Four-in-one multifunctional self-driven photoelectrocatalytic system for water purification: Organics degradation, U(VI) reduction, electricity generation and disinfection against bacteria.

This study addresses the energy-intensive nature of conventional wastewater treatment processes and proposes a solution through the development of a green, low-energy, and multifunctional wastewater treatment technology. The research focuses on a multifunctional self-driven photoelectrocatalytic (PEC) system, exploring its four-in-one applications in eliminating organic pollutants, reducing U(VI), generating electrical energy, and disinfecting pathogenic microorganisms. A TiO2-decorated carbon felt (CF@TiO2) cathode is synthesized to enhance interfacial charge transfer, with TiO2 coating improving surface binding sites (edge TiO and adsorbed -OH) for UO22+ adsorption and reduction. The self-driven PEC system, illuminated solely with simulated sunlight, exhibits remarkable efficiency in removing nearly 100 % of uranium within 0.5 h and simultaneously degrading 99.9 % of sulfamethoxazole (SMX) within 1.5 h, all while generating a maximum power output density (Pmax) of approximately 1065 µW·cm-2. The system demonstrates significant anti-interference properties across a wide pH range and coexisting ions. Moreover, 49.4 % of the fixed uranium on the cathode is reduced into U(IV) species, limiting its migration. The self-driven PEC system also excels in detoxifying various toxic organic compounds, including tetracycline, chlortetracycline, and oxytetracycline, and exhibits exceptional sterilization ability by disinfecting nearly 100 % of Escherichia coli within 0.5 h. This work presents an energy-saving, sustainable, and easily recyclable wastewater purification system with four-in-one capabilities, relying solely on sunlight for operation.

Acetyl-CoA synthetase 2 induces pyroptosis and inflammation of renal epithelial tubular cells in sepsis-induced acute kidney injury by upregulating the KLF5/NF-κB pathway.

BACKGROUND: Pyroptosis of the renal tubular epithelial cells (RTECs) and interstitial inflammation are central pathological characteristics of acute kidney injury (AKI). Pyroptosis acts as a pro-inflammatory form of programmed cell death and is mainly dependent on activation of the NLRP3 inflammasome. Previous studies revealed that acetyl-CoA synthetase 2 (ACSS2) promotes inflammation during metabolic stress suggesting that ACSS2 might regulate pyroptosis and inflammatory responses of RTECs in AKI. METHODS AND RESULTS: The expression of ACSS2 was found to be significantly increased in the renal epithelial cells of mice with lipopolysaccharide (LPS)-induced AKI. Pharmacological and genetic strategies demonstrated that ACSS2 regulated NLRP3-mediated caspase-1 activation and pyroptosis through the stimulation of the KLF5/NF-κB pathway in RTECs. The deletion of ACSS2 attenuated renal tubular pathological injury and inflammatory cell infiltration in an LPS-induced mouse model, and ACSS2-deficient mice displayed impaired NLRP3 activation-mediated pyroptosis and decreased IL-1ß production in response to the LPS challenge. In HK-2 cells, ACSS2 deficiency suppressed NLRP3-mediated caspase-1 activation and pyroptosis through the downregulation of the KLF5/NF-κB pathway. The KLF5 inhibitor ML264 suppressed NF-κB activity and NLRP3-mediated caspase-1 activation, thus protecting HK-2 cells from LPS-induced pyroptosis. CONCLUSION: Our results suggested that ACSS2 regulates activation of the NLRP3 inflammasome and pyroptosis by inducing the KLF5/NF-κB pathway in RTECs. These results identified ACSS2 as a potential therapeutic target in AKI.

Multi-objective and multi-solution source mask optimization using NSGA-II for more direct process window enhancement.

Source and mask optimization (SMO) technology is increasingly relied upon for resolution enhancement of photolithography as critical dimension (CD) shrinks. In advanced CD technology nodes, little process variation can impose a huge impact on the fidelity of lithography. However, traditional source and mask optimization (SMO) methods only evaluate the imaging quality in the focal plane, neglecting the process window (PW) that reflects the robustness of the lithography process. PW includes depth of focus (DOF) and exposure latitude (EL), which are computationally intensive and unfriendly to gradient-based SMO algorithms. In this study, we propose what we believe to be a novel process window enhancement SMO method based on the Nondominated Sorting Genetic Algorithm II (NSGA-II), which is a multi-objective optimization algorithm that can provide multiple solutions. By employing the variational lithography model (VLIM), a fast focus-variation aerial image model, our method, NSGA-SMO, can directly optimize the PW performance and improve the robustness of SMO results while maintaining the in-focus image quality. Referring to the simulations of two typical patterns, NSGA-SMO showcases an improvement of more than 20% in terms of DOF and EL compared to conventional multi-objective SMO, and even four times superior to single-objective SMO for complicated patterns.

Adaptive mask-based brain extraction method for head CT images.

Brain extraction is an important prerequisite for the automated diagnosis of intracranial lesions and determines, to a certain extent, the accuracy of subsequent lesion identification, localization, and segmentation. To address the problem that the current traditional image segmentation methods are fast in extraction but poor in robustness, while the Full Convolutional Neural Network (FCN) is robust and accurate but relatively slow in extraction, this paper proposes an adaptive mask-based brain extraction method, namely AMBBEM, to achieve brain extraction better. The method first uses threshold segmentation, median filtering, and closed operations for segmentation, generates a mask for the first time, then combines the ResNet50 model, region growing algorithm, and image properties analysis to further segment the mask, and finally complete brain extraction by multiplying the original image and the mask. The algorithm was tested on 22 test sets containing different lesions, and the results showed MPA = 0.9963, MIoU = 0.9924, and MBF = 0.9914, which were equivalent to the extraction effect of the Deeplabv3+ model. However, the method can complete brain extraction of approximately 6.16 head CT images in 1 second, much faster than Deeplabv3+, U-net, and SegNet models. In summary, this method can achieve accurate brain extraction from head CT images more quickly, creating good conditions for subsequent brain volume measurement and feature extraction of intracranial lesions.

Comparison of the Watson formula and bioimpedance spectroscopy for measuring body volume and calculating kt/V in patients with peritoneal dialysis.

CONCLUSION: There were significant differences between Vwat and Vbis and between Kt/Vwat and Kt/Vbis. Kt/Vwat may underestimate small-solute dialysis adequacy in most cases. Kt/Vbis instead of Kt/Vwat could be accounted for in creating individualized dialysis prescriptions if the patient has no obvious clinical symptoms.

Prognosis of Peritoneal Dialysis Patients with Different Peritoneal Transport Characteristics: A Retrospective Cohort Study.

INTRODUCTION: We aimed to examine the clinical characteristics of peritoneal dialysis (PD) patients with different baseline peritoneal transport characteristics and the effect of peritoneal transport characteristics on the prognosis of PD patients. METHODS: Patients who received PD for more than 3 months were included. Clinical characteristics, risk factors for high peritoneal transport, and risk factors for death and technique failure were examined. All patients were treated with glucose-containing peritoneal dialysis solution, and the peritoneal dialysis protocol was either day ambulatory peritoneal dialysis (DAPD) or continuous ambulatory peritoneal dialysis (CAPD). RESULTS: A total of 351 patients were enrolled, comprising 70 in the low transport group, 149 in the low average transport group, 88 in the high average transport group, and 44 in the high transport group. Multivariate logistic regression analysis showed that a high Charlson's comorbidity index (CCI) and low albumin were risk factors for a high baseline transport status. In the nonhigh transport group, the proportion of patients with albumin less than 30 g/L, who developed high transport status, was higher than those with albumin more than 30 g/L (P = .029). The survival rate in the high transport group was significantly lower than that in the other three groups (P < .001). Multivariate Cox regression analysis showed that age, systolic blood pressure, CCI, C-reactive protein (CRP) and high transport were independent risk factors for all-cause mortality. Male sex, triglycerides and CRP were independent risk factors for technique failure. CONCLUSION: High peritoneal transport status is an independent risk factor for death. High CCI and low albumin are determinants of baseline high peritoneal transport. To avoid development of a high transport state, serum albumin should be increased to more than 30 g/L.  DOI: 10.52547/ijkd.7617.

A self-driven solar coupling system with TiO2@MXene cathode for effectively eliminating uranium and organics from complex wastewater accompanying with electricity generation.

The inevitable organic matters in radioactive wastewater and contaminated waters pose great challenge in uranium recycling by traditional techniques. Here, a self-driven solar coupling system (SSCS), which was assembled by a TiO2 @MXene/CF cathode and a monolithic photoanode, was proposed for synergistically recycling uranium and degrading organics from complex radioactive wastewater, combining with electricity production. The TiO2 @MXene/CF was prepared via a simple annealing process with in-situ derived TiO2 nanoparticles decorated Ti3C2 MXene coated on carbon felt (CF). Under sunlight illumination, the photoanode captured electrons of organics, and drove electrons to the TiO2 @MXene/CF, which exhibited an exceptional UO22+ adsorption and reduction capacity because TiO2 nanoparticles provided plenty of surface hydroxyl groups for UO22+ adsorption, and the unique two-dimensional MXene facilitated the charge transfer. The SSCS with TiO2 @MXene/CF removed almost 100% UO22+ and organics with rate constants of ∼21 and ∼6.9 times those of the system with CF, accompanying with excellent power output (∼1000 µW·cm-2). The fixed uranium on TiO2 @MXene/CF was effectively reduced into insoluble UO2 (91.1%), and no obvious decay was observed after 15 repeated uses. This study proposes a multi-functional and easy-operated way for remediating radioactive wastewater and contaminated waters, and gives valuable insights in designing cathode materials for uranium reduction.

Oxygen evolution reaction (OER) active sites in BiVO4 studied using density functional theory and XPS experiments.

Bismuth vanadate (BiVO4/BVO) has been widely studied as a photocatalytic water splitting semiconductor material in recent years because of its many advantages, such as its ease of synthesis and suitable band gap (2.4 eV). However, BVO still has some disadvantages, one of which is the low photocatalytic water oxidation activity. It is intriguing and unexpected to note that in the current literature, Bi atoms are taken as the oxygen evolution reaction (OER) active sites, while V metal atoms are not investigated in the OER, and the underlying reason for this remains unknown. In this work, using density functional theory (DFT) calculations and ab initio molecular dynamics simulations, we found that in BVO, the VO4 tetrahedron structure is very stable and there is strong surface reconstruction that leads to the V atoms on the surface having the same coordinates as in the bulk. For some high index surfaces, there are some theoretically predicted unsaturated V sites, but it is very easy to form a VO4 tetrahedron structure again by taking oxygen atoms from water. The other intermediates of OER are difficult to adsorb or desorb on this VO4 structure, which makes the V sites in BVO unsuitable as OER active sites. This VO4 structure remained stable during the molecular dynamics simulation at 300 and 673 K. The XPS characterization of various BVO morphologies validates our primary findings from DFT and molecular dynamics simulations. It reveals the presence of unsaturated Bi sites on the BVO surface, while unsaturated V sites are not observed. This study provides novel insights into the enhancement of OER activity of BVO and offers a fundamental understanding of OER activity in other photocatalysts containing V atoms.

Antibiotic cured chronic endometritis remains a risk factor for early pregnancy loss in the subsequent frozen euploid embryo transfer.

RESEARCH QUESTION: Do patients with antibiotic-cured chronic endometritis (CCE) have a comparable pregnancy outcome to those with non-chronic endometritis (NCE) in the subsequent frozen embryo transfer (FET) cycle? DESIGN: A retrospective cohort analysis included 833 patients in their first FET cycles with single euploid embryo transfer. Chronic endometritis (≥5 CD138+ plasma cells per high-power field [CD138+/HPF]) was treated with standard antibiotic therapy. Patients were classified into two groups: the NCE group (n = 611, <5 CD138+/HPF) and the CCE group (n = 222, ≥5 CD138+/HPF and cured after antibiotic treatment). Pregnancy outcomes were compared. NCE group was divided into subgroup 1 (CD138+/HPF = 0) and subgroup 2 (CD138+/HPF = 1-4) for further analysis. RESULTS: The rate of early pregnancy loss (EPL), incorporating all losses before 10 weeks' gestation, was significantly higher in the CCE group than the NCE group (21.2% versus 14.2%, P = 0.016), and the difference was statistically significant (adjusted odds ratio [AOR] 1.68, 95% confidence interval [CI] 1.11-2.55). No significant differences were observed between the two groups with regard to other pregnancy outcomes. In the subgroup analysis, the EPL rate and biochemical pregnancy rate were significantly higher in subgroup 2 than subgroup 1 (17.2% versus 9.4%, AOR 2.21, 95% CI 1.30-3.74; 12.2% versus 6.9%, AOR 2.01, 95% CI 1.09-3.68). CONCLUSIONS: Chronic endometritis cured by standard antibiotic therapy remains a risk factor for EPL in FET cycles, although no differences were found in live birth rates between patients with CCE or with NCE.

The role of murine M1 macrophages from different sources in unilateral ureteral obstruction.

Introduction: The unilateral ureteral obstruction (UUO) model is the most extensively used model to investigate chronic renal fibrosis. Macrophages play a critical role in the UUO model. We aimed to analyze the phenotype of macrophages from different sources activated in vitro and explore the role of M1 macrophages from various sources in UUO. Material and methods: C57BL/6 mice were randomly allocated to five different groups (n = 5 per group): the sham-operated control group, PBS-treated (UUO + PBS) group, bone marrow-derived M1 macrophage-treated (UUO + BM1) group, peritoneal M1 macrophage-treated (UUO + PM1) group, and splenic M1 macrophage-treated (UUO + SPM1) group. After M1 macrophages were injected into the tail vein of UUO-treated mice, renal fibrosis indexes were determined using HE, Masson staining, and α-SMA. Results: Compared to those in the UUO + PBS group, the pathological changes were much more severe in the UUO + BM1, UUO + PM1, and UUO + SPM1 groups. Compared to that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1 group, the collagen area in the UUO + PM1 group was higher at post-UUO day 5 (p < 0.01). The expression of α-SMA in the UUO + PM1 group was higher than that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1group (p < 0.001). Conclusions: The M1 macrophages cultured in vitro were reinjected into mice and aggravated kidney injury and fibrosis. Compared with BM1 and SPM1, PM1 demonstrated a stronger effect on inducing renal injury and fibrosis.

Soybean WRINKLED1 protein GmWRI1a promotes flowering under long-day conditions via regulating expressions of flowering-related genes.

Flowering time is an important agronomic character that influences the adaptability and yield of soybean [Glycine max (L.) Merrill]. WRINKLED 1 (WRI1) plays an important regulatory role in plant growth and development. In this study, we found that the expression of GmWIR1a could be induced by long days. Compared with the wild type, transgenic soybean overexpressing GmWRI1a showed earlier flowering and maturity under long days but no significant changes under short days. Overexpression of GmWRI1a led to up-regulated expression of genes involved in the regulation of flowering time. The GmWRI1a protein was able to directly bind to the promoter regions of GmAP1, GmFUL1a, GmFUL2 and up-regulated their expression. GmCOL3 was identified by yeast one-hybrid library screening using the GmWRI1a promoter as bait. GmCOL3 was revealed to be a nucleus-localized protein that represses the transcription of GmWRI1a. Expression of GmCOL3 was induced by short days. Taken together, the results show that overexpression of GmWRI1a promotes flowering under long days by promoting the transcriptional activity of flowering-related genes in soybean, and that GmCOL3 binds to the GmWRI1a promoter and directly down-regulates its transcription. This discovery reveals a new function for GmWRI1a, which regulates flowering and maturity in soybean.

Synergistically adsorbing and reducing Uranium from water by a novel nano zero-valent copper/MXene 0D/2D nanocomposite.

Proper disposal of uranium-containing waste is of utmost importance for safeguarding the environment and human health. In this study, we proposed a novel zero-dimensional (0D)/two-dimensional (2D) nanocomposite material, nZVC/Ti3C2, composed of nano zero-valent copper (nZVC) nanoparticles loaded onto Ti3C2 MXene nanoflakes, which was prepared using a simple in situ chemical reduction method. The uniform dispersion of 0D nZVC nanoparticles, with a size of approximately 5 nm, onto the 2D ultrathin Ti3C2 MXene effectively prevented agglomeration and corrosion of nZVC. This unique configuration provided numerous adsorption sites for UO22+and facilitated a fascinating charge channel for reducing adsorbed UO22+ into low-mobilized UO2 by nZVC. Under the synergistic effect of Ti3C2 MXene and nZVC, remarkable efficiency and selectivity of nZVC/Ti3C2 for U (VI) removal were demonstrated, which exhibited an exceptional adsorption capacity of up to 360 mg/g, coupled with a high removal efficiency of 97.5 % and rapid kinetics. Importantly, the presence of humic acid did not significantly affect the U (VI) removal efficiency of the composite because of the reduction effect of nZVC. The underlying mechanism of U (VI) removal was elucidated, revealing the involvement of reductive immobilization in the form of UO2 (as high as 73.6 %), inner-sphere surface complexation, and hydrolytic precipitation. This mechanism was dependent on the availability of active nZVC and the solution's pH. These findings highlight the potential of nZVC/Ti3C2 composites as efficient decontaminants for radioactive wastewater, thus contributing to advancements in environmental remediation endeavors.

HMGB1 induces macrophage pyroptosis in chronic endometritis.

BACKGROUND: Chronic endometritis (CE) reflects the local imbalance in the endometrial immune microenvironment after inflammation. High mobility group box 1 (HMGB1) is highly involved in both immunity and inflammation. In this study, we aimed to explore the roles of HMGB1 in the endometrium of patients with CE. METHODS: Endometrium and uterine fluid HMGB1 were tested in a cohort of infertile patients with or without CE. Expression levels of the pyroptosis marker, gasdermin D (GSDMD)-N-terminal (NT), in the human endometrium of patients with CE and controls were determined. Next, the role of HMGB1 as a driver of macrophage pyroptosis was investigated using human THP-1 cells in vitro and a CE mouse model in vivo. RESULTS: High expression levels of HMGB1 in biopsied endometrial tissue and uterine fluid were confirmed in a cohort of patients with CE. Positive correlation between the number of CD138+ cells and HMGB1 mRNA expression level were detected (rs = 0.592, P < 0.001). Meanwhile, we found that GSDMD-NT expression was significantly increased in the CE endometrium at both the transcriptional and translational levels. Moreover, co-localization of GSDMD-NT and macrophages was confirmed via the double immunostaining of GSDMD-NT and CD68. In vitro experiments revealed that macrophage pyroptosis was induced by HMGB1 in human THP-1-derived macrophages. Treatment with glycyrrhizic acid, an inhibitor of HMGB1, significantly suppressed endometrial pyroptosis and inflammation in the CE mouse model. CONCLUSIONS: HMGB1 effectively induced macrophage pyroptosis in the human endometrium, suggesting that its inhibition may serve as a novel treatment option for CE.

Kunxian capsule alleviates podocyte injury and proteinuria by inactivating ß-catenin in db/db mice.

Background: Diabetic kidney disease (DKD) remains the primary cause of end-stage renal disease (ESRD) globally, but treatment options are limited. Kunxian capsule (KXC) has been utilized for the treatment of autoimmune diseases and IgA nephropathy in China. However, its effect on DKD remains poorly investigated. Therefore, this study aimed to explore the protective effect of KXC in db/db mice and elucidate its underlying mechanism. Methods: The renoprotective effects of KXC were assessed in a DKD mouse model using male BKS db/db diabetic mice. After 8 weeks of treatment, the urinary albumin-to-creatinine ratio (UACR), blood biochemical parameters, renal histopathological manifestation, and podocyte ultrastructural changes were evaluated. Additionally, the expression of podocyte epithelial-to-mesenchymal transition (EMT) markers [WT1, ZO-1, and collogen I (Col1a1)] was quantitatively analyzed. Furthermore, we explored the role of KXC in the ß-catenin signaling pathway to elucidate the underlying mechanism of KXC's renoprotective effect. Results: KXC treatment effectively reduced albuminuria and attenuated renal structural abnormalities in db/db mice. Additionally, KXC restored the protein and mRNA expression of WT1 and ZO-1 while suppressing the expression of Col1a1 in db/db mice, indicating its ability to alleviate podocyte EMT. Mechanistically, KXC exerted a significant suppressive effect on the activation of ß-catenin signaling in diabetic kidneys. Conclusion: KXC has the potential to protect podocytes during DKD by alleviating podocyte EMT through inactivating ß-catenin signaling.

Impact of antibiotic cured chronic endometritis on perinatal outcomes: Re-evaluation of a cohort study with a detailed follow-up.

PROBLEM: The impact of antibiotic-cured chronic endometritis (CE) on perinatal outcomes of patients conceived with frozen embryo transfer (FET) was unclear. METHOD: This study was to re-evaluate the perinatal outcomes of a cohort of infertile patients who had undergone endometrial biopsy for CE detection from February 2018 to December 2019 and successfully delivered babies after FET. The study population was divided into two groups: the non-CE (NCE) group (0-4/HPF CD138) and the cured-CE (CCE) group (CD138+/HPF≥5 and has been cured after one or two rounds of antibiotic treatment). For subgroup analysis, the NCE group was further divided into subgroup 1 (CD138+/HPF = 0), subgroup 2 (CD138+/HPF = 1-4 with antibiotic treatment), and subgroup 3 (CD138+/HPF = 1-4 without antibiotic treatment) RESULTS: A total of 321 live births, including 210 in the NCE group and 111 in the CCE group were analyzed. The prevalence rates of premature rupture of the membrane and preterm birth were comparable between NCE and CCE (6.2% vs. 7.1% and 10.8% vs. 10.1%, respectively) groups. In addition, no differences were detected in the rates of placenta-mediated complications, such as preeclampsia, placenta abruption, or low birthweight. Multiple logistic analyses confirmed that CCE was not associated with an increased risk of any adverse perinatal outcomes. Subgroup analysis in NCE failed to find any significant differences in the incidences of obstetrical and neonatal complications. CONCLUSIONS: CCE might not increase the risks of adverse perinatal outcomes after antibiotic treatment.

TMT-based quantitative proteomic analysis of spheroid cells of endometrial cancer possessing cancer stem cell properties.

BACKGROUND: Cancer stem cells (CSCs) play an important role in endometrial cancer progression and it is potential to isolate CSCs from spheroid cells. Further understanding of spheroid cells at protein level would help find novel CSC markers. METHODS: Spheroid cells from endometrial cancer cell lines, Ishikawa and HEC1A, exhibited increased colony forming, subsphere forming, chemo-drug resistance, migration, invasion ability and tumorigenicity, verifying their cancer stem-like cell properties. The up-regulated CD90, CD117, CD133 and W5C5 expression also indicated stemness of spheroid cells. TMT-based quantitative proteomic analysis was performed to explore the potential alterations between parent cells and cancer stem-like spheroid cells. HK2-siRNA was transfected to Ishikawa and HEC1A cells to explore the roles and molecular mechanism of HK2 in endometrial cancer. RESULTS: We identified and quantified a total of 5735 proteins and 167 overlapped differentially expressed proteins of two cell types, 43 proteins were up-regulated and 124 were down-regulated in spheroid cells comparing with parent cells. KEGG pathway revealed a significant role of HIF-1 pathway in spheroid cells. qRT-PCR and western blot results of GPRC5A, PFKFB3 and HK2 of HIF-1 pathway confirmed their elevated expressions in spheroid cells which were consistent with proteomic results. HK2 promoted cancer stemness in endometrial cancer. CONCLUSION: These findings indicate that spheroid cells from endometrial cancer cell lines possess cancer stem-like cell properties and enrich CSCs. HIF-1 pathway is activated in endometrial cancer stem-like spheroid cells.

LncRNA CRNDE is involved in the pathogenesis of renal fibrosis by regulating renal epithelial cell mesenchymal-epithelial transition via targeting miR-29a-3p.

Results of previous studies suggested that renal fibrosis and epithelial-mesenchymal transition (EMT) plays an important role in the process of renal fibrosis, but the underlying mechanism remains unclear. Long coding RNA (lncRNA) CRNDE has emerged as potent regulators of EMT programs, therefore, in present work, we examined the roles of LncRNA CRNDE/miR-29a-3p axis in renal fibrosis and the underlying mechanism. We found that in both renal fibrosis animal and cell models, lncRNA CRNDE was dynamically upregulated in animal models or cells by the treatment of TGF-ß. Furthermore, knockdown of CRNDE to rat significantly inhibited EMT, prevented renal fibrosis. Finally, CRNDE regulates renal fibrosis through suppression of miR-29a-3p expression. Together, our results demonstrated that CRNDE acted as a regulator of renal fibrosis via targeting miR-29a-3p. Our findings may provide a potential therapeutic target for the treatment of renal fibrosis.

Knockdown of AK142426 suppresses M2 macrophage polarization and inflammation in peritoneal fibrosis via binding to c-Jun.

BACKGROUND: Peritoneal fibrosis is a common complication of peritoneal dialysis, which may lead to ultrafiltration failure and ultimately treatment discontinuation. LncRNAs participate in many biological processes during tumorigenesis. We investigated the role of AK142426 in peritoneal fibrosis. METHODS: The AK142426 level in peritoneal dialysis (PD) fluid was detected by quantitative real-time-PCR assay. The M2 macrophage distribution was determined by flow cytometry. The inflammatory cytokines of TNF-α and TGF-ß1 were measured by ELISA assay. The direct interaction between AK142426 and c-Jun was evaluated by RNA pull-down assay. In addition, the c-Jun and fibrosis related proteins were assessed by western blot analysis. RESULTS: The PD-induced peritoneal fibrosis mouse model was successfully established. More importantly, PD treatment induced M2 macrophage polarization and the inflammation in PD fluid, which might be associated with exosome transmission. Fortunately, AK142426 was observed to be upregulated in PD fluid. Mechanically, knockdown of AK142426 suppressed M2 macrophage polarization and inflammation. Furthermore, AK142426 could upregulate c-Jun through binding c-Jun protein. In rescue experiments, overexpression of c-Jun could partially abolish the inhibitory effect of sh-AK142426 on the activation of M2 macrophages and inflammation. Consistently, knockdown of AK142426 alleviated peritoneal fibrosis in vivo. CONCLUSIONS: This study demonstrated that knockdown of AK142426 suppressed M2 macrophage polarization and inflammation in peritoneal fibrosis via binding to c-Jun, suggesting that AK142426 might be a promising therapeutic target for patients of peritoneal fibrosis.

Intraday exposure to ambient ozone and emergency department visits among children: a case-crossover study in southern China.

Most existing studies have investigated short-term associations between ozone exposure and acute disease events among children at a daily timescale, which might neglect risk effects happening within several hours after ozone exposure. In this research, we aimed to depict intraday associations between pediatric emergency department visits (PEDVs) and exposure to ozone in order to better detect ultra-short-term effects of ozone exposure on children. We obtained hourly data of all-cause PEDVs, air pollutants, and meteorological factors in Shenzhen and Guangzhou, China, 2015-2018. We applied time-stratified case-crossover design and conditional logistic regression models to estimate odds ratios per 10-µg/m3 rise of ozone concentrations at various exposure periods (e.g., 0-3, 4-6, 7-12, 13-24, 25-48, and 49-72 h) prior to PEDVs, controlling for hourly relative humidity and temperature. Subgroup analyses divided by gender, age, and season were undertaken to identify the potential susceptible population and period. A total of 358,285 cases of PEDVs were included in two cities, and hourly average concentration of ozone was 45.5 µg/m3 in Guangzhou and 58.9 µg/m3 in Shenzhen, respectively. Increased risks of PEDVs occurred within a few hours (0-3 h) after exposure to ozone and remained up to 48 h. Population risks for PEDVs increased by 0.8% (95% confidence interval, 0.6 to 1.0) in Shenzhen and 0.7% (0.5 to 0.9) in Guangzhou for a 10-µg/m3 increase in ozone concentrations at lag 4-6 h and lag 7-12 h, respectively. These findings were robust to co-exposure adjustments in our sensitivity analyses. Significantly greater ozone-associated risks were consistently observed during cold months (October to March of the following year) in both cities, while we did not identify evidence for effect modification of children's age and gender. This study provided novel evidence for increased risks of acute disease events among children within several hours after ozone exposure, highlighting the significant implications for policymakers to establish hourly air quality standards for better protecting children's health.

Chemoimmunological Cascade Cancer Therapy Using Fluorine Assembly Nanomedicine.

Classical chemotherapeutic drugs may cause immunogenic cell death (ICD), followed by activating CD8+ T cells to promote cell-mediated antitumor immune responses. However, CD8+ T cells become exhausted due to tumor antigens' continuous stimulation, creating a major obstacle to effectively suppressing tumor growth and metastasis. Here, we develop an approach of chemo-gene combinational nanomedicine to bridge and reprogram chemotherapy and immunotherapy. The dually loaded nanomedicine induces ICD in tumor cells through doxorubicin and reverses the antitumor effects of exhausted CD8+ T cells through the small interfering RNA. The synergistic chemo-gene and fluorine assembly nanomedicine enriched in reactive oxygen species and acid-sensitive bonds results in enhanced cancer immunotherapy to inhibit tumor growth and the lung metastasis of breast cancer in a mouse model of breast cancer and melanoma. This study provides an efficient strategy and insights into chemoimmunological cascade therapy for combating malignant metastatic tumors.