The Effect of Cosmetic Makeup on Body Imagery and Anxiety and Depression in Patients Undergoing Postoperative Chemotherapy for Breast Cancer: A Randomized Controlled Study.

Purpose: The objective was to compare the body images of breast cancer patients undergoing postoperative chemotherapy and the varying degrees of their anxiety and depression. The comparison involved those who received four consecutive cycles of cosmetic makeup and those who did not. Patients and Methods: Seventy-four breast cancer patients receiving postoperative chemotherapy were randomly assigned to either the control group or the intervention group. The control group received usual care, while the intervention group received four consecutive cycles of chemotherapy along with cosmetic makeup intervention on top of usual care. The intervention was carried out on the first day after the completion of each chemotherapy cycle. Assessments were made before the first intervention and 1 month after the fourth intervention using the Hospital Anxiety and Depression Scale and the Scale of Body Imagery. Results: After four cycles of intervention, significant differences emerged between the intervention and control groups regarding anxiety, depression, and body imagery. Additionally, within the intervention group, notable changes in these aspects were observed over time. Conclusion: The results showed that cosmetic interventions can effectively reduce the level of anxiety and depression of breast cancer patients receiving postoperative chemotherapy and effectively improve the body imagery of patients.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19-induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24- cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted.

Single-Cell Transcriptomic Analysis Reveals Dynamic Cellular Processes in Corneal Epithelium During Wound Healing in Cynomolgus Monkeys.

Purpose: Corneal wounding healing is critical for maintaining clear vision, however, a complete understanding of its dynamic regulatory mechanisms remains elusive. Here, we used single-cell RNA sequencing (scRNA-seq) to analyze the cellular activities and transcriptional changes of corneal limbal epithelial cells at different stages after wound healing in cynomolgus monkeys, which exhibit a closer transcriptomic similarity to humans. Methods: Corneal limbal tissues were collected during uninjured, 1-day and 3-day healing stages, dissociated into single cells, and subjected to scRNA-seq using the 10× Genomics platform. Cell types were clustered by graph-based visualization methods and unbiased computational analysis. Additionally, cell migration assays and immunofluorescent staining were performed on cultured human corneal epithelial cells. Results: We characterized nine cell clusters by scRNA-seq analysis of the cynomolgus monkey corneal epithelium. By comparing heterogeneous transcriptional changes in major cell types during corneal healing, we highlighted the importance of limbal epithelial cells (LEPCs) and basal epithelial cells (BEPCs) in extracellular matrix (ECM) formation and wound healing, as well as suprabasal epithelial cells (SEPCs) in epithelial differentiation during the healing processes. We further identified five different sub-clusters in LEPC, including the transit amplifying cell (TAC) sub-cluster that promotes early healing through the activation of thrombospondin-1 (THBS1) expression. Conclusions: Our study represents the first comprehensive exploration of the detailed transcriptome profile of individual corneal cells during the wound healing process in nonhuman primates. We demonstrate the intricate mechanisms involved in corneal healing and provide a promising avenue for potential therapies in corneal wound healing.

Quantitative prediction of water quality in Dongjiang Lake watershed based on LUCC.

Land Use/ Cover Change (LUCC) plays a crucial role in influencing hydrological processes, nutrient cycling, and sediment transport in watersheds, ultimately impacting water quality on both spatial and temporal scales. Accurately predicting changes in watershed water quality is beneficial for the sustainable management of water resources. Current models often lack the ability to effectively predict water quality changes in a dynamic spatio-temporal context, particularly in complex watershed environments. The overall purpose of the study is to establish a comprehensive and dynamic modeling framework that links LUCC with water quality, allowing for accurate predictions of future water quality under varying land use scenarios. The model, which uses water quality as the dependent variable and LUCC as the independent variable, was developed to quantitatively predict changes in watershed water quality. To achieve this, annual multi-period remote sensing images from Landsat-5, Landsat-8 or Sentinel-2 satellites spanning from 1992 to 2022 were analyzed. Random Forest (achieving a Kappa coefficient of 0.9468) were employed to classify land use within the watershed. Based on classification results, a Cellular Automata-Markov chain model (CA-Markov) was constructed to simulate and predict the spatio-temporal patterns of land use, incorporating driving factors such as proximity to water systems, roads, elevation, and slope. Validation of the model using LUCC data from 2020 yielded a high prediction accuracy with a Kappa coefficient of 0.9505. The CA-Markov model was further utilized to project LUCC under three different scenarios-natural development, ecological protection, and arable land protection-between 2023 and 2033. Based on these projections, the coupled water quality and LUCC model was employed to predict water quality changes in the watershed over the same period. Key findings indicate that water quality is likely to improve under ecological protection scenario, while deterioration is expected under natural development scenario and cropland protection scenario due to urban expansion, agricultural practices, and water diversion for irrigation. This study provides a robust framework for watershed management, offering scientific guidance for source management and water purification efforts, thereby contributing significantly to the sustainable development of water resources.

The role of artificial intelligence in the development of anticancer therapeutics from natural polyphenols: Current advances and future prospects.

Natural polyphenols, abundant in the human diet, are derived from a wide variety of sources. Numerous preclinical studies have demonstrated their significant anticancer properties against various malignancies, making them valuable resources for drug development. However, traditional experimental methods for developing anticancer therapies from natural polyphenols are time-consuming and labor-intensive. Recently, artificial intelligence has shown promising advancements in drug discovery. Integrating AI technologies into the development process for natural polyphenols can substantially reduce development time and enhance efficiency. In this study, we review the crucial roles of natural polyphenols in anticancer treatment and explore the potential of AI technologies to aid in drug development. Specifically, we discuss the application of AI in key stages such as drug structure prediction, virtual drug screening, prediction of biological activity, and drug-target protein interaction, highlighting the potential to revolutionize the development of natural polyphenol-based anticancer therapies.

The influence of COVID-19 on short-term mortality in acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the differences in short-term mortality risk between acute ischemic stroke (AIS) patients with and without SARS-CoV-2 infection. METHODS: PubMed, EMBASE, Scopus, and Cochrane Databases were systematically searched from December 1, 2019 to May 20, 2022 using the keywords coronavirus disease 2019 (COVID-19), COVID-19, SARS-CoV-2, and ischemic stroke. A random-effects model was estimated, and subgroup analysis and meta-regressions were performed. The quality of eligible studies was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 26 eligible studies with 307,800 patients were included in this meta-analysis. The overall results show that in-hospital and 90-day mortality was 3.31-fold higher in AIS with SARS-CoV-2 patients compared with those without SARS-CoV-2. When matched for age and National Institutes of Health Stroke Scale score at admission, the risk ratio of in-hospital mortality from AIS among patients with SARS-CoV-2 versus without decreased to 2.83. Reperfusion therapy and endovascular thrombectomy may further reduce the risk of death in patients to some extent but do not increase the incidence of symptomatic intracerebral hemorrhage. Meta-regression showed that in-hospital mortality decreased with increasing National Institutes of Health Stroke Scale score in AIS with SARS-CoV-2 compared to those without SARS-CoV-2 and that the difference in mortality risk between the 2 was independent of age and sex. CONCLUSIONS: The results of this study suggest that AIS patients with SARS-CoV-2 have higher short-term mortality compared to AIS patients without SARS-CoV-2, and reperfusion and endovascular thrombectomy therapy may reduce the risk of short-term mortality to some extent. The differences in in-hospital mortality risk were similar across ages and sexes. Focused attention is therefore needed on AIS patients with SARS-CoV-2 to control mortality.

COVID-19 epidemic investigation study of a follow-up cohort of patients with diabetic kidney disease.

Introduction: The impact of coronavirus disease 2019 (COVID-19) on diabetic kidney disease (DKD) patients in China is not fully understood. This study aimed to investigate infection status in a DKD cohort post-renal biopsy and analyze vaccination and infection rates, as well as symptom severity, across various renal pathologies in DKD patients. Methods: This epidemiological survey, centered on COVID-19, employed a Chinese DKD and renal puncture follow-up cohort. A customized questionnaire enabled standardized data gathering. It collected data on clinical characteristics, vaccination and infection statuses, and diverse pathological types. The study analyzed the relationship between vaccination and infection statuses across various pathological types, evaluating characteristics and treatment outcomes in patients with infections. Results: In total, 437 patients with DKD from 26 Chinese provinces were followed up for a median of 44.6 ± 20 months. COVID-19 infection, vaccination, and novel coronavirus pneumonia (NCP) rates were 73.68%, 59.3%, and 6.63%, respectively. Ten patients with NCP had severe pneumonia or died of COVID-19. Renal pathology revealed that 167 (38.22%) patients had diabetic nephropathy (DN), 171 (39.13%) had non-diabetic renal disease (NDRD), and 99 had DN and NDRD (22.65%). The DN group had the lowest vaccination (54.5%), highest all-cause mortality (3.6%), and highest endpoint rates (34.10%). Compared to patients who were not vaccinated pre-infection (117 cases), vaccinated patients (198 cases) had reduced NCP (6.6% vs. 13.7%), severity (1.0% vs. 3.4%), and endpoint (9.10% vs. 31.60%) rates. Conclusion: Vaccination can prevent infection and diminish COVID-19 severity in patients with DKD; therefore, increasing vaccination rates is particularly important. Clinical Trial registration: ClinicalTrails.gov, NCT05888909.

The U -shape relationship between free fatty acid level and adverse outcomes in coronary artery disease patients with hypertension: evidence from a large prospective cohort study.

BACKGROUND: Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. METHODS: A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. RESULTS: A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a "U -shape" relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240-3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495-4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077-1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013-1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187-2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070-1.798), P = 0.013). CONCLUSIONS: Baseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension. TRIAL REGISTRATION: The details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143).

HDL Levels as a Novel Predictor of Long-Term Adverse Outcomes in Patients with Heart Failure: A Retrospective Cohort Study.

Background: The role of high-density lipoprotein cholesterol (HDL-C) in heart failure (HF) outcomes is contentious. We aimed to assess HDL-C's prognostic value in HF patients. Methods: In this retrospective cohort study (2012-2022) at the First Affiliated Hospital of Xinjiang Medical University, we analyzed 4442 patients, categorized by HDL-C quartiles. We applied the Cox proportional hazards model to assess survival and report hazard ratios (HR) with 95% confidence intervals (CI). Results: Over a decade, we recorded 1354 fatalities (42.3%) and 820 readmissions. The third HDL-C quartile (0.93-1.14 mmol/L) showed the lowest mortality rates, with reduced risks in the second and third quartiles compared to the first (Q2 HR=0.809, 95% CI 0.590-1.109; Q3 HR=0.794, 95% CI 0.564-1.118). The fourth quartile presented a lower mortality risk compared to the first (Q4 HR=0.887, 95% CI 0.693-1.134). A significant correlation existed between HDL-C levels and cardiovascular risk (HR=0.85, 95% CI 0.75-0.96, p<0.01). Conclusion: HDL-C levels exhibit a complex association with mortality in HF, indicating the importance of HDL-C in HF prognosis and the need for tailored management strategies.

Evaluating the Efficacy of Wrist-Ankle Acupuncture Combined With Patient-Controlled Intravenous Analgesia for Managing Post Uvulopalatopharyngoplasty.

OBJECTIVE: The aim of this study is to investigate the impact of combining wrist-ankle acupuncture with patient-controlled intravenous analgesia (PCIA) on active pain and food intake in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) after undergoing uvulopalatopharyngoplasty (UPPP). METHODS: Sixty patients with OSAHS who underwent UPPP at our hospital's Department of Otorhinolaryngology from January 2020 to October 2023 were selected and randomly divided into 2 groups of 30 each: an observation group and a control group. The control group received general anesthesia administered by an anesthesiologist and used a PCIA pump. In addition to this treatment, the observation group received the combined intervention of wrist-ankle acupuncture. Active pain levels were monitored at 0, 6, 12, 24, 36, and 48 hours after UPPP, and food intake was observed at 24, 36, and 48 hours postoperation. The results were compared and recorded for both groups. RESULTS: The analgesic effect on active pain in the observation group was significantly greater than in the control group at 6, 12, 24, 36, and 48 hours postoperation, and the differences were statistically significant (P<0.05). In addition, when comparing food intake scores at 24, 36, and 48 hours postoperation, the observation group had significantly higher food intake than the control group, and the differences were statistically significant (P<0.05). CONCLUSIONS: The combined intervention of wrist-ankle acupuncture and PCIA provides effective pain relief for OSAHS patients after UPPP, enhances their food intake, improves their quality of life, and supports early recovery.

The relationship between HbA1c and the activities of daily living in complex chronic patients with and without intracerebral hemorrhage.

BACKGROUND: Associations between HbA1c and adverse outcomes in ischemic and hemorrhagic stroke have been confirmed. It is still unclear whether HbA1c is related to the activities of daily living (ADL) score in complex chronic patients (CCP) with and without intracerebral hemorrhage (ICH). AIM: The associations between HbA1c and ADL (Barthel score) in CCP with ICH and without ICH were evaluated, respectively. METHODS: We have analyzed data from a previous cohort study involving in 3594 CCPs without a ICH history at baseline, who were followed up for 5 years to assess ICH episode. RESULTS: One hundred sixty-one ICH case were detected in a total of 3594 patients during the period of follow up for 5 years. Our nonlinear analysis suggested positive trends on the association between HBA1c and Barthel score in ICH and non-ICH patients, respectively. The multivariate linear regression analysis showed that elevated HbA1c was positively associated with a higher Barthel score among all study population (ß = 1.25, 95% CI: 0.92, 1.59; P < 0.0001) with adjusted age and sex. Among non-ICH patients, increased HbA1c was still positively associated with an increased Barthel score (ß = 1.24, 95% CI: 0.90, 1.58; P < 0.001). However, HbA1c appeared to have no any relationship with Barthel score in ICH patients (ß = 1.87, 95% CI: -0.07, 3.82; P = 0.0613) after adjustment for age and sex. By additionally using sensitivity analysis, we still observed that the strong relationship was still existed in non-ICH patients (ß = 0.90, 95% CI: 0.56, 1.24; P < 0.001) but not in ICH patients (ß = 1.88, 95% CI: -0.10, 3.86; P = 0.0649). CONCLUSION: We observed for the first time that elevated HbA1c is associated with better ADL in CCPs without ICH but not in those with ICH. This interesting discovery contradicts the traditional adverse effects of elevated HbA1c.

Sensitive colorimetric detection of glutathione in human serum based on peroxidase-like activity of chitosan-stabilized gold nanoparticles.

A colorimetric sensor for the rapid and sensitive detection of GSH was developed. The hydrothermal method was utilized to synthesize chitosan-stabilized gold nanoparticles (CS-AuNPs). The synthesized CS-AuNPs were characterized by UV-vis absorption spectroscopy, transmission electron microscopy (TEM), X-ray diffractograms (XRD), and Fourier transform infrared spectroscopy (FTIR). The CS-AuNPs are well-dispersed and possess a spherical shape with an average particle size of 10.05 ± 2.26 nm in aqueous solution. They show an intrinsic peroxidase-like activity, which could efficiently catalyze the decomposition of H2O2 to produce •OH radicals. These radicals then oxidized 3, 3´, 5, 5´-tetramethylbenzidine (TMB), resulting in the formation of the blue oxidized product oxTMB, observed a visible color change (from colorless to blue), and oxTMB had an obvious absorption peak at 652 nm. The presence of GSH could inhibit the peroxidase-like activity of CS-AuNPs, thereby reducing the formation of oxTMB. The solution's blue hue underwent a reduction in absorption intensity. Based on this fact, a novel and sensitive colorimetric sensor for detection of GSH was constructed. Under optimal conditions, the results of detection had an excellent linear relationship between the concentration of GSH and ∆A within the range 0.5 ~ 50.0 × 10-6 mol/L. The limit of detection (LOD) for GSH was 2.10 × 10-7 mol/L, which was much lower than those in most previous works. Furthermore, for detection in real human serum samples, the recoveries of GSH and the relative standard deviations (RSD) in the serum were in the range 98.40 ~ 103.32% and 1.85 ~ 3.54%, respectively. Thus, this visual colorimetric method has good precision and can be used for GSH detection in practical applications, promising in the fields of bioanalysis and illness diagnostics.

Comparative study of synergistic antibacterial activity of ciprofloxacin-capped gold nanoparticles under different ultrasound frequency.

Sonodynamic antimicrobial chemotherapy (SACT), as a novel anti-infective program, has received tremendous attention due to its good tissue penetration depth and low invasion. Ultrasound (US) frequency was one of the important parameters for SACT. To investigate the influence of different US frequencies on sonodynamic antimicrobial activity of ciprofloxacin-capped gold nanoparticles (CIP:GNPs). C. albicans and E. coli were chosen as the action objects. The bacterial survival rate was used in the assessment index and measured by plate colony-counting methods. The reactive oxygen species (ROS) produced under US irradiation were detected by ROS fluorescence probe and used to analyze the sonodynamic antibacterial mechanism of CIP:GNPs following different US frequencies. High-frequency US combined with CIP:GNPs had a good synergistic antimicrobial impact on C. albicans, while medium-frequency US showed a strong effect on E. coli. Moreover, the mechanism research experiment proved that intracellular ROS levels were closely related to changes in US frequency, and significantly affected the synergistic activity of CIP:GNPs. The injury of E. coli appearance showed more sensitivity to the change of US frequency than that of C. albicans, but its action laws were relatively complicated and needed to be further studied.

Boosting seawater denitrification in an electrochemical flow cell.

Nitrogen compounds in current seawater treatment processes typically are converted to nitrate, threatening seawater quality and marine ecology. Electrochemical denitrification is a promising technique, but its efficiency is severely limited by the presence of excess chloride ions. In this work, a flow-through cell went through an on-demand chlorine-mediated electrochemical-chemical tandem reaction process was designed for efficient seawater denitrification. Equipped with ultrathin cobalt-based nanosheets as the cathode catalyst and commercial IrO2-RuO2/Ti as the anode, the newly designed flow-through cell achieved nitrate removal efficiency that was about 50 times greater than the batch cell and nearly 100 % N2 selectivity. Moreover, nitrite and ammonia can also be removed with over 93 % efficiency in total nitrogen (TN) removal. Furthermore, the concentration of active chlorine in the effluent could be adjusted within two orders of magnitude, enabling on-demand release of active chlorine. Finally, this flow-through cell reduced the TN of actual mariculture tailwater (40.1 mg N L-1 nitrate) to only 5.7 mg N L-1, meeting the discharge standard for aquaculture tailwater of Fujian, China. This work demonstrates the paradigm of deep denitrification from ultra-concentrated chlorine ion wastewater using an on-demand active chlorine-mediated electrochemical-chemical tandem reaction process.

Mendelian randomization analysis reveals causal effects of blood lipidome on gestational diabetes mellitus.

BACKGROUND: Observational studies have revealed associations between maternal lipid metabolites and gestational diabetes mellitus (GDM). However, whether these associations are causal remain uncertain. OBJECTIVE: To evaluate the causal relationship between lipid metabolites and GDM. METHODS: A two-sample Mendelian randomization (MR) analysis was performed based on summary statistics. Sensitivity analyses, validation analyses and reverse MR analyses were conducted to assess the robustness of the MR results. Additionally, a phenome-wide MR (Phe-MR) analysis was performed to evaluate potential side effects of the targeted lipid metabolites. RESULTS: A total of 295 lipid metabolites were included in this study, 29 of them had three or more instrumental variables (IVs) suitable for sensitivity analyses. The ratio of triglycerides to phosphoglycerides (TG_by_PG) was identified as a potential causal biomarker for GDM (inverse variance weighted (IVW) estimate: odds ratio (OR) = 2.147, 95% confidential interval (95% CI) 1.415-3.257, P = 3.26e-4), which was confirmed by validation and reverse MR results. Two other lipid metabolites, palmitoyl sphingomyelin (d18:1/16:0) (PSM(d18:1/16:0)) (IVW estimate: OR = 0.747, 95% CI 0.583-0.956, P = 0.021) and triglycerides in very small very low-density lipoprotein (XS_VLDL_TG) (IVW estimate: OR = 2.948, 95% CI 1.197-5.215, P = 0.015), were identified as suggestive potential biomarkers for GDM using a conventional cut-off P-value of 0.05. Phe-MR results indicated that lowering TG_by_PG had detrimental effects on two diseases but advantageous effects on the other 13 diseases. CONCLUSION: Genetically predicted elevated TG_by_PG are causally associated with an increased risk of GDM. Side-effect profiles indicate that TG_by_PG might be a target for GDM prevention, though caution is advised due to potential adverse effects on other conditions.

BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise.

BACKGROUND: Resistance exercise leads to improved muscle function and metabolic homeostasis. Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive. METHODS: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin. Based on rhythmicity of Fibronectin type III domain containing 5 (FNDC5/irisin), we trained wild type and FNDC5 knockout mice at late active phase (high FNDC5/irisin level) or late rest phase (low FNDC5/irisin level) to analyze exercise benefits on muscle function and metabolic homeostasis. Molecular analysis was performed to understand the regulatory mechanisms of FNDC5 rhythmicity and downstream signaling transduction in skeletal muscle. RESULTS: In this study, we showed that regular resistance exercises performed at different times of day resulted in distinct training outcomes in humans, including exercise benefits and altered plasma metabolomics. We found that muscle FNDC5/irisin levels exhibit rhythmicity. Consistent with human data, compared to late rest phase (low irisin level), mice trained chronically at late active phase (high irisin level) gained more muscle capacity along with improved metabolic fitness and metabolomics/lipidomics profiles under a high-fat diet, whereas these differences were lost in FNDC5 knockout mice. Mechanistically, Basic helix-loop-helix ARNT like 1 (BMAL1) and Peroxisome proliferative activated receptor, gamma, coactivator 1 alpha 4 (PGC1α4) induce FNDC5/irisin transcription and rhythmicity, and the signaling is transduced via αV integrin in muscle. CONCLUSION: Together, our results offered novel insights that exercise performed at distinct times of day determines training outcomes and metabolic benefits through the rhythmic regulation of the BMAL1/PGC1α4-FNDC5/irisin axis.

Copper overload exacerbates testicular aging mediated by lncRNA:CR43306 deficiency through ferroptosis in Drosophila.

Testicular aging manifests as impaired spermatogenesis and morphological alterations in Drosophila. Nonetheless, the comprehensive molecular regulatory framework remains largely undisclosed. This investigation illustrates the impact of copper overload on testicular aging and underscores the interplay between copper overload and lncRNA. Copper overload triggers Cuproptosis through the mitochondrial TCA cycle, facilitating intracellular interactions with Ferroptosis, thereby governing testicular aging. Dysfunction of lncRNA:CR43306 also contributes to testicular aging in Drosophila, emphasizing the significance of lncRNA:CR43306 as a novel aging-associated lncRNA. Moreover, copper overload exacerbates spermatid differentiation defects mediated by lncRNA:CR43306 deficiency through oxidative stress, copper, and iron transport. Therapeutically, Ferrostatin-1 and Resveratrol emerge as potential remedies for addressing testicular aging. This study offers perspectives on the regulatory mechanisms involving copper overload and lncRNA:CR43306 deficiency in the context of testicular aging.

Endothelial Cell Transcription Modulation in Cerebral Aneurysms After Endovascular Flow Diversion.

PURPOSE: Flow diverting stents (FDS) are used to treat cerebral aneurysms, by promoting thrombosis and occlusion of the aneurysm sac. However, retreatment is required in some cases, and the biologic basis behind treatment outcome is not known. The goal of this study was to understand how changes in hemodynamic flow after FDS placement affect aneurysmal endothelial cell (EC) activity. METHODS: Three-dimensional models of patient-specific aneurysms were created to quantify the EC response to FDS placement. Computational fluid dynamic simulations were used to determine the hemodynamic impact of FDS. Two identical models were created for each patient; into one a FDS was inserted. Each model was then populated with human carotid ECs and subjected to patient-specific pulsatile flow for 24 h. ECs were isolated from aneurysm dome from each model and bulk RNA sequencing was performed. RESULTS: Paired untreated and treated models were created for four patients. Aneurysm dome EC analysis revealed 366 (2.6%) significant gene changes between the untreated and FDS conditions, out of 13909 total expressed genes. Gene set enrichment analysis of the untreated models demonstrated enriched gene ontology terms related to cell adhesion, growth/tensile activity, cytoskeletal organization, and calcium ion binding. In the FDS models, enriched terms were related to cellular proliferation, ribosomal activity, RNA splicing, and protein folding. CONCLUSION: Treatment of cerebral aneurysms with FDS induces significant EC gene transcription changes related to aneurysm hemodynamics in patient-specific in vitro 3D-printed models subjected to pulsatile flow. Further investigation is needed into the relationship between transcriptional change and treatment outcome.

Correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). Methods: The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. Results: In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P < .05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Conclusions: Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.