A novel drug prejudice scaffold-imidazopyridine-conjugate can promote cell death in a colorectal cancer model by binding to ß-catenin and suppressing the Wnt signaling pathway.

INTRODUCTION: Globally, colorectal cancer (CRC) is the third most common type of cancer, and its treatment frequently includes the utilization of drugs based on antibodies and small molecules. The development of CRC has been linked to various signaling pathways, with the Wnt/ß-catenin pathway identified as a key target for intervention. OBJECTIVES: We have explored the impact of imidazopyridine-tethered chalcone-C (CHL-C) in CRC models. METHODS: To determine the influence of CHL-C on apoptosis and autophagy, Western blot analysis, annexin V assay, cell cycle analysis, acridine orange staining, and immunocytochemistry were performed. Next, the activation of the Wnt/ß-catenin signaling pathway and the anti-cancer effects of CHL-C in vivo were examined in an orthotopic HCT-116 mouse model. RESULTS: We describe the synthesis and biological assessment of the CHL series as inhibitors of the viability of HCT-116, SW480, HT-29, HCT-15, and SNU-C2A CRC cell lines. Further biological evaluations showed that CHL-C induced apoptosis and autophagy in down-regulated ß-catenin, Wnt3a, FZD-1, Axin-1, and p-GSK-3ß (Ser9), and up-regulated p-GSK3ß (Tyr216) and ß-TrCP. In-depth analysis using structure-based bioinformatics showed that CHL-C strongly binds to ß-catenin, with a binding affinity comparable to that of ICG-001, a well-known ß-catenin inhibitor. Additionally, our in vivo research showed that CHL-C markedly inhibited tumor growth and triggered the activation of both apoptosis and autophagy in tumor tissues. CONCLUSION: CHL-C is capable of inducing apoptosis and autophagy by influencing the Wnt/ß-catenin signaling pathway.

Sika Deer Velvet Antler Peptide Exerts Neuroprotective Effect in a Parkinson's Disease Model via Regulating Oxidative Damage and Gut Microbiota.

Parkinson's disease (PD) is the second most common neurodegenerative disorder globally. Recognizing the potential of velvet antler in the nervous system, as shown in numerous studies, this research was aimed at evaluating the neuroprotective effects of Sika Deer velvet antler peptide (VAP), along with the underlying mechanisms in neurotoxin-induced PD models. Initially, a peptidomic analysis of the VAP, which comprised 189 varieties of peptides, was conducted using LC-MS. Nine sequences were identified as significant using Proteome Discoverer 2.5 software. In a cellular model of PD, where PC12 cells are treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP+), the administration of the VAP reduced the cell damage and apoptosis induced by MPP+. This protective effect was associated with a decrease in oxidative stress. This protective mechanism was found to be mediated through the activation of the SIRT1-dependent Akt/Nrf2/HO-1-signaling pathway. In animal models, specifically in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD, the administration of the VAP effectively reduced the dopaminergic neuron damage and reversed the neurobehavioral deficits. They also diminished microglia activation and apoptosis, all without any noticeable adverse effects. Additionally, the VAP was observed to beneficially alter the gut microbiota, as marked by an increase in the abundances of Prevotellaceae, Helicobacteraceae, and Prevotella. These findings suggest that VAP exerts its neuroprotective effect against neurodegeneration by inhibiting oxidative stress and modulating gut microbiota.

A transient transcriptional activation governs unpolarized-to-polarized morphogenesis during embryo implantation.

During implantation, embryos undergo an unpolarized-to-polarized transition to initiate postimplantation morphogenesis. However, the underlying molecular mechanism is unknown. Here, we identify a transient transcriptional activation governing embryonic morphogenesis and pluripotency transition during implantation. In naive pluripotent embryonic stem cells (ESCs), which represent preimplantation embryos, we find that the microprocessor component DGCR8 can recognize stem-loop structures within nascent mRNAs to sequester transcriptional coactivator FLII to suppress transcription directly. When mESCs exit from naive pluripotency, the ERK/RSK/P70S6K pathway rapidly activates, leading to FLII phosphorylation and disruption of DGCR8/FLII interaction. Phosphorylated FLII can bind to transcription factor JUN, activating cell migration-related genes to establish poised pluripotency akin to implanting embryos. Resequestration of FLII by DGCR8 drives poised ESCs into formative pluripotency. In summary, we identify a DGCR8/FLII/JUN-mediated transient transcriptional activation mechanism. Disruption of this mechanism inhibits naive-poised-formative pluripotency transition and the corresponding unpolarized-to-polarized transition during embryo implantation, which are conserved in mice and humans.

In-situ co-immobilization of lipase, lipoxygenase and L-cysteine within a metal-amino acid framework for conversion of soybean oil into higher-value products.

We propose a co-immobilized chemo-enzyme cascade system to mitigate random intermediate diffusion from the mixture of individual immobilized catalysts and achieve a one-pot reaction of multi-enzyme and reductant. Catalyzed by lipase and lipoxygenase, unsaturated lipid hydroperoxides (HPOs) were synthesized. 13(S)-hydroperoxy-9Z, 11E-octadecadienoic acid (13-HPODE), one compound of HPOs, was subsequently reduced to 13(S)-hydroxy-9Z, 11E-octadecadienoic acid (13-HODE) by cysteine. Upon the optimized conditions, 75.28 mg of 13-HPODE and 4.01 mg of 13-HODE were produced from per milliliter of oil. The co-immobilized catalysts exhibited improved yield compared to the mixture of individually immobilized catalysts. Moreover, it demonstrated satisfactory durability and recyclability, maintaining a relative HPOs yield of 78.5% after 5 cycles. This work has achieved the co-immobilization of lipase, lipoxygenase and the reductant cysteine for the first time, successfully applying it to the conversion of soybean oil into 13-HODE. It offers a technological platform for transforming various oils into high-value products.

Construction and validation of a nomogram prediction model for the progression to septic shock in elderly patients with urosepsis.

Background: Septic shock is a clinical syndrome characterized by the progression of sepsis to a severe stage. Elderly patients with urosepsis in the intensive care unit (ICU) are more likely to progress to septic shock. This study aimed to establish and validate a nomogram model for predicting the risk of progression to septic shock in elderly patients with urosepsis. Methods: We extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV dataset was split into a training set for model development and an internal validation set to assess model performance. Further external validation was performed using a distinct dataset sourced from the eICU-CRD. Predictors were screened using least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression analyses. The evaluation of model performance included discrimination, calibration, and clinical usefulness. Results: The study demonstrated that the Glasgow Coma Scale (GCS), white blood count (WBC), platelet, blood urea nitrogen (BUN), calcium, albumin, congestive heart failure (CHF), and invasive ventilation were closely associated with septic shock in the training cohort. Nomogram prediction, utilizing eight parameters, demonstrated strong predictive accuracy with area under the curve (AUC) values of 0.809 (95 % CI 0.786-0.834), 0.794 (95 % CI 0.756-0.831), and 0.723 (95 % CI 0.647-0.801) in the training, internal validation, and external validation sets, respectively. Additionally, the nomogram demonstrated a promising calibration performance and significant clinical usefulness in both the training and validation sets. Conclusion: The constructed nomogram is a reliable and practical tool for predicting the risk of progression to septic shock in elderly patients with urosepsis. Its implementation in clinical practice may enhance the early identification of high-risk patients, facilitate timely and targeted interventions to mitigate the risk of septic shock, and improve patient outcomes.

Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

Variations in Quinolinic Acid Levels in Tuberculosis Patients with Diabetes Comorbidity: A Pilot Prospective Cohort Study.

Objective: We aimed to investigate dysregulated metabolic pathways and identify diagnostic and therapeutic targets in patients with tuberculosis-diabetes (TB-DM). Methods: In our prospective cohort study, plasma samples were collected from healthy individuals, diabetic (DM) patients, untreated TB-only (TB-0)/TB-DM patients (TB-DM-0), and cured TB (TB-6)/TB-DM patients (TB-DM-6) to measure the levels of amino acids, fatty acids, and other metabolites in plasma using high-throughput targeted quantification methods. Results: Significantly different biological processes and biomarkers were identified in DM, TB-DM-0, and TB-DM-6 patients. Moreover, quinolinic acid (QA) showed excellent predictive accuracy for distinguishing between DM patients and TB-DM-0 patients, with an AUC of 1 (95% CI 1-1). When differentiating between TB-DM-0 patients and TB-DM-6 patients, the AUC was 0.9297 (95% CI 0.8460-1). Compared to those in DM patients, the QA levels were significantly elevated in TB-DM-0 patients and decreased significantly after antituberculosis treatment. We simultaneously compared healthy controls and untreated tuberculosis patients and detected an increase in the level of QA in the plasma of tuberculosis patients, which decreased following treatment. Conclusion: These findings improve the current understanding of tuberculosis treatment in patients with diabetes. QA may serve as an ideal diagnostic biomarker for TB-DM patients and contribute to the development of more effective treatments.

Isolation and purification of carbohydrate components in functional food: a review.

Medicinal plants, increasingly utilized in functional foods, possess potent therapeutic properties and health-promoting functions, with carbohydrates playing a crucial role and exhibiting a range of effects, such as antioxidant, antitumor, immune-enhancing, antibacterial, anticoagulant, and hypoglycemic activities. However, comprehensively, accurately, rapidly, and economically assessing the quality of carbohydrate components is challenging due to their diverse and complex nature. Additionally, the purification and identification of carbohydrates also guarantee related efficacy research. This paper offers a thorough review of research progress carried out by both domestic and international scholars in the last decade on extracting, purifying, separating, identifying, and determining the content of carbohydrate components from functional foods, which are mainly composed of medicinal plants, and also explores the potential for achieving comprehensive quantitative analysis and evaluating structure-activity relationships of carbohydrate components. These findings aim to serve as a valuable reference for the future development and application of natural carbohydrate components in functional food and medicine.

Identification, expression, and characterization of a marine-derived chitinase Ce0303 from Chitiniphilus eburneus YS-30 with exo- and endo-hydrolytic properties.

N-acetyl-oligosaccharides exhibit antioxidant and antibacterial activities. However, the low catalytic efficiency of chitinase on crystalline chitin hinders the eco-friendly production of N-acetyl-oligosaccharides. A marine-derived chitinase-producing strain Chitiniphilus eburneus YS-30 was screened in this study. The genome of C. eburneus YS-30 spans 4,522,240 bp, with a G + C content of 63.96 % and 4244 coding genes. Among the chitinases secreted by C. eburneus YS-30, Ce0303 showed the highest content at 19.10 %, with a molecular weight of 73.5 kDa. Recombinant Ce0303 exhibited optimal activity at 50 °C and pH 5.0, maintaining stability across pH 4.0-10.0. Ce0303 demonstrated strict substrate specificity, with a specific activity toward colloidal chitin of 6.41 U mg-1, Km of 2.34 mg mL-1, and kcat of 3.27 s-1. The specific activity of Ce0303 toward α-chitin was 18.87 % of its activity on colloidal chitin. Ce0303 displayed both exo- and endo-hydrolytic properties, primarily producing (GlcNAc)1-3 from colloidal chitin. The structure of Ce0303 includes one catalytic domain and two chitin-binding domains. Docking results revealed that the GlcNAc at -1 subsite formed two hydrogen bonds with conserved Trp380. The hydrolytic properties of Ce0303 will provide technical support for the comprehensive utilization of crustacean raw materials.

Integrative Analysis of Hepatopancreas Transcriptome and Proteome in Female Eriocheir sinensis under Thermal Stress.

The Chinese mitten crab (Eriocheir sinensis), an economically important crustacean that is endemic to China, has recently experienced high-temperature stress. The high thermal tolerance of E. sinensis points to its promise in being highly productive in an aquacultural context. However, the mechanisms underlying its high thermal tolerance remain unknown. In this study, female E. sinensis that were heat exposed for 24 h at 38.5 °C and 33 °C were identified as high-temperature-stressed (HS) and normal-temperature-stressed (NS) groups, respectively. The hepatopancreas of E. sinensis from the HS and NS groups were used for transcriptome and proteomic analyses. A total of 2350 upregulated and 1081 downregulated differentially expressed genes (DEGs) were identified between the HS and NS groups. In addition, 126 differentially expressed proteins (DEPs) were upregulated and 35 were downregulated in the two groups. An integrated analysis showed that 2641 identified genes were correlated with their corresponding proteins, including 25 genes that were significantly differentially expressed between the two omics levels. Ten Gene Ontology terms were enriched in the DEGs and DEPs. A functional analysis revealed three common pathways that were significantly enriched in both DEGs and DEPs: fluid shear stress and atherosclerosis, leukocyte transendothelial migration, and thyroid hormone synthesis. Further analysis of the common pathways showed that MGST1, Act5C, HSP90AB1, and mys were overlapping genes at the transcriptome and proteome levels. These results demonstrate the differences between the HS and NS groups at the two omics levels and will be helpful in clarifying the mechanisms underlying the thermal tolerance of E. sinensis.

Bio-Skin-Inspired Flexible Pressure Sensor Based on Carbonized Cotton Fabric for Human Activity Monitoring.

With the development of technology, people's demand for pressure sensors with high sensitivity and a wide working range is increasing. An effective way to achieve this goal is simulating human skin. Herein, we propose a facile, low-cost, and reproducible method for preparing a skin-like multi-layer flexible pressure sensor (MFPS) device with high sensitivity (5.51 kPa-1 from 0 to 30 kPa) and wide working pressure range (0-200 kPa) by assembling carbonized fabrics and micro-wrinkle-structured Ag@rGO electrodes layer by layer. In addition, the highly imitated skin structure also provides the device with an extremely short response time (60/90 ms) and stable durability (over 3000 cycles). Importantly, we integrated multiple sensor devices into gloves to monitor finger movements and behaviors. In summary, the skin-like MFPS device has significant potential for real-time monitoring of human activities in the field of flexible wearable electronics and human-machine interaction.

Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

BACKGROUND: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

Effects of different tooth movement patterns and aligner thicknesses on maxillary arch expansion with clear aligners: a three-dimensional finite element study.

Objectives: The objective of this study was to investigate the biomechanical effects of different tooth movement patterns and aligner thicknesses on teeth and periodontal tissues during maxillary arch expansion with clear aligners, to facilitate more precise and efficient clinical orthodontic treatments. Methods: Three-dimensional models including teeth, maxilla, periodontal ligament, and aligner were constructed and subjected to finite element analysis. Tooth displacement trends and periodontal ligament stresses were measured for seven tooth displacement patterns (divided into three categories including overall movement of premolars and molars with gradually increasing molar expansion in each step; distributed movement of premolars and molars; and alternating movement between premolars and molars at intervals) and two aligner thicknesses (0.5 mm and 0.75 mm) during maxillary arch expansion with clear aligners. Results: When expanding the maxillary arch with clear aligners, the effective expansion of the target teeth mainly showed a tilting movement trend. Increasing the amount of molar expansion increased the buccal displacement of the first molar but decreased the buccal displacement of the premolars. The mean buccal displacement of the target teeth was greater in the posterior teeth interval alternating movement group (0.026 mm) than in the premolar/molar distributed movement group (0.016 mm) and the overall movement group (0.015 mm). Increasing aligner thickness resulted in greater buccal displacement of the crowns and increased stress on the periodontal ligaments. Conclusion: Increasing the amount of molar expansion reduces the efficiency of premolar expansion. Alternating movement of premolars and molars at intervals achieves a higher arch expansion efficiency, but attention should be paid to the anchorage of adjacent teeth. Increasing the thickness of the aligner increases the expansion efficiency but may also increase the burden on the periodontal tissues.

Identification of immune-related genes and small-molecule drugs in hypertension-induced left ventricular hypertrophy based on machine learning algorithms and molecular docking.

Background: Left ventricular hypertrophy (LVH) is a common consequence of hypertension and can lead to heart failure. The immune response plays an important role in hypertensive LVH; however, there is no comprehensive method to investigate the mechanistic relationships between immune response and hypertensive LVH or to find novel therapeutic targets. This study aimed to screen hub immune-related genes involved in hypertensive LVH as well as to explore immune target-based therapeutic drugs. Materials and methods: RNA-sequencing data from a mouse model generated by angiotensin II infusion were subjected to weighted gene co-expression network analysis (WGCNA) to identify core expression modules. Machine learning algorithms were applied to screen immune-related LVH characteristic genes. Heart structures were evaluated by echocardiography and cardiac magnetic resonance imaging (CMRI). Validation of hub genes was conducted by RT-qPCR and western blot. Using the Connectivity Map database and molecular docking, potential small-molecule drugs were explored. Results: A total of 1215 differentially expressed genes were obtained, most of which were significantly enriched in immunoregulation and collagen synthesis. WGCNA and multiple machine learning strategies uncovered six hub immune-related genes (Ankrd1, Birc5, Nuf2, C1qtnf6, Fcgr3, and Cdca3) that may accurately predict hypertensive LVH diagnosis. Immune analysis revealed that fibroblasts and macrophages were closely correlated with hypertensive LVH, and hub gene expression was significantly associated with these immune cells. A regulatory network of transcription factor-mRNA and a ceRNA network of miRNA-lncRNA was established. Notably, six hub immune-related genes were significantly increased in the hypertensive LVH model, which were positively linked to left ventricle wall thickness. Finally, 12 small-molecule compounds with the potential to reverse the high expression of hub genes were ruled out as potential therapeutic agents for hypertensive LVH. Conclusion: This study identified and validated six hub immune-related genes that may play essential roles in hypertensive LVH, providing new insights into the potential pathogenesis of cardiac remodeling and novel targets for medical interventions.

Effects of different parameters of Tai Chi on the intervention of chronic low back pain: A meta-analysis.

OBJECTIVE: To evaluate the effects of Tai Chi in the treatment of patients with chronic low back pain by Meta-analysis and to investigate its influencing factors. METHODS: The study searched eight databases (PubMed, Embase, The Cochrane Library, Web of Science, China Knowledge Network, Wanfang, VIP, and CBM) from inception to October 2023. Two investigators independently selected 10 eligible randomized controlled trials (RCT) against inclusion and exclusion criteria, followed by data extraction and study quality assessment by ROB 2. The outcomes of interest were pain intensity and disability. The studies were combined using meta-analysis when statistical pooling of data was possible. The quality of the evidence was assessed using the GRADE approach. RESULTS: 10 randomized controlled studies with a total sample of 886 cases were included, of which 4 (40%) were assessed as low risk of bias. The effect size of Tai Chi for chronic low back pain was [Weighted Mean Difference (WMD) with 95% Confidence Interval (CI) = -1.09 (-1.26, -0.92), p < 0.01], all achieving large effect sizes and statistically significant; the effect size for disability was [Standard Mean Difference (SMD) with 95% CI = -1.75 (-2.02, -1.48), p < 0.01], and the combined effect sizes of physical health and mental health for quality of life were [WMD (95% CI) = 4.18 (3.41, 4.95), p < 0.01; WMD (95% CI) = 3.23 (2.42, 4.04), p < 0.01] respectively. The incidence of adverse reactions was low. Meta regression and subgroup analysis showed that there was no significant effect on intervention measures (Tai Chi alone, Tai Chi as additional therapy, water Tai Chi), Tai Chi school (Chen and Yang) and the number of total intervention sessions (> 30 and ≤ 30). The evidence quality evaluation showed that the evidence of pain, physical health of quality of life and mental health score was medium quality, while the evidence of disability and adverse reactions was low quality. CONCLUSIONS: Tai Chi has an obvious effect of in relieving chronic low back pain. Tai Chi alone and Tai Chi as supplementary therapy have good effects. Tai Chi in water have not been verified. Chen style Tai Chi and Yang's Tai Chi, intervention more than 30 times or less than 30 times had no significant difference in the effect of intervention on CLBP.

CuxO decorated Ti3C2Tx MXene composites for non-enzymatic glucose sensing with large linear ranges.

Ti3C2Tx MXene/CuxO composites were prepared by acid etching combined with electrochemical technique. The abundant active sites on the surface of MXene greatly increase the loading of CuxO nanoparticles, and the synergistic effect between the different components of the composite can accelerate the oxidation reaction of glucose. The results indicate that at the working potential of 0.55 V (vs. Ag/AgCl), the glucose sensor based on Ti3C2Tx MXene/CuxO composite presents large linear concentration ranges from 1 µM to 4.655 mM (sensitivity of 361 µA mM-1 cm-2) and from 5.155 mM to 16.155 mM (sensitivity of 133 µA mM-1 cm-2). The limit of detection is 0.065 µM. In addition, the sensor effectively avoids the oxidative interference of common interfering species such as ascorbic acid, dopamine and uric acid. The sensor has good reproducibility, stability and acceptable recoveries for the detection of glucose in human sweat sample (97.5-103.3%) with RSD values less than 4%. Based on these excellent properties it has great potential for the detection of glucose in real samples.

High biomass yields of Chlorella protinosa with efficient nitrogen removal from secondary effluent in a membrane photobioreactor.

Further treatment of secondary effluents before their discharge into the receiving water bodies could alleviate water eutrophication. In this study, the Chlorella proteinosa was cultured in a membrane photobioreactor to further remove nitrogen from the secondary effluents. The effect of hydraulic retention time (HRT) on microalgae biomass yields and nutrient removal was studied. The results showed that soluble algal products concentration reduced in the suspension at low HRT, thereby alleviating microalgal growth inhibition. In addition, the lower HRT reduced the nitrogen limitation for Chlorella proteinosa's growth through the phase-out of nitrogen-related functional bacteria. As a result, the productivity for Chlorella proteinosa increased from 6.12 mg/L/day at an HRT of 24 hr to 20.18 mg/L/day at an HRT of 8 hr. The highest removal rates of 19.7 mg/L/day, 23.8 mg/L/day, and 105.4 mg/L/day were achieved at an HRT of 8 hr for total nitrogen (TN), ammonia, and chemical oxygen demand (COD), respectively. However, in terms of removal rate, TN and COD were the largest when HRT is 24 hr, which were 74.5% and 82.6% respectively. The maximum removal rate of ammonia nitrogen was 99.2% when HRT was 8 hr.

8-l-Cystinyl Bis(1,8-diazaspiro[4.5]decane) as an Orally Bioavailable l-Cystine Crystallization Inhibitor for Cystinuria.

Cystinuria, a rare genetic disorder, is characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of l-cystine and subsequent l-cystine crystallization in urine and stone formation in the urinary tract. Inhibition of l-cystine crystallization by l-cystine diamides such as LH708 (2) represents a promising new approach to prevent stone formation in patients with cystinuria. While 2 shows promising in vivo efficacy and a good safety profile in a Slc3a1-knockout mouse model of cystinuria, further structural modification of 2 led to the discovery of 8-l-cystinyl bis(1,8-diazaspiro[4.5]decane) (LH1753, 3) incorporating a bioisosteric spiro bicyclic diamine 1,8-diazaspiro[4.5]decane for the N-methylpiperazine terminal groups in 2 as a promising candidate with 3 being about 120× more potent than l-cystine dimethyl ester (CDME, 1) and about 2× more potent than 2 in inhibiting l-cystine crystallization. Furthermore, 3 demonstrated good oral bioavailability and in vivo efficacy in preventing l-cystine stone formation in the Slc3a1-knockout mouse model of cystinuria.

Temporal trends in mortality and associated factors among persons with mental disorders: A register-based cohort study.

This study aims to examine 20-year temporal trends in all-cause mortality among psychiatric patients and investigating impacts of risk factors on the time trends based on 218,703 Finnish adults with mental disorders who were discharged from 87 psychiatric hospitals between 1 Jan 1995 and 31 Dec 2014. The age-period-cohort analysis of Poisson model with random hospital effects estimated temporal trends in death rate and associated factors at individual, healthcare system, and society levels, following the WHO multilevel intervention framework model for six major psychiatric diagnosis. The adjusted annual mortality declined by 2.2 % annually (RR: 0.978 [95 % CI 0.976-0.980]) for all individuals, and by 2.8 % after adjusting for all risk factors, with varied decreasing rate between 2.0 % and 3.6 % by diagnosis. Individual level factors accounted for the declining rate by 54.5 % for all patients, with the highest impact on patients with personality disorders, followed by patients with affective disorders and patients with schizophrenia. Identified declining trends and associated factors which are preventable and modifiable for individuals with specific psychiatric diagnosis may lead to develop targeted service and intervention strategies in bringing down mortality further for the population.