Healthy diet habits attenuate the association of poor sleep quality with nonfatal ischemic stroke: A prospective rural cohort.

OBJECTIVES: The combined impact of sleep quality and diet habits on ischemic stroke remains unclear, particularly in rural populations. Therefore, this study aimed to estimate the individual and joint associations of sleep quality and diet habits with nonfatal ischemic stroke among rural adults. METHODS: A total of 22 536 participants free of stroke were enrolled from the Henan Rural Cohort. Sleep quality and diet habits were evaluated with the Pittsburgh Sleep Quality Index and food frequency questionnaire, respectively. The ischemic stroke incidence was analyzed using Kaplan-Meier curves. Cox regression and restricted cubic spline were employed to estimate the correlation of sleep quality or diet habits with ischemic stroke. RESULTS: During an average 3.92 y of follow-up, 665 ischemic stroke patients were identified. The adjusted hazard ratio (95% confidence interval) of ischemic stroke risk compared with good sleep quality was 1.276 (1.057-1.542). The hazard ratio (95% confidence interval) of nonfatal ischemic stroke compared with unhealthy diet habits was 0.693 (0.589-0.814). The restricted cubic spline indicated that the risk of ischemic stroke increased with the increase of the Pittsburgh Sleep Quality Index. And the higher the diet quality score, the lower the risk of ischemic stroke. (Ptrend < 0.05). Further analysis indicated that the association of poor sleep quality with ischemic stroke was alleviated by healthy diet habits (P < 0.05). Additionally, a robust correlation remained after excluding individuals with ischemic stroke in the first year. CONCLUSIONS: Poor sleep quality was positively associated with nonfatal ischemic stroke among rural adults, and healthy diet habits attenuated this relationship. Developing healthy diet and sleep habits may have potential health implications for preventing ischemic stroke. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (registration no. ChiCTR-OOC-15006699). Date of registration: July 6, 2015.

Verapamil Enhances the Activity of Caspofungin against Cryptococcus neoformans Coincides with Inhibited Ca2+ /CN Pathway and Damage with Cell Wall Integrity.

Currently, the therapeutic effect on cryptococcal infection patients is hindered by toxicity and drug resistance, making it urgent to discover alternative antifungals. Calcium channel blockers, verapamil (VER), have shown effective antifungal effects in several fungi. Here, we found that VER has a significant antifungal effect on Cryptococcus neoformans (C. neoformans). Furthermore, VER has significant synergistic effects with multiple antifungals, even caspofungin (CAS). We confirmed that VER and CAS had a synergistic antifungal effect in the Galleria mellonella. We conducted in-depth research on the possible mechanism of the synergistic impact of VER and CAS. After treatment with VER, the chitosan content of C. neoformans ' cell wall decreased and in dopamine liquid culture medium, we observed the leakage of melanin. Through cell wall fluorescence staining and stress sensitivity analysis, we further demonstrated that VER impaired the integrity of the C. neoformans' cell wall. Another side, VER+CAS modification of C. neoformans membrane permeability, leading to intracellular ROS accumulation and mitochondrial membrane potential changes. VER eliminated the cytoplasmic calcium fluctuations caused by CAS stimulation and down-regulated the genes expression associated with the calcineurin pathway. In addition, we found that the enzyme activity of chitin deacetylase of C. neoformans is significantly influenced by the presence of Ca2+, suggesting that the use of VER may affect the activity. In summary, the synergistic antifungal effect of VER and CAS makes them effective and promising candidates for fungal treatment.

Retinal microvascular changes in patients with pancreatitis and their clinical significance.

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

3D Bioprinted Tissue-Engineered Bone with Enhanced Mechanical Strength and Bioactivities: Accelerating Bone Defect Repair through Sequential Immunomodulatory Properties.

In this study, a new-generation tissue-engineered bone capable of temporally regulating the immune response, balancing proinflammatory and anti-inflammatory activities, and facilitating bone regeneration and repair to address the challenges of delayed healing and nonunion in large-sized bone defects, is innovatively developed. Using the innovative techniques including multiphysics-assisted combined decellularization, side-chain biochemical modification, and sterile freeze-drying, a novel photocurable extracellular matrix hydrogel, methacrylated bone-derived decellularized extracellular matrix (bdECM-MA), is synthesized. After incorporating the bdECM-MA with silicon-substituted calcium phosphate and bone marrow mesenchymal stem cells, the tissue-engineered bone is fabricated through digital light processing 3D bioprinting. This study provides in vitro confirmation that the engineered bone maintains high cellular viability while achieving MPa-level mechanical strength. Moreover, this engineered bone exhibits excellent osteogenesis, angiogenesis, and immunomodulatory functions. One of the molecular mechanisms of the immunomodulatory function involves the inhibition of the p38-MAPK pathway. A pioneering in vivo discovery is that the natural biomaterial-based tissue-engineered bone demonstrates sequential immunomodulatory properties that activate proinflammatory and anti-inflammatory responses in succession, significantly accelerating the repair of bone defects. This study provides a new research basis and an effective method for developing autogenous bone substitute materials and treating large-sized bone defects.

Gender-specific prognosis models reveal differences in subarachnoid hemorrhage patients between sexes.

BACKGROUND: Subarachnoid hemorrhage (SAH) represents a severe stroke subtype. Our study aims to develop gender-specific prognostic prediction models derived from distinct prognostic factors observed among different-gender patients. METHODS: Inclusion comprised SAH-diagnosed patients from January 2014 to March 2016 in our institution. Collected data encompassed patients' demographics, admission severity, treatments, imaging findings, and complications. Three-month post-discharge prognoses were obtained via follow-ups. Analyses assessed gender-based differences in patient information. Key factors underwent subgroup analysis, followed by univariate and multivariate analyses to identify gender-specific prognostic factors and establish/validate gender-specific prognostic models. RESULTS: A total of 929 patients, with a median age of 57 (16) years, were analyzed; 372 (40%) were male, and 557 (60%) were female. Differences in age, smoking history, hypertension, aneurysm presence, and treatment interventions existed between genders (p < 0.01), yet no disparity in prognosis was noted. Subgroup analysis explored hypertension history, aneurysm presence, and treatment impact, revealing gender-specific variations in these factors' influence on the disease. Screening identified independent prognostic factors: age, SEBES score, admission GCS score, and complications for males; and age, admission GCS score, intraventricular hemorrhage, treatment interventions, symptomatic vasospasm, hydrocephalus, delayed cerebral ischemia, and seizures for females. Evaluation and validation of gender-specific models yielded an AUC of 0.916 (95% CI: 0.878-0.954) for males and 0.914 (95% CI: 0.885-0.944) for females in the ROC curve. Gender-specific prognostic models didn't significantly differ from the overall population-based model (model 3) but exhibited robust discriminative ability and clinical utility. CONCLUSION: Variations in baseline and treatment-related factors among genders contribute partly to gender-based prognosis differences. Independent prognostic factors vary by gender. Gender-specific prognostic models exhibit favorable prognostic performance.

Prediction of lung adenocarcinoma prognosis and diagnosis with a novel model anchored in circadian clock-related genes.

Lung adenocarcinoma is the most common primary lung cancer seen in the world, and identifying genetic markers is essential for predicting the prognosis of lung adenocarcinoma and improving treatment outcomes. It is well known that alterations in circadian rhythms are associated with a higher risk of cancer. Moreover, circadian rhythms play a regulatory role in the human body. Therefore, studying the changes in circadian rhythms in cancer patients is crucial for optimizing treatment. The gene expression data and clinical data were sourced from TCGA database, and we identified the circadian clock-related genes. We used the obtained TCGA-LUAD data set to build the model, and the other 647 lung adenocarcinoma patients' data were collected from two GEO data sets for external verification. A risk score model for circadian clock-related genes was constructed, based on the identification of 8 genetically significant genes. Based on ROC analyses, the risk model demonstrated a high level of accuracy in predicting the overall survival times of lung adenocarcinoma patients in training folds, as well as external data sets. This study has successfully constructed a risk model for lung adenocarcinoma prognosis, utilizing circadian rhythm as its foundation. This model demonstrates a dependable capacity to forecast the outcome of the disease, which can further guide the relevant mechanism of lung adenocarcinoma and combine behavioral therapy with treatment to optimize treatment decision-making.

Expansion of Structure Property in Cascade Nazarov Cyclization and Cycloexpansion Reaction to Diverse Angular Tricycles and Total Synthesis of Nominal Madreporanone.

A cascade Nazarov cyclization/dicycloexpansions reaction was developed for the precise synthesis of the angularly fused M/5/N (M = 5, 6; N = 4-9, 13) tricyclic skeletons. The prioritized expansion of the first ring played a critical role in the transformations, due to the release of ring strain, and the nature of the substituents present on the substrate is another influencing factor. This pioneering cascade reaction features broad substrates scope (33 examples), short reaction time, exceptional yields (up to 95%), and remarkable regioselectivities (> 20:1). Exploiting the synthetic application of this cascade reaction, we successfully executed a succinct total synthesis of nominal madreporanone for the first time.

Intracellular Gold Nanocluster/Organic Semiconductor Heterostructure for Enhancing Photosynthesis.

Photosynthetic microorganisms, which rely on light-driven electron transfer, store solar energy in self-energy carriers and convert it into bioenergy. Although these microorganisms can operate light-induced charge separation with nearly 100% quantum efficiency, their practical applications are inherently limited by the photosynthetic energy conversion efficiency. Artificial semiconductors can induce an electronic response to photoexcitation, providing additional excited electrons for natural photosynthesis to improve solar conversion efficiency. However, challenges remain in importing exogenous electrons across cell membranes. In this work, we have developed an engineered gold nanocluster/organic semiconductor heterostructure (AuNC@OFTF) to couple the intracellular electron transport chain of living cyanobacteria. AuNC@OFTF exhibits a prolonged excited state lifetime and effective charge separation. The internalized AuNC@OFTF permits its photogenerated electrons to participate in the downstream of photosystem II and construct an oriented electronic highway, which enables a five-fold increase in photocurrent in living cyanobacteria. Moreover, the binding events of AuNC@OFTF established an abiotic-biotic electronic interface at the thylakoid membrane to enhance electron flux and finally furnished nicotinamide adenine dinucleotide phosphate. Thus, AuNC@OFTF can be exploited to spatiotemporally manipulate and enhance the solar conversion of living cyanobacteria in cells, providing an extended nanotechnology for re-engineering photosynthetic pathways.

Analysis of seasonal H3N2 influenza virus epidemic characteristics and whole genome features in Jining City from 2018 to 2023.

Seasonal H3N2 influenza virus, known for its rapid evolution, poses a serious threat to human health. This study focuses on analyzing the influenza virus trends in Jining City (2018-2023) and understanding the evolving nature of H3N2 strains. Data on influenza-like cases were gathered from Jining City's sentinel hospitals: Jining First People's Hospital and Rencheng Maternal and Child Health Hospital, using the Chinese Influenza Surveillance Information System. Over the period from 2018 to 2023, 7844 throat swab specimens were assessed using real-time fluorescence quantitative PCR for influenza virus nucleic acid detection. For cases positive for seasonal H3N2 influenza virus, virus isolation was followed by whole genome sequencing. Evolutionary trees were built for the eight gene segments, and protein variation analysis was performed. From 2018 to 2023, influenza-like cases in Jining City represented 6.99% (237 299/3 397 247) of outpatient visits, peaking in December and January. Influenza virus was detected in 15.67% (1229/7844) of cases, primarily from December to February. Notably, no cases were found in the 2020-2021 season. Full genome sequencing was conducted on 70 seasonal H3N2 strains, revealing distinct evolutionary branches across seasons. Significant antigenic site variations in the HA protein were noted. No resistance mutations to inhibitors were found, but some strains exhibited mutations in PA, NS1, PA-X, and PB1-F2. Influenza trends in Jining City saw significant shifts in the 2020-2021 and 2022-2023 seasons. Seasonal H3N2 exhibited rapid evolution. Sustained vigilance is imperative for vaccine updates and antiviral selection.

Detection of differentially methylated CpGs between tumour and adjacent benign cells in diagnostic prostate cancer samples.

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-ß ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (npaired = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; npaired = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests.

Synergistic effects of bivalve and microalgae co-cultivation on carbon dynamics and water quality.

Aquaculture of bivalve shellfish and algae offers significant ecological benefits, yet the complex interactions between these organisms can substantially impact local carbon dynamics. This study investigated the effects of co-culturing four intertidal bivalve species Pacific oysters (Crassostrea gigas), Manila clams (Ruditapes philippinarum), Chinese clams (Cyclina sinensis), and hard clams (Mercenaria mercenaria) with microalgae (Isochrysis galbana) on specific water quality parameters, including total particulate matter (TPM), total organic matter (TOM), dissolved inorganic carbon (DIC), dissolved carbon dioxide (dCO2), dissolved oxygen (DO), and ammonium (NH4+) concentrations. The bivalves were divided into smaller and larger groups and cultured under two conditions: with algae (WP) and without (NP), along with matched controls. Total particulate matter (TPM), total organic matter (TOM), dissolved oxygen (DO), ammonium nitrogen (NH4+), dissolved inorganic carbon (DIC), and CO2 (dCO2) were measured before and after 3-h cultivation. Results revealed species-specific impacts on water chemistry. C. gigas, C. sinensis and R. philippinarum showed the strongest reduction in DIC and dCO2 in WP groups, indicating synergistic bioremediation with algae. M. mercenaria notably reduced TPM, highlighting its particle carbon sequestration potential. DO concentrations decreased in most WP or NP groups, reflecting respiration of the cultured bivalves or microalgae. NH4+ levels also declined for most species, indicating nitrogen assimilation by these creatures. Overall, the bivalve size significantly impacted carbon and nitrogen processing capacities. These findings reveal species-specific capabilities in regulating water carbon dynamics. Further research should explore integrating these bivalves in carbon-negative aquaculture systems to mitigate environmental impacts. This study provides valuable insights underlying local carbon dynamics in shallow marine ecosystems.

Facile synthesis of a novel CeCO3OH@(H/C-CdS) catalyst with synergistic effect of heterophase junction and heterojunction for enhanced visible-light photocatalytic degradation efficiency at room temperature.

A new CeCO3OH@(hexagonal/cubic phases-CdS) (CeCO3OH@(H/C-CdS)) composite catalyst was facilely synthesized by a simple microinjection titration-stirring method, in which CdS nanoparticles were dispersed on the surface of CeCO3OH nanolines. The optimal conditions for the preparation of composite catalysts with high photocatalytic performance were determined by single-factor experiments and response surface experiments. Under these conditions, the degradation rate of 30 mL 2.000 g/L rhodamine B (Rh B) by CeCO3OH@(H/C-CdS) in a photocatalytic reaction for 1 h at 25 °C was up to 86.81 % and its degradation rate in a photocatalytic reaction for 150 min was up to 99.62 %. The degradation rate could be maintained above 80 % even after six times recycling. Especially, the photocatalytic degradation efficiency of 2.000 g/L Rh B on the composite catalyst under sunlight and at room temperature for 30 min reached 97.66 %. Meanwhile, the large size of CeCO3OH considerably alleviated the agglomeration of CdS, providing more adsorption and active sites for visible light-mediated degradation of Rh B. Importantly, the Z-scheme charge transfer realized by CdS and CeCO3OH enhanced the efficient separation of photogenerated electrons and holes, and successfully inhibited the recombination of photogenerated electrons with holes. At the same time, owing to the low energy band difference between the two phases of CdS, charge was transferred between the hexagonal and cubic phases, leaving more effective photogenerated charge to participate in the degradation of Rh B. The synergism of the heterophase junction and heterojunction and the presence of oxygen and sulfur vacancies considerably enhanced the degradation performance of the catalyst. Thus, this study provides a new strategy for the modification and enhanced visible-light catalysis performance of CdS-based catalysts.

Herb-Nanoparticle Hybrid System for Improved Oral Delivery Efficiency to Alleviate Breast Cancer Lung Metastasis.

Background: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging. Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC-Orbitrap-MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated. Results: The HNS reduced particle-mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer's patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-ß1, which altered the TME in 4T1 tumor-bearing mice. Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.

A repeated cross-sectional pilot study of the relationship between perceived a community with shared future for doctor-patient and benefit finding: the mediating role of health self-consciousness and moderating role of anxiety.

OBJECTIVE: Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19. METHODS: Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected. RESULTS: Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage. CONCLUSIONS: The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage.

A newly identified algicidal bacterium of Pseudomonas fragi YB2: Algicidal compounds and effects.

Harmful algal bloom (HAB) is an unresolved existing problem worldwide. Here, we reported a novel algicidal bacterium, Pseudomonas fragi YB2, capable of lysing multiple algal species. To Chlorella vulgaris, YB2 exhibited a maximum algicidal rate of 95.02 % at 120 h. The uniqueness of YB2 lies in its ability to self-produce three algicidal compounds: 2-methyl-1, 3-cyclohexanedione (2-MECHD), N-phenyl-2-naphthylamine, and cyclo (Pro-Leu). The algicidal properties of 2-MECHD have not been previously reported. YB2 significantly affected the chloroplast and mitochondrion, thus decreasing in chlorophyll a by 4.74 times for 120 h and succinate dehydrogenase activity by 103 times for 36 h. These physiological damages disrupted reactive oxygen species and Ca2+ homeostasis at the cellular level, increasing cytosolic superoxide dismutase (23 %), catalase (35 %), and Ca2+ influx. Additionally, the disruption of Ca2+ homeostasis rarely reported in algicidal bacteria-algae interaction was observed using the non-invasive micro-test technology. We proposed a putative algicidal mechanism based on the algicidal outcomes and physiological algicidal effects and explored the potential of YB2 through an algicidal simulation test. Overall, this study is the first to report the algicidal bacterium P. fragi and identify a novel algicidal compound, 2-MECHD, providing new insights and a potent microbial resource for the biocontrol of HAB.

Study on ultrasound-enhanced molecular transport in articular cartilage.

Local intra-articular administration with minimal side effects and rapid efficacy is a promising strategy for treating osteoarthritis(OA). Most drugs are rapidly cleared from the joint space by capillaries and lymphatic vessels before free diffusion into cartilage. Ultrasound, as a non-invasive therapy, enhances molecular transport within cartilage through the mechanisms of microbubble cavitation and thermal effects. This study investigated the mass transfer behavior of solute molecules with different molecular weights (479 Da, 40 kDa, 150 kDa) within porcine articular cartilage under low-frequency ultrasound conditions of 40 kHz and ultrasound intensities of 0.189 W/cm2 and 0.359 W/cm2. The results revealed that under the conditions of 0.189 W/cm2 ultrasound intensity, the mass transfer concentration of solute molecules were higher compared to passive diffusion, and with an increase in ultrasound intensity to 0.359 W/cm2, the mass transfer effect within the cartilage was further enhanced. Ultrasound promotes molecular transport in different layers of cartilage. Under static conditions, after 2 h of mass transfer, the concentration of small molecules in the superficial layer is lower than that in the middle layer. After applying ultrasound at 0.189 W/cm2, the molecular concentration in the superficial layer significantly increases. Under conditions of 0.359 W/cm2, after 12 h of mass transfer, the concentration of medium and large molecules in the deep layer region increased by more than two times. In addition, this study conducted an assessment of damage to porcine articular cartilage under ultrasound exposure, revealing the significant potential of low-frequency, low-intensity ultrasound in drug delivery and treatment of OA.

Vaginal involvement as a rare extranodal manifestation in advanced-stage follicular lymphoma: a case report and literature review.

Apart from bone marrow involvement, extranodal involvement of follicular lymphoma (FL) is rare. Gynecologic FL is seldom reported, among which the vagina is the rarest involved site. No vaginal involvement in advanced-staged FL was reported before. Here, we report a case of FL with systemic involvement including the vagina.

The influence of CLEC5A on early macrophage-mediated inflammation in COPD progression.

Chronic obstructive pulmonary disease (COPD) is a complex syndrome with poorly understood mechanisms driving its early progression (GOLD stages 1-2). Elucidating the genetic factors that influence early-stage COPD, particularly those related to airway inflammation and remodeling, is crucial. This study analyzed lung tissue sequencing data from patients with early-stage COPD (GSE47460) and smoke-exposed mice. We employed Weighted Gene Co-Expression Network Analysis (WGCNA) and machine learning to identify potentially pathogenic genes. Further analyses included single-cell sequencing from both mice and COPD patients to pinpoint gene expression in specific cell types. Cell-cell communication and pseudotemporal analyses were conducted, with findings validated in smoke-exposed mice. Additionally, Mendelian randomization (MR) was used to confirm the association between candidate genes and lung function/COPD. Finally, functional validation was performed in vitro using cell cultures. Machine learning analysis of 30 differentially expressed genes identified 8 key genes, with CLEC5A emerging as a potential pathogenic factor in early-stage COPD. Bioinformatics analyses suggested a role for CLEC5A in macrophage-mediated inflammation during COPD. Two-sample Mendelian randomization linked CLEC5A single nucleotide polymorphisms (SNPs) with Forced Expiratory Volume in One Second (FEV1), FEV1/Forced Vital Capacity (FVC) and early/later on COPD. In vitro, the knockdown of CLEC5A led to a reduction in inflammatory markers within macrophages. Our study identifies CLEC5A as a critical gene in early-stage COPD, contributing to its pathogenesis through pro-inflammatory mechanisms. This discovery offers valuable insights for developing early diagnosis and treatment strategies for COPD and highlights CLEC5A as a promising target for further investigation.

Discovery of 4-(Arylethynyl)piperidine Derivatives as Potent Nonsaccharide O-GlcNAcase Inhibitors for the Treatment of Alzheimer's Disease.

Inhibiting O-GlcNAcase and thereby up-regulation of the O-GlcNAc levels of tau was a potential approach for discovering AD treatments. Herein, a series of novel highly potent OGA inhibitors embracing a 4-(arylethynyl)piperidine moiety was achieved by capitalizing on the substrate recognition domain. Extensive structure-activity relationships resulted in compound 81 with significant enzymatic inhibition (IC50 = 4.93 ± 2.05 nM) and cellular potency (EC50 = 7.47 ± 3.96 nM in PC12 cells). It markedly increased the protein O-GlcNAcylation levels and reduced the phosphorylation on Ser199, Thr205, and Ser396 of tau in the OA-injured SH-SY5Y cell model, suggesting its potential role for AD treatment. In fact, an in vivo efficacy of ameliorating cognitive impairment was observed following treatment of APP/PS1 mice with compound 81 (100 mg/kg). Additionally, the appropriate plasma PK and beneficial BBB penetration properties were also observed. Compound 81 deserves to be further explored as an anti-AD agent.

Evaluation of ultrasound-assisted tomato sour soup marination on beef: Insights into physicochemical, sensory, microstructural, and flavour characteristics.

This study evaluated the quality attributes of tomato sour soup marinade and investigated the effects of ultrasound-assisted marination on the physicochemical properties, microstructure, texture, sensory quality, and flavour profile of beef. The results showed that tomato sour soup significantly increased the marinade absorption rate and improved beef tenderloin's physicochemical properties, texture, and flavour attributes compared to static brine (P < 0.05), with organic acids playing an essential role in the marinade tenderisation process. Compared to static sour soup marination, ultrasound treatment significantly accelerated the marination process, reducing beef's shear force, hardness, and chewiness while increasing its tenderness. Microstructural observations revealed that sour soup marination induced a fragmented and irregular muscle fibre structure. Furthermore, sour soup marination significantly increased the relative concentrations of volatile flavour compounds, including alkanes, organic sulphides, alcohols, aldehydes, and aromatic compounds. Appropriate ultrasound treatment positively affects the texture and flavour characteristics of beef marinated with tomato sour soup, and the optimal approach was 320 W ultrasound treatment for 60 min. Overall, tomato sour soup improved beef's textural and flavour attributes, while ultrasound-assisted marination is an effective processing method to improve the quality of meat products.