Development and validation of a nomogram to estimate fatigue probability in hemodialysis patients.

OBJECTIVE: This study aims to investigate the factors that influence fatigue in hemodialysis (HD) patients and to develop and validate a nomogram to estimate the probability of fatigue in this population. METHODS: This cross-sectional study collected 453 patients who underwent HD at the tertiary hospital in Hubei, China, from April to December 2023. They were randomly divided into a 70% training group (n = 316) and a 30% validation group (n = 137). In the training set, factors influencing fatigue were screened using multivariate logistic regression analysis, and a nomogram was developed to estimate fatigue probability in HD patients. The discrimination and calibration of the nomogram were validated in both the training and validation sets through the area under the receiver operating characteristic (ROC) curve (AUC) and the Hosmer-Lemeshow (H-L) test. RESULTS: In the training group, logistic regression showed that age, dialysis vintage, inter-dialysis weight gain, hemoglobin, depression, insomnia, and social support were variables associated with fatigue in HD patients. Based on these factors, a nomogram for assessing fatigue probability in HD patients was developed. The AUC was 0.955 (95% CI: 0.932-0.977) and 0.979 (95% CI: 0.961-0.997) in the training and validation sets. The results from the H-L test indicated a good fit. CONCLUSION: The nomogram can evaluate fatigue probability in HD patients and may serve as a convenient clinical tool.

NL13, a novel curcumin analogue and polo like kinase 4 inhibitor, induces cell cycle arrest and apoptosis in prostate cancer models.

BACKGROUND AND PURPOSE: Prostate cancer remains a major public health burden worldwide. Polo like kinase 4 (PLK4) has emerged as a promising therapeutic target in prostate cancer due to its key roles in cell cycle regulation and tumour progression. This study aims to develop and characterize the novel curcumin analogue NL13 as a potential therapeutic agent and PLK4 inhibitor against prostate cancer. EXPERIMENTAL APPROACH: NL13 was synthesized and its effects were evaluated in prostate cancer cells and mouse xenograft models. Kinome screening and molecular modelling identified PLK4 as the primary target. Antiproliferative and proapoptotic mechanisms were explored via cell cycle, apoptosis, gene and protein analyses. KEY RESULTS: Compared with curcumin, NL13 exhibited much greater potency in inhibiting PC3 (IC50, 3.51 µM vs. 35.45 µM) and DU145 (IC50, 2.53 µM vs. 29.35 µM) prostate cancer cells viability and PLK4 kinase activity (2.32 µM vs. 246.88 µM). NL13 induced G2/M cell cycle arrest through CCNB1/CDK1 down-regulation and triggered apoptosis via caspase-9/caspase-3 cleavage. These effects were mediated by PLK4 inhibition, which led to the inactivation of the AKT signalling pathway. In mice, NL13 significantly inhibited tumour growth and modulated molecular markers consistent with in vitro findings, including decreased p-AKT and increased cleaved caspase-9/3. CONCLUSION AND IMPLICATIONS: NL13, a novel PLK4-targeted curcumin analogue, exerts promising anticancer properties against prostate cancer by disrupting the PLK4-AKT-CCNB1/CDK1 and apoptosis pathways. NL13 represents a promising new agent for prostate cancer therapy.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy.

BACKGROUND: The intrapapillary capillary loop (IPCL) characteristics, visualized using magnifying endoscopy, are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma (ESCC). Japan Esophageal Society (JES) classification is the most widely used classification. Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor: tortuosity, dilatation, irregular caliber, and different shapes. However, the pathological characteristics of IPCLs have not been thoroughly investigated, especially the microvascular structures corresponding to the deepest parts of the lesions' infiltration. AIM: To investigate differences in pathological microvascular structures of ESCC, which correspond to the deepest parts of the lesions' infiltration. METHODS: Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023. Patients first underwent magnified endoscopic examination, followed by endoscopic submucosal dissection or surgical treatment. Pathological images were scanned using a three-dimensional slice scanner, and the pathological structural differences in different types, according to the JES classification, were analyzed using nonparametric tests and t-tests. RESULTS: The 35 lesions were divided into four groups according to the JES classification: A, B1, B2, and B3. Statistical analyses revealed significant differences (a P < 0.05) in the short and long calibers, area, location, and density between types A and B. Notably, there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3 (P > 0.05). However, significant differences in the short calibers, long calibers, and area of IPCL were observed between types B1 and B3 (a P < 0.05); no significant differences were found in the density or location (P > 0.05). CONCLUSION: Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy, especially between the types A and B.

Serotonylation in tumor-associated fibroblasts contributes to the tumor-promoting roles of serotonin in colorectal cancer.

Accumulated studies have highlighted the diverse roles of 5-hydroxytryptamine (5-HT), or serotonin, in cancer biology, particularly in colorectal cancer (CRC). While 5-HT primarily exerts its effects through binding to various 5-HT receptors, receptor-independent mechanisms such as serotonylation remain unclear. This study revealed that depleting 5-HT, either through genetic silencing of Tph1 or using a selective TPH1 inhibitor, effectively reduced the growth of CRC tumors. Interestingly, although intrinsic 5-HT synthesis exists in CRC, it is circulating 5-HT that mediates the cancer-promoting function of 5-HT. Blocking the function of 5-HT receptors showed that the oncogenic roles of 5-HT in CRC operate through a mechanism that is separate from its receptor. Instead, serotonylation of histone H3Q5 (H3Q5ser) was found in CRC cells and cancer-associated fibroblasts (CAFs). H3Q5ser triggers a phenotypic switch of CAFs towards an inflammatory-like CAF (iCAF) subtype, which further enhances CRC cell proliferation, invasive characteristics, and macrophage polarization. Knockdown of the 5-HT transporter SLC22A3 or inhibition of TGM2 reduces H3Q5ser levels and reverses the tumor-promoting phenotypes of CAFs in CRC. Collectively, this study sheds light on the serotonylation-dependent mechanisms of 5-HT in CRC progression, offering insights into potential therapeutic strategies targeting the serotonin pathway for CRC treatment.

[Shallow Groundwater Around Plateau Lakes： Spatiotemporal Distributions of Dissolved Carbon and Its Driving Factors].

Dissolved carbon in groundwater plays an important role in carbon cycling and ecological function maintenance, and its concentration level affects the migration and transformation of pollutants in groundwater. To understand the spatiotemporal variation characteristics of dissolved carbon and its driving factors in shallow groundwater around plateau lakes, variations in the concentrations of dissolved organic carbon （DOC）, inorganic carbon （DIC）, and total carbon （DTC） and their driving factors in shallow groundwater （n = 404） around eight plateau lakes were analyzed. The results indicated that the average values of ρ（DOC）, ρ（DIC）, and ρ（DTC） in shallow groundwater around plateau lakes were 8.23, 49.01, and 57.84 mg·L-1, respectively, with the ρ（DOC） in 79.0% of shallow groundwater samples exceeding 5 mg·L-1. There were no significant differences in the DOC, DIC, and DTC concentrations between rainy and dry seasons, whereas the change in dissolved carbon concentrations in shallow groundwater were strongly affected by the intensity of agricultural intensification and the depth of groundwater table； the DOC, DIC, and DTC concentrations in shallow groundwater from facility agricultural regions （SFAR）, cropland fallow agricultural regions （CFAR）, and intensive agricultural regions with deeper groundwater tables （DIAR） were significantly reduced by 25.8% - 56.6%, 14.0% - 32.9%, and 16.6% - 36.7%, respectively, compared with those in intensive agricultural regions with shallower groundwater tables （SIAR）. Additionally, the dissolved carbon concentrations in shallow groundwater from DIAR were significantly lower than those of SFAR and CFAR. RDA revealed that physicochemical factors in water and soil significantly explained the changes in the dissolved carbon concentrations. Moreover, the dissolved carbon concentrations in shallow groundwater around Yilong Lake were significantly higher than those of other lakes, whereas that of Chenghai Lake was significantly lower than that of other lakes. Our study highlights that agricultural intensification intensity and groundwater table depth jointly drove the variations in dissolved carbon concentrations in shallow groundwater around plateau lakes. The study results are expected to provide a scientific basis for understanding the carbon cycle in plateau lake areas with underground runoff flowing into lakes and evaluating the attenuation of pollutants by dissolved carbon in shallow groundwater.

Tuning Octahedron Sites of CoV2O4 via Cationic Competition for Efficient Oxygen Evolution Reaction.

Doping transition metal oxide spinels with metal ions represents a significant strategy for optimizing the electronic structure of electrocatalysts. Herein, a bimetallic Fe and Ru doping strategy to fine-tune the crystal structure of CoV2O4 spinel for highly enhanced oxygen evolution reaction (OER) is presented performance. The incorporation of Fe and Ru is observed at octahedral sites within the CoV2O4 structure, effectively modulating the electronic configuration of Co. Density functional theory calculations have confirmed that Fe acts as a novel reactive site, replacing V. Additionally, the synergistic effect of Fe, Co, and Ru effectively optimizes the Gibbs free energy of the intermediate species, reduces the reaction energy barrier, and accelerates the kinetics toward OER. As expected, the best-performing CoVFe0.5Ru0.5O4 displays a low overpotential of 240 mV (@10 mA cm-2) and a remarkably low Tafel slope of 38.9 mV dec-1, surpassing that of commercial RuO2. Moreover, it demonstrates outstanding long-term durability lasting for 72 h. This study provides valuable insights for the design of highly active polymetallic spinel electrocatalysts for energy conversion applications.

Altering electronic structure of nickel foam supported CoNi-based oxide through Al ions modulation for efficient oxygen evolution reaction.

Developing highly active and durable non-precious metal-based electrocatalysts for the oxygen evolution reaction (OER) is crucial in achieving efficient energy conversion. Herein, we reported a CoNiAl0.5O/NF nanofilament that exhibits higher OER activity than previously reported IrO2-based catalysts in alkaline solution. The as-synthesized CoNiAl0.5O/NF catalyst demonstrates a low overpotential of 230 mV at a current density of 100 mA cm-2, indicating its high catalytic efficiency. Furthermore, the catalyst exhibits a Tafel slope of 26 mV dec-1, suggesting favorable reaction kinetics. The CoNiAl0.5O/NF catalyst exhibits impressive stability, ensuring its potential for practical applications. Detailed characterizations reveal that the enhanced activity of CoNiAl0.5O/NF can be attributed to the electronic modulation achieved through Al3+ incorporation, which promotes the emergence of higher-valence Ni metal, facilitating nanofilament formation and improving mass transport and charge transfer processes. The synergistic effect between nanofilaments and porous nickel foam (NF) substrate significantly enhances the electrical conductivity of this catalyst material. This study highlights the significance of electronic structures for improving the activity of cost-effective and non-precious metal-based electrocatalysts for the OER.

Early Diagnosis of Colorectal Cancer Based on Bisulfite-free Site-specific Methylation Identification PCR Strategy: High-Sensitivity, Accuracy, and Primary Medical Accessibility.

Due to its decade-long progression, colorectal cancer (CRC) is most suitable for population screening to achieve a significant reduction in its incidence and mortality. DNA methylation has emerged as a potential marker for the early detection of CRC. However, the current mainstream methylation detection method represented by bisulfite conversion has issues such as tedious operation, DNA damage, and unsatisfactory sensitivity. Herein, a new high-performance CRC screening tool based on the promising specific terminal-mediated polymerase chain reaction (STEM-PCR) strategy is developed. CRC-related methylation-specific candidate CpG sites are first prescreened through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases using self-developed bioinformatics. Next, 9 homebrew colorectal cancer DNA methylated STEM‒PCR assays (ColoC-mSTEM) with high sensitivity (0.1%) and high specificity are established to identify candidate sites. The clinical diagnostic performance of these selected methylation sites is confirmed and validated by a case-control study. The optimized diagnostic model has an overall sensitivity of 94.8% and a specificity of 95.0% for detecting early-stage CRC. Taken together, ColoC-mSTEM, based on a single methylation-specific site, is a promising diagnostic approach for the early detection of CRC which is perfectly suitable for the screening needs of CRC in primary healthcare institutions.

Deoxynivalenol Inhibits Progenitor Leydig Cell Development by Stimulating Mitochondrial Fission in Rats.

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 µM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.

Carbon-chain length determines the binding affinity and inhibitory strength of per- and polyfluoroalkyl substances on human and rat steroid 5α-reductase 1 activity.

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 µM significantly inhibited human SRD5A1, with IC50 values ranged from 10.99 µM (C11) to 105.01 µM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC50 value of 8.15 µM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1.

Positive psychological capital, post-traumatic growth, social support, and quality of life in patients with systemic lupus erythematosus: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. RESULTS: The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. CONCLUSION: Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.

Mining channel-regulated peptides from animal venom by integrating sequence semantics and structural information.

Channel-regulated peptides (CRPs) derived from animal venom hold great promise as potential drug candidates for numerous diseases associated with channel proteins. However, discovering and identifying CRPs using traditional bio-experimental methods is a time-consuming and laborious process. While there were a few computational studies on CRPs, they were limited to specific channel proteins, relied heavily on complex feature engineering, and lacked the incorporation of multi-source information. To address these problems, we proposed a novel deep learning model, called DeepCRPs, based on graph neural networks for systematically mining CRPs from animal venom. By combining the sequence semantic and structural information, the classification performance of four CRPs was significantly enhanced, reaching an accuracy of 0.92. This performance surpassed baseline models with accuracies ranging from 0.77 to 0.89. Furthermore, we employed advanced interpretable techniques to explore sequence and structural determinants relevant to the classification of CRPs, yielding potentially valuable bio-function interpretations. Comprehensive experimental results demonstrated the precision and interpretive capability of DeepCRPs, making it an accurate and bio-explainable suit for the identification and categorization of CRPs. Our research will contribute to the discovery and development of toxin peptides targeting channel proteins. The source data and code are freely available at https://github.com/liyigerry/DeepCRPs.

Endogenous chemicals guard health through inhibiting ferroptotic cell death.

Ferroptosis is a new form of regulated cell death caused by iron-dependent accumulation of lethal polyunsaturated phospholipids peroxidation. It has received considerable attention owing to its putative involvement in a wide range of pathophysiological processes such as organ injury, cardiac ischemia/reperfusion, degenerative disease and its prevalence in plants, invertebrates, yeasts, bacteria, and archaea. To counter ferroptosis, living organisms have evolved a myriad of intrinsic efficient defense systems, such as cyst(e)ine-glutathione-glutathione peroxidase 4 system (cyst(e)ine-GPX4 system), guanosine triphosphate cyclohydrolase 1/tetrahydrobiopterin (BH4) system (GCH1/BH4 system), ferroptosis suppressor protein 1/coenzyme Q10 system (FSP1/CoQ10 system), and so forth. Among these, GPX4 serves as the only enzymatic protection system through the reduction of lipid hydroperoxides, while other defense systems ultimately rely on small compounds to scavenge lipid radicals and prevent ferroptotic cell death. In this article, we systematically summarize the chemical biology of lipid radical trapping process by endogenous chemicals, such as coenzyme Q10 (CoQ10), BH4, hydropersulfides, vitamin K, vitamin E, 7-dehydrocholesterol, with the aim of guiding the discovery of novel ferroptosis inhibitors.

[Identification of Nitrate Source and Transformation Process in Shallow Groundwater Around Dianchi Lake].

Elucidating the main sources and transformation process of nitrate for the prevention and control of groundwater nitrogen pollution and the development and utilization of groundwater resources has great significance. To explore the current situation and source of nitrate pollution in shallow groundwater around the Dianchi Lake, 73 shallow groundwater samples were collected in the rainy season in 2020(October) and dry season in 2021(April). Using the hydrochemistry and nitrogen and oxygen isotopes(δ15N-NO3- and δ18O-NO3-), the spatial distribution, source, and transformation process of nitrate in shallow groundwater were identified. The contribution of nitrogen from different sources to nitrate in shallow groundwater was quantitatively evaluated using the isotope mixing model(SIAR). The results showed that in nearly 40.5% of sampling points in the shallow groundwater in the dry season, ρ(NO3--N) exceeded the 20 mg·L-1 specified in the Class Ⅲ water quality standard for groundwater(GB/T 14848), and in more than 47.2% of sampling points in the rainy season, ρ (NO3--N) exceeded 20 mg·L-1. The analysis results of nitrogen and oxygen isotopes and SIAR model showed that soil organic nitrogen, chemical fertilizer nitrogen, and manure and sewage nitrogen were the main sources of nitrate in shallow groundwater; these nitrogen sources contributed 13.9%, 11.8%, and 66.5% to nitrate in shallow groundwater in the dry season and 33.7%, 31.1%, and 25.9% in the rainy season, respectively. However, the contribution rate of atmospheric nitrogen deposition was only 8.5%, which contributed little to the source of nitrate in shallow groundwater in the study area. Nitrification was the leading process of nitrate transformation in shallow groundwater in the dry season, denitrification was the dominant process in the rainy season, and denitrification was more noticeable in the rainy season than that in the dry season.

Effects of Moringa Oleifera Leaf Extract Plus Rosiglitazone on Serum Leptin and Glucose and Lipid Metabolism in Type 2 Diabetic Rats.

Objective: To investigate the effects of Moringa Oleifera Leaf Extract (MOLE) plus rosiglitazone (RSG) on glucose and lipid metabolism, serum leptin, and the Akt/GSK3ß/ß-Catenin signaling pathway in type 2 diabetic (T2D) rats. Methods: Sixty male Sprague-Dawley (SD) rats were randomly divided into six groups: the normal group, the model group, the RSG group, the low- and high-dose MOLE group, and the MOLE+RSG group. The normal group was fed a standard rat diet, while the other groups were given a single intraperitoneal injection of low-dose streptozomycin (STZ) (35 mg/kg) and fed a high-sugar and high-fat diet. After 8 weeks, the treatment outcomes were evaluated by measuring key parameters of blood glucose and lipid metabolism and the protein kinase B (AKT) / Glycogen synthase kinase 3beta (GSK3ß) /ß-Catenin signaling pathway in the T2D rats. Results: Compared with the normal group, the model group showed significantly increased levels of blood glucose, blood lipids, serum leptin, free fatty acid (FFA), and tumor necrosis factor-α (TNF-α). Compared with the model group, the RSG, low-dose MOLE, and high-dose MOLE groups displayed effective control of blood glucose, blood lipids, serum leptin, FFA, and TNF-α. The MOLE+RSG group surpassed the RSG group in regulating glucose, lipid metabolism, and serum leptin levels in T2D rats. In addition, the MOLE+RSG group also had superiority over the RSG group in activating the AKT/GSK3ß/ß-Catenin pathway. Conclusion: MOLE plus RSG can effectively reduce blood glucose and blood lipids in T2DM rats.

Metabonomics analysis of microalga Scenedesmus obliquus under ciprofloxacin stress.

The wide use of antibiotics in aquaculture has triggered global ecological security issue. Microalgal bioremediation is a promising strategy for antibiotics elimination due to carbon recovery, detoxification and various ecological advantages. However, a lack of understanding with respect to the corresponding regulation mechanism towards antibiotic stress may limit its practical applicability. The microalga Scenedesmus obliquus was shown to be capable of effectively eliminating ciprofloxacin (CIP), which is a common antibiotic used in aquaculture. However, the corresponding transcriptional alterations require further investigation and verification at the metabolomic level. Thus, this study uncovered the metabolomic profiles and detailed toxic and defense mechanisms towards CIP in S. obliquus using untargeted metabolomics. The enhanced oligosaccharide/polyol/lipid transport, up-regulation of carbohydrate and arachidonic acid metabolic pathways and increased energy production via EMP metabolism were observed as defense mechanisms of microalgal cells to xenobiotic CIP. The toxic metabolic responses included: (1) down-regulation of parts of mineral and organic transporters; (2) electrons competition between antibiotic and NAD during intracellular CIP degradation; and (3) suppressed expression of the hem gene in chlorophyll biosynthesis. This study describes the metabolic profile of microalgae during CIP elimination and reveals the key pathways from the perspective of metabolism, thereby providing information on the precise regulation of antibiotic bioremediation via microalgae.

Simultaneous removal of sulfamethoxazole during fermentative production of short-chain fatty acids.

This study explores the simultaneous sulfamethoxazole (SMX) removal and short-chain fatty acids (SCFAs) production by a Clostridium sensu stricto-dominated microbial consortium. SMX is a commonly prescribed and persistent antimicrobial agent frequently detected in aquatic environments, while the prevalence of antibiotic-resistant genes limits the biological removal of SMX. Under strictly anaerobic conditions, sequencing batch cultivation coupled with co-metabolism resulted in the production of butyric acid, valeric acid, succinic acid, and caproic acid. Continuous cultivation in a CSTR achieved a maximum butyric acid production rate and yield of 0.167 g/L/h and 9.56 mg/g COD, respectively, while achieving a maximum SMX degradation rate and removal capacity of 116.06 mg/L/h and 55.8 g SMX/g biomass. Furthermore, continuous anaerobic fermentation reduced sul genes prevalence, thus limiting the transmission of antibiotic resistance genes during antibiotic degradation. These findings suggest a promising approach for efficient antibiotic elimination while simultaneously producing valuable products (e.g., SCFAs).

Recovery of Li and Co in Waste Lithium Cobalt Oxide-Based Battery Using H1.6Mn1.6O4.

H1.6Mn1.6O4 lithium-ion screen adsorbents were synthesized by soft chemical synthesis and solid phase calcination and then applied to the recovery of metal Li and Co from waste cathode materials of a lithium cobalt oxide-based battery. The leaching experiments of cobalt and lithium from cathode materials by a citrate hydrogen peroxide system and tartaric acid system were investigated. The experimental results showed that under the citrate hydrogen peroxide system, when the temperature was 90 °C, the rotation speed was 600 r·min-1 and the solid-liquid ratio was 10 g·1 L-1, the leaching rate of Co and Li could reach 86.21% and 96.9%, respectively. Under the tartaric acid system, the leaching rates of Co and Li were 90.34% and 92.47%, respectively, under the previous operating conditions. The adsorption results of the lithium-ion screen showed that the adsorbents were highly selective for Li+, and the maximum adsorption capacities were 38.05 mg·g-1. In the process of lithium removal, the dissolution rate of lithium was about 91%, and the results of multiple cycles showed that the stability of the adsorbent was high. The recovery results showed that the purity of LiCl, Li2CO3 and CoCl2 crystals could reach 93%, 99.59% and 87.9%, respectively. LiCoO2 was regenerated by the sol-gel method. XRD results showed that the regenerated LiCoO2 had the advantages of higher crystallinity and less impurity.

Copper-mediated chemodynamic therapy with ultra-low copper consumption by doping cupric ion on cross-linked (R)-(+)-lipoic acid nanoparticles.

Cu-mediated chemodynamic therapy (CDT) has attracted prominent attention owing to its advantages of pH independence and high efficiency comparing to Fe-mediated CDT, while the application of Cu-based CDT agents was impeded due to the high copper consumption caused by the metabolism loss of copper and the resultant potential toxicity. Herein, we developed a new copper-mediated CDT agent with extremely low Cu usage by anchoring copper on cross-linked lipoic acid nanoparticles (Cu@cLAs). After endocytosis into tumor cells, the Cu@cLAs were dissociated into LA and dihydrolipoic acid (DHLA) (reduced form of LA) and released Cu2+ and Cu+ (oxidized form of Cu2+), the two redox couples recycled each other in cells to achieve the efficient killing of cancer cells by delaying metabolic loss and increasing the ROS level of tumor cells. The self-recycling was confirmed in cells by the sustained high Cu/DHLA content and persistent ROS generation process. The antitumor study based on the MCF-7/R nude mice gave the Cu@cLAs a tumor inhibitory rate up to 77.9% at the copper of 0.05 mg kg-1, the first dosage reported so far lower than that of normal serum copper (0.83 ± 0.21 mg kg-1). This work provides not only a new promising clinical strategy for the copper excessive use in copper-mediated CDT, but also gives a clue for other metal mediated disease therapies with the high metal consumption.

Nanodrug constructed using dietary antioxidants for immunotherapy of metastatic tumors.

Immunogenic cell death (ICD) induced by reactive oxygen species (ROS) represents a particular form of tumor cell death for approaching the problem of low immunogenicity of tumors in immunotherapy, while the oxidative damage to normal cells of current ICD inducers hinders their clinical application. Herein, a new ICD inducer VC@cLAV constructed solely by dietary antioxidants, lipoic acid (LA) and vitamin C (VC), is developed, which could promote heavy intracellular ROS production in cancer cells for ICD induction while acting as an anti-oxidant in non-cancer cells for cytoprotection, and thus hold high biosafety. In vitro studies show that VC@cLAV induced a release of antigens and a maturation rate of DCs up to 56.5%, approaching the positive control (58.4%). In vivo combined with αPD-1, VC@cLAV showed excellent antitumor activity against both primary and distant metastatic tumors with an inhibition rate of 84.8% and 79.0% compared to 14.2% and 10.0% in the αPD-1 alone group. Notably, VC@cLAV established a long-term antitumor immune memory effect against tumor rechallenging. This study not only presents a new kind of ICD inducer but also provides an impetus for the development of dietary antioxidant-based cancer drugs.