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Selenium nanospheres (SeNPs) show less toxicity and greater bioavailability than selenite salts. This research demonstrated the substantial tolerance and efficient conversion of Se(IV) into SeNPs by Lactiplantibacillus plantarum NML21. The bioreduction process of Se(IV) and the properties of SeNPs, including their morphology, particle size, and stability, were investigated with techniques including SEM, EDX, TEM, XPS, FT-IR, dynamic light scattering, XRD, and Raman spectroscopy. Under high selenium stress, certain cells displayed significant deformation and rupture, and released SeNPs as the main product of the bioreduction of Se(IV). These SeNPs were red, amorphous, zero-valent, and spherical, with an average diameter of 160 nm. Spectroscopic analysis highlighted that the functional groups of CO and CO are key to the bioreduction of Se(IV). The study suggested preliminary mechanisms for the bioreduction of Se(IV) and the formation and release of SeNPs by lactic acid bacteria. NML21 may therefore be a promising candidate for SeNPs synthesis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) is a frequent and severe complication of sepsis and is characterized by significant mortality and morbidity. However, the pathogenesis of septic acute kidney injury (S-AKI) remains elusive. Metabolic reprogramming, which was originally referred to as the Warburg effect in cancer, is strongly related to S-AKI. At the onset of sepsis, both inflammatory cells and renal parenchymal cells, such as macrophages, neutrophils and renal tubular epithelial cells, undergo metabolic shifts toward aerobic glycolysis to amplify proinflammatory responses and fortify cellular resilience to septic stimuli. As the disease progresses, these cells revert to oxidative phosphorylation, thus promoting anti-inflammatory reactions and enhancing functional restoration. Alterations in mitochondrial dynamics and metabolic reprogramming are central to the energetic changes that occur during S-AKI. In this review, we summarize the current understanding of the pathogenesis of metabolic reprogramming in S-AKI, with a focus on each cell type involved. By identifying relevant key regulatory factors, we also explored potential metabolic reprogramming-related therapeutic targets for the management of S-AKI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microscale swimmers are attractive for targeted drug delivery, noninvasive microsurgery and environmental remediation at different length scales, among which, Marangoni-based swimmers have garnered considerable attention due to their independence of external energy supply. However, applications of most existing chemical swimmers are limited by complex fabrication, high cost, utilization of organic (or even toxic) solvents, poor motility performance, and lack of controllability. To address these challenges, we propose an approach for all-aqueous soft milli-swimmers that utilizes biodegradable hydrogels and biocompatible fuels. This innovative method achieves swimmer body generation and fuel loading in one step by simply dripping one aqueous solution into another, saving fabrication time and minimizing fuel loss during transfer. These all-aqueous soft milli-swimmers have rove beetle-like self-propulsion, which stores low-surface-energy compounds within their body for propulsion on liquid surfaces. Isotropic and anisotropic all-aqueous soft milli-swimmers are formed with precise control over their dimension, morphology, and movement velocity. Through their motion within engineered channels, intricate labyrinths, dynamic air-liquid interfaces, and collective self-assemblies, their remarkable adaptability in complex aqueous environments is demonstrated. Furthermore, the integration of functional nanoparticles endows these all-aqueous milli-swimmers with multifunctionality, expanding their applications in cargo transportation, sensing, and environmental remediation.

Anti-glomerular basement membrane (GBM) nephritis is a rare autoimmune disorder characterized by acute and rapidly progressive glomerulonephritis. In this report, we present the case of a 52-year-old woman with anti-GBM nephritis who was treated with Staphylococcus Protein A immunoadsorption in combination with glucocorticoids and cyclophosphamide. After 8 cycles of immunoadsorption, the patient's anti-GBM antibodies decreased from 363 AU/mL to less than 20 AU/mL, accompanied by a dropped immunoglobin G level, although renal impairment persisted. We reviewed the therapeutic options for anti-GBM nephritis and compared plasma exchange, double filtration plasmapheresis, and immunoadsorption with regard to plasma consumption, allergic events, and plasma components loss. Protein A immunoadsorption appears to be a promising treatment modality for anti-GBM nephritis., Competing Interests: The authors declared that there was no competing interest., (© 2024 The Authors.)

Background: Neutrophil-to-lymphocyte ratio (NLR) has been suggested to be a prognostic marker for various diseases, but whether NLR dynamics (ΔNLR) is related to mortality and disease severity in patients with septic acute kidney injury (AKI) has not been determined., Methods: Between August 2013 and August 2021, septic AKI patients at our center were retrospectively enrolled. ΔNLR was defined as the difference between the NLR at septic AKI diagnosis and at hospital admission. The relationship between the ΔNLR and mortality was evaluated by Kaplan-Meier curves, Cox proportional hazards, and cubic spline analyses. The prediction values were compared by area under the receiver-operating characteristic curve (AUROC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses., Results: Of the 413 participants, the mean age was 63 ± 17 years, and 134 were female (32.4%). According to the median value, patients in the high-ΔNLR group had significantly greater 90-d mortality (74.4% vs . 46.6%, p  <  0. 001). After adjustment for potential confounders, high ΔNLR remained an independent predictor of 90-d mortality (HR = 2.80; 95% CI = 1.74-4.49, p  < 0.001). Furthermore, ΔNLR had the highest AUROC for 90-d mortality (0.685) among the various biomarkers and exhibited an improved NRI (0.314) and IDI (0.027) when incorporated with PCT and CRP. For secondary outcomes, patients with high ΔNLR had increased risk of 30-d mortality ( p  = 0.004), need for renal replacement therapy ( p =  0.011), and developing stage-3 AKI (p =  0.040) according to the adjusted models., Conclusions: High ΔNLR is independently associated with increased risk of patient mortality and adverse outcomes. ΔNLR might be utilized to facilitate risk stratification and optimize septic AKI management.

Introduction: Macrophages play an important role in chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) impairs autophagy in alveolar macrophages from COPD patients, and autophagic impairment leads to reduced clearance of protein aggregates, dysfunctional mitochondria, and defective bacterial delivery to lysosomes. However, the exact function of lung macrophage autophagy in the pathogenesis of CS-induced COPD remains largely unknown., Methods: Western blot detected the expression of autophagy-related proteins induced by CSE. The model of COPD mice was established by CS exposure combined with CSE intraperitoneal injection. Double immunofluorescence was used to measure the CD206+LC3B+ cells. The morphological changes and effects on lung function were observed. Masson staining detected the changes in collagen fibers in lung tissue. The expression levels of E-cadherinb and N-cadherinb were detected by immunohistochemistry. Western blot detected the expression of ATP6V1E1 in lung tissue., Results: At 24 hours of exposure to CSE, the expression levels of LC3B (microtubule-associated protein 1A/1B-light chain 3B) and P62 (nucleoporin 62) were highest at 1% CSE and AGT5 (nucleoporin 62) at 2.5% CSE; at 48 hours, the expression levels of LC3B, P62 and AGT5 were highest at 2.5% CSE, and as the intervention time increased.CD206+LC3B+ cells were significantly higher in the COPD group. Enhanced macrophage autophagy may promote emphysema formation and aggravate lung function damage. The expression of E-cadherinb in lung tissue of the COPD group was decreased, and N-cadherinb expression was increased; the expression of E-cadherinb was increased, and N-cadherinb expression was decreased in ATG5 myeΔ COPD mice. The expression of ATP6V1E1 in the lung tissue was increased in the COPD group; ATP6V1E1 expression was decreased in the lung tissues of ATG5 myeΔ COPD mice., Conclusions: CSE enhanced macrophage autophagy, leads to increased lung function impairment and collagenous fiber in lung tissue, as well as promotes epithelial-mesenchymal transition, and eventually leads to small airway remodeling, which may be achieved through the ATG5/ATP6V1E1 pathway., Competing Interests: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported., (© 2024 Zhang L. et al.)

Background: Neonatal respiratory distress syndrome (NRDS) is a prevalent cause of respiratory failure and death among newborns, and prompt diagnosis is imperative. Historically, diagnosis of NRDS relied mostly on typical clinical manifestations, chest X-rays, and CT scans. However, recently, ultrasound has emerged as a valuable and preferred tool for aiding NRDS diagnosis. Nevertheless, evaluating lung ultrasound imagery necessitates rigorous training and may be subject to operator-dependent bias, limiting its widespread use. As a result, it is essential to investigate a new, reliable, and operator-independent diagnostic approach that does not require subjective factors or operator expertise. This article aims to explore the diagnostic potential of ultrasound-based radiomics in differentiating NRDS from other non-NRDS lung disease., Methods: A total of 150 neonatal lung disease cases were consecutively collected from the department of neonatal intensive care unit of the Quanzhou Maternity and Children's Hospital, Fujian Province, from September 2021 to October 2022. Of these patients, 60 were diagnosed with NRDS, whereas 30 were diagnosed with neonatal pneumonia, meconium aspiration syndrome (MAS), and transient tachypnea (TTN). Two ultrasound images with characteristic manifestations of each lung disease were acquired and divided into training (n = 120) and validation cohorts (n = 30) based on the examination date using an 8:2 ratio. The imaging texture features were extracted using PyRadiomics and, after the screening, machine learning models such as random forest (RF), logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), and multilayer perceptron (MLP) were developed to construct an imaging-based diagnostic model. The diagnostic efficacy of each model was analyzed. Lastly, we randomly selected 282 lung ultrasound images and evaluated the diagnostic efficacy disparities between the optimal model and doctors across differing levels of expertise., Results: Twenty-two imaging-based features with the highest weights were selected to construct a predictive model for neonatal respiratory distress syndrome. All models exhibited favorable diagnostic performances. Analysis of the Youden index demonstrated that the RF model had the highest score in both the training (0.99) and validation (0.90) cohorts. Additionally, the calibration curve indicated that the RF model had the best calibration (P = 0.98). When compared to the diagnostic performance of experienced and junior physicians, the RF model had an area under the curve (AUC) of 0.99; however, the values for experienced and junior physicians were 0.98 and 0.85, respectively. The difference in diagnostic efficacy between the RF model and experienced physicians was not statistically significant (P = 0.24), whereas that between the RF model and junior physicians was statistically significant (P < 0.0001)., Conclusion: The RF model exhibited excellent diagnostic performance in the analysis of texture features based on ultrasound radiomics for diagnosing NRDS., (© 2024. The Author(s).)

Objective: Sepsis is the leading cause of acute kidney injury (AKI). Increasing evidence shows that serum total protein-to-albumin ratio (TAR) could serve as an inflammation- and nutrition-based prognostic marker in various diseases. The purpose of this study was to assess the prognostic value of TAR in predicting the clinical outcomes of septic AKI patients., Methods: We retrospectively enrolled septic AKI patients between August 2015 and August 2022 at West China Hospital of Sichuan University. Patients admitted between August 2015 and August 2021 were defined as the original cohort. The primary outcomes were 30-day and 90-day all-cause mortality of septic AKI patients. The secondary outcomes were septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, and stage 3 AKI. The utility of TAR was further verified in a validation cohort of septic AKI patients admitted between September 2021 and August 2022., Results: In the original cohort, a total of 309 eligible patients with a median age of 58 years were enrolled, of which 70.2 % were males. In multivariate Cox analysis, after adjustments for age, sex, and other confounding factors, higher TAR at admission was associated with an increased risk of 30-day and 90-day all-cause mortality in septic AKI patients (HR 1.91, 95 % CI 1.18-3.09, P = 0.008; HR 1.54, 95 % CI 1.01-2.34, P = 0.043, respectively). Subgroup analysis revealed no significant interactions in most strata. TAR at AKI diagnosis or discharge was not significantly related to 30-day (P = 0.120 and 0.153, respectively) or 90-day mortality (P = 0.147 and 0.124, respectively). We found no relationship between baseline TAR and septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, or stage 3 AKI (all P > 0.05). In the validation cohort of 81 septic AKI patients, TAR at admission remained a significant prognosticator for 30-day and 90-day mortality (HR 4.367, 95 % CI 1.20-15.87, P = 0.025; HR 4.237, 95 % CI 1.59-11.27, P = 0.004)., Conclusions: TAR at admission is an independent risk factor for 30-day and 90-day mortality in septic AKI patients and could be used as a convenient and economic septic AKI prognostic indicator., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Erhualian pigs exhibit one of the highest reproductive rates globally, and cryptorchidism is a crucial factor affecting reproductive abilities of boars. This investigation focused on cryptorchid tissues from Erhualian pigs, where the histological structure of cryptorchidism was observed using specialized staining. In addition, protein expression of P53/NF-κB in cryptorchid tissues was assessed using Western blot and immunohistochemistry. In comparison to normal Erhualian testes, Masson's trichrome staining indicated a reduction in collagen fibers in the connective tissue and around the basal membrane of the seminiferous tubules in cryptorchid testes. Moreover, collagen fiber distribution was observed to be disordered. Verhoeff Van Gieson (EVG) and argyrophilic staining demonstrated brownish-black granular nucleoli organized regions in mesenchymal cells and germ cells. When compared to normal testicles, the convoluted seminiferous tubules of cryptorchids exhibited a significantly reduced number and diameter ( p < 0.01). Notably, VEGF/EGFR and P53/NF-κB expression in cryptorchidism significantly differed from that in normal testes. In particular, the expression of VEGF and P53 in cryptorchid tissues was significantly higher than that in normal testes tissues, whereas the expression of EGFR in cryptorchid tissues was significantly lower than that in normal testes tissues (all p < 0.01). NF-κB expressed no difference in both conditions. The expressions of VEGF and NF-κB were observed in the cytoplasm of testicular Leydig cells and spermatogenic cells, but they were weak in the nucleus. EGFR and P53 were more positively expressed in the cytoplasm of these cells, with no positive expression in the nucleus. Conclusion: There were changes in the tissue morphology and structure of the cryptorchid testis, coupled with abnormally high expression of VEGF and P53 proteins in Erhualian pigs. We speculate that this may be an important limiting factor to fecundity during cryptorchidism.

Background: APN (adiponectin) and APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) are potent vasculoprotective molecules, and their deficiency (eg, hypoadiponectinemia) contributes to diabetic vascular complications. However, the molecular mechanisms that govern their vasculoprotective genes as well as their alteration by diabetes remain unknown., Methods: Diabetic medium-cultured rat aortic endothelial cells, mouse aortic endothelial cells from high-fat-diet animals, and diabetic human aortic endothelial cells were used for molecular/cellular investigations. The in vivo concept-prove demonstration was conducted using diabetic vascular injury and diabetic hindlimb ischemia models., Results: In vivo animal experiments showed that APN replenishment caused APPL1 nuclear translocation, resulting in an interaction with HDAC (histone deacetylase) 2, which inhibited HDAC2 activity and increased H3Kac27 levels. Based on transcriptionome pathway-specific real-time polymerase chain reaction profiling and bioinformatics analysis, Angpt1 (angiopoietin 1), Ocln (occludin), and Cav1 (caveolin 1) were found to be the top 3 vasculoprotective genes suppressed by diabetes and rescued by APN in an APPL1-dependent manner. APN reverses diabetes-induced inhibition of Cav1 interaction with APPL1. APN-induced Cav1 expression was not affected by Angpt1 or Ocln deficiency, whereas APN-induced APPL1 nuclear translocation or upregulation of Angpt1/Ocln expression was abolished in the absence of Cav1 both in vivo and in vitro, suggesting Cav1 is upstream molecule of Angpt1/Ocln in response to APN administration. Chromatin immunoprecipitation-qPCR (quantitative polymerase chain reaction) demonstrated that APN caused significant enrichment of H3K27ac in Angpt1 and Ocln promoter region, an effect blocked by APPL1/Cav1 knockdown or HDAC2 overexpression. The protective effects of APN on the vascular system were attenuated by overexpression of HDAC2 and abolished by knocking out APPL1 or Cav1. The double knockdown of ANGPT1/OCLN blunted APN vascular protection both in vitro and in vivo. Furthermore, in diabetic human endothelial cells, HDAC2 activity is increased, H3 acetylation is decreased, and ANGPT1/OCLN expression is reduced, suggesting that the findings have important translational implications., Conclusions: Hypoadiponectinemia and dysregulation of APPL1-mediated epigenetic regulation are novel mechanisms leading to diabetes-induced suppression of vasculoprotective gene expression. Diabetes-induced pathological vascular remodeling may be prevented by interventions promoting APPL1 nuclear translocation and inhibiting HDAC2., Competing Interests: Disclosures None.

The wastewater treatment performance in an inverted A 2 /O reactor supplemented with fermentation liquid of primary sludge was explored comparing to commercial carbon sources sodium acetate and glucose. Similar COD removal rate was observed with the effluent COD stably reaching the discharge standard for those 3 carbon sources. However, the fermentation liquid distributed more carbon source in the anaerobic zone. Fermentation liquid and sodium acetate tests achieved better nitrogen removal rate than glucose test. The fermentation liquid test showed the best biological phosphorus removal performance with the effluent phosphorus barely reaching the discharge standard. The microbial community characterization revealed that the fermentation liquid test was dominated by phylum Proteobacter in all the anoxic, anaerobic and aerobic zones. Denitrifying phosphorus accumulating organisms (PAOs) (i.e., genera Dechloromonas and unclassified&#95;f&#95;&#95;Rhodocyclaceae) were selectively enriched with high abundances (over 20%), which resulted in improved phosphorus removal efficiency. Moreover, the predicted abundances of enzymes involved in nitrogen and phosphorus removal were also enhanced by the fermentation liquid., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Synovial fibroblasts are critical for maintaining homeostasis in major autoimmune diseases involving joint inflammation, including osteoarthritis and rheumatoid arthritis. However, little is known about the interactions among different cell subtypes and the specific sets of signaling pathways and activities that they trigger., Methods: Using social network analysis, pattern recognition, and manifold learning approaches, we identified patterns of single-cell communication in OA (osteoarthritis) and RA (rheumatoid arthritis)., Results: Our results suggest that OA and RA have distinct cellular communication patterns and signaling pathways. The LAMININ (Laminin) and COLLAGEN (Collagen) pathways predominate in osteoarthritis, while the EGF (Epidermal growth factor), NT (Neurotrophin) and CDH5 (Cadherin 5) pathways predominate in rheumatoid arthritis, with a central role for THY1 (Thy-1 cell surface antigen) + CDH11 (Cadherin 11) + cells. The OA opens the PDGF (Platelet-derived growth factors) pathway (driver of bone angiogenesis), the RA opens the EGF pathway (bone formation) and the SEMA3 (Semaphorin 3A) pathway (involved in immune regulation). Interestingly, we found that OA no longer has cell types involved in the MHC complex (Major histocompatibility complex) and their activity, whereas the MHC complex functions primarily in RA in the presentation of inflammatory antigens, and that the complement system in OA has the potential to displace the function of the MHC complex. The specific signaling patterns of THY1 + CDH11 + cells and their secreted ligand receptors are more conducive to cell migration and lay the foundation for promoting osteoclastogenesis. This subpopulation may also be involved in the accumulation of lymphocytes, affecting the recruitment of immune cells. Members of the collagen family (COL1A1 (Collagen Type I Alpha 1 Chain), COL6A2 (Collagen Type VI Alpha 2 Chain) and COL6A1 (Collagen Type VI Alpha 1 Chain)) and transforming growth factor (TGFB3) maintain the extracellular matrix in osteoarthritis and mediate cell migration and adhesion in rheumatoid arthritis, including the PTN (Pleiotrophin) / THBS1 (Thrombospondin 1) interaction., Conclusion: Increased understanding of the interaction networks between synovial fibroblast subtypes, particularly the shared and unique cellular communication features between osteoarthritis and rheumatoid arthritis and their hub cells, should help inform the design of therapeutic agents for inflammatory joint disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The synergy between radiotherapy and immunotherapy in treating thoracic cancers presents a potent therapeutic advantage, yet it also carries potential risks. The extent and nature of cumulative cardiac toxicity remain uncertain, prompting the need to discern its mechanisms and devise effective mitigation strategies. Radiation alone or in combination with an anti- Programmed cell death protein1 (PD-1) antibody significantly reduced cardiac function in C57BL/6J mice, and this pathologic effect was aggravated by anti-PD-1 (anti-PD-1  +  radiation). To examine the cellular mechanism that causes the detrimental effect of anti-PD-1 upon cardiac function after radiation, AC16 human cardiomyocytes were used to study cardiac apoptosis and cardiac autophagy. Radiation-induced cardiomyocyte apoptosis was significantly promoted by anti-PD-1 treatment, while anti-PD-1 combined radiation administration blocked the cardiac autophagic flux. Adenosine 5'-triphosphate (ATP) (a molecule that promotes lysosomal acidification) not only improved autophagic flux in AC16 human cardiomyocytes, but also attenuated apoptosis induced by radiation and anti-PD-1 treatment. Finally, ATP administration in vivo significantly reduced radiation-induced and anti-PD-1-exacerbated cardiac dysfunction. We demonstrated for the first time that anti-PD-1 can aggravate radiation-induced cardiac dysfunction via promoting cardiomyocyte apoptosis without affecting radiation-arrested autophagic flux. ATP enhanced cardiomyocyte autophagic flux and inhibited apoptosis, improving cardiac function in anti-PD-1/radiation combination-treated animals., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jimin Cao reports equipment, drugs, or supplies was provided by Shanxi Medical University. Jimin cao reports a relationship with Shanxi Medical University that includes: employment. No has patent na pending to na. NA., (© 2023 The Authors.)

Purpose: Exosomes are able to exchange their bioactive RNA cargo to recipient cells. In COPD, exosomes can be controlled and engineered for its use as targeted diagnostic and therapeutic tool. Our study explored novel lncRNAs and mRNAs in plasma exosomes that could be involved in the pathogenesis of COPD., Methods: High-throughput sequencing was conducted to detect the alterations in the expression of exosomal lncRNAs and mRNAs. Gene ontology (GO) functional analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to determine the significant functions and pathways associated with differentially expressed (DE) lncRNAs. The mRNA expression profile dataset, GSE76925, and microRNA expression profile dataset, GSE70080, were obtained from the GEO database. Venn diagrams were used to find common DE mRNAs between my mRNAs dataset and GSE76925. These common DEGs were subjected to PPI analyses to identify Hub genes. Subsequently, Venn diagrams were used to identify common genes between the target genes of DE-miRNAs and Hub genes as well as DE-miRNAs and my lncRNAs dataset. Finally, a lncRNA-miRNA-mRNA co-expression network was constructed by prediction using proprietary software. The lncRNA and mRNA expressions were then validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR)., Results: We identified 1578 differentially regulated lncRNAs and 3071 differentially regulated mRNAs. GO and KEGG pathway analyses suggested that the DE lncRNAs are involved in the pathogenesis of COPD. A lncRNA-miRNA-mRNA meshwork was established to predict the potential interactions among these RNAs. RP3-329A5.8 and MRPS11 expression was then subjected to qRT-PCR for validation. Correlations between MRPS11 and clinic-pathological features were explored., Conclusion: Our study provided a set of lncRNAs and mRNAs that may be involved in the pathogenesis of COPD, thereby highlighting the need for further research on both diagnostic biomarkers and molecular mechanisms., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Lin et al.)

The patterns of communication among different chondrocyte subtypes in human cartilage degeneration and regeneration help us understand the microenvironment of osteoarthritis and optimize cell-targeted therapies. Here, a single-cell transcriptome dataset of chondrocytes is used to explore the synergistic and communicative patterns of different chondrocyte subtypes. We collected 1600 chondrocytes from 10 patients with osteoarthritis and analyzed the active communication patterns for the first time based on network analysis and pattern recognition at the single-cell level. Manifold learning and quantitative contrasts were performed to analyze conserved and specific communication pathways. We found that ProCs (Proliferative chondrocytes), ECs (Effector chondrocytes), preHTCs (Prehypertrophic chondrocytes), HTCs (Hypertrophic chondrocytes), and FCs (Fibrocartilage chondrocytes) are more active in incoming and outgoing signaling patterns, which is consistent with studies on their close functional cooperation. Among them, preHTCs play multiple roles in chondrocyte communication, and ProCs and preHTCs have many overlapping pathways. These two subtypes are the most active among all chondrocyte subtypes. Interestingly, ECs and FCs are a pair of "mutually exclusive" subtypes, of which ECs are predominant in incoming patterns and FCs in outgoing patterns. The active signaling pathways of ECs and FCs largely do not overlap. COLLAGEN and LAMININ are the main pivotal pathways, which means they are very important in the repair and expansion of joint homeostasis. Notably, only preHTCs assume multiple roles (including sender, receiver, mediator, and influencer) and are involved in multiple communication pathways. We have examined their communication patterns from the perspective of cellular interactions, revealed the relationships among different chondrocyte subtypes, and, in particular, identified a number of active subtypes and pathways that are important for targeted therapy in the osteoarthritic microenvironment. Our findings provide a new research paradigm and new insights into understanding chondrocyte activity patterns in the osteoarthritic microenvironment., (© 2023. Springer Nature Limited.)

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and SARS-CoV-2 variants, has become a global pandemic resulting in significant morbidity and mortality. Severe cases of COVID-19 are characterized by hypoxemia, hyper-inflammation, cytokine storm in lung. Clinical studies have reported an association between COVID-19 and cardiovascular disease (CVD). Patients with CVD tend to develop severe symptoms and mortality if contracted COVID-19 with further elevations of cardiac injury biomarkers. Furthermore, COVID-19 itself can induce and promoted CVD development, including myocarditis, arrhythmia, acute coronary syndrome, cardiogenic shock, and venous thromboembolism. Although the direct etiology of SARS-CoV-2 induced cardiac injury remains unknown and under-investigated, it is suspected that it is related to myocarditis, cytokine-mediated injury, microvascular injury, and stress-related cardiomyopathy. Despite vaccinations having provided the most effective approach to reducing mortality overall, an adapted treatment paradigm and regular monitoring of cardiac injury biomarkers is critical for improving outcomes in vulnerable populations at risk for severe COVID-19. In this review, we focus on the latest progress in clinic and research on the cardiovascular complications of COVID-19 and provide a perspective of treating cardiac complications deriving from COVID-19 in Emergency Medicine., Competing Interests: Conflict of interest statement Xinliang Ma is the Associate Editor of Emergency and Critical Care Medicine, and Yajing Wang, Theodore A. Christopher, Bernard J. Lopez are Editorial Board members of Emergency and Critical Care Medicine. The article was subject to the journal’s standard procedures, with peer review handled independently of the Associate Editor, Editorial Board members, and their research groups. The authors declare no conflict of interest.

Diabetes enhances myocardial ischemic/reperfusion (MI/R) injury via an incompletely understood mechanism. Adiponectin (APN) is a cardioprotective adipokine suppressed by diabetes. However, how hypoadiponectinemia exacerbates cardiac injury remains incompletely understood. Dysregulation of miRNAs plays a significant role in disease development. However, whether hypoadiponectinemia alters cardiac miRNA profile, contributing to diabetic heart injury, remains unclear. Methods and Results: Wild-type (WT) and APN knockout (APN-KO) mice were subjected to MI/R. A cardiac microRNA profile was determined. Among 23 miRNAs increased in APN-KO mice following MI/R, miR-449b was most significantly upregulated (3.98-fold over WT mice). Administrating miR-449b mimic increased apoptosis, enlarged infarct size, and impaired cardiac function in WT mice. In contrast, anti-miR-449b decreased apoptosis, reduced infarct size, and improved cardiac function in APN-KO mice. Bioinformatic analysis predicted 73 miR-449b targeting genes, and GO analysis revealed oxidative stress as the top pathway regulated by these genes. Venn analysis followed by luciferase assay identified Nrf-1 and Ucp3 as the two most important miR-449b targets. In vivo administration of anti-miR-449b in APN-KO mice attenuated MI/R-stimulated superoxide overproduction. In vitro experiments demonstrated that high glucose/high lipid and simulated ischemia/reperfusion upregulated miR-449b and inhibited Nrf-1 and Ucp3 expression. These pathological effects were attenuated by anti-miR-449b or Nrf-1 overexpression. In a final attempt to validate our finding in a clinically relevant model, high-fat diet (HFD)-induced diabetic mice were subjected to MI/R and treated with anti-miR-449b or APN. Diabetes significantly increased miR-449b expression and downregulated Nrf-1 and Ucp3 expression. Administration of anti-miR-449b or APN preserved cardiac Nrf-1 expression, reduced cardiac oxidative stress, decreased apoptosis and infarct size, and improved cardiac function. Conclusion: We demonstrated for the first time that hypoadiponectinemia upregulates miR-449b and suppresses Nrf-1/Ucp3 expression, promoting oxidative stress and exacerbating MI/R injury in this population. Dysregulated APN/miR-449b/oxidative stress pathway is a potential therapeutic target against diabetic MI/R injury., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Phytoextraction is a promising technology that uses plants to remediate contaminated soil. However, its feasibility for per- and polyfluoroalkyl substances (PFAS) and the impact of PFAS properties and plant traits on phytoextraction efficacy remains unknown. In this study, we conducted greenhouse experiment and evaluated the potential of weeds for phytoextraction of PFAS from soil and assessed the effects of PFAS properties and plant traits on PFAS uptake via systematic correlation analyses and electron probe microanalyzer with energy dispersive spectroscopy (FE-EPMA-EDS) imaging. The results showed that 1) phytoextraction can remove 0.04%- 41.4%wt of PFAS from soil, with extracted PFAS primarily stored in plant shoots; 2) Weeds preferentially extracted short-chain PFAS over long-chain homologues from soil. 3) PFAS molecular size and hydrophilicity determined plant uptake behavior, while plant morphological traits, particularly root protein and lipid content, influenced PFAS accumulation and translocation. Although plants with thin roots and small leaf areas exhibited greater PFAS uptake and storage ability, the impact of PFAS physicochemical properties was more significant. 4) Finally, short-chain PFAS were transported quickly upwards in the plant, while uptake of long-chain PFOS was restricted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This study investigates the removal efficiency of anionic, cationic, and zwitterionic per- and polyfluoroalkyl substances (PFAS) by nanofiltration (NF) in the presence of three representative natural organic matter (NOM) types: bovine serum albumin (BSA), humic acid (HA), and sodium alginate (SA). In particular, effects of PFAS molecular structure and coexisting NOM on the transmission and adsorption efficiency of PFAS during NF treatment were analyzed. The results indicate that NOM types dominate membrane fouling behavior despite the coexistence of PFAS. SA exhibits the most significant fouling propensity, resulting in maximum water flux decline. NF effectively removed both ether and precursor PFAS. The effects of the three typical NOM on the membrane-passing behavior of PFAS were consistent for all PFAS investigated. Generally, PFAS transmission decreased in the order of SA-fouled > pristine > HA-fouled > BSA-fouled, indicating that the presence of HA and BSA enhanced PFAS removal while SA declined. Furthermore, reduced PFAS transmission was observed with increased perfluorocarbon chain length or molecular weight (MW), regardless of the presence or type of the NOM. The impacts of NOM on PFAS filtration diminished when the PFAS van der Waals radius was > 4.0 Å, MW > 500 Da, polarization > 20 Å, or LogKow > 3. These findings suggest that both steric repulsion and hydrophobic interactions, especially the former, play important roles in PFAS rejection by NF. This study provides insights into the specific applicability and performance of membrane-based processes for eliminating PFAS during drinking and wastewater treatments, and highlighting the importance of coexisting NOM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Thallium contamination in water can cause great danger to the environment. In this study, we synthesized manganese oxide-coated sand (MOCS) and investigated the transport and retention behaviors of Tl(I) in MOCS under different conditions. Characterization methods combined with a two-site nonequilibrium transport model were applied to explore the retention mechanisms. The results showed that Tl(I) mobility was strongly inhibited in MOCS media, and the retention capacity calculated from the fitted model was 510.41 mg/g under neutral conditions. The retention process included adsorption and oxidative precipitation by the manganese oxides coated on the sand surface. Cotransport with the same concentration of Mn(II) led to halving Tl(I) retention due to competition for reactive sites. Enhanced Tl(I) retention was observed under alkaline conditions, as increasing pH promoted electronegativity on the media surface. Moreover, the competitive cation Ca 2+ significantly weakened Tl(I) retention by occupying adsorption sites. These findings provide new insights into understanding Tl(I) transport behavior in water-saturated porous media and suggest that manganese oxide-coated sand can be a cost-effective filter media for treating Tl-contaminated water., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022. Published by Elsevier B.V.)

To investigate the effect of n -butanol on postharvest membrane lipid metabolism of Hami melon (Cucumis melo 'Hami'), the fruits were soaked in a 1.0% solution of n -butanol for 30 min with water as the control. Symptoms of chilling injury were observed regularly, and the indices related to permeability and membrane lipid metabolism of pericarp cells were measured. The results showed that treatment with n -butanol inhibited the increase in chilling injury index, membrane permeability, and malondialdehyde content of Hami melon fruits, promoted an increase in the contents of phosphatidyl alcohol and unsaturated fatty acids, such as linoleic acid, linolenic acid, oleic acid (except 14 d), and erucic acid (28-42 d), and decreased the content of saturated fatty acids, stearic acid (0-28 d), phosphatidic acid (except for 21 d), and the key enzymes of membrane lipid metabolism compared with the control. The activities of phospholipase D (PLD) and lipoxygenase (LOX) and the downregulation of the levels of expression CmPLD-β and CmLOX (42 d only) genes reduced the chilling injury index of Hami melon and alleviated the further expansion of chilling injury symptoms in the fruits. We also cloned the key gene of membrane lipid metabolism CmPLD-β , which was obtained by pre-transcriptome screening of the pericarp. We found that CmPLD-β of Hami melon had the closest affinity with cucumber (CsXP5), indicating that the CmPLD-β gene of Hami melon was functionally similar to that of cucumber. In addition, a two-fold alignment analysis of CmPLD-β and CmXP5 base sequences indicated that the base sequences of the two promoter regions differed from each other.

The practical application of solid phase denitrification (SPD) was hindered by either poor water quality from natural plant-like materials or high cost of pure synthetic biodegradable polymers. In this study, by combining polycaprolactone (PCL) with new natural materials (peanut shell, sugarcane bagasse), two novel economical solid carbon sources (SCSs) named as PCL/PS and PCL/SB were developed. Pure PCL and PCL/TPS (PCL with thermal plastic starch) were supplied as controls. During the 162-day operation, especially in the shortest HRT (2 h), higher NO 3 - -N removal was achieved by PCL/PS (87.60%±0.06%) and PCL/SB (87.93%±0.05%) compared to PCL (83.28%±0.07%) and PCL/TPS (81.83%±0.05%). The predicted abundance of functional enzymes revealed the potential metabolism pathways of major components of SCSs. The natural components entered the glycolytic cycle by enzymatical generation of intermediates, while biopolymers being converted into small molecule products under specific enzyme activities (i.e., carboxylesterase, aldehyde dehydrogenase), together providing electrons and energy for denitrification., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We aimed to investigate whether exosomes (Exo) affected chronic obstructive pulmonary disease (COPD) by influencing ferroptosis of bronchial epithelial cells (BECs) and the mechanisms involved. Here we took the peripheral blood samples of normal subjects and COPD patients, extracted and identified endothelial progenitor cells (EPCs) and EPC-Exo. An animal model of COPD was established. Then human BECs were taken and treated with cigarette smoke extract (CSE) for 24 h to construct a COPD cell model. Next, we screened differentially expressed ferroptosis-related genes in COPD patients by bioinformatics. Bioinformatics predicted the miRNA targeting PTGS2. Then, the mechanism of action of miR-26a-5p and Exo-miR-26a-5p was investigated in vitro. We successfully isolated and identified EPC and Exo. In vitro, EPC alleviated CSE-induced ferroptosis in BECs by transporting Exo. In vivo, Exo alleviated cigarette smoke-induced ferroptosis and airway remodeling in mice. Through further validation, we found that CSE-induced ferroptosis promoted the epithelial-mesenchymal transition (EMT) of BECs. Bioinformatics analysis and validation showed that PTGS2/PGE2 pathway affected CSE-induced ferroptosis in BECs. Meanwhile, miR-26a-5p targeting PTGS2 affected CSE-induced ferroptosis in BECs. Additionally, we found that miR-26a-5p affected CSE-induced BECs EMT. Exo-miR-26a-5p alleviated CSE-induced ferroptosis and EMT. In conclusion, EPC-exosomal miR-26a-5p improved airway remodeling in COPD by inhibiting ferroptosis of BECs via the PTGS2/PGE2 pathway., (© 2023. The Author(s).)

Background: Myocardial insulin resistance is a hallmark of diabetic cardiac injury. However, the underlying molecular mechanisms remain unclear. Recent studies demonstrate that the diabetic heart is resistant to other cardioprotective interventions, including adiponectin and preconditioning. The "universal" resistance to multiple therapeutic interventions suggests impairment of the requisite molecule(s) involved in broad prosurvival signaling cascades. Cav (Caveolin) is a scaffolding protein coordinating transmembrane signaling transduction. However, the role of Cav3 in diabetic impairment of cardiac protective signaling and diabetic ischemic heart failure is unknown., Methods: Wild-type and gene-manipulated mice were fed a normal diet or high-fat diet for 2 to 12 weeks and subjected to myocardial ischemia and reperfusion. Insulin cardioprotection was determined., Results: Compared with the normal diet group, the cardioprotective effect of insulin was significantly blunted as early as 4 weeks of high-fat diet feeding (prediabetes), a time point where expression levels of insulin-signaling molecules remained unchanged. However, Cav3/insulin receptor-β complex formation was significantly reduced. Among multiple posttranslational modifications altering protein/protein interaction, Cav3 (not insulin receptor-β) tyrosine nitration is prominent in the prediabetic heart. Treatment of cardiomyocytes with 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride reduced the signalsome complex and blocked insulin transmembrane signaling. Mass spectrometry identified Tyr 73 as the Cav3 nitration site. Phenylalanine substitution of Tyr 73 (Cav3 Y73F ) abolished 5-amino-3-(4-morpholinyl)-1,2,3-oxadiazolium chloride-induced Cav3 nitration, restored Cav3/insulin receptor-β complex, and rescued insulin transmembrane signaling. It is most important that adeno-associated virus 9-mediated cardiomyocyte-specific Cav3 Y73F reexpression blocked high-fat diet-induced Cav3 nitration, preserved Cav3 signalsome integrity, restored transmembrane signaling, and rescued insulin-protective action against ischemic heart failure. Last, diabetic nitrative modification of Cav3 at Tyr 73 also reduced Cav3/AdipoR1 complex formation and blocked adiponectin cardioprotective signaling., Conclusions: Nitration of Cav3 at Tyr 73 and resultant signal complex dissociation results in cardiac insulin/adiponectin resistance in the prediabetic heart, contributing to ischemic heart failure progression. Early interventions preserving Cav3-centered signalsome integrity is an effective novel strategy against diabetic exacerbation of ischemic heart failure.

Objective: P-type atypical lymphocytes may play important roles in the aetiology and therapy of schizophrenia. However, there is merely a direct immunological characterisation of it. The aim of this study is to explore the surface antigens of these cells and their comparative ultrastructure in schizophrenia., Methods: We recruited 25 age-and gender-matched patients with unmedicated schizophrenia, other mental diseases and healthy individuals. Peripheral venous blood was smeared and stained. CD4+, CD8+ and CD19+ cell surface antigen- positive lymphocytes were purified using magnetic beads and prepared for light microscopy and electron microscopy., Results: The percentages of P-type atypical lymphocytes (34.53% ± 9.92%) were significantly higher ( p  < 0.0001) in schizophrenia than that of other mental diseases (9.79% ± 3.45%). These cells could present CD4+, CD8+ and CD19+ surface antigens. Their relative ultrastructure differed from that of normal lymphocytes, especially in mitochondria, which showed abundant, aggregated and quite irregular mitochondria; for example, slight dilation of the foci, swelling, degeneration, and even cavity., Conclusions: P-type atypical lymphocytes could be found among CD4+, CD8+, and CD19 + lymphocytes with schizophrenia. Their abnormal ultrastructure of mitochondria implied that energy metabolism might play an important role in the aetiology of schizophrenia.

The present study assessed the bioaccumulation potential of per- and polyfluoroalkyl substances (PFAS) in ferns and linked root uptake behaviors to root characteristics and PFAS molecular structure. Tissue and subcellular-level behavioral differences between alternative and legacy PFAS were compared via an electron probe microanalyzer with energy dispersive spectroscopy (EPMA-EDS) and differential centrifugation. Our results show that ferns can accumulate PFAS from water, immobilize them in roots, and store them in harvestable tissue. The PFAS loading in roots was dominated by PFOS; however, a substantial amount of associated PFOS could be rinsed off by methanol. Correlation analyses indicated that root length, surface and project area, surface area per unit length of the root system, and molecular size and hydrophobicity of PFAS were the most significant factors affecting the magnitude of root uptake and upward translocation. EPMA-EDS images together with exposure experiments suggested that long-chain hydrophobic compounds tend to be adsorbed and retained on the root epidermis, while short-chain compounds are absorbed and quickly translocated upward. Our findings demonstrated the feasibility of using ferns in phytostabilization and phytoextraction initiatives of PFAS in the future.

Objective: To analyse the effect of chromosomal microarray analysis (CMA) in the prenatal diagnosis of fetuses with abnormal ultrasonographic soft markers., Study Design: Descriptive study. Place and Duration of the Study: Prenatal Diagnostic Centre, Huizhou Central People's Hospital, from January 2020 to January 2022., Methodology: A total of 160 pregnant women with abnormal soft markers in the fetuses on prenatal ultrasonography were selected. Amniotic fluid in the second trimester of pregnancy was extracted for CMA. In addition, karyotype analysis of chromosomal G-banding was carried out to analyse the effect of CMA in prenatal diagnosis., Results: The detection rate of copy number variants (CNVs) by CMA was higher than that by karyotype analysis, which was not statistically significant (p=0.059). Compared with karyotype detection, CMA detected five additional cases of pathogenic CNVs, all of which were cases of microdeletion and microduplication. VOUS cases detected by CMA were mostly concentrated in NT thickening, among which cases of uncertain significance were the most., Conclusion: The application of CMA in the prenatal diagnosis of fetuses with abnormal ultrasonographic soft markers can improve the detection rate of pathogenicity. As a prenatal diagnostic method, CMA has high application value and is worthy of clinical promotion., Key Words: Chromosomal microarray analysis, Abnormal ultrasonographic soft markers, Prenatal diagnosis, Diagnostic efficiency.

Background: Acute kidney injury (AKI) is a frequent complication of sepsis associated with increased mortality and morbidity. The neutrophil-to-lymphocyte ratio (NLR) has been shown as a risk factor for septic AKI. In this study, we aimed to further evaluate NLR's prediction value on the prognosis of septic AKI patients., Methods: Septic AKI patients at a tertiary university-affiliated medical center were retrospectively enrolled from August 2015 to August 2021. The primary outcomes were 30-day and 90-day mortality, and secondary outcomes were disease severity, length of stay, and rehospitalization in survivors. Kaplan-Meier curves, Cox proportional hazards, cubic spline and logistics regression analyses were performed for adverse outcomes basing on NLR. The predictive value of NLR on morality was also estimated by the area under the receiver operating characteristic curve (AUROC)., Results: A total of 309 septic AKI patients were included with a mean age of 57.8 ± 18.1 years and 92 (29.8 %) being female. The 30-day mortality was 43.4 % and 90-day morality was 61.8 %. When divided by the median of NLR at hospital admission, patients in the high NLR group were associated with an increased 30-day/90-day mortality. After adjusting for multiple covariates, the predictive value of NLR remained significant for 30-day mortality (HR: 2.96, 95 % CI: 1.48-5.92, p = 0.002) and 90-day mortality (HR: 1.88, 95 % CI: 1.11-3.16, p = 0.018). NLR at admission had the highest AUROC (0.618) for 30-day mortality compared with other parameters such as white blood cell (0.573), neutrophil (0.579), lymphocyte (0.567), platelet (0.546), BUN (0.580), albumin (0.545), C-reactive protein (0.571) and procalcitonin (0.534). A similar predictive value on mortality was also observed for NLR measured at septic AKI diagnosis. For secondary outcomes, high NLR was associated with increased risk of transfer to ICU, mechanical ventilation, stage-3 AKI and renal replacement therapy, but not with length of hospital/ICU stay or long-term rehospitalization., Conclusion: High NLR is independently associated with 30-day/90-day mortality and disease severity in septic AKI patients. NLR may serve as an economic and widely available biomarker of septic AKI prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A mitochondria-targeted NIR probe based on the FRET mechanism was developed. It shows ultra-large Stokes shifts (460 nm) and emission shifts (285 nm). Furthermore, we also realized the imaging of SO 2 in living SKOV-3 cells, zebrafish and living mice which may be useful for understanding the biological roles of SO 2 in mitochondria and in vivo.

Understanding the migration behavior of thallium (TI) in subsurface environments is essential for Tl pollution prevention. With the wide production and utilization of biochar, the notable ability of biochar colloids to carry environmental contaminants may make these colloids important for Tl(I) mobility. This study systematically investigated the impact of wood-derived biochar (WB) and corn straw-derived biochar (CB) colloids on Tl(I) transport in water-saturated porous media under different pH (5, 7 and 10) and ionic strengths (ISs) (1, 5 and 50 mM NaNO 3 ). WB colloids improved Tl(I) transport under all IS conditions at pH 7 due to the adsorption capacity of biochar and competition for adsorption sites on the sand surface. However, at IS 50 mM, CB colloids slightly impeded Tl(I) mobility due to the straining. In addition, both WB and CB colloids accelerated Tl(I) mobility under all pH conditions at IS 5 mM. At pH 10, the promotion effect was more obvious due to the deprotonation of O-containing functional groups and higher fluidity of biochar colloids. Furthermore, the two-site nonequilibrium model and two-site kinetic attachment/detachment model suitably described the breakthrough curves (BTCs) of Tl(I) and biochar colloids, respectively. The colloid-facilitated solute transport model could also describe Tl(I) transport influenced by biochar colloids reasonably well. This study provides insight into the migration and fate of Tl(I) in the presence of biochar colloids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To confirm the diagnosis of a 13-year-old adolescent with familial diabetes and further examine his genetic pathogeny., Research Design and Methods: Clinical data were collected, and genetic examination was performed. PolyPhen-2 and Mutation Taster were used to predict the deleterious effects of the variant. Clustal Omega software was used to confirm the conservation of amino acid substitutions. To examine changes in the expression of proteins, recombinant vectors were constructed, and the expression of wild-type and variant target genes was detected through quantitative polymerase chain reaction. Furthermore, the wild-type and variant eukaryotic recombinant vectors were treated with a ubiquitin degradation inhibitor (MG132) and a lysosomal degradation pathway inhibitor (CQ, 3-mA). The expression of target proteins was detected through Western blot analysis., Results: The patient had hyperglycaemia (27 mmol/L), a high HbA1c level (13.1%), a decreased C-peptide level (0.63 ng/ml) and no diabetes antibodies. The patient had a family history of diabetes. The novel variation of ABCC8 c.2477G>A was detected in the proband and his relatives. The mutation was predicted to be harmful. Changes in the protein structure were observed. The ABCC8 c.2477G >A variant resulted in an increase in ABCC8 expression. Furthermore, changes in the expression of the ABCC8 variant was observed after 3-MA treatment, especially after treatment with MG132. At the follow-up, the patient's glucose level was normal without drug therapy for more than 2 years until until he started taking Trelagliptin Succinate to control hyperglycemia within the recent 6 months., Conclusions: The diagnosis of maturity-onset diabetes of the young (MODY)12 was confirmed in our patient. The ABCC8 variant inhibited both ubiquitination and autophagy lysosome degradation pathways, especially the ubiquitination degradation pathway., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aiming at the problems of lack of carbon sources for nitrogen removal and low phosphorus removal efficiency of constructed wetlands (CWs) in treating wastewater treatment plant (WWTP) effluent, an electrolysis assisted constructed wetland (E-CW) with coconut fiber as substrate and solid carbon sources was constructed. The synthetic secondary effluent was used as the influent of the E-CW with a wastewater treatment capacity of 140 L d -1 . The total nitrogen (TN) and the total phosphorus (TP) removal efficiency of the E-CW with coconut fiber treating WWTP effluent were 69.4% and 93.3%, respectively, which were 54.3% and 88.2% higher than those of CW with coconut fiber and no electrolysis. The removal efficiency of TN was 39.9% higher than that of E-CW with gravel. The current intensity had significant effect on nitrogen removal efficiency and the release of carbon sources from coconut fiber. When current intensity increased from 0.25 A to 1.00 A, the TN removal efficiency and nitrate removal rate increased by 21.1% and 0.21 mg L -1 h -1 , respectively, and the volatile fatty acids (VFAs) released from coconut fiber increased by 57.7 mg L -1 . The 16S rRNA high-throughput sequencing results indicated that the main functional nitrogen-removing microbes were Hydrogenophaga, Thauera, Rhodanobacteraceae&#95;norank, Xanthobacteraceae&#95;norank, etc. Multiple paths including autotrophic denitrification with hydrogen and Fe 2+ as electron donors and heterotrophic denitrification were achieved in the system. Meanwhile, the main functional lignocellulose degradation microbes were enriched in the system, including Cytophaga&#95;xylanolytica&#95;group, and Caldilineaceae. Because electrolysis created a favorable environment for them to release carbon sources from coconut fiber. This study provided a new perspective for advanced nutrients removal of WWTP effluent in CWs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The reversibility of monovalent thallium (Tl) absorption on widely distributed iron/manganese secondary minerals may affect environmental Tl migration and global cycling. Nevertheless, quantitative and mechanistic studies on the interfacial retention and release reactions involving Tl(I) are limited. In this study, batch and stirred-flow experiments, unified kinetics modeling, spectral detection, and theoretical calculations were used to elucidate the retention behaviors of Tl(I) on goethite, hematite, and manganite with different solution pH values and Tl loading concentrations. Sustained Tl(I) retention (k d, MeOHTl =0.005∼0.018 min -1 ) was induced by hydration of the surface hydroxyl groups. Rapid Tl(I) retention (k d,MeOTlOH =1.232∼2.917 min -1 ) was enhanced by the abundant hydroxide ions and deprotonated hydroxyl groups, which increased the Tl(I) binding ability. Compared to the ambient Tl concentration, pH had a more substantial effect on the formation and distribution of surface Tl(I) binding species. In alkaline environments, the large adsorption energy for Tl(I) binding to surface species (E ads =-6.14 eV) induced fast Tl(I) binding response on the surfaces of iron/manganese secondary minerals. This study provides new insights into the heterogeneous surface complexation and retention behaviors of Tl(I) and contributes to an in-depth understanding of the environmental fate of Tl and the remediation of Tl contamination., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In this study, highly antimicrobial CuNPs were integrated into a hydrophilic polydopamine (PDA) coating and immobilized on a RO TFC membrane via a mild and facile reduction approach to form a stable and durable dual-functional layer. Based on the XDLVO analysis, the introduction of PDA increased the membrane-foulant total interaction energy (ΔG mwf ) to 14.13 mJ/m 2 , resulting in improved anti-adhesive properties as demonstrated by a 37% decrease in BSA adsorption for the modified membranes. The well dispersed and high loadings of CuNPs induced by PDA conferred strong bacterial toxicity to the modified membranes, reducing the viability of E. coli by 76%. Furthermore, the presence of catechol groups on PDA favors the formation of covalent bond with CuNPs, thus prolonging the durability of the copper-based anti-biofouling membranes. The combination of PDA coating and CuNPs functionalization imparts the membrane with simultaneous anti-adhesive and anti-microbial properties, leading to a substantial reduction in biofouling propensity in dynamic biofouling experiments. Specifically, the flux decline due to biofouling observed for the modified membranes significantly decreased from 65% to 39%, and biofilm thickness and TOC biomass were 58%, and 55% lower, respectively. This study provides a facile and versatile strategy to construct high performance RO membranes with excellent anti-biofouling functionality., (Copyright © 2022. Published by Elsevier Ltd.)

Although shale gas has shown promising potential to alleviate energy crisis as a clean energy resource, more attention has been paid to the harmful environmental impacts during exploitation. It is a critical issue for the management of shale gas wastewater (SGW), especially the organic compounds. This review focuses on analytical methods and corresponding treatment technologies targeting organic matters in SGW. Firstly, detailed information about specific shale-derived organics and related organic compounds in SGW were overviewed. Secondly, the state-of-the art analytical methods for detecting organics in SGW were summarized. The gas chromatography paired with mass spectrometry was the most commonly used technique. Thirdly, relevant treatment technologies for SGW organic matters were systematically explored. Forward osmosis and membrane distillation ranked the top two most frequently used treatment processes. Moreover, quantitative analyses on the removal of general and single organic compounds by treatment technologies were conducted. Finally, challenges for the analytical methods and treatment technologies of organic matters in SGW were addressed. The lack of effective trace organic detection techniques and high cost of treatment technologies are the urgent problems to be solved. Advances in the extraction, detection, identification and disposal of trace organic matters are critical to address the issues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Mammalian LEM-domain proteins (LEMs) are encoded by seven genes, including LAP2, EMD, LEMD1, LEMD2, LEMD3, ANKLE1, and ANKLE2. Though some LEMs were involved in various tumor progression, the expression and prognostic values of LEMs in prostate adenocarcinoma (PRAD) have yet to be analyzed., Methods: Herein, we investigated the expression, survival data, and immune infiltration levels of LEMs in PRAD patients from ATCG, TIMER, LinkedOmics, and TISIDB databases. We also further validated the mRNA and protein expression levels of ANKLE1, EMD, and LEMD2 in human prostate tumor specimens by qPCR, WB, and IHC., Results: We found that all LEM expressions, except for that of LAP2, were markedly altered in PRAD compared to the normal samples. Among all LEMs, only the expressions of ANKLE1, EMD, and LEMD2 were correlated with advanced tumor stage and survival prognosis in PRAD. Consistent with the predicted computational results, the mRNA and protein expression levels of these genes were markedly increased in the PRAD group. We then found that ANKLE1, EMD, and LEMD2 expressions were markedly correlated with immune cell infiltration levels. High ANKLE1, EMD, and LEMD2 expressions predicted a worse prognosis in PRAD based on immune cells. DNA methylation or/and copy number variations may contribute to the abnormal upregulation of ANKLE1, EMD, and LEMD2 in PRAD., Conclusions: Taken together, this study implied that ANKLE1, EMD, and LEMD2 were promising prognosis predictors and potential immunotherapy targets for PRAD patients., (© 2022. The Author(s).)

Aim: The study aimed to investigate the effect of early mobilization combined with early nutrition (EMN) on intensive care unit-acquired weakness (ICU-AW) in intensive care unit (ICU) settings compared with early mobilization (EM) or routine care., Methods: A prospective, dual-center, randomized controlled trial was conducted. The control group underwent standard care without a pre-established routine for mobilization and nutrition. The EM group underwent early, individualized, progressive mobilization within 24 h of ICU admission. The EMN group underwent early mobilization, similar to the EM group plus guideline-based early nutrition (within 48 h of ICU admission). The primary outcome was the occurrence of ICU-AW at discharge from the ICU. Secondary outcomes included muscle strength, functional independence, organ failure, nutritional status, duration of mechanical ventilation (MV), length of ICU stay, and ICU mortality at ICU discharge., Results: A total of 150 patients were enrolled and equally distributed into the three groups. Patients undergoing routine care only were more susceptible to ICU-AW upon ICU discharge than those in the EM or EMN groups (16% vs. 2%; p = 0.014 for both), and had a lower Barthel Index than others (control vs. EM/EMN: 57.5 vs 70.0; p = 0.022). The EMN group had improved muscle strength (p = 0.028) and better nutritional status than the control group (p = 0.031). Both interventions were associated with a lower ICU-AW (EM vs. control: p = 0.027, OR [95% CI] = 0.066 [0.006-0.739]; EMN vs. control: p = 0.016, OR [95% CI] = 0.065 [0.007-0.607])., Conclusion: EM and EMN had positive effects. There was little difference between the effects of EM and EMN, except for muscle strength improvement. Both EM and EMN may lead to a lower occurrence of ICU-AW and better functional independence than standard care. EMN might benefit nutritional status more than usual care and promote improvement in muscle strength., Competing Interests: The authors have declared that no competing interests exist.

Brownfield regeneration (BR) is an important initiative for sustainable land development and the promotion of carbon neutrality. Insufficient stakeholder engagement is one of the main obstacles to the progress of BR. The relationship network formed through continuous interaction among stakeholders ensures the exchange and transfer of information resources. Different structural features of the relationship network may lead to differences in the engagement level of stakeholders. Therefore, based on network embeddedness theory, this study conducts an empirical analysis to explore the impact of the relationship network structure on engagement behavior, for the purpose of increasing the stakeholder engagement level. A theoretical model is developed, in which network centrality, behavioral willingness and involvement climate are selected as the dependent variables of engagement behavior. Using an effective sample of 245 stakeholders involved in BR from ten cities in China, we find that stakeholder network centrality positively affects engagement behavior. There is also a positive relationship between network centrality and behavioral willingness. The behavioral willingness plays an intermediary role between network centrality and engagement behavior, and the involvement climate has a moderating role between behavioral willingness and engagement behavior. Additionally, various strategies can be adopted to promote the engagement level of stakeholders. The findings are useful in establishing a benchmarking framework for BR stakeholder engagement.

Objective: To investigate the effects of Curcumol on invasion, migration and epithelial-mesenchymal transformation of IGROV-1 and OVCAR-3 cells in ovarian cancer and its potential mechanism. Meanwhile, the effect of Curcumol on the antitumor activity of Niraparib was analyzed., Methods: Cell Counting Kit 8 (CCK-8) was used to detect the effects of Curcumol on the activity of IGROV-1 and OVCAR 3 cells. In vitro invasion assay (Transwell) was used to test the invasiveness of cells. Cell migration was detected by scratch assay. The inhibitory effect of Curcumol on PAX8 was detected by QRT-PCR. To evaluate the antitumor effect of Curcumol in subcutaneous tumor-bearing animal model., Results: Knockdown of PAX8 could inhibit the proliferation, invasion and migration of ovarian cancer cells. After Curcumol treated IGROV-1 and OVCAR-3 cells, the cell proliferation ability was decreased, the number of invasive cells was significantly reduced, and the scratch closure rate was significantly reduced, in a dose-dependent manner. Mechanism studies showed that Curcumol increased the antitumor activity of Niraparib by inhibiting PAX8., Conclusion: Curcumol can inhibit the invasion, migration and epithelial-mesenchymal transformation of IGROV-1 and OVCAR-3 cells in ovarian cancer, and its mechanism is related to the targeted inhibition of PAX8. Curcumol also increased the sensitivity of Niraparib chemotherapy by inhibiting PAX8., Competing Interests: The author(s) declare(s) that they have no conflicts of interestble request., (Copyright © 2022 Caihong Liu.)

The transformations of monovalent thallium (Tl) in an aqueous environment may be affected significantly by Tl(I) partitioning at the solid-water interface during sorption. Models used to quantify the kinetics of Tl(I) adsorption on heterogeneous adsorbents and formation of multiple complexes under a wide range of water chemistry conditions can accurately predict the environmental fate of thallium. In this study, Tl(I) sorption on representative titanium dioxide at different solution pH values and loading concentrations was investigated with two unified adsorption models, diffuse layer modeling and kinetics modeling. Three Tl(I) surface complexes, TiOTl, TiOHTl + , and TiOTlOH - , were used in the diffuse layer model and successfully described batch adsorption and the results of spectroscopic analyses. The contribution of TiOHTl + to the adsorption capacity was much higher than those of TiOTl and TiOTlOH - under neutral and weakly alkaline conditions, while the species TiOTlOH - predominated among Tl(I) complexes in strongly alkaline environments. The adsorption and desorption rate coefficients derived from thermodynamics and kinetics coupling modeling suggested the influence of different complex characteristics on adsorption and desorption of Tl(I). Our results provide a comprehensive model for predicting the dynamic binding behavior of Tl at heterogeneous solid-water interfaces., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Microbial-derived metabolites play important roles in Alzheimer's disease (AD) pathology, yet how intestinal microbes influence AD progression remains uncertain. Xanthoceraside (XAN), a triterpenoid saponin with anti-AD activity, was extracted from the husks of Xanthoceras sorbifolia Bunge. However, it is still unclear that how XAN modulates the gut microbiota community to regulate AD progression through changing the levels of microbial-derived metabolites., Purpose: In this study, we investigated the mechanism underlying the anti-AD effect of XAN., Methods: The current combination studies of multiple-targeted metabolomics, natural product chemistry and pharmacology revealed that oral XAN mediated intestinal microbiota to ameliorate Aβ1-42-induced learning and memory deficits in rats, which were confirmed through antibiotic treatments and fecal microbiota transplantation., Results: As a poor water solubility and low permeability compound that hardly be absorbed into blood-brain barrier, XAN significantly regulated Aβ1-42-induced metabolism disorders directly or indirectly in gut, including neurotransmitters, amino acids, bile acids and SCFAs metabolism that were detected by UHPLC-MS/MS and GC-MS/MS. In particularly, the in vitro evaluation of XAN on SCFAs production not only found a striking increase in the production of SCFAs after fermentation, but revealed the inner relationship among XAN, gut microbiota and SCFAs in vivo. All results demonstrated that XAN could improve AD rats' learning and memory deficits by modulating the community of gut microbiota which was connected through 16S rRNA sequencing and CCA analyses., Conclusions: Our study provided a novel mechanism for developing XAN as a potential anti-AD drug and revealed that the gut microbiota might be a potential target for AD treatment ., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Aiming at the problems of target model drift or loss of target tracking caused by serious deformation, occlusion, fast motion, and out of view of the target in long-term moving target tracking in complex scenes, this paper presents a robust multi-feature single-target tracking algorithm based on a particle filter. The algorithm is based on the correlation filtering framework. First, to extract more accurate target appearance features, in addition to the manual features histogram of oriented gradient features and color histogram features, the depth features from the conv3-4, conv4-4 and conv5-4 convolutional layer outputs in VGGNet-19 are also fused. Secondly, this paper designs a re-detection module of a fusion particle filter for the problem of how to return to accurate tracking after the target tracking fails, so that the algorithm in this paper can maintain high robustness during long-term tracking. Finally, in the adaptive model update stage, the adaptive learning rate update and adaptive filter update are performed to improve the accuracy of target tracking. Extensive experiments are conducted on dataset OTB-2015, dataset OTB-2013, and dataset UAV123. The experimental results show that the proposed multi-feature single-target robust tracking algorithm with fused particle filtering can effectively solve the long-time target tracking problem in complex scenes, while showing more stable and accurate tracking performance.

Aerobic granular sludge (AGS), a novel strategy for nutrient removal which exhibits compact structure, good settleability, and resilience against high organic load, has been considered as a highly potential wastewater treatment technology. However, the long start-up period for granulation prevented its widespread development. In this study, the distinct pathways of PAC-enhanced AGS granulation were systematically investigated. Four identical sequencing batch reactors (SBR) with different PAC dosages (with 0, 50, 100, 400 mg/L effective Al 3+ respectively) were applied. It was observed that the presence of PAC accelerated granules formation, promoted mechanical strength as well as denitrification rate of granules, and thus notably enhanced removal efficacies of COD, NH 4 + -N, NO 2 - and NO 3 - . According to the dissolved oxygen (DO) distribution inside the sludge and the denitrification rate (SDNR) measurements, distinguishing structures of granules under different PAC addition were discovered. Comparatively, AGS under low PAC addition (i.e., 50 mg/L) resulted in the largest granule size, the biggest anaerobic zone and the highest denitrification rate. Presumably, for the system with the low PAC addition (50 mg/L), appropriate aluminum ions (Al 3+ ) neutralized part of the negative charge on the microorganism surface, thereby promoting cells aggregation. In contrast, a high dosage of PAC (400 mg/L) induced excessive Al 3+ absorbed on the cell surface after neutralization, which increased the repulsive force between microorganisms, leading to more cavities and channels existed inside the granules. Therefore, granules under low PAC dosage (i.e., 50 mg/L) presented large anaerobic zone and high denitrification rate, thus favored the best internal structure and nutrients removal efficiencies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Exploring the transport behaviors of thallium (Tl) in porous media is crucial for predicting Tl pollution in natural soils and groundwater. In recent years, the misuse of plastics has led to plastic becoming an emerging pollutant in soil. In this work, the effects of plastic particles on Tl(I) transport in water-saturated sand columns were investigated under different ionic strengths (ISs), pH values, and plastic particle sizes. The two-site nonequilibrium model was selected to fit the breakthrough curves (BTCs) of Tl(I). The results demonstrated that nanoplastics (NPs) accelerated Tl(I) transport at pH 7, which might be attributed to the competitive adsorption of NPs and Tl(I) on sand surfaces. However, at pH 5, the deposited NPs might provide more adsorption sites for Tl(I), and thus enhance its retention in the columns. In addition, the "straining" process could intercept microplastics (MPs) with Tl(I) that was attached under unfavorable attachment conditions, which would result in the inhibited mobility of Tl(I). On the other hand, the migration of plastics was restrained to some extent when Tl(I) was present. Overall, the findings from this work provided a new perspective for understanding the transport of Tl(I) and plastics in subsurface environments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Selenite, which is extremely toxic at high concentrations, can easily be enriched in natural aquatic environments due to human activities, which causes great harm to ecosystems. Sulfur reduction can effectively reduce soluble selenite in large quantities to nontoxic solid elemental selenium, which plays a significant role in controlling the toxicity and cycle of selenium. In view of the bright prospects of the sulfur reduction reaction of selenite, this review comprehensively summarizes the continuous development in the sulfidation of selenite. First, the geochemical characteristics of aqueous selenium in different sulfur systems involving species distribution and various phase types at Eh-pH conditions were summarized. Second, sulfur reductions of selenite with chemical sulfide in natural water environments, sulfur reductase and extracellular polymer substances containing thiol groups in sulfate-reducing bacteria have been reviewed to further understand the corresponding mechanisms, rates and influencing factors. Furthermore, applications of sulfur reduction of selenium, including removal of selenium, enrichment of selenium, synthesis of selenoproteins and prevention of leakage of selenium, were also summarized. Finally, this review identified future research needs for the sulfidation of selenite for environmental applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)