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Background Previous research indicates that coronavirus disease 2019 (COVID-19) infection may have a role in triggering immunoglobulin A (IgA) nephropathy. However, limited research has explored the clinical implications of COVID-19 infection in individuals already diagnosed with IgA nephropathy. This study aimed to determine whether COVID-19 infection independently affects the subsequent trajectory of kidney function in IgA nephropathy patients. Methods This was a single-center cohort study. The study included 199 patients diagnosed with IgA nephropathy. The COVID-19 infection status was determined using a combined method: a questionnaire and the Health Code application, both administered at the end of 2022 in northern China. Kidney function trajectory was assessed by the estimated glomerular filtration rate (eGFR), calculated based on serum creatinine levels measured during follow-up outpatient visits. The primary endpoint of interest was the eGFR trajectory. Results Out of the 199 participants, 75% (n  = 181) reported a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, determined through antigen or polymerase chain reaction tests, accounting for 79% (n  = 143) of the infected patients. A significant majority (98%) experienced mild to moderate symptoms. Over a median follow-up period of 10.7 months post-COVID-19 infection, notable clinical events included gross hematuria in 30 patients (16.6%), which normalized within an average of 3 days. Additionally, a 2-fold increase in proteinuria or progression to the nephrotic range was observed in 10 individuals (5.5%). No cases of acute kidney injury were noted. COVID-19 exposure was associated with an absolute change in eGFR of 2.98 mL/min/1.73 m2 per month (95% confidence interval 0.46 to 5.50). However, in a fully adjusted model, the estimated changes in eGFR slope post-COVID-19 were –0.39 mL/min/1.73 m2 per month (95% confidence interval –0.83 to 0.06, P  = .088) which included the possibility of no significant effect. Notably, a higher rate of kidney function decline was primarily observed in patients with a baseline eGFR <45 mL/min/1.73 m2 [–0.56 mL/min/1.73 m2 (–1.11 to –0.01), P  = .048]. In the cohort, there were few instances of severe COVID-19 cases. The absence of long-term follow-up outcomes was observed. Conclusions Overall, mild to moderate COVID-19 infection does not appear to significantly exacerbate the subsequent decline in kidney function among IgA nephropathy patients, particularly in those with preserved baseline kidney function. [ABSTRACT FROM AUTHOR]

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60 years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2–3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p < 0.001), with the optimal threshold set at 0.81 (ng/mL)2/1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant public health issue globally. The importance of its timely identification and early intervention is paramount. However, a systematic approach for early CKD management in the primary care setting is currently lacking, receiving less attention compared to upstream risk factors such as diabetes and hypertension. This oversight may lead to a failure in meeting quality-of-care indicators. Digital health interventions (DHIs), which leverage digital tools to enhance healthcare delivery, have shown effectiveness in managing chronic diseases and improving the quality, safety, and efficiency of primary care. Our research aimed to evaluate the effectiveness of DHIs in the care process, focusing on their reach, uptake, and feasibility. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and ClinicalTrials.gov for randomized controlled trials (RCTs) assessing DHIs' effectiveness in CKD patient care among adults in primary care settings. The search, conducted on 30 June 2023, included studies published in English from 1 January 2009. Screening was conducted using Covidence, adhering to Cochrane's guidelines for data extraction. We primarily evaluated changes in care processes (testing, documentation, medication use, etc.) and the use of renin–angiotensin–aldosterone system inhibitors (RAASi), referrals, among others. Multilevel meta-analysis was employed to address within-study clustering, and meta-regression analyzed the impact of study characteristics on heterogeneity in effect sizes. Clinical endpoints were recorded where available. Bias risk was assessed using the Cochrane Risk of Bias 2 tool. Data on reach, uptake, and feasibility were narratively summarized. The study is registered with PROSPERO (CRD42023449098). Results: From 679 records, 12 RCTs were included in the narrative synthesis, and 6 studies (encompassing 7 trials) in the meta-analysis. The trials indicated a −0.85% change (95%CI, −5.82% to 4.11%) in the proportion of patients receiving desired care. This result showed considerable heterogeneity (I2 = 91.9%). One study characteristic (co-intervention, education) correlated with larger effects. Although including co-intervention in multivariable meta-regression was significant, it did not diminish heterogeneity. The reported reach varied and was not high, while the uptake was relatively high. Most studies did not explicitly address feasibility, though some statements implied its evaluation. Conclusions: The current literature on the impact of DHIs in community-based CKD care is limited. The studies suggest a non-significant effect of DHIs on enhancing CKD management in community settings, marked by significant heterogeneity. Future research should focus on rigorous, methodologically sound implementations to better assess the effectiveness of DHIs in the primary care management of CKD. [ABSTRACT FROM AUTHOR]

The lack of early renal function recovery among geriatric patients with acute kidney injury (AKI) in the intensive care unit (ICU) is a commonly observed and acknowledged poor prognostic factor, especially for older adults. However, no reliable prognostic biomarker is available for identifying individuals at risk of renal non-recovery or mortality in older adults. In this prospective observational cohort study, we enrolled critically ill older adults (aged ≥ 60years) with AKI from the ICU and followed their disease progression. The primary endpoint was renal non-recovery within seven days of follow-up, while the secondary endpoint was the determinants of 30-day mortality after AKI. We assessed the predictive accuracy using receiver operating characteristic curves and performed between-group comparisons using the log-rank test. Among 209 older adults, 117 (56.0%) experienced renal recovery. Multiple regression analysis revealed that urine levels of tissue inhibitor of metalloproteinase-2 (TIMP-2) multiplied by insulin-like growth factor-binding protein 7 (IGFBP7) ([TIMP-2]*[IGFBP7]), AKI stages 2–3, and the Acute Physiology and Chronic Health Evaluation (APACHE II) score were independently associated with renal non-recovery. The regression model incorporating [TIMP-2]*[IGFBP7] demonstrated a fair predictive value (AUC 0.774, p<0.001), with the optimal threshold set at 0.81 (ng/mL)² /1000. When [TIMP-2]*[IGFBP7] was combined with AKI severity and the APACHE score, the AUC increased to 0.851. In conclusion, urine [TIMP-2]*[IGFBP7] is a reliable biomarker associated with renal non-recovery in critically ill older adults, and its predictive efficacy can be further enhanced when combined with AKI severity and the APACHE score. [ABSTRACT FROM AUTHOR]

Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3–5. The primary outcome was hospital death of AKI patients. A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8–13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3–20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1–5.9%, p = 0.825). The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. registration number ChiCTR-ECH-13003934 [ABSTRACT FROM AUTHOR]

Background: Poor prognosis has been associated with the absence of renal recovery after acute kidney injury (AKI). This study aimed to investigate whether urinary biomarkers at 0 and 24 h could be used independently or in conjunction with a clinical model to predict renal non-recovery in septic AKI. Methods: A prospective observational study was conducted to measure the urinary levels of insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) at the time of AKI diagnosis (0 h) and 24 h later. Renal non-recovery within 7 days was defined as the outcome. The predictive value of urinary biomarkers for renal non-recovery in septic AKI was assessed using the area under the curve (AUC). Results: A total of 198 individuals with septic AKI were included in the final analysis. Among them, 38.9% (n = 77) did not experience renal recovery within 7 days. The combination of urinary IGFBP7 and TIMP-2 at the initial time point demonstrated prognostic value for non-recovery of renal function, with an AUC of 0.782. When [TIMP-2]*[IGFBP7] was measured at 0 h, the clinical prognostic model, incorporating AKI stage 2–3 and the non-renal sequential organ failure assessment score, showed an improved AUC of 0.822 (with a sensitivity of 88.3% and specificity of 59.5%). Conclusions: The combination of urinary [TIMP-2]*[IGFBP7] at 0 h exhibited moderate predictive ability for renal non-recovery in cases of septic AKI. However, there is potential to enhance the prognostic capabilities of the [TIMP-2]*[IGFBP7]–clinical prediction model. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) exhibits the highest morbidity among endocrine diseases in women ranging from age 18 to 44. However, its pathogenesis remains unclear. The imbalance between systemic and ovarian oxidative stress (OS) is a key characteristic of PCOS, and accumulating evidence indicates that the antioxidative protein nuclear factor erythroid-2-related factor 2 (Nrf2) is implicated in cell apoptosis and inflammation caused by OS. The activated kinase 2 (PAK2)/-catenin/c-Myc/pyruvate kinase M2 (PKM2) axis is a newly identified signaling pathway that may regulate Nrf2 expression and thereby influence OS. In this study, we sought to identify PAK2 expression and function in PCOS cells. PAK2 and downstream PKM2 expression in KGN cells and tissues were detected by microarray and qPCR. Cell viability was determined using CCK-8 and colony formation assays (CFAs). Apoptosis was examined by flow cytometry. qPCR and ELISA were used to examine cell inflammation. Oxidant and OS-related enzymes were examined by ELISA. We found that PAK2 and PKM2 expression levels were reduced in KGN cells and PCOS ovarian cortex tissues. PAK2 overexpression activated β-catenin/c-Myc/PKM2 while PAK2 silencing deactivated it. PAK2 overexpression was reduced, whereas PAK2 silencing promoted, KGN cell proliferation and colony formation. Cell apoptosis and inflammation were also induced by PAK2 overexpression but were alleviated by its silencing. Furthermore, increased peroxidation product levels decreased antioxidative protein activities, and deactivated antioxidative Nrf2/HO-1 pathway were detected in PAK2-overexpressing KGN cells, whereas these effects were counteracted in PAK2 silenced cells. Our data suggest that PAK2 and its associated β-catenin/c-Myc/PKM2 inhibited cell viability and induced apoptosis and inflammation by triggering OS by deactivating the Nrf2/HO-1 pathway, suggesting the potential of PAK2 as a therapeutic PCOS treatment target. • PAK2 and PKM2 expression was reduced in ovarian cortex tissues and KGN cells. • KGN cell viability was suppressed by PAK2 overexpression. • PAK2 induced cell inflammation, apoptosis, and elevated OS levels by affecting the Nrf2/HO-1 axis. • PAK2 may become a therapeutic PCOS treatment target. [ABSTRACT FROM AUTHOR]

Ingression of the plasma membrane is an essential part of the cell topology-distorting repertoire and a key element in animal cell cytokinesis. Many embryos have rapid cleavage stages in which they are furrowing powerhouses, quickly forming and disassembling cleavage furrows on timescales of just minutes. Previous work has shown that cytoskeletal proteins and membrane trafficking coordinate to drive furrow ingression, but where these membrane stores are derived from and how they are directed to furrowing processes has been less clear. Here, we identify an extensive Rab35/Rab4>Rab39/ Klp98A>trans-Golgi network (TGN) endocytic recycling pathway necessary for fast furrow ingression in the Drosophila embryo. Rab39 is present in vesiculotubular compartments at the TGN where it receives endocytically derived cargo through a Rab35/Rab4-dependent pathway. A Kinesin-3 family member, Klp98A, drives the movements and tubulation activities of Rab39, and disruption of this Rab39-Klp98A-Rab35 pathway causes deep furrow ingression defects and genomic instability. These data suggest that an endocytic recycling pathway rapidly remobilizes membrane cargo from the cell surface and directs it to the trans-Golgi network to permit the initiation of new cycles of cleavage furrow formation. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a frequent syndrome in the intensive care unit (ICU). AKI patients with kidney function recovery have better short-term and long-term prognoses compared with those with non-recovery. Numerous studies focus on biomarkers to distinguish them. To better understand the predictive performance of urinary biomarkers of renal recovery in patients with AKI, we evaluated C–C motif chemokine ligand 14 (CCL14) and two first-generation biomarkers (cell cycle arrest biomarkers and neutrophil gelatinase-associated lipocalin) in two ICU settings. Methods: We performed a prospective study to analyze urinary biomarkers for predicting renal recovery from AKI. Patients who developed AKI after ICU admission were enrolled and urinary biomarkers including tissue inhibitor of metalloproteinase-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7), CCL14, and neutrophil gelatinase-associated lipocalin (NGAL) were detected on the day of AKI diagnosis. The primary endpoint was non-recovery from AKI within 7 days. The individual discriminative ability of CCL14, [TIMP-2] × [IGFBP7] and NGAL to predict renal non-recovery were evaluated by the area under receiver operating characteristics curve (AUC). Results: Of 164 AKI patients, 64 (39.0%) failed to recover from AKI onset. CCL14 showed a fair prediction ability for renal non-recovery with an AUC of 0.71 (95% CI 0.63–0.77, p < 0.001). [TIMP-2] × [IGFBP7] showed the best prediction for renal non-recovery with an AUC of 0.78 (95% CI 0.71–0.84, p < 0.001). However, NGAL had no use in predicting non-recovery with an AUC of 0.53 (95% CI 0.45–0.60, p = 0.562). A two-parameter model (non-renal SOFA score and AKI stage) predicted renal non-recovery with an AUC of 0.77 (95% CI 0.77–0.83, p = 0.004). When [TIMP-2] × [IGFBP7] was combined with the clinical factors, the AUC was significantly improved to 0.82 (95% CI 0.74–0.87, p = 0.049). Conclusions: Urinary CCL14 and [TIMP-2] × [IGFBP7] were fair predictors of renal non-recovery from AKI. Combing urinary [TIMP-2] × [IGFBP7] with a clinical model consisting of non-renal SOFA score and AKI stage enhanced the predictive power for renal non-recovery. Urinary CCL14 showed no significant advantage in predicting renal non-recovery compared to [TIMP-2] × [IGFBP7]. [ABSTRACT FROM AUTHOR]

Background and objectives: In light of the growing burden of chronic kidney disease (CKD), it is of particular importance to create disease prediction models that can assist healthcare providers in identifying cases of CKD individual risk and integrate risk-based care for disease progress management. The objective of this study was to develop and validate a new pragmatic end-stage kidney disease (ESKD) risk prediction utilizing the Cox proportional hazards model (Cox) and machine learning (ML). Design, setting, participants, and measurements: The Chinese Cohort Study of Chronic Kidney Disease (C-STRIDE), a multicenter CKD cohort in China, was employed as the model's training and testing datasets, with a split ratio of 7:3. A cohort from Peking University First Hospital (PKUFH cohort) served as the external validation dataset. The participants' laboratory tests in those cohorts were conducted at PKUFH. We included individuals with CKD stages 1~4 at baseline. The incidence of kidney replacement therapy (KRT) was defined as the outcome. We constructed the Peking University-CKD (PKU-CKD) risk prediction model employing the Cox and ML methods, which include extreme gradient boosting (XGBoost) and survival support vector machine (SSVM). These models discriminate metrics by applying Harrell's concordance index (Harrell's C-index) and Uno's concordance (Uno's C). The calibration performance was measured by the Brier score and plots. Results: Of the 3216 C-STRIDE and 342 PKUFH participants, 411 (12.8%) and 25 (7.3%) experienced KRT with mean follow-up periods of 4.45 and 3.37 years, respectively. The features included in the PKU-CKD model were age, gender, estimated glomerular filtration rate (eGFR), urinary albumin–creatinine ratio (UACR), albumin, hemoglobin, medical history of type 2 diabetes mellitus (T2DM), and hypertension. In the test dataset, the values of the Cox model for Harrell's C-index, Uno's C-index, and Brier score were 0.834, 0.833, and 0.065, respectively. The XGBoost algorithm values for these metrics were 0.826, 0.825, and 0.066, respectively. The SSVM model yielded values of 0.748, 0.747, and 0.070, respectively, for the above parameters. The comparative analysis revealed no significant difference between XGBoost and Cox, in terms of Harrell's C, Uno's C, and the Brier score (p = 0.186, 0.213, and 0.41, respectively) in the test dataset. The SSVM model was significantly inferior to the previous two models (p < 0.001), in terms of discrimination and calibration. The validation dataset showed that XGBoost was superior to Cox, regarding Harrell's C, Uno's C, and the Brier score (p = 0.003, 0.027, and 0.032, respectively), while Cox and SSVM were almost identical concerning these three parameters (p = 0.102, 0.092, and 0.048, respectively). Conclusions: We developed and validated a new ESKD risk prediction model for patients with CKD, employing commonly measured indicators in clinical practice, and its overall performance was satisfactory. The conventional Cox regression and certain ML models exhibited equal accuracy in predicting the course of CKD. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common disease in the intensive care unit (ICU). AKI patients with nonrecovery of renal function have a markedly increased risk of death compared with patients with recovery. The current study aimed to explore and validate the utility of urinary cell cycle arrest biomarkers for predicting nonrecovery in patients who developed AKI after ICU admission. Methods: We prospectively and consecutively enrolled 379 critically ill patients who developed AKI after admission to the ICU, which were divided into a derivation cohort (194 AKI patients) and a validation cohort (185 AKI patients). The biomarkers of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected at inclusion immediately after AKI diagnosis (day 0) and 24 h later (day 1). The optimal cut-off values of these biomarkers for predicting nonrecovery were estimated in the derivation cohort, and their predictive accuracy was assessed in the validation cohort. The primary endpoint was nonrecovery from AKI (within 7 days). Results: Of 379 patients, 159 (41.9%) patients failed to recover from AKI onset, with 79 in the derivation cohort and 80 in the validation cohort. Urinary [TIMP-2]*[IGFBP7] on day 0 showed a better prediction ability for nonrecovery than TIMP-2 and IGFBP7 alone, with an area under the reciever operating characteristic curve (AUC) of 0.751 [95% confidence interval (CI) 0.701–0.852, p < 0.001] and an optimal cut-off value of 1.05 ((ng/mL)2/1000). When [TIMP-2]*[IGFBP7] was combined with the clinical factors of AKI diagnosed by the urine output (UO) criteria, AKI stage 2–3 and nonrenal SOFA score for predicting nonrecovery, the AUC was significantly improved to 0.852 (95% CI 0.750–0.891, p < 0.001), which achieved a sensitivity and specificity of 88.8% (72.9, 98.7) and 92.6% (80.8, 100.0), respectively. However, urine [TIMP-2]*[IGFBP7], TIMP-2 alone, and IGFBP7 alone on day 1 performed poorly for predicting AKI recovery. Conclusion: Urinary [TIMP-2]*[IGFBP7] on day 0 showed a fair performance for predicting nonrecovery from AKI. The predictive accuracy can be improved when urinary [TIMP-2]*[IGFBP7] is combined with the clinical factors of AKI diagnosed by the UO criteria, AKI stage 2–3 and nonrenal SOFA score. [ABSTRACT FROM AUTHOR]

Actomyosin networks are some of the most crucial force-generating components present in developing tissues. The contractile forces generated by these networks are harnessed during morphogenesis to drive various cell and tissue reshaping events. Recent studies of these processes have advanced rapidly, providing us with insights into how these networks are initiated, positioned and regulated, and how they act via individual contractile pulses and/or the formation of supracellular cables. Here, we review these studies and discuss the mechanisms that underlie the construction and turnover of such networks and structures. Furthermore, we provide an overview of how ratcheted processivity emerges from pulsed events, and how tissuelevel mechanics are the coordinated output of many individual cellular behaviors. [ABSTRACT FROM AUTHOR]

In this paper, stochastic perturbations into HIV models with saturated incidence is proposed and discussed. Some sufficient conditions on the boundedness, extinction, persistence, and stability in distribution are established. Asymptotic behaviors around equilibria for infection-free and endemic of deterministic system are obtained. Finally, numerical simulations are carried out to validate our analytical results. [ABSTRACT FROM AUTHOR]

During Drosophila melanogaster gastrulation, the invagination of the prospective mesoderm is driven by the pulsed constriction of apical surfaces. Here, we address the mechanisms by which the irreversibility of pulsed events is achieved while also permitting uniform epithelial behaviors to emerge. We use MSD-based analyses to identify contractile steps and find that when a trafficking pathway initiated by Sbf is disrupted, contractile steps become reversible. Sbf localizes to tubular, apical surfaces and associates with Rab35, where it promotes Rab GTP exchange. Interestingly, when Sbf/Rab35 function is compromised, the apical plasma membrane becomes deeply convoluted, and nonuniform cell behaviors begin to emerge. Consistent with this, Sbf/Rab35 appears to prefigure and organize the apical surface for efficient Myosin function. Finally, we show that Sbf/Rab35/CME directs the plasma membrane to Rab11 endosomes through a dynamic interaction with Rab5 endosomes. These results suggest that periodic ratcheting events shift excess membrane from cell apices into endosomal pathways to permit reshaping of actomyosin networks and the apical surface. [ABSTRACT FROM AUTHOR]

Isoflurane/surgery (I/S) may induce neurocognitive disorders, but detailed mechanisms and appropriate treatment remain largely unknown. This experiment was designed to determine whether ginsenoside Rg1 could attenuate I/S-induced neurocognitive disorders and Sirtuin3 (Sirt3) dysfunction. C57BL/6J male mice received 1.4% isoflurane plus abdominal surgery for 2 h. Ginsenoside Rg1 10 mg/kg was intraperitoneally given for 8 days before surgery. Neurocognitive function was assessed by the Barnes Maze test. Levels of reactive oxygen species (ROS), oxygen consumption rate (OCR), mitochondrial membrane potential (MMP), expression and deacetylation activity of Sirt3 in the hippocampus tissues were measured. Results showed that I/S induced hippocampus-dependent learning and memory impairments, with increased ROS levels, and reduced OCR, MMP, and expression and deacetylation activity of Sirt3 in hippocampus tissues. Ginsenoside Rg1 treatment before I/S intervention significantly ameliorated learning and memory performance, reduced ROS levels and improved the OCR, MMP, expression and deacetylation activity of Sirt3. In conclusion, this experiment demonstrates that ginsenoside Rg1 treatment can attenuate I/S-induced neurocognitive disorders and Sirt3 dysfunction. [ABSTRACT FROM AUTHOR]

Recent studies indicate that presynaptic long-term potentiation in the anterior cingulate cortex may contribute to chronic pain-related anxiety. In addition to the anterior cingulate cortex, the insular cortex has also been indicated in chronic pain and its related emotional disorders. In the present study, we used a 64-channel multielectrode dish (MED64) system to record pre-long-term potentiation in the insular cortex. We showed that low-frequency stimulation paired with a GluK1-containing kainate receptor agonist induced N-methyl-D-aspartic acid receptor-independent pre-long-term potentiation in the insular cortex of wild-type mice. This form of pre-long-term potentiation was blocked in the insular cortex of adenylyl cyclase subtype 1 (AC1) knockout mice. Furthermore, a selective AC1 inhibitor NB001 blocked pre-long-term potentiation in the insular cortex with a dose-dependent manner. Taken together, our results suggest that AC1 contributes to pre-long-term potentiation in the insular cortex of adult mice and NB001 may produce anxiolytic effects by inhibiting prelong-term potentiation in the anterior cingulate cortex and insular cortex. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the dynamical properties for an HIV infection model with saturation incidence and two delays describing time needed for infection of cell and CTL response generation. Moreover, the effect of time delays on stability of the equilibria for the CTL response has been studied. Finally, numerical simulations are carried out to validate our analytical results. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the therapeutic effects of saikosapoin D (SSD) on bleomycin (BLM)-induced pulmonary fibrosis (PF) in mice and its probable mechanisms. Methods: PF mice were prepared by intraperitoneal (i.p.) injection of BLM (5 mg/kg). Twenty-four hours later, 72 mice in SSD group were administered SSD (1.8 mg/kg, ip). After 3, 7, 14 and 28 days of injection, the mice were sacrificed. Blood samples and lung tissues were collected from 6 mice in each group. The lung tissues were subjected to histological examination. In addition, expressions of MyD88, TRAF6, IL-33 and ST2 in lung tissue were determined by western blotting assay. Serum levels of hydroxyproline (HYP), interleukin (IL)-4, IL-13 and interferon (IFN)-γ were measured by enzyme-linked immunosorbent assay (ELISA). Results: Pathological results showed that SSD treatment alleviated alveolitis and lung fibrosis (p < 0.05) in lung tissues of PF mice at 14 and 28 days post-BLM injection. HYP and IL-13 levels of mice in SSD group were significantly lower than that in BLM group at days 14 and 28 post-BLM injection (p < 0.05). Levels of IL-4 and IFN-γ were significantly lower when compared with values in BLM group on day 28 (p < 0.05). Western blotting results revealed that expressions of MyD88, TRAF6, IL-33 and ST2 proteins were significantly decreased by SSD treatment (p < 0.05). Conclusion: SSD exerts therapeutic effects on BLM-induced experimental PF in mice via regulation of IL-33/ST2 pathway. [ABSTRACT FROM AUTHOR]

A fractional order HIV model with both virus-tocell and cell-to-cell transmissions and therapy effect is investigated. The conditions for the existence of the equilibria are determined. Local stability analysis of the HIV model is studied by using the fractional Routh-Hurwitz stability conditions. We have generalized the integer LaSalle's invariant theorem into fractional system and given some sufficient conditions for the disease-free equilibrium and endemic equilibrium being globally asymptotical stability. We applied an efficient numerical method based on converting the fractional derivative to integer derivative to solve the HIV model. Some numerical examples are provided to illustrate our results. The fractional derivatives are described in the Caputo sense. [ABSTRACT FROM AUTHOR]

In this paper, the global dynamical behaviors for a four-dimensional HIV infection model with intracellular delay and production delay which describes the interactions of cytotoxic T-lymphocyte (CTL) immune responses and general incidence rate are investigated. By using suitable Lyapunov functionals and LaSalle's invariance principle, the global stability of infection-free equilibrium, CTL-absent infection equilibrium and CTL-present infection equilibrium are established, respectively. These results can be applied to a variety of viral infection diseases that would make it possible to devise optimal treatment strategies. Numerical simulations are presented to verify the analytical results. [ABSTRACT FROM AUTHOR]

Background: CancerMath is a set of web-based prognostic tools which predict nodal status and survival up to 15 years after diagnosis of breast cancer. This study validated its performance in a Southeast Asian setting. Methods: Using Singapore Malaysia Hospital-Based Breast Cancer Registry, clinical information was retrieved from 7064 stage I to III breast cancer patients who were diagnosed between 1990 and 2011 and underwent surgery. Predicted and observed probabilities of positive nodes and survival were compared for each subgroup. Calibration was assessed by plotting observed value against predicted value for each decile of the predicted value. Discrimination was evaluated by area under a receiver operating characteristic curve (AUC) with 95 % confidence interval (CI). Results: The median predicted probability of positive lymph nodes is 40.6 % which was lower than the observed 43.6 % (95 % CI, 42.5 %-44.8 %). The calibration plot showed underestimation for most of the groups. The AUC was 0.71 (95 % CI, 0.70-0.72). Cancermath predicted and observed overall survival probabilities were 87.3 % vs 83.4 % at 5 years after diagnosis and 75.3 % vs 70.4 % at 10 years after diagnosis. The difference was smaller for patients from Singapore, patients diagnosed more recently and patients with favorable tumor characteristics. Calibration plot also illustrated overprediction of survival for patients with poor prognosis. The AUC for 5-year and 10-year overall survival was 0.77 (95 % CI: 0.75-0.79) and 0.74 (95 % CI: 0.71-0.76). Conclusions: The discrimination and calibration of CancerMath were modest. The results suggest that clinical application of CancerMath should be limited to patients with better prognostic profile. [ABSTRACT FROM AUTHOR]

Purpose: To determine the mechanism underlying the anti-hyperprolactinemia effects of Radix bupleuri extract (RBE) in rats. Methods: Rats were divided into six groups (n=10 each group): healthy controls, untreated hyperprolactinemic rats, hyperprolactinemic rats treated with bromocriptine (0.6 mg/kg), and hyperprolactinemic rats treated with RBE (4.8, 9.6, or 19.2 g/kg). After 30 days, hypothalamic protein levels of dopamine D2 receptor, protein kinase A (PKA), and cyclic adenosine monophosphate (cAMP) were determined. Results: Dopamine D2 receptor levels were lower in untreated hyperprolactinemic rats than in healthy controls (p < 0.01), but this decrease was attenuated by RBE (p < 0.05). Elevated PKA levels in untreated hyperprolactinemic rats (0.61 ± 0.04 μg/ml, p < 0.01) were decreased by RBE (4.8 g/kg, 0.42 ± 0.03 μg/ml, p < 0.05; 9.6 g/kg, 0.33 ± 0.02 μg/ml, p < 0.01; 19.2 g/kg, 0.27 ± 0.03 μg/ml, p < 0.01). Similarly, elevated cAMP levels in hyperprolactinemic rats (2.4 ± 0.4 ng/ml) were decreased by RBE (4.8 g/kg, 1.8 ± 0.3 ng/ml, p < 0.05; 9.6 g/kg, 1.5 ± 0.3 ng/ml, p < 0.01; 19.2 g/kg, 1.2 ± 0.2 ng/ml, p < 0.01). Conclusions: RBE anti-hyperprolactinemia activity is mediated by dopamine D2 receptor signaling via the cAMP/PKA pathway. [ABSTRACT FROM AUTHOR]

Novel Ag/CdLa2S4 catalysts with different weight percents of Ag were synthesized by a simple hydrothermal method combined with photo-reduction process, and the obtained Ag/CdLa2S4 composites were characterized by various techniques. The activities of as-prepared samples were evaluated by the photo-degradation of methyl orange (MO) and photocatalytic H2 evolution under visible light (λ>400 nm) irradiation. The results have shown that there is nearly no change in the crystal structure of CdLa2S4 after the loading of Ag nanoparticles, but Ag content in Ag/CdLa2S4 composites played an important role towards the photocatalytic activities of Ag/CdLa2S4 catalysts and 3.18% Ag/CdLa2S4 possessed the best photocatalytic properties. The photo-degradation of MO and hydrogen evolution rate of 3.18% Ag/CdLa2S4 were about 6.7 and 2.0 times than that of pure CdLa2S4, respectively, and the mechanism of activity enhancement was discussed. [ABSTRACT FROM AUTHOR]

We investigate global dynamics for a system of delay differential equations which describes a virus-immune interaction in vivo. The model has two time delays describing time needed for infection of cell and CTLs generation. Our model admits three possible equilibria: infection-free equilibrium, CTL-absent infection equilibrium, and CTL-present infection equilibrium. The effect of time delay on stability of the equilibria of the CTL immune response model has been studied. [ABSTRACT FROM AUTHOR]

Abstract: The flow-line manufacturing cell scheduling problem (FMCSP) with sequence dependent family setup times (SDFSTs) is a topic of great concern for many industrial applications, but under-represented in the research literature. In this study, a two-level iterated greedy (TLIG) heuristic is proposed to minimize makespan of this strongly NP-hard problem. The performance of the proposed TLIG heuristic is compared against eight existing algorithms on a benchmark problem set used in earlier studies. The experimental results reveal that the proposed TLIG heuristic is very effective and efficient at finding near-optimal solutions for FMCSPs with SDFSTs. [Copyright &y& Elsevier]

Abstract: Topics related to parallel machine scheduling problems have been of continuing interest for researchers and practitioners. However, the dynamic parallel machine scheduling problem with sequence-dependent setup times still remains under-represented in the research literature. In this study, an iterated greedy heuristic for this problem is presented. Extensive computational experiments reveal that the proposed heuristic is highly effective as compared to state-of-the-art algorithms on the same benchmark problem data set. [Copyright &y& Elsevier]

Abstract: A novel conjugated molecule, L, based on 2,4,5-triphenylimidazole and 6-phenyl-2,2′-bipyridine (HC∧N∧N) was synthesized in two steps. The molecule can recognize Fe3+ in aqueous solution (THF/H2O, 1/1, v/v) by the appearance of new emission bands at 416 and 442nm, which can be attributed to the emission of the newly formed L–Fe3+ complex. The binding constant of the complex was calculated to be (6.6±0.39)×103 M−1, and its formation was also confirmed by the appearance of isosbestic points at 312 and 381nm in the UV–visible spectral titration experiment. While other transition and rare-earth metal ions, such as Mn2+, Fe2+, Co2+, Ni2+, Zn2+, Cd2+, Hg2+, Pb2+, Eu3+ and Nd3+, can only cause some decrease of L''s fluorescence, alkali and alkaline earth metal ions, such as Li+, Na+, K+, Mg2+ and Ca2+, almost have no effect on L''s fluorescence. The fluorescence of L can be recovered by the addition of EDTA to the L–Fe3+ system just due to EDTA''s stronger chelating ability than that of L. [Copyright &y& Elsevier]

Abstract: This paper examines lunisolar calendar anomalies in the Taiwan stock market, particularly the solar term effect. Using the Taiwan Stock Exchange Capitalization Weighted Stock Index (TAIEX), the significance of the solar term effect was tested. Statistical results showed that the lowest and the highest average stock returns are observed on Cold Dew and White Dew, respectively. Additionally, we found that all of the solar terms with negative average stock returns occurred during the period of Grain Fills to Winter Solstice. Although many investors believe that the solar term effect exists in the Taiwan stock market, the results of this study appear to show that the solar term effect is a mere superstition. The analytical results may prove useful for future theoretical and empirical work on the stock market in Taiwan and elsewhere. [Copyright &y& Elsevier]

This study empirically investigates the causality between prices and volume in mini Taiwan exchange (MiNi-TAIEX) futures. Using hourly data from the MiNi-TAIEX futures prices and trading volume, the Granger causality test was applied to examine the price–volume relationship. The results show that there is a significant long-run and bidirectional causality between hourly prices and trading volume. The finding of this study can provide a future expert system with useful information about whether the knowledge of past future price movements can improve the short-run forecasts of current and future movements of trading volume, and vice versa. In addition, the analytical results may prove useful for future theoretical and empirical work on the future market. [Copyright &y& Elsevier]

A flexible ligand bis(7-methyl-1,8-naphthyridine-2-ylamino)methane (L), having κ4-chelating and κ2-bridging modes, and its intriguing structural complexes of Zn(II) with μ-OH, κ1-OAc, μ-κ1-OAc and μ-κ2-OAc ligands, [Zn2(L)2(OH)](ClO4)3(1), [Zn4(L)2(OAc)6(OH)2]·CH2Cl2(2·CH2Cl2) and [Zn5(L)2(OAc)10]n·4nH2O (3·4H2O) were synthesized and their structures were determined by X-ray crystallography. These compounds exhibited intense blue fluorescent emissions with a λmaxin the range of 380–410 nm in CH2Cl2, CH3CN and CH3OH solutions, and solid-state emissions centered at 416, 463, 490 and 451 nm were observed for the compounds L, 1, 2and 3at room temperature, respectively. The investigated fluorescence properties of Lassociated with various metal ions showed that the fluorescence enhancement of Lwith Cd(II) was more sensitive than with other interfering cations. [ABSTRACT FROM AUTHOR]

von Hippel-Lindau (VHL) disease is a cancer syndrome, which includes renal cell carcinoma (RCC), and is caused by VHL mutations. Most, but not all VHL phenotypes are due to failure of mutant VHL to regulate constitutive proteolysis of hypoxia-inducible factors (HIF5). Janus kinases (JAK1, 2, 3, and TYK2) promote cell survival and proliferation, processes tightly controlled by SOCS proteins, which have sequence and structural homology to VHL. We hypothesized that in VHL disease, RCC pathogenesis results from enhanced SOCS 1 degradation, leading to upregulated JAK activity. We find that baseline JAK2, JAK3, and TYK2 activities are increased in RCC cell lines, even after serum deprivation or coincubation with cytokine inhibitors. Furthermore, JAK activity is sustained in RCC stably expressing HIF2a shRNA. Invasion through Matrigel and migration in wound-healing assays, in vitro correlates of metastasis, are significantly greater in VHL mutant RCC compared with wild-type cells, and blocked by dominant-negative JAK expression or JAK inhibitors. Finally, we observe enhanced SOCS2/SOCS 1 coprecipitation and reduced SOCS 1 expression due to proteasomal degradation in VHL-null RCC compared with wild-type cells. The data support a new HIF-independent mechanism of RCC metastasis, whereby SOCS2 recruits SOCS 1 for ubiquitination and proteasome degradation, which lead to unrestricted JAK-dependent RCC invasion. In addition to commonly proposed RCC treatment strategies that target HIFs, our data suggest that JAK inhibition represents an alternative therapeutic approach. [ABSTRACT FROM AUTHOR]

Genetic studies have shown that Eph receptor tyrosine kinases have both kinase-dependent and kinase-independent functions through incompletely understood mechanisms. We report here that ephrin-B1 stimulation of endogenous EphB kinases in LS174T colorectal epithelial cells inhibited integrin-mediated adhesion and HGF/SF-induced directional cell migration. Using 293 cells stably transfected with wild type (WT)- or kinase-deficient (KDEphB3), we found that inhibition of integrin-mediated cell adhesion and induction of cell rounding was kinase-dependent. Unexpectedly, in two independent assays, both KD- and WT-EphB3 significantly inhibited directional cell migration. Upon ephrin-B1 stimulation, the activities of Rat1 and Cdc42 were reduced in both WT- and KD-EphB3-expressing cells that were induced to migrate. Pharmacological evidence demonstrates that a relative increase in RhoA signaling as a result of decreased Rac1/Cdc42 activities contributes to the inhibitory effects. Furthermore, EphB3-mediated inhibitory effect on cell adhesion but not migration was abolished by the integrin activating antibodies, suggesting that the inhibition of cell migration is not because of down-regulation of integrin function. These results uncover a differential requirement for EphB3 catalytic activity in the regulation of cell adhesion and migration, and suggest that while catalytic activity of EphB3 is required for inhibition of integrin-mediated cell adhesion, a distinct signaling pathway to Rho GTPases shared by WT- and KD-EphB3 receptor mediates inhibition of directional cell migration. [ABSTRACT FROM AUTHOR]

Atherosclerosis occurs preferentially at vascular curvature and branch sites where the vessel walls are exposed to fluctuating shear stress and have high endothelial permeability. Endothelial permeability is modulated by intercellular adhesion molecules such as VE-cadherin. This study was designed to elucidate the effects of different flow patterns on the localization and expression of VE-cadherin in endothelial cells (ECs) both in vivo and in vitro. VE-cadherin staining at EC borders was much stronger in the descending thoracic aorta and abdominal aorta, where the pulsatile flow has a strong net forward component than in the aortic arch and the poststenotic dilatation site beyond an experimental constriction, where the flow near the wall is complex and reciprocating with little net flow. With the use of flow chambers the effects of pulsatile flow (12 ± 4 dyn/cm2 at 1 Hz) and reciprocating flow (0.5 ± 4 dyn/cm2 at 1 Hz) on VE-cadherin organization in endothelial monolayers were studied in vitro. VE-cadherin staining was continuous along cell borders in static controls. Following 6 h of either pulsatile or reciprocating flow, the VE-cadherin staining at cell borders became intermittent. When the pulsatile flow was extended to 24, 48 or 72 h the staining around the cell borders became continuous again, but the staining was still intermittent when the reciprocating flow was similarly extended. Exposure to pulsatile or reciprocating flow for 6 and 24 h neither change the expression level of VE-cadherin nor its distribution between membrane and cytosol fractions as determined by Western blot and compared with static controls. These findings suggest that the cell junction remodeling induced by different flow patterns may result from a redistribution of VE-cadherin within the cell membrane. Both the in vivo and in vitro data indicate that pulsatile and reciprocating flow patterns have different effects on cell junction remodeling. The lack of junction reorganization in regions of reciprocating flow in vivo and in vitro may provide a mechanistic basis for the high permeability and the preferential localization of atherosclerosis in regions of the arterial stress with complex flow patterns and fluctuating shear stress. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Reports on Eph kinases and their ephrin ligands which are widely expressed in epithelial cells in vitro and in vivo. Regulation of hepatocyte growth factor/scatter factor (HGF)-induced branching morphogenesis in collagen gel, by the activation of endogenous EphA kinases in Madin-Darby canine kidney (MDCK) cells; Mechanism by which EphA kinase activation inhibits HGF-induced MDCK branching morphogenesis.

Examines the interplay between integrins and FLK-1 in shear stress-induced signaling. Activation of integrins; Induction of signal transduction hierarchy by shear stress; Isolation of membrane receptors in mechnotransduction.

Introduction: Patients with impaired citrate metabolism may experience citrate accumulation (CA), which causes life-threatening metabolic acidosis and hypocalcemia. CA poses a challenge for clinicians when deciding on the use of regional citrate anticoagulation (RCA) for patients with liver dysfunction. This study aimed to develop a prediction model integrating multiple clinical variables to assess the risk of CA in liver transplant patients. Methods: This single-center prospective cohort study included postoperative liver transplant patients who underwent continuous renal replacement therapy (CRRT) with RCA. The study end point was CA. A prediction model was developed using a generalized linear mixed-effect model based on the Akaike information criterion. The predictive values were assessed using the receiver operating characteristic curve and bootstrap resampling (times = 500) to estimate the area under the curve (AUC) and the corresponding 95% confidence interval (CI). A nomogram was used to visualize the model. Results: This study included 32 patients who underwent 133 CRRT sessions with RCA. CA occurred in 46 CRRT sessions. The model included lactate, norepinephrine >0.1 μg/kg/min, alanine aminotransferase, total bilirubin, and standard bicarbonate, which were tested before starting each CRRT session and body mass index, diabetes mellitus, and chronic kidney disease as predictors. The AUC of the model was 0.867 (95% CI 0.786–0.921), which was significantly higher than that of the single predictor (p < 0.05). A nomogram visualized the prediction model. Conclusions: The prediction model integrating multiple clinical variables showed a good predictive value for CA. A nomogram visualized the model for easy application in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of a combination therapy involving calcium dobesilate and candesartan in the treatment of proliferative diabetic retinopathy and its impact on the transforming growth factor b1 (TGF-b1), vascular endothelial growth factor (VEGF) and interleukin-19 (IL-19) levels in the vitreous humor. Methods: Between January 2020 and May 2023, 112 patients with proliferative diabetic retinopathy from Handan City Eye Hospital, China were enrolled in this study. They were divided into two groups: study group (n = 56) - orally administered 500 mg of calcium dobesilate combined with 50 mg of candesartan daily - and control group (n = 56), received calcium dobesilate only. Patients began treatment with calcium dobesilate and candesartan as soon as diabetic retinopathy was diagnosed. Treatment efficacy, changes in hemorrhage area, macular thickness and best-corrected visual acuity were assessed before and after treatment (for a duration of 60 days). Results: Study group had significantly higher (p < 0.05) treatment efficacy compared to control group, achieving a total effective rate of 92.86 %. It also exhibited reduced hemorrhage area and macular thickness, which were significantly lower (p < 0.05) than those in control group. Best-corrected visual acuity was significantly higher in the study group (p < 0.05) followed by improved peak systolic velocity and end-diastolic velocity after treatment (p < 0.05). Additionally, TGF-b1, VEGF and IL-19 levels in the vitreous humor were significantly lower in study group compared to control group (p < 0.05). Conclusion: The combination of calcium dobesilate and candesartan demonstrates significant therapeutic efficacy in treating proliferative diabetic retinopathy while reducing the TGF-b1, VEGF and IL-19 levels in the vitreous humor. Large-scale studies are needed to validate these findings and delve into treatment mechanisms and long-term effects. [ABSTRACT FROM AUTHOR]

In this article, we report a facile solvothermal route, via using green and nontoxic absolute ethyl alcohol as the solvent and surfactant. Hydrazine hydrate is a reductant. A thin flake-like InSe nanocrystals successfully synthesized by a two-step solvothermal-annealing process. In addition, we have optimized the experimental conditions, included solvothermal time, annealing temperature and annealing time to explore the change in photoelectric response and analyzes the reason of enhancement of photocurrent densities from mechanism of photocurrent generation in detail. The InSe powders have shown a high absorption coefficient in the visible range (λ  >  420 nm). By optimizing preparation conditions, the as-synthesized film of 180 °C, 12 h–250 °C, 2 h shows the highest photocurrent density of 15.9 µA cm−2 at 0.5 V (versus SCE) under visible light. Photocurrent densities of thin film samples increased by approximately 2.8 times that of unoptimized nanosheets. It was shown that InSe nanosheets have superior photoelectric response characteristics under visible light illumination. [ABSTRACT FROM AUTHOR]

Urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are G1 cell cycle arrest biomarkers. This systematic review aimed to evaluate the prognostic value of urinary [TIMP-2]·[IGFBP7] in patients at high risk for AKI. The MEDLINE (via PubMed), Ovid, EMBASE and Cochrane Library databases were systematically searched from inception to December 25, 2016. Original clinical studies which met the eligibility criteria were included in this study. The prognostic accuracy of urinary [TIMP-2]·[IGFBP7] for assessing the need for renal replacement therapy (RRT) and mortality was evaluated by pooled sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curves. A total of four prospective cohort studies evaluating 277 patients were included. The estimated area under the receiver operating characteristic curve (AUC) of urinary [TIMP-2]·[IGFBP7] for predicting the need for RRT in patients at high risk for AKI was 0.915 (standard error [SE] = 0.040). Pooled sensitivity and specificity with corresponding 95% confidence intervals (CI) were 0.69 (95% CI 0.53-0.82) and 0.81 (95% CI 0.75-0.86), respectively. Urinary [TIMP-2]·[IGFBP7] for mortality prediction in patients at high risk for AKI was assessed by qualitative description. Based on the above data, urinary [TIMP-2]·[IGFBP7] performs well in predicting the need for RRT and mortality in patients at high risk for AKI. However, further meta-analyses are warranted as more data become available. [ABSTRACT FROM AUTHOR]

Genetic polymorphism and endosymbiont infection are ubiquitous in aphid populations. It has been known that the obligate symbiont Buchnera provides aphids with essential amino acids which cannot be ingested from plant sap. Buchnera often coexists with facultative endosymbionts in aphids. However, it is unclear whether the facultative endosymbionts affect the aphid’s amino acid requirements from diet. In this study, we found that the facultative endosymbiont status in populations of the cotton-melon aphid Aphis gossypii was associated with aphid genotype or host plant. The infection frequency of Arsenophonus in aphids living on cotton was significantly higher than that in aphids on cucumber, and cucumber leaves contained higher titers of free amino acids than cotton leaves, especially amino acids Leu, Arg, Ile, Val, and Phe. The net reproductive rates of five aphid genotypes infected with Arsenophonus were not different on the complete-amino-acid diet, but the values were significantly different among seven Arsenophonus-free aphid genotypes. Moreover, the net reproductive rates of aphids on the amino-acid-deficient diet were significantly affected by Arsenophonus infection and aphid genotype. Arsenophonus infection decreased aphid performance on the Phe-free diet but improved performance on the Leu-free diet and did not affect the performance on the Ile-free or Val-free diet. Arsenophonus infections altered aphid requirements for amino acids that were significantly different in cotton and cucumber leaves, suggesting this endosymbiont would modulate the host specialization of this aphid. IMPORTANCE The facultative endosymbiont Arsenophonus plays an important role in regulating reproduction through son killing, enemy resistance, and the dietary breadth of its insect hosts. In this study, we found Arsenophonus could alter aphid performance on the amino-acid-deficient diets. Arsenophonus infection increased aphid requirements for the amino acid Phe, but decreased requirements for the Leu. Cotton and cucumber leaves contained drastically different titers of free amino acids Phe and Leu, and aphids living on these two plants were infected with different incidences of Arsenophonus. We hypothesize that host specialization or the host plant range of aphids may be mediated by Arsenophonus. [ABSTRACT FROM AUTHOR]

The multiplex and simultaneous determination of blood glucose, creatinine and uric acid is essential for the early screening of chronic diseases or regular disease monitoring. Here, we report for the first time a biosensing array for the multiplex and simultaneous determination of plasma glucose, creatinine and uric acid. The sensing electrodes are fabricated on a PET surface, including three working electrodes, one reference electrode, and one counter electrode. Each specific enzyme is immobilized on its corresponding working electrode. The biosensing array can exhibit high sensitivity and selectivity for the simultaneous determination of blood glucose, creatinine and uric acid in real blood samples, and the measurement results are accurate and consistent with those from the clinical biochemistry analyzer in the hospital. It is expected that this work could provide new avenues for the fundamental study of biosensing device construction, as well as practical applications of the detection of biomarkers in chronic diseases. [ABSTRACT FROM AUTHOR]

In this paper, anatase TiO2 nanotube (NT) film photoelectrodes are successfully fabricated by a simple and effective hydrothermal method. Subsequently, an aqueous-phase processing technique is adopted to construct highly dispersed ZnSe quantum dots (QDs) on Au/TiO2 NT films prepared by microwave-assisted chemical reduction, which formed composite ZnSe/Au/TiO2 NT film systems (ZATs) with excellent performance in photoelectrocatalytic (PEC) applications. The morphology and performance of as-obtained ZATs were investigated based on various characterizations. The investigation revealed that as-obtained ZATs not only greatly extend spatial separation of charges and restrain the recombination rate of photogenerated electron–hole pairs, but also improve the efficiency to use visible light and display a wide and strong absorption in the visible light region ranging from 400 nm to 800 nm. Moreover, we observe a larger fluorescence quenching of ZATs compared with that of pure TiO2 NT films and binary composites. Experimental results indicate that the photocurrent densities of pure TiO2, 0.8 Au/TiO2, 60 min ZnSe/TiO2, and ZATs are 0.020 mA cm−2, 0.032 mA cm−2, 0.037 mA cm−2 and 0.070 mA cm−2, respectively, which is approximately 2–3.5 times higher than that of pure TiO2 NT films and binary compound photoelectrodes. Additionally, experimental results suggest that the as-prepared ZATs photoelectrode has exhibited considerable stability and significantly increased PEC activity for the degradation of methylene blue (MB) in distilled water under 100 mW cm−2 xenon lamp irradiation. The degradation efficiency on MB of 45 min ZnSe/0.8 Au/TiO2 NT films approaches 91%; however, the counterpart of TiO2 NT films is less than 10%. Eventually, the mechanism for the improvement of the PEC performance of ZATs is discussed to point out that ZATs display prominent charges transport performance, and a stepwise band alignment structure is built up in its photoelectrode, which indicates that charge separation and migration across the interfaces should favor vectorial electron transfer according to the scheme of ZnSe  →  TiO2  →  Au  →  Ti substrates. [ABSTRACT FROM AUTHOR]

Diamond-like-carbon (DLC) films are considered ideal solid lubricating films for friction reduction and anti-wear on material surfaces. However, the microtribological properties of DLC films are sensitive to many factors. In this study, DLC films were prepared through three techniques by using a self-made microwave-electron cyclotron resonance-plasma source ion implantation apparatus to determine their microtribological properties under the working conditions in a microelectromechanical system (MEMS). The three adopted techniques were unbalanced magnetron sputtering, plasma source ion implantation, and plasma-enhanced chemical vapor deposition. The diamond-like properties of the prepared films were characterized by X-ray photoelectron spectroscopy. The microtribological properties of the DLC films were analyzed by atomic force microscopy. The effects of preparation techniques, slide number, load, and relative sliding velocity on the microtribological features of the thin films were also investigated. Results reveal that in the load range of 2-20 µN, the friction coefficients of the DLC films prepared by the three techniques are 1.8, 1.4, and 0.9 mV/nN. The prepared DLC films have lower friction coefficients than that of the Si surface (2.6 mV/nN). Under the same loading conditions, the changes of the frictional force are related to the slope of the rough peak, and the increase in frictional force is proportional to the square of the slope. The wearing depth of the DLC films is nonlinearly related to the number of wear cycles, and the wear resistance on the surface of the DLC film is worse than that in the deeper layers. Sliding velocity slightly affects the friction coefficients when the normal load is several nanonewtons. This study provides references for the application of DLC films in the surface modification of MEMS devices. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect the host tissue cells' mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand the role of intestinal flora in ovarian cells inflammation by regulating mRNA m6A modification particularly the inflammatory state in PCOS. The gut microbiome composition of PCOS and Control groups was analyzed by 16S rRNA sequencing, and the short chain fatty acids were detected in patients' serum by mass spectrometry methods. The level of butyric acid was found to be decreased in the serum of the obese PCOS group (FAT) compared to other groups, and this was correlated with increased Streptococcaceae and decreased Rikenellaceae based on the Spearman's rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq and MeRIP-seq methodologies. Cellular experiments demonstrated that the addition of butyric acid led to a decrease in FOSL2 m6A methylation levels and mRNA expression by suppressing the expression of METTL3, an m6A methyltransferase. Additionally, NLRP3 protein expression and the expression of inflammatory cytokines (IL-6 and TNF-α) were downregulated in KGN cells. Butyric acid supplementation in obese PCOS mice improved ovarian function and decreased the expression of local inflammatory factors in the ovary. Taken together, the correlation between the gut microbiome and PCOS may unveil crucial mechanisms for the role of specific gut microbiota in the pathogenesis of PCOS. Furthermore, butyric acid may present new prospects for future PCOS treatments. [ABSTRACT FROM AUTHOR]

The crosstalk between obesity and insulin resistance (IR) in polycystic ovary syndrome (PCOS) may be related to miRNA regulation secreted by exosomes. However, the underlying mechanism remains to be explored. A model of PCOS with IR was constructed in mice with dehydroepiandrosterone (DHEA) and a high-fat diet (HFD). Serum exosomes were extracted and characterized using transmission electron microscopy (TEM) and western blot analysis (for CD9, CD63, and CD81). The expression of miR-20b-5p and miR-106a-5p in serum exosomes was detected by qRT-PCR. The effects of serum exosomal miR-20b-5p and miR-106a-5p on lipid metabolism and ovary histological structure in PCOS model with IR were also explored. Serum exosomal miR-20b-5p and miR-106a-5p overexpression could inhibit adipocyte differentiation in 3T3-L1 cells with IR and PCOS mice model. Furthermore, the predicted targets of miR-20b-5p and miR-106a-5p were also analyzed with bioinformatics. In DHEA + HFD serum-derived exosomes, the miR-20b-5p and miR-106a-5p levels were markedly decreased. Overexpression of miR-20b-5p and miR-106a-5p alleviated adipocyte differentiation–related genes and triglyceride content in 3T3-L1 cells and liver steatosis in mice. Bioinformatics analysis of miR-20b-5p and miR-106a-5p predicted targets indicated that miR-20b-5p and miR-106a-5p were highly related to lipid metabolism. Serum-derived exosome miR-20b-5p and miR-106a-5p inhibited adipocyte differentiation during the process of PCOS with IR, which might be a novel therapeutic target. [ABSTRACT FROM AUTHOR]

In this work, the primary amine template has been extracted from freshly synthesized hexagonal mesoporous silica (HMS) materials by means of modified supercritical carbon dioxide at 60-85 °C under 10.0-20.0 MPa. The influences of amine identity and matrix Al/Si ratio on the extraction efficiencies and structural properties of HMS thus obtained are investigated in detail. The results show that the extraction efficiency is strongly dependent on the pore size of the HMS materials produced by five different templates. For aluminium-incorporated samples, the extraction efficiency is observed to decrease with the Al/Si molar ratio since as the Al/Si molar ratio increases, more amine will get protonated and the matrix/template interactions become stronger, subsequently rendering the extraction more difficult and the efficiency decrease. The formic acid modifier has resulted in better extraction performance than methanol, yielding higher extraction efficiencies. The SFE-treated materials exhibit better structural properties like higher pore volume and specific surface area as compared to those prepared by conventional calcinations. Besides, results of pyridine adsorption and conversion of 2-propanol to propylene suggest that the SFE-treated HMS materials may have higher acidity than the directly calcined samples. [ABSTRACT FROM AUTHOR]

With the emergence of combined surgical treatments, complemented by radiotherapy and chemotherapy, survival rates for esophageal cancer patients have improved, but the overall 5-year survival rate remains low. Therefore, there is an urgent need for further research into the pathogenesis of esophageal cancer and the development of effective prevention, diagnosis, and treatment methods. We initially utilized the GeneCards and DisGeNET databases to identify the esophageal cancer-associated gene WWOX (WW domain containing oxidoreductase). Subsequently, we employed RT-qPCR (Reverse transcription-quantitative PCR) and WB (western blot) to investigate the differential expression of WWOX in HEEC (human esophageal endotheliocytes) and various ESCC (esophageal squamous cell carcinoma) cell lines. We further evaluated alterations in cell proliferation, migration and apoptosis via CCK8 (cell counting kit-8) and clonal formation, Transwell assays and flow cytometry. Additionally, we investigated changes in protein expressions related to the Hippo signaling pathway (YAP/TEAD) through RT-qPCR and WB. Lastly, to further elucidate the regulatory mechanism of WWOX in ESCC, we performed exogenous YAP rescue experiments in ESCC cells with WWOX overexpression to investigate the alterations in apoptosis and proliferation. Results indicated that the expression of WWOX in ESCC was significantly downregulated. Subsequently, upon overexpression of WWOX, ESCC cell proliferation and migration decreased, while apoptosis increased. Additionally, the expression of YAP and TEAD were reduced. However, the sustained overexpression of YAP attenuated the inhibitory effects of WWOX on ESCC cell malignancy. In conclusion, WWOX exerts inhibitory effects on the proliferation and migration of ESCC and promotes apoptosis by suppressing the Hippo signaling pathway. These findings highlight the potential of WWOX as a novel target for the diagnosis and treatment of esophageal cancer. [ABSTRACT FROM AUTHOR]

Introduction. Studies have indicated that immune reactions contribute to endothelial dysfunction and atherosclerosis. It is unclear whether thyroid dysfunction or elevated thyroid autoantibodies are associated with atherosclerosis. Therefore, we investigated the influence of thyroid autoimmunity related to elevated thyroid autoantibodies on functional outcome in euthyroidism with acute ischemic stroke (AIS). Methods. All patients with AIS underwent tests for thyroid function and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin autoantibody). We divided the patients suffering from euthyroidism and AIS into positive thyroid autoantibody and negative thyroid autoantibody groups. Demographic profiles, risk factors, and functional outcomes were compared between the two groups. Results. Out of the total 422 patients, 50 (11.8%) were included in the positive thyroid autoantibody group. The National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge was higher in the positive thyroid autoantibody group than the negative thyroid autoantibody group (P < 0.05). In addition, there was significant difference in the mortality during hospitalizations between the two groups (P < 0.01). Conclusion. This study showed that thyroid autoantibodies aggravate stroke severity in euthyroidism with AIS. We speculate that vascular damage related to thyroid autoimmunity may aggravate the increased risk of unfavorable outcomes, independent of thyroid function. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine K-12 physical education teachers' perceptions of ability and usage of technology. Physical educators (n=114) completed the Physical Education Technology Usage Survey assessing their perceived technology competency, how and why they utilize technology, challenges they face in implementing technology, and where they learned to use technology. Results indicated a high level of perceived competency with many forms of technology but differences based on gender, teaching level, and years of experience. Low competency levels were shown for website creation, PDAs, heart rate monitors, and body composition analyzers. The teachers reported that student learning can be enhanced with technology because it aids the visual learner, facilitates individual development, and is useful for assessment purposes. [ABSTRACT FROM AUTHOR]

Adhesions of cells to extracellular matrix and adjacent cells are mediated by integrins and VE-cadherin, respectively. Although these adhesion processes play crucial roles in vascular cell migration and angiogenesis, it remains unclear as to how they are coordinated to regulate cellular functions. We report here that integrin engagement by treating bovine endothelial aortic cell monolayers with beads coated with fibronectin (Fn) led to disruption of the VE-cadherin-containing adherens junctions. This disruption was accompanied by increases of tyrosine phosphorylation of β-catenin, γ-catenin, and p120ctn, as well as the dissociation of α-catenin and γ-catenin from VE-cadherin. We applied a membrane-targeted Src reporter based on the fluorescence resonance energy transfer technique to visualize the dynamic Src activation at subcellular levels in live cells. The integrin engagement induced by Fn-coated beads caused the activation of Src around the beads and at adherens junctions, which are subsequently disrupted. The inhibition of Src with PP1 blocked the effects of integrin engagement on adherens junctions. Although Ras can also modulate adherens junctions, the resulting patterns of phosphorylation and association of junction proteins were distinct from those induced by integrin engagement. The inhibition of Ras by RasN17 did not rescue the disruption of adherens junctions induced by integrin engagement or by Src activation. Integrin engagement by Fn-coated beads also induced a significant alteration of cortical actin filaments at adherens junctions. The results indicate that integrin engagement disrupts VE-cadherin-containing adherens junctions via the activation of Src, but not Ras, possibly as a result of modulation of the actin network. [ABSTRACT FROM AUTHOR]