via CEC.

Xanthophyllomyces dendrorhous Is a Safe Dietary Supplement with Potent Antioxidant Defense Enhancing Activity.

Xanthophyllomyces dendrorhous (X. dendrorhous), previously known as Phaffia rhodozyma, is a red yeast that is widely recognized as a rich source of carotenoids, particularly astaxanthin, which exhibits potent antioxidant activity and other health-promoting functions. However, there is currently a lack of research on the safety of consuming X. dendrorhous. To address this, we conducted an acute toxicity study followed by a 90-day subchronic toxicity trial to evaluate the safety of X. dendrorhous and investigate its in vivo antioxidant activity. In the acute toxicity study, Sprague-Dawley rats were administered a maximum of 12 g/kg body weight of X. dendrorhous powder by gavage and survived without any adverse effects for 14 days. In the subsequent subchronic toxicity test, the rats were randomly divided into five groups, each with free access to their diet adulterated with 0% (control), 2.5% (low), 5% (middle), 10% (high), and 20% (extreme high) X. dendrorhous powder. The rats' behavior, body weight, and food intake were monitored during the 90-day experiment. At the end of the experiment, urine, blood, and organs were collected from the rats for biochemical testing. Additionally, the antioxidant activity in rat sera was evaluated. The results of the acute toxicity test demonstrated that the LD50 of X. dendrorhous was greater than 12 g/kg body weight, indicating that the substance was not toxic. Throughout the 90-day period of subchronic toxicity, the triglyceride levels of male rats fed with 10 and 20% X. dendrorhous increased to 1.54 ± 0.17 and 1.55 ± 0.25 mmol/L (P < 0.05), respectively. This may be attributed to the elevated fat content of the diet in the high-dose and extreme high-dose groups, which was 5.5 and 2.5% higher than that in the control, respectively. Additionally, the white pulp in the spleen exhibited an increase, and the number of white blood cells in the extreme high-dose group increased by 2.41 × 109/L (P < 0.05), which may contribute to enhanced immunity. Finally, the body weight, food intake, blood and urine indexes, and histopathological examination results of the organs of the rats did not demonstrate any regular toxic effects. With the adulteration of X. dendrorhous, the activity of GSH-Px in male rats increased by 16-36.32%. The activity of GSH-Px in female rats of the extreme high-dose group increased by 14.70% (P < 0.05). The free radical scavenging ability of ABTS in male rats in the two high-dose groups exhibited an increase of 6.5 and 11.41% (P < 0.05). In contrast, the MDA content of male rats in the extreme high-dose group demonstrated a reduction of 2.73 nmol/mL (P < 0.05). These findings indicate that X. dendrorhous has no toxic effects, can be taken in high doses, and has a beneficial antioxidant effect that may enhance the body's immunity.

Formation mechanism and regulation analysis of trumpet leaf in Ginkgo biloba L.

Introduction: The research on plant leaf morphology is of great significance for understanding the development and evolution of plant organ morphology. As a relict plant, the G. biloba leaf morphology typically exhibits bifoliate and peltate forms. However, throughout its long evolutionary history, Ginkgo leaves have undergone diverse changes. Methods: This study focuses on the distinct "trumpet" leaves and normal fan-shaped leaves of G. biloba for analysis of their phenotypes, photosynthetic activity, anatomical observations, as well as transcriptomic and metabolomic analyses. Results: The results showed that trumpet-shaped G. biloba leaves have fewer cells, significant morphological differences between dorsal and abaxial epidermal cells, leading to a significantly lower net photosynthetic rate. Additionally, this study found that endogenous plant hormones such as GA, auxin, and JA as well as metabolites such as flavonoids and phenolic acids play roles in the formation of trumpet-shaped G. biloba leaves. Moreover, the experiments revealed the regulatory mechanisms of various key biological processes and gene expressions in the trumpet-shaped leaves of G. biloba. Discussion: Differences in the dorsal and abdominal cells of G. biloba leaves can cause the leaf to curl, thus reducing the overall photosynthetic efficiency of the leaves. However, the morphology of plant leaves is determined during the primordia leaf stage. In the early stages of leaf development, the shoot apical meristem (SAM) determines the developmental morphology of dicotyledonous plant leaves. This process involves the activity of multiple gene families and small RNAs. The establishment of leaf morphology is complexly regulated by various endogenous hormones, including the effect of auxin on cell walls. Additionally, changes in intracellular ion concentrations, such as fluctuations in Ca2+ concentration, also affect cell wall rigidity, thereby influencing leaf growth morphology.

Identification and experimental verification of a biomarker by combining the unfolded protein response with the immune cells in colon cancer.

BACKGROUND: The unfolded protein response (UPR) is associated with immune cells that regulate the biological behavior of tumors. This article aims to combine UPR-associated genes with immune cells to find a prognostic marker and to verify its connection to the UPR. METHODS: Univariate cox analysis was used to screen prognostically relevant UPRs and further screened for key UPRs among them by machine learning. ssGSEA was used to calculate immune cell abundance. Univariate cox analysis was used to screen for prognostically relevant immune cells. Multivariate cox analysis was used to calculate UPR_score and Tumor Immune Microenvironment score (TIME_score). WGCNA was used to screen UPR-Immune-related (UI-related) genes. Consensus clustering analysis was used to classify patients into molecular subtype. Based on the UI-related genes, we classified colon adenocarcinoma (COAD) samples by cluster analysis. Single-cell analysis was used to analyze the role of UI-related genes. We detected the function of TIMP1 by cell counting and transwell. Immunoblotting was used to detect whether TIMP1 was regulated by key UPR genes. RESULTS: Combined UPR-related genes and immune cells can determine the prognosis of COAD patients. Cluster analysis showed that UI-related genes were associated with clinical features of COAD. Single-cell analysis revealed that UI-related genes may act through stromal cells. We defined three key UI-related genes by machine learning algorithms. Finally, we found that TIMP1, regulated by key genes of UPR, promoted colon cancer proliferation and metastasis. CONCLUSIONS: We found that TIMP1 was a prognostic marker and experimentally confirmed that TIMP1 was regulated by key genes of UPR.

The hormone regulatory mechanism underlying parthenocarpic fruit formation in tomato.

Parthenocarpic fruits, known for their superior taste and reliable yields in adverse conditions, develop without the need for fertilization or pollination. Exploring the physiological and molecular mechanisms behind parthenocarpic fruit development holds both theoretical and practical significance, making it a crucial area of study. This review examines how plant hormones and MADS-box transcription factors control parthenocarpic fruit formation. It delves into various aspects of plant hormones-including auxin, gibberellic acid, cytokinins, ethylene, and abscisic acid-ranging from external application to biosynthesis, metabolism, signaling pathways, and their interplay in influencing parthenocarpic fruit development. The review also explores the involvement of MADS family gene functions in these processes. Lastly, we highlight existing knowledge gaps and propose directions for future research on parthenocarpy.

The impact of widowhood on the quality of life of older adults: the mediating role of intergenerational support from children.

BACKGROUND: China's transition into an aging society is accelerated by the simultaneous decline in fertility rates and the prolonged life expectancy of older adults. The impact of widowhood, a significant stressor in old age, has emerged as a crucial factor affecting the quality of life among the elderly. METHODS: This study is based on data from the 2018 China Health and Aging Tracking Survey. Multiple linear regression models were employed to investigate the influence of widowhood on the quality of life of older adults in China. Additionally, Bootstrap mediation effects were utilized to assess the mediating role of intergenerational support, considering both financial and emotional support from children. RESULTS: The findings indicate a substantial reduction in the quality of life index among older adults following widowhood. Moreover, the impact is more pronounced among older men compared to older women. Rural older adults experience a significant decline in quality of life post-widowhood, while the effect on urban counterparts is not statistically significant. CONCLUSIONS: Intergenerational financial support was identified as a partial mediator between widowhood and the quality of life among older adults. This underscores the importance of familial financial assistance in mitigating the adverse effects of widowhood on the well-being of the elderly. These results offer valuable insights into the nuanced impact of widowhood on the quality of life among older adults in China, emphasizing the need for targeted interventions, especially in rural areas. CLINICAL TRIAL: Not applicable.

IL-22/IL-22RA1 Promotes Human Tenon's Capsule Fibroblasts Proliferation and Regulates Fibrosis Through STAT3 Signaling Pathway.

Purpose: Although it is now understood that most antiglaucoma surgeries fail because of scarring of the filtering tract, the underlying mechanism remains to be elucidated. The present study investigated the mechanism by which the interleukin (IL)-22/IL-22 receptor alpha 1 (IL-22RA1) signaling pathway regulates scar formation in glaucoma patients. Method: A total of 31 glaucoma patients who underwent trabeculectomy surgery with uncontrollable intraocular pressure because of scarring and 19 strabismus patients as the control patient group were included in the present study. ELISA was performed to measure the content of IL-22 in peripheral blood. Serum from patients was used to incubate human Tenon's capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and Western blot were performed to determine IL-22RA1 mRNA and protein expression levels. Flow cytometry was performed to assess the cell cycle distribution and the Cell Counting Kit-8 assay was used to analyze cell proliferation. Results: The ELISA assay revealed that the serum IL-22 level of glaucoma patients was significantly higher than the healthy group (29.80 ± 5.1 ng/µL vs. 5.21 ± 0.9 ng/µL). After incubation with patient serum, the proliferation and activation of human Tenon fibroblasts (HTFs) were promoted. IL-22 mediated the biological function of HTFs via directly binding IL-22RA1. Moreover, transfection of the siR-IL-22RA1 or IL-22RA1 gene resulted in significant antifibrosis or profibrosis in HTFs. When a signal transducer and activator of transcription (STAT) 3 inhibitor (BAY) was introduced to the IL-22RA1 overexpression group, IL-22-induced proliferation was reduced in HTFs. Additionally, glaucoma patients had increased levels of IL-22 expression following surgery. Conclusions: The IL-22/IL-22RA1/STAT3 signaling pathway promoted fibroblast cell proliferation and alpha-smooth muscle actin, potentially regulating fibrosis in glaucoma filtration tracts. Our results provide hitherto undocumented insights into the pathophysiology of postoperative scarring.

Mechanism of mangiferin in the treatment of oral submucous fibrosis based on Gene Expression Omnibus database chip mining combined with network pharmacology and molecular docking.

OBJECTIVES: This study aims to investigate the primary target and potential mechanism of mangiferin (MF) in treating oral submucous fibrosis (OSF) through Gene Expression Omnibus (GEO) database chip mining, network pharmacology, and molecular docking techniques. METHODS: Potential therapeutic targets for OSF were identified using GEO chip data. The potential targets of MF were predicted, and disease-related targets for OSF were collected from databases. A Venn diagram was created using the EVenn platform to identify overlapping targets. The protein-protein interaction (PPI) network was constructed using the STRING database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the DAVID platform. Cytoscape 3.10.1 software was used to visualize a drug-target-pathway-disease network, while AutoDocktools 1.5.6 software was employed for molecular docking analysis. RESULTS: A total of 356 potential targets for MF and 360 disease-related targets for OSF were obtained from multiple databases. The top 15 key target proteins in the PPI network were selected as significant candidates. GO function and KEGG pathway enrichment analyses revealed that MF treatment primarily involved advanced glycation end products-receptor (AGE-RAGE), epidermal growth factor receptor (EGFR), and other signaling pathways associated with OSF pathogenesis. Molecular docking analysis demonstrated that MF exhibited a strong binding activity toward AKT serine kinase 1 (AKT1), tumor necrosis factor (TNF), and other core targets. CONCLUSIONS: These findings suggest that MF may exert its therapeutic effects on OSF through a multitarget approach involving various signaling pathways.

Elongatibacter sediminis gen. nov., sp. nov., isolated from intertidal sediment, and genomic comparison with all genera in the family Wenzhouxiangellaceae.

A novel slightly halophilic, aerobic, and Gram-stain-negative strain, designated as CH-27T, was isolated during a bacterial resource investigation of intertidal sediment collected from Xiaoshi Island in Weihai, PR China. Cells of strain CH-27T were rod-shaped with widths of 0.3-0.6 µm and lengths of 2.0-11.0 µm. Strain CH-27T grew optimally at 37 °C, pH 7.0 and with 2.0 % (w/v) NaCl. Catalase activity was weakly positive and oxidase activity was positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CH-27T was most related to Marinihelvus fidelis KCTC 92639T (93.6 %), followed by Wenzhouxiangella marina MCCC 1K00261T (92.0 %). Based on genome comparisons between strain CH-27T and M. fidelis KCTC 92639T, the average amino acid identity was 63.6 % and the percentage of conserved proteins was 48.3 %. The major cellular fatty acid of strain CH-27T (≥10 %) was iso-C15 : 0 and the sole respiratory quinone was quinone-8. The polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, and aminophospholipid. The DNA G+C content was 62.7 mol%. Based on comprehensive analysis of its phylogenetic, physiological, biochemical, and chemotaxonomic characteristics, strain CH-27T represents a novel species in a novel genus, for which the name Elongatibacter sediminis gen. nov., sp.nov. is proposed. The type strain is CH-27T (=MCCC 1H00480T=KCTC 8011T).

A Mitochondria-Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR-II Fluorescence/Photoacoustic Imaging-Guided Phototherapy.

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, a lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential in cancer treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation of photosensitizers (PSs), many PSs lack specific subcellular targets and are limited to the first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy is essential for cancer treatment strategies. Here, we synthesized four molecules with varying benzene ring numbers in thiopyrylium structures to preliminarily explore their photodynamic properties. The near-infrared-II (NIR-II) PS Z1, with a higher benzene ring count, exhibited superior ROS generation and mitochondria-targeting abilities, and a large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high ROS generation (especially type-I ROS) upon 808 nm laser irradiation, leading to efficient mitochondria dysfunction and combined pyroptosis and apoptosis. Moreover, they exhibited exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) and photoacoustic imaging (PAI). Furthermore, Z1 NPs-mediated phototherapy effectively inhibited tumor growth with minimal adverse effects. Our findings offer a promising strategy for cancer therapy, warranting further preclinical investigations in PDT.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and obstructive sleep apnea: a cross-sectional study from NHANES.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a widespread sleep disturbance linked to metabolic and cardiovascular conditions. The Non-High-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol Ratios (NHHR) has been proposed as being a potential biomarker to gauge cardiovascular risk. However, its relationship with OSA remains unclear. METHODS: This survey investigated the link NHHR to OSA in American citizens aged 20 and older using information collected via the National Health and Nutrition Examination Survey (NHANES) during the years 2017 to 2020. Logistic regression models with multivariable adjustments were employed to assess this relationship. Nonlinear associations were explored using smooth curve fitting, with a two-part linear regression model identifying a threshold effect. Subgroup analyses were conducted to evaluate population-specific differences. RESULTS: The survey encompassed 6763 participants, with an average age of 50.75 ± 17.32. The average NHHR stood at 2.74, accompanied by a standard deviation of 1.34, while the average frequency of OSA was 49.93%. Upon adjusting for covariates, each unit increase in NHHR may be associated with a 9% rise in OSA incidence. (95% confidence intervals 1.04-1.14; P < 0.0001). Notably, a U-shaped curve depicted the NHHR-OSA relationship, with an inflection point at 4.12. Subgroup analyses revealed consistent associations, with educational attainment and diabetes status modifying the NHHR-OSA relationship. CONCLUSION: The study highlights NHHR as a potential tool for OSA prediction, presenting avenues for advanced risk evaluation, tailored interventions, personalized treatment approaches, and preventive healthcare.

Mapping global prevalence of menopausal symptoms among middle-aged women: a systematic review and meta-analysis.

BACKGROUND: Women at middle age are puzzled by a series of menopausal disturbances, can be distressing and considerably affect the personal, social and work lives. We aim to estimate the global prevalence of nineteen menopausal symptoms among middle-aged women by performing a systematic review and meta-analysis. METHODS: Comprehensive search was performed in multiple databases from January, 2000 to March, 2023 for relevant studies. Random-effect model with double-arcsine transformation was used for data analysis. RESULTS: A total of 321 studies comprised of 482,067 middle-aged women were included for further analysis. We found varied prevalence of menopausal symptoms, with the highest prevalence of joint and muscular discomfort (65.43%, 95% CI 62.51-68.29) and lowest of formication (20.5%, 95% CI 13.44-28.60). Notably, South America shared dramatically high prevalence in a sort of menopausal symptoms including depression and urogenital symptoms. Besides, countries with high incomes (49.72%) had a significantly lower prevalence of hot flashes than those with low (65.93%), lower-middle (54.17%), and upper-middle (54.72%, p < 0.01), while personal factors, such as menopausal stage, had an influence on most menopausal symptoms, particularly in vaginal dryness. Prevalence of vagina dryness in postmenopausal women (44.81%) was 2-fold higher than in premenopausal women (21.16%, p < 0.01). Furthermore, a remarkable distinction was observed between body mass index (BMI) and prevalence of sleep problems, depression, anxiety and urinary problems. CONCLUSION: The prevalence of menopausal symptoms affected by both social and personal factors which calls for attention from general public.

Research progress of nano delivery systems for intraocular pressure lowering drugs.

Glaucoma is a chronic ocular disease characterized by optic atrophy and visual field defect. The main risk factor for glaucoma onset and progression is elevated intraocular pressure, which is caused by increased aqueous humor outflow resistance. Currently, the primary method for glaucoma therapy is the use of intraocular pressure lowering drugs. However, these drugs, when administered through eye drops, have low bioavailability, require frequent administration, and often result in adverse effects. To overcome these challenges, the application of nanotechnology for drug delivery has emerged as a promising approach. Nanoparticles can physically adsorb, encapsulate, or chemically graft drugs, thereby improving their efficacy, retention time, and reducing adverse reactions. Moreover, nanotechnology has opened up new avenues for ocular administration. This article provides a comprehensive review of nano systems for intraocular pressure lowering drugs, encompassing cholinergic agonists, ß-adrenergic antagonists, α-adrenergic agonists, prostaglandin analogs, carbonic anhydrase inhibitors, Rho kinase inhibitors, and complex preparations. The aim is to offer novel insights for the development of nanotechnology in the field of intraocular pressure lowering drugs.