Disrupting circadian control of autophagy induces podocyte injury and proteinuria.

The circadian clock influences a wide range of biological process and controls numerous aspects of physiology to adapt to the daily environmental changes caused by Earth's rotation. The kidney clock plays an important role in maintaining tubular function, but its effect on podocytes remains unclear. Here, we found that podocytes expressed CLOCK proteins, and that 2666 glomerular gene transcripts (13.4%), including autophagy related genes, had 24-hour circadian rhythms. Deletion of Clock in podocytes resulted in 1666 gene transcripts with the loss of circadian rhythm including autophagy genes. Podocyte-specific Clock knockout mice at age three and eight months showed deficient autophagy, loss of podocytes and increased albuminuria. Chromatin immunoprecipitation (ChIP) sequence analysis indicated autophagy related genes were targets of CLOCK in podocytes. ChIP-PCR further confirmed Clock binding to the promoter regions of Becn1 and Atg12, two autophagy related genes. Furthermore, the association of CLOCK regulated autophagy with chronic sleep fragmentation and diabetic kidney disease was analyzed. Chronic sleep fragmentation resulted in the loss of glomerular Clock rhythm, inhibition of podocyte autophagy, and proteinuria. Rhythmic oscillations of Clock also disappeared in high glucose treated podocytes and in glomeruli from diabetic mice. Finally, circadian differences in podocyte autophagy were also abolished in diabetic mice. Deletion Clock in podocytes aggravated podocyte injury and proteinuria in diabetic mice. Thus, our findings demonstrate that clock-dependent regulation of autophagy may be essential for podocyte survival. Hence. loss of circadian controlled autophagy may play an important role in podocyte injury and proteinuria.

Interface Dipole Management of D-A-Type Molecules for Efficient Perovskite Solar Cells.

Interfacial engineering of perovskite films has been the main strategies in improving the efficiency and stability of perovskite solar cells (PSCs). In this study, three new donor-acceptor (D-A)-type interfacial dipole (DAID) molecules with hole-transporting and different anchoring units are designed and employed in PSCs. The formation of interface dipoles by the DAID molecules on the perovskite film can efficiently modulate the energy level alignment, improve charge extraction, and reduce non-radiative recombination. Among the three DAID molecules, TPA-BAM with amide group exhibits the best chemical and optoelectrical properties, achieving a champion PCE of 25.29 % with the enhanced open-circuit voltage of 1.174 V and fill factor of 84.34 %, due to the reduced defect density and improved interfacial hole extraction. Meanwhile, the operational stability of the unencapsulated device has been significantly improved. Our study provides a prospect for rationalized screening of interfacial dipole materials for efficient and stable PSCs.

Self-Polymerized Spiro-Type Interfacial Molecule toward Efficient and Stable Perovskite Solar Cells.

In the pursuit of highly efficient perovskite solar cells, spiro-OMeTAD has demonstrated recorded power conversion efficiencies (PCEs), however, the stability issue remains one of the bottlenecks constraining its commercial development. In this study, we successfully synthesize a novel self-polymerized spiro-type interfacial molecule, termed v-spiro. The linearly arranged molecule exhibits stronger intermolecular interactions and higher intrinsic hole mobility compared to spiro-OMeTAD. Importantly, the vinyl groups in v-spiro enable in situ polymerization, forming a polymeric protective layer on the perovskite film surface, which proves highly effective in suppressing moisture degradation and ion migration. Utilizing these advantages, poly-v-spiro-based device achieves an outstanding efficiency of 24.54 %, with an enhanced open-circuit voltage of 1.173 V and a fill factor of 81.11 %, owing to the reduced defect density, energy level alignment and efficient interfacial hole extraction. Furthermore, the operational stability of unencapsulated devices is significantly enhanced, maintaining initial efficiencies above 90 % even after 2000 hours under approximately 60 % humidity or 1250 hours under continuous AM 1.5G sunlight exposure. This work presents a comprehensive approach to achieving both high efficiency and long-term stability in PSCs through innovative interfacial design.

A Novel Strategy to Directly Quantify Polyethylene Microplastics in PM2.5 Based on Pyrolysis-Gas Chromatography-Tandem Mass Spectrometry.

The broad application of plastic products has resulted in a considerable release of microplastics (MPs) into the ecosystem. While MPs in other environmental matrices (e.g., soil and water) have been studied for a long time, the atmospheric fine particulate matter (PM2.5)-bound MPs are rarely investigated due to the lack of an appropriate analytical approach. The prevalently used visual and spectroscopic means (e.g., optical microscopy, Fourier-transform infrared spectroscopy, and Raman spectroscopy) suffer from obvious drawbacks that cannot precisely detect MPs of tiny sizes and provide quantitative information. In the present study, a novel strategy that does not require sample pretreatment was developed to first effectuate accurate quantification of polyethylene MP (PE-MP) in PM2.5 based on pyrolysis-gas chromatography-tandem mass spectrometry (Pyr-GC-MS/MS). It featured acceptable recoveries (97%-110%), high sensitivity (LOD = 1 pg), and qualified precisions (RSD of 3%-13%). Employing this approach, for the first time, exact atmospheric concentrations of PE-MPs in PM2.5 from megacities in North (Zhengzhou and Taiyuan) and South (Guangzhou) China were obtained, and relatively serious pollution was found in Taiyuan. The 100% sample detection rates also suggested the widespread occurrence and possible human exposure risks of PM2.5-bound PE-MPs. In brief, the new strategy could conduct direct, sensitive, and accurate quantification of PE-MP in PM2.5, favoring further studies of environmental fates, distributions, and toxicities of atmospheric MPs.

Therapeutic massage/Tuina for treatment of functional dyspepsia: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: A systematic review of randomized controlled trials (RCTs) was conducted to assess the potential effect of therapeutic massage/Tuina on functional dyspepsia (FD) patients. METHOD: Twelve databases and three clinical trial registries were searched until December 2021, for RCTs that compared Tuina combined with or without conventional therapy versus conventional therapy in FD. We assessed the methodological quality of included trials by the Cochrane Risk of Bias tool, and graded the quality of the evidence. The data were presented as risk ratio (RR) or mean difference (MD) respectively with their 95% confidence interval (CI). RESULTS: In total, 14 RCTs with 1128 FD participants were included. Compared with conventional therapy, Tuina showed significant beneficial effects on improving overall symptom (RR = 1.12, 95% CI 1.06 to 1.19, low certainty evidence), and early satiation (MD -0.44 scores, 95% CI -0.72 to -0.16, very low certainty evidence). Compared with conventional therapy, Tuina plus conventional therapy also significantly improved overall symptom (RR = 1.14, 95% CI 1.06-1.23, low certainty evidence), quality of life (MD 10.44 scores, 95% CI 7.65-13.23, low certainty evidence), and epigastric pain (MD -0.76 scores, 95% CI -1.11 to -0.41, low certainty evidence). No adverse events related to Tuina and cost-effectiveness were reported. CONCLUSION: Low certainty evidence showed that Tuina significantly improved overall symptom of FD participants compared with conventional therapy. Low certainty evidence showed that Tuina plus conventional therapy obviously improved overall symptom and quality of life of FD participants compared with conventional therapy.

Pancreatic follicular dendritic cell sarcoma: a rare case report and systematic literature review of 7 cases.

INTRODUCTION: Pancreatic follicular dendritic cell sarcoma (FDCS) is an exceptionally rare and low-to-moderate malignancy, with only seven reported cases to date. Clinical diagnosis of FDCS is challenging due to the lack of distinct biological and radiographic features. CASE PRESENTATION: A 67-year-old woman presented to the hospital with a 4-day history of severe abdominal pain. Imaging studies (CT and MRI) revealed a large cystic mass located at the tail of the pancreas, which was suspected to be myeloid sarcoma (MS) based on EUS and CT-guided pancreatic puncture. Postoperative pathology and immunohistochemistry confirmed the diagnosis of pancreatic FDCS. After the diagnosis was confirmed, the patient received postoperative chemotherapy with the CHOP regimen. At 11 months of follow-up, there was no evidence of recurrence. Seven published cases have been reviewed to comprehensively summarize the clinical characteristics, diagnosis, and treatment options of FDCS. CONCLUSION: While imaging can be useful in detecting pancreatic FDCS, it should be interpreted with caution as it can be challenging to differentiate from other pancreatic tumors. Pathology and immunohistochemistry are considered the gold standard for diagnosis, with CD21, CD23, and CD35 being specific tumor cell markers. However, preoperative diagnosis of pancreatic FDCS remains difficult, and the pancreatic puncture may further increase the risk of misdiagnosis. The disease is highly prone to recurrence and metastasis, and surgery is the preferred method for both diagnosis and treatment of localized disease.

Contamination profiles and potential health risks of environmentally persistent free radicals in PM2.5 over typical central Chinese megacity.

As one of the most important transportation hubs and industrial bases in China, Zhengzhou has suffered from serious PM2.5 pollution for a long time. However, the investigation of contamination status and possible exposure risks of environmentally persistent free radicals (EPFRs) in PM2.5 from Zhengzhou is rare. In this work, a comprehensive study of pollution levels, seasonal variations, sources, and potential health risks of PM2.5-bound EPFRs in Zhengzhou was conducted for the first time. The atmospheric concentrations of EPFRs in PM2.5 from Zhengzhou ranged from 1.732 × 1012 spin m-3 to 7.182 × 1014 spin m-3 between 2019 and 2020. Relatively serious contamination was noticed in winter and spring. Primary fossil fuel combustion and Fe-mediated secondary formation were apportioned as possible sources of PM2.5-bound EPFRs in Zhengzhou. Moreover, to avert the bias of the toxicity assessment induced by utilization of incompletely extracted EPFRs from sample filter, simulatively generated EPFRs were applied to toxicological evaluations (cell viability and reactive oxygen species assays). Corresponding experimental dosages were based on the estimated adults' annual exposure amounts of EPFRs in real PM2.5 samples. The results elucidated that EPFRs might cause growth inhibition and oxidative stress of human lung cells, suggesting the possible exposure-induced health concerns for local people in Zhengzhou. This study provides practical information of real contamination status of PM2.5-bound EPFRs in Zhengzhou, which is favorable to local air pollution control and reduction of exposure risks on public health in central China.

Association between sleep quality and cardiovascular disease in maintenance hemodialysis patients: a prospective cohort study.

OBJECTIVE: This study aimed to analyze the association between sleep quality and cardiovascular disease in patients on maintenance hemodialysis (MHD). METHODS: A total of 601 patients with MHD in the second affiliated hospital of Nanjing Medical University, were prospectively enrolled in this cohort study from January 2019 to December2019. The global Pittsburgh sleep quality index (PSQI) score > 7 indicates that a person with poor sleep quality. Patients were divided into two groups according to the PSQI score. Follow-up was conducted about 3 years with all-cause death and major adverse cardiovascular events (MACEs) as the endpoint events. RESULTS: Of the 601 patients, 595 patients completed the PSQI assessment, with 278 patients having poor sleep quality. Patients in the PSQI > 7 group were older and had a higher proportion of cardiovascular disease or diabetes. Years of education, diastolic blood pressure, and heart rate were lower in the PSQI > 7 group. At a mean follow-up period of 3 years, 116 patients died, 64 patients were lost to follow-up, and 115 patients experienced MACEs. After adjusting for confounding factors such as age, gender, dialysis age, and previous cardiovascular disease, the risk of MACE in patients with poor sleep quality was twice that of patients with good sleep quality (HR = 2.037 (1.339, 3.097), p = 0.001). There was no significant difference in the risk of all-cause death between the two groups. CONCLUSION: The prevalence of poor sleep quality was 46.7% in patients with MHD. Poor sleep quality was an independent risk factor for MACEs in patients with MHD.

Effects of carbon nanotubes on biodegradation of pollutants: Positive or negative?

Recently, a large quantity of carbon nanotubes (CNTs) enters the environment due to the increasing production and applications. More and more researches are focused on the fate and possible ecological risks of CNTs. Some literatures summarized the effects of CNTs on the chemical behavior and fate of pollutants. However, little reviewed the effects of CNTs on the biodegradation of pollutants. In general, the effects of CNTs on the biodegradation of pollutants and the related mechanisms were summarized in this review. CNTs have positive or negative effects on the biodegradation of contaminants by affecting the functional microorganisms, enzymes and the bioavailability of pollutants. CNTs may affect the microbial growth, activity, biomass, community composition, diversity and the activity of enzymes. The decrease of the bioavailability of pollutants due to the sorption on CNTs also causes the reduction of the biodegradation of contaminants. In addition, the roles of CNTs are controlled by multiple mechanisms, which are divided into three aspects i.e., properties of CNTs, environment condition, and microorganisms themself. The better understanding of the fate of CNTs and their impacts on the biochemical process in the environment is conducive to determine the release of CNTs into the environment.

Influence of surfactants on anaerobic digestion of waste activated sludge: acid and methane production and pollution removal.

The objective of this study is to summarize the effects of surfactants on anaerobic digestion (AD) of waste activated sludge (WAS). The increasing amount of WAS has caused serious environmental problems. Anaerobic digestion, as the main treatment for WAS containing three stages (i.e. hydrolysis, acidogenesis, and methanogenesis), has been widely investigated. Surfactant addition has been demonstrated to improve the efficiency of AD. Surfactant, as an amphipathic substance, can enhance the efficiency of hydrolysis by separating large sludge and releasing the encapsulated hydrolase, providing more substance for subsequent acidogenesis. Afterwards, the short chain fatty acids (SCFAs), as the major product, have been produced. Previous investigations revealed that surfactant could affect the transformation of SCFA. They changed the types of acidification products by promoting changes in microbial activity and in the ratio of carbon to nitrogen (C/N), especially the ratio of acetic and propionic acid, which were applied for either the removal of nutrient or the production of polyhydroxyalkanoate (PHA). In addition, the activity of microorganisms can be affected by surfactant, which mainly leads to the activity changes of methanogens. Besides, the solubilization of surfactant will promote the solubility of contaminants in sludge, such as organic contaminants and heavy metals, by increasing the bioavailability or desorbing of the sludge.

Cuffless Blood Pressure Estimation Using Pressure Pulse Wave Signals.

Pulse transit time (PTT) has received considerable attention for noninvasive cuffless blood pressure measurement. However, this approach is inconvenient to deploy in wearable devices because two sensors are required for collecting two-channel physiological signals, such as electrocardiogram and pulse wave signals. In this study, we investigated the pressure pulse wave (PPW) signals collected from one piezoelectric-induced sensor located at a single site for cuffless blood pressure estimation. Twenty-one features were extracted from PPW that collected from the radial artery, and then a linear regression method was used to develop blood pressure estimation models by using the extracted PPW features. Sixty-five middle-aged and elderly participants were recruited to evaluate the performance of the constructed blood pressure estimation models, with oscillometric technique-based blood pressure as a reference. The experimental results indicated that the mean ± standard deviation errors for the estimated systolic blood pressure and diastolic blood pressure were 0.70 ± 7.78 mmHg and 0.83 ± 5.45 mmHg, which achieved a decrease of 1.33 ± 0.37 mmHg in systolic blood pressure and 1.14 ± 0.20 mmHg in diastolic blood pressure, compared with the conventional PTT-based method. The proposed model also demonstrated a high level of robustness in a maximum 60-day follow-up study. These results indicated that PPW obtained from the piezoelectric sensor has great feasibility for cuffless blood pressure estimation, and could serve as a promising method in home healthcare settings.

A Wearable Context-Aware ECG Monitoring System Integrated with Built-in Kinematic Sensors of the Smartphone.

Continuously monitoring the ECG signals over hours combined with activity status is very important for preventing cardiovascular diseases. A traditional ECG holter is often inconvenient to carry because it has many electrodes attached to the chest and because it is heavy. This work proposes a wearable, low power context-aware ECG monitoring system integrated built-in kinetic sensors of the smartphone with a self-designed ECG sensor. The wearable ECG sensor is comprised of a fully integrated analog front-end (AFE), a commercial micro control unit (MCU), a secure digital (SD) card, and a Bluetooth module. The whole sensor is very small with a size of only 58 × 50 × 10 mm for wearable monitoring application due to the AFE design, and the total power dissipation in a full round of ECG acquisition is only 12.5 mW. With the help of built-in kinetic sensors of the smartphone, the proposed system can compute and recognize user's physical activity, and thus provide context-aware information for the continuous ECG monitoring. The experimental results demonstrated the performance of proposed system in improving diagnosis accuracy for arrhythmias and identifying the most common abnormal ECG patterns in different activities. In conclusion, we provide a wearable, accurate and energy-efficient system for long-term and context-aware ECG monitoring without any extra cost on kinetic sensor design but with the help of the widespread smartphone.

[Spatial Effect of the Dams and Sluices on the Risk of Schistosomiasis in Dongting Lake Region of Hunan Province].

OBJECTIVE: To determine the spatial effect of the dams and the sluices on the risk of schistosomiasis in Dongting Lake Region, and its mechanism, type and degree. METHODS: The positions, levels and types of the dams and the sluices in Dongting Lake Region of Hunan Province were marked on the base map. Epidemiological data of schistosomiasis among populations in 334 Townships in the Region were collected during March and July in each year of 2010-2014, and the 5-year average infection rate was calculated. A grid system composed of 1 220 hexagons was built to spatially quantify the effect of the dams and the sluices on the risk of schistosomiasis and the infection rates among populations. A two-step clustering was used to analyze the grid system, and the areas of infection peak were identified. The centrifugal model was used to simulate the degree and scope of the influence of these infection peak areas on the surrounding regions. The correlation coefficient model was used to determine the correlation coefficients between the dams and sluices and the spatial distribution of schistosomiasis. The correlation coefficients were then weighted, the integrated weighted risk of all grid cells calculated, and the weighted distribution figure for schistosomiasis risk produced. RESULTS: The results of two-step clustering revealed 15 areas of infection peak in the Region. The results of centrifugal model showed that the areas of infection peak significantly promoted the effect of the surrounding regions on the risk of infection. The correlation coefficients of the dams and the sluices with the infection rate among populations were 0.82 and 0.86, with the weights being 0.488 1 and 0.511 9, respectively. The areas with high and relatively high risks of infection had a Crescent-shaped distribution along the Lishui River, West Dongting Lake, South Dongting Lake, East Dongting Lake and Chenglingji. The results were further verified by MAE testing. CONCLUSION: The dams and sluices correlated strongly and positively with the risk of schistosomiasis. Fifteen areas of infection peak are identified to be determinant for schistosomiasis infection and spread, and have significant gradient spatial effect on schistosomiasis risk in surrounding areas.

Gastric metastasis of small cell lung carcinoma: Three case reports and review of literature.

BACKGROUND: Small cell lung carcinoma (SCLC) is highly susceptible to metastasis in the early stages of the disease. However, the stomach is an uncommon site of metastasis in SCLC, and only a few cases of this type of metastasis have been reported. Therefore, SCLC gastric metastases have not been systematically characterized and are easily missed and misdiagnosed. CASE SUMMARY: We report three cases of gastric metastasis from SCLC in this article. The first patient presented primarily with cough, hemoptysis, and epigastric fullness. The other two patients presented primarily with abdominal discomfort, epigastric distension, and pain. All patients underwent gastroscopy and imaging examinations. Meanwhile, the immunohistochemical results of the lesions in three patients were suggestive of small cell carcinoma. Finally, the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive analysis. The three patients did not receive appropriate treatment and died within a short time. CONCLUSION: Here, we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians' understanding of this disease.

Photocatalytic degradation of perfluorooctanoic acid (PFOA) from water: A mini review.

Perfluorooctanoic acid (PFOA) has drawn increasing attention as a highly persistent organic pollutant. The inherent stability, rigidity and potential toxicities characteristics make it a challenge to develop efficient technologies to eliminate it from water. Photocatalytic technology, as one advanced method, has been widely used in the degradation of PFOA in water. In this review, recent progress in the design of photocatalysts including doping, defects engineering, heterojunction and surface modification to boost the photocatalytic performance toward PFOA is summarized. The relevant degradation mechanisms were also discussed in detail. Finally, future prospect and challenges are proposed. This review may provide new guidelines for researchers to design much more efficient photocatalysts applied in the elimination of PFOA.

Association between cognitive function and skeletal muscle in patients undergoing maintenance hemodialysis.

Background: Patients on hemodialysis have a higher burden of cognitive impairment than individuals of the same age in the general population. Studies have found a link between cognition and skeletal muscle function. However, few studies have investigated these associations and the underlying mechanisms in patients on hemodialysis. Methods: A total of 166 patients on hemodialysis were enrolled in this longitudinal study. Cognitive function was assessed by Montreal Cognitive Assessment (MoCA) scores. Skeletal muscle indicators were evaluated using Inbody S10. Plasma brain-derived neurotrophic factor (BDNF) concentrations were measured by enzyme-linked immunosorbent assay. The primary outcome was a change in the MoCA scores. A mediation analysis was performed to examine the indirect effect of skeletal muscle on cognitive decline through BDNF. Results: Among the 166 patients, the average age was 49.9 ± 11.2 years. Of these patients with a median follow-up of 1,136 days, 133 participated in the study. We defined MoCA scores decreased by ≥2 points at 3 years from the baseline measurement as cognitive decline (CD). Compared to the cognitively unchanged group, patients with CD had significantly lower fat-free mass, soft lean mass, skeletal muscle mass, and skeletal muscle index (all P<0.05). After adjusting for potential confounders, skeletal muscle indicators were protective predictors of CD. A significant increase in plasma BDNF levels was observed in the CD group. Mediation analysis suggested that BDNF played a mediating role of 20-35% between cognitive impairment and skeletal muscle. Conclusion: Skeletal muscle is a protective predictor of CD in patients undergoing dialysis. BDNF mediates the relationship between cognitive impairment and skeletal muscle function.

A data-driven robust EVaR-PC with application to portfolio management.

We investigate the robust chance constrained optimization problem (RCCOP), which is a combination of the distributionally robust optimization (DRO) and the chance constraint (CC). The RCCOP plays an important role in modeling uncertain parameters within a decision-making framework. The chance constraint, which is equivalent to a constraint of Value-at-risk (VaR), is approximated by risk measures such as Entropic Value-at-risk (EVaR) or Conditional Value-at-risk (CVaR) due to its difficulty to be evaluated. An excellent approximation requires both tractability and non-conservativeness. In addition, the DRO assumes that we know partial information about the distribution of uncertain parameters instead of their known true underlying probability distribution. In this article, we develop a novel approximation EVaR- PC based on EVaR for CC. Then, we evaluate the proposed approximation EVaR- PC using a discrepancy-based ambiguity set with the wasserstein distance. From a theoretical perspective, the EVaR- PC is less conservative than EVaR and the wasserstein distance possesses many good theoretical properties; from a practical perspective, the discrepancy-based ambiguity set can make full use of the data to estimate the nominal distribution and reduce the sensitivity of decisions to priori knowledges. To show the advantages of our method, we show its application in portfolio management in detail and give the relevant experimental results.

Pyruvate kinase M2 regulates mitochondrial homeostasis in cisplatin-induced acute kidney injury.

An important pathophysiological process of acute kidney injury (AKI) is mitochondrial fragmentation in renal tubular epithelial cells, which leads to cell death. Pyruvate kinase M2 (PKM2) is an active protein with various biological functions that participates in regulating glycolysis and plays a key role in regulating cell survival. However, the role and mechanism of PKM2 in regulating cell survival during AKI remain unclear. Here, we found that the phosphorylation of PKM2 contributed to the formation of the PKM2 dimer and translocation of PKM2 into the mitochondria after treatment with staurosporine or cisplatin. Mitochondrial PKM2 binds myosin heavy chain 9 (MYH9) to promote dynamin-related protein 1 (DRP1)-mediated mitochondrial fragmentation. Both in vivo and in vitro, PKM2-specific loss or regulation PKM2 activity partially limits mitochondrial fragmentation, alleviating renal tubular injury and cell death, including apoptosis, necroptosis, and ferroptosis. Moreover, staurosporine or cisplatin-induced mitochondrial fragmentation and cell death were reversed in cultured cells by inhibiting MYH9 activity. Taken together, our results indicate that the regulation of PKM2 abundance and activity to inhibit mitochondrial translocation may maintain mitochondrial integrity and provide a new therapeutic strategy for treating AKI.