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The abuse of oxytetracycline (OTC) leaves serious environmental residues and triggers accumulation in organisms, constituting a threat to human health. Constructing an effective platform based on dual-functional materials for monitoring and removing OTC residues is a preferable solution. Herein, we proposed a novel composite material by doping carbon dots (CDs) into melamine–formaldehyde microsphere (MFM) through a one-pot method and named CDs@MFM, which inherited the fluorescence property of CDs and porous structure of MFM simultaneously. CDs@MFM demonstrated dual functions for the detection and removal of OTC concurrently within a few minutes, with its performance compared in detail with bare CDs and MFM as controls. By virtue of the pre-enrichment effect attributed to its porous structure, CDs@MFM exhibited a lower detection limit for OTC than bare CDs (0.027 mg/L vs 0.067 mg/L) and a higher adsorption capacity than MFM (73.01 mg/g vs 68.76 mg/g) resulting from more affiliated functional groups available for OTC provided by the CDs. Overall, CDs@MFM has proven to be an efficient and convenient candidate capable of monitoring and removing OTC synchronously, and this work offers an avenue for the design of dual-functional materials in the field of environmental science.

Summary: Ferroptosis is a form of nonapoptotic cell death characterized by iron-dependent peroxidation of polyunsaturated phospholipids. However, much remains unknown about the regulators of ferroptosis. Here, using CRISPR-Cas9-mediated genetic screening, we identify protein arginine methyltransferase 1 (PRMT1) as a crucial promoter of ferroptosis. We find that PRMT1 decreases the expression of solute carrier family 7 member 11 (SLC7A11) to limit the abundance of intracellular glutathione (GSH). Moreover, we show that PRMT1 interacts with ferroptosis suppressor protein 1 (FSP1), a GSH-independent ferroptosis suppressor, to inhibit the membrane localization and enzymatic activity of FSP1 through arginine dimethylation at R316, thus reducing CoQ10H2 content and inducing ferroptosis sensitivity. Importantly, genetic depletion or pharmacological inhibition of PRMT1 in mice prevents ferroptotic events in the liver and improves the overall survival under concanavalin A (ConA) exposure. Hence, our findings suggest that PRMT1 is a key regulator of ferroptosis and a potential target for antiferroptosis therapeutics.

Jointed soft-hard composite rock mass is very common in engineering. The existence of joint and the uncoordinated deformation of soft-hard layer make the failure behavior more complicated. In this study, soft-hard composite rock with three parallel joints (two coplanar joints and one out-of-plane parallel joint) were fabricated to carry out uniaxial compression experiment. With the aid of digital imagine correlation (DIC) and acoustic emission (AE) technology, the influence of joint angle, ligament angle and the location of out-of-plane joint on crack propagation behavior of specimen is analyzed. The results show that when the hard layer contains more joints, the rock mass presents more obvious brittleness. The variation of peak strength with ligament angle also depends on the rock layer where the out-of-plane crack is located. Three failure modes and ten crack coalescence modes are summarized, which are affected by joint angle and ligament angle. The transition of crack coalescence between adjacent rock layer is mainly influenced by the space of wing cracks at joint tips. The coalescence of rock bridge in the layer with double joints is affected by ligament angle and the relative strength of layer. When the out-of-plane joint is in the hard layer, the coalescence possibility is greatly reduced.

The clinical success of KRASG12C inhibitors (G12Ci) including AMG510 and MRTX849 is limited by the eventual development of acquired resistance. A novel and effective treatment to revert or target this resistance is urgent. To this end, we established G12Ci (AMG510 and MRTX849) resistant KRASG12C mutant cancer cell lines and screened with an FDA-approved drug library. We found the ferroptosis inducers including sorafenib and lapatinib stood out with an obvious growth inhibition in the G12Ci resistant cells. Mechanistically, the G12Ci resistant cells exhibited reactivation of MAPK signaling, which repressed SOX2-mediated expression of cystine transporter SLC7A11 and iron exporter SLC40A1. Consequently, the low intracellular GSH level but high iron content engendered hypersensitivity of these resistant tumors to ferroptosis inducers. Ectopic overexpression of SOX2 or SLC7A11 and SLC40A1 conferred resistance to ferroptosis in the G12Ci resistant cells. Ferroptosis induced by sulfasalazine (SAS) achieved obvious inhibition on the tumor growth of xenografts derived from AMG510-resistant KRASG12C-mutant cells. Collectively, our results suggest a novel therapeutic strategy to treat patients bearing G12Ci resistant cancers with ferroptosis inducers.

Background: Dry eye disease (DED) is a commonly reported ocular complaint that has garnered significant attention in recent research. The global occurrence of DED ranges from 5% to 50%, impacting a substantial proportion of individuals worldwide with increasing frequency. Although topical administration remains the mainstream drug delivery method for ocular diseases, it suffers from drawbacks such as low bioavailability, rapid drug metabolism, and frequent administration requirements. Fortunately, the advancements in nanomedicine offer effective solutions to address the aforementioned issues and provide significant assistance in the treatment of DED. Main text: DED is considered a multifactorial disease of the ocular surface and tear film, in which the integrity of tear film function and structure plays a crucial role in maintaining the homeostasis of the ocular surface. The conventional treatment for DED involves the utilization of artificial tear products, cyclosporin, corticosteroids, mucin secretagogues, and nonsteroidal anti-inflammatory drugs. Furthermore, nanomedicine is presently a significant field of study, with numerous clinical trials underway for various nanotherapeutics including nanoemulsions, nanosuspensions, liposomes, and micelles. Notably, some of these innovative nanoformulations have already received FDA approval as novel remedies for DED, and the advancement of nanomedicine is poised to offer enhanced prospects to solve the shortcomings of existing treatments for DED partially. Conclusions: This article provides an overview of the latest advancements in nanomedicine for DED treatment, while the field of DED treatment is expected to witness a remarkable breakthrough shortly with the development of nanomedicine, bringing promising prospects for patients worldwide suffering conditions.

Objective: To prospectively determine the median effective dose (ED50) of propofol for inhibiting a response to laryngeal mask airway (LMA) insertion when combined with different doses of esketamine in female patients. Methods: A total of 58 female patients (aged 20–60 years, ASAⅠ–Ⅱ) scheduled for elective hysteroscopy were enrolled and randomly divided into 2 groups, one of which was administered 0.2 mg/kg of esketamine (K1 group, n = 28) and the other 0.3 mg/kg of esketamine (K2 group, n = 30). The 2 groups received the corresponding doses of esketamine intravenously, followed by an intravenous injection of propofol (injection time was 30 s). The initial dose of propofol was 2 mg/kg, and the dose ratio of propofol in the adjacent patients was 0.9. If a positive reaction occurred due to LMA insertion, the dose ratio in the next patient was increased by 1 gradient; if not, the dose ratio was decreased by 1 gradient. The ED50, 95 % effective dose (ED95) and 95 % confidence interval (CI) of propofol for inhibiting a response to LMA insertion in the 2 esketamine groups were calculated using probit analysis. Results: The ED50 of propofol for inhibiting a response to LMA insertion in female patients was 1.95 mg/kg (95 % CI, 1.82–2.08 mg/kg) in the K1 group and 1.60 mg/kg (95 % CI, 1.18–1.83 mg/kg) in the K2 group. The ED95 of propofol for inhibiting a response to LMA insertion in female patients was 2.22 mg/kg (95 % CI, 2.09–2.86 mg/kg) in the K1 group and 2.15 mg/kg (95 % CI, 1.88–3.09 mg/kg) in the K2 group. Conclusion: Propofol combined with 0.3 mg/kg of esketamine has low ED50 and ED95 effective doses for inhibiting an LMA insertion response in female patients undergoing hysteroscopy and surgery. There were no significant adverse effects, but the additional dose of propofol and airway pressure were significantly higher than those in the group administered 0.2 mg/kg of esketamine. Based on the results, we recommend the combination of propofol with 0.2 mg/kg esketamine for optimal conditions during LMA insertion in women undergoing hysteroscopy.

Summary: The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8+ T lymphocytes (CD8+ CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8+ CTLs in mouse tumors and patients. Blocking the Hippo pathway effector Yes-associated protein/transcriptional enhanced associate domain (YAP/TEAD) potently improves antitumor immunity. Mechanistically, the YAP/TEAD complex cooperates with the nucleosome remodeling and deacetylase complex to repress NLRC5 transcription. The upregulation of NLRC5 by YAP/TEAD depletion or pharmacological inhibition increases the expression of MHC class I APP genes and enhances CD8+ CTL-mediated killing of cancer cells. Collectively, our results suggest a crucial tumor-promoting function of YAP depending on NLRC5 to impair the MHC class I APP pathway and provide a rationale for inhibiting YAP activity in immunotherapy for cancer.

The rotes of attempted and completed suicide among adolescents are increasing globally. Social support can help decrease the risk of adolescent suicide, but this aspect has been rarely studied in China. The present study aimed to use the Delphi methodology to establish a set of guidelines for the development of social support resources, with the goal of collectively reducing suicide risks among adolescents in Shanghai. We commenced the study in April 2021, established a research team, searched the keywords using Web of Science from 2016 to 2021 and ultimately designed a pre-evaluation index. Next, following Donabedian’s Structure–Process-Outcome model, the research developed a questionnaire comprising 3 level-1, 12 level-2, and 73 level-3 indicators. Ten experts were enlisted to conduct three rounds of e-mail inquiries in order to finalize the indicator system, resulting in 2 level-1, 11 level-2, and 52 level-3 indicators, as well as expert consensus. Our findings indicate that the social support systems should include parents, schools, psychiatric hospitals, social organizations, and government departments, with the government sector being the most important ((M = 9.4). Furthermore, our study revealed that school counselors and psychologists play similar roles to psychiatrists within the interdisciplinary team (M ± S = 9.2 ± 1.1). As per the expert consensus, social support systems should strengthen government-led and interdisciplinary collaboration, prioritize suicide prevention in schools and encourage greater involvement from social organizations.

Mitochondria-associated ferroptosis exacerbates cardiac microvascular dysfunction in diabetic cardiomyopathy (DCM). Nicorandil, an ATP-sensitive K+ channel opener, protects against endothelial dysfunction, mitochondrial dysfunction, and DCM; however, its effects on ferroptosis and mitophagy remain unexplored. The present study aimed to assess the beneficial effects of nicorandil against endothelial ferroptosis in DCM and the underlying mechanisms. Cardiac microvascular perfusion was assessed using a lectin perfusion assay, while mitophagy was assessed via mt-Keima transfection and transmission electron microscopy. Ferroptosis was examined using mRNA sequencing, fluorescence staining, and western blotting. The mitochondrial localization of Parkin, ACSL4, and AMPK was determined via immunofluorescence staining. Following long-term diabetes, nicorandil treatment improved cardiac function and remodeling by alleviating cardiac microvascular injuries, as evidenced by the improved microvascular perfusion and structural integrity. mRNA-sequencing and biochemical analyses showed that ferroptosis occurred and Pink1/Parkin-dependent mitophagy was suppressed in cardiac microvascular endothelial cells after diabetes. Nicorandil treatment suppressed mitochondria-associated ferroptosis by promoting the Pink1/Parkin-dependent mitophagy. Moreover, nicorandil treatment increased the phosphorylation level of AMPKα1 and promoted its mitochondrial translocation, which further inhibited the mitochondrial translocation of ACSL4 via mitophagy and ultimately suppressed mitochondria-associated ferroptosis. Importantly, overexpression of mitochondria-localized AMPKα1 (mitoAα1) shared similar benefits with nicorandil on mitophagy, ferroptosis and cardiovascular protection against diabetic injury. In conclusion, the present study demonstrated the therapeutic effects of nicorandil against cardiac microvascular ferroptosis in DCM and revealed that the mitochondria-localized AMPK-Parkin-ACSL4 signaling pathway mediates mitochondria-associated ferroptosis and the development of cardiac microvascular dysfunction.

Water inflow poses a critical safety concern in coal mining. The pressing challenge in current mine water inflow research is the need to enhance the prediction of dynamic changes in mine water inflow across different mining stages. In this study, the hydrogeological conditions and aquifer structural characteristics of the Wutongzhuang Coal Mine in Hebei Province, China were analyzed, and the results were combined with pumping test and drilling data. A numerical model of groundwater flow in the study area was established using Visual MODFLOW and the model was calibrated and verified by comparing its results with the measured values to ensure that it realistically reflected the state of groundwater movement in the study area. The results of numerical simulation indicated that: (1) The water level of the Ordovician aquifer varies significantly by season. A large exposed area of Ordovician limestone in the western mountainous region receives a large amount of rainfall infiltration recharge in the summer rainy period that raises the water level of the Ordovician aquifer in the study area. (2) The groundwater system in the study area is in an equilibrium state, with the water inflow approximately equal to the outflow. (3) The recharge of mine drainage water has a slight positive effect on the Ordovician water level and the floor water inflow, with the impact on the water level of the aquifer decreasing as the distance from the recharge well and the import of Ordovician limestone water increase. In cases in which there is mine water recharge, the water level of the Ordovician aquifer is approximately 0.33 to 1.37 m higher than in cases without recharge, resulting in an increase in water inflow of approximately 10.6 m3/d. (4) In cases in which there is recharge of all drainage water, the maximum water inflow into the fifth mining area is 3,491.3 m3/d, which is 12.5 m3/d higher than in the case without recharge. These results provide important technical references for the formulation of mining schemes and water prevention measures in mining areas.

Myo-inositol and its derivatives play important roles in the tolerance of higher plants to abiotic stresses, and myo-inositol-1-phosphate synthase (MIPS) is the rate-limiting enzyme in myo-inositol biosynthesis. In this study, we found that increased myo-inositol biosynthesis enhanced drought tolerance in MdMIPS1-overexpressing apple lines under short-term progressive drought stress. The effect of myo-inositol appeared to be mediated by the increased accumulation of osmoprotectants such as glucose, sucrose, and proline, and by the increased activities of antioxidant enzymes that eliminate reactive oxygen species. Moreover, enhanced water-use efficiency (WUE) was observed in MdMIPS1-overexpressing apple lines under long-term moderate water deficit conditions that mimicked the water availability in the soil of the Loess Plateau. Enhanced WUE may have been associated with the synergistic regulation of osmotic balance and stomatal aperture mediated by increased myo-inositol biosynthesis. Taken together, our findings shed light on the positive effects of MdMIPS1-mediated myo-inositol biosynthesis on drought tolerance and WUE in apple.

The source–sink ratio during grain filling is a critical factor that affects crop yield in wheat, and the main objective of this study was to determine the source–sink relations at both the canopy scale and the individual culm level under two nitrogen (N) levels at the post-jointing stage. Nine widely-used cultivars were chosen for analyzing source–sink relations in southwestern China; and three typical cultivars of different plant types were subjected to artificial manipulation of the grain-filling source–sink ratio to supplement crop growth measurements. A field experiment was conducted over two consecutive seasons under two N rates (N+, 150 kg ha−1; N–, 60 kg ha−1), and three manipulations were imposed after anthesis: control (Ct), removal of flag and penultimate leaves (Lr) and removal of spikelets on one side of each spike (Sr). The results showed that the single grain weights in the three cultivars were significantly decreased by Lr and increased by Sr, which demonstrated that wheat grain yield potential seems more source-limited than sink-limited during grain filling, but the source–sink balance was obviously changed by climatic variations and N deficient environments. Grain yield was highly associated with sink capacity (SICA), grain number, biomass, SPAD values, and leaf area index during grain filling, indicating a higher degree of source limitation with an increase in sink capacity. Therefore, source limitation should be taken into account by breeders when SICA is increased, especially under non-limiting conditions. Chuanmai 104, a half-compact type with a mid-sized spike and a long narrow upper leaf, showed relatively better performance in source–sink relations. Since this cultivar showed the characteristics of a lower reduction in grain weight after Lr, a larger increase after Sr, and a lower reduction in post-anthesis dry matter accumulation, then the greater current photosynthesis during grain filling contributed to the grain after source and sink manipulation.

Gemcitabine has been extensively applied in treating various solid tumors. Nonetheless, the clinical performance of gemcitabine is severely restricted by its unsatisfactory pharmacokinetic parameters and easy deactivation mainly because of its rapid deamination, deficiencies in deoxycytidine kinase (DCK), and alterations in nucleoside transporter. On this account, repeated injections with a high concentration of gemcitabine are adopted, leading to severe systemic toxicity to healthy cells. Accordingly, it is highly crucial to fabricate efficient gemcitabine delivery systems to obtain improved therapeutic efficacy of gemcitabine. A large number of gemcitabine pro-drugs were synthesized by chemical modification of gemcitabine to improve its biostability and bioavailability. Besides, gemcitabine-loaded nano-drugs were prepared to improve the delivery efficiency. In this review article, we introduced different strategies for improving the therapeutic performance of gemcitabine by the fabrication of pro-drugs and nano-drugs. We hope this review will provide new insight into the rational design of gemcitabine-based delivery strategies for enhanced cancer therapy.

Bone is one of the most preferred sites of metastasis in lung cancer. Currently, bisphosphonates and denosumab are major agents for controlling tumor-associated skeletal-related events (SREs). However, both bisphosphonates and denosumab significantly increase the risk for jaw osteonecrosis. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and the most frequently prescribed cholesterol-lowering agents, have been reported to inhibit tumor progression and induce autophagy in cancer cells. However, the effects of statin and role of autophagy by statin on bone metastasis are unknown. In this study, we report that fluvastatin effectively prevented lung adenocarcinoma bone metastasis in a nude mouse model. We further reveal that fluvastatin-induced anti-bone metastatic property was largely dependent on its ability to induce autophagy in lung adenocarcinoma cells. Atg5 or Atg7 deletion, or 3-methyadenine (3-MA) or Bafilomycin A1 (Baf A1) treatment prevented the fluvastatin-induced suppression of bone metastasis. Furthermore, we reveal that fluvastatin stimulation increased the nuclear p53 expression, and fluvastatin-induced autophagy and anti-bone metastatic activity were mostly dependent on p53.

Purpose: Osteosarcoma is an aggressive malignant neoplasm, and conflicting findings have been reported on the survival and function recovery in osteosarcoma patients experiencing limb salvage or amputation. In the present study, we compared clinical outcomes regarding limb salvage surgery vs. amputation for osteosarcoma patients by a meta-analysis. Method: Literature search was conducted in CNKI, Medline, Embase, the Cochrane Database, and Web of Sciences, and the quality of included studies was evaluated based on Newcastle-Ottawa scale quality assessment. Odds ratio and 95% confidence interval of the local recurrence, 5-year overall survival, and metastasis occurrence were calculated. Results: 17 articles were included according to selection criteria. There were 1343 patients in total derived from these studies. Our result showed that there was no significant difference between limb salvage surgery and amputation with respect to local recurrence, and patients with limb salvage surgery had a higher 5-year overall survival, and a lower metastasis occurrence. Conclusions: The present study provided more comprehensive evidences to support limb salvage surgery as an optimal treatment of osteosarcoma patients.

The N170 component of EEG evoked by visual words is an index of perceptual expertise for the visual word across different writing systems. In the present study, we investigated whether these N170 markers for Chinese, a very complex script, could emerge quickly after short-term learning (∼100 min) in young Chinese children, and whether early writing experience can enhance the acquisition of these neural markers for expertise. Two groups of preschool children received visual identification and free writing training respectively. Short-term character training resulted in selective enhancement of the N170 to characters, consistent with normal expert processing. Visual identification training resulted in increased N170 amplitude to characters in the right hemisphere, and N170 amplitude differences between characters and faces were decreased; whereas the amplitude difference between characters and tools increased. Writing training led to the disappearance of an initial amplitude difference between characters and faces in the right hemisphere. These results show that N170 markers for visual expertise emerge rapidly in young children after word learning, independent of the type of script young children learn; and visual identification and writing produce different effects.

Recent technological advancements have permitted high-throughput measurement of the human genome, epigenome, metabolome, transcriptome, and proteome at the population level. We hypothesized that subsets of genes identified from omic studies might have closely related biological functions and thus might interact directly at the network level. Therefore, we conducted an integrative analysis of multi-omic datasets of non-small cell lung cancer (NSCLC) to search for association patterns beyond the genome and transcriptome. A large, complex, and robust gene network containing well-known lung cancer-related genes, including EGFR and TERT, was identified from combined gene lists for lung adenocarcinoma. Members of the hypoxia-inducible factor (HIF) gene family were at the center of this network. Subsequent sequencing of network hub genes within a subset of samples from the Transdisciplinary Research in Cancer of the Lung-International Lung Cancer Consortium (TRICL-ILCCO) consortium revealed a SNP (rs12614710) in EPAS1 associated with NSCLC that reached genome-wide significance (OR = 1.50; 95% CI: 1.31–1.72; p = 7.75 × 10−9). Using imputed data, we found that this SNP remained significant in the entire TRICL-ILCCO consortium (p = .03). Additional functional studies are warranted to better understand interrelationships among genetic polymorphisms, DNA methylation status, and EPAS1 expression.

Holes and joints are widespread and coexisting flaws in natural rock. The spatial distribution of combined flaw significantly affects the instability process of fractured rock. To study the influence of ligament length and joint angle on failure characteristics, uniaxial compression experiments are carried out on specimens containing hole-joint combined flaw assisted by acoustic emission (AE) and digital image correlation (DIC) technologies. As the ligament length increases, the mechanical parameter curves decrease first and then rise, showing a U-shape or V-shape. DIC results show that the hole performs a strong inhibition on the crack propagation from the inner joint tips, which will be weakened with the increase of ligament length. The driving displacement field of wing cracks and the type of cracks outside the joint are affected by joint angle variation. The cracks in rock bridge area are generally tensile-shear or shear type. According to AE analysis, the proportion of tensile signals decreased from the pre-peak failure stage to the post-peak stage, and the tensile signal is lower than 50% in the late loading stage, indicating that the shear crack dominates the final failure of specimens.

The Shangri-La region, located in southwest China, is known for its dry climate and intense UltraViolet (UV) radiation due to its high altitude. Research conducted in the past has demonstrated that UV radiation, particularly UV-B radiation, enhances plants' ability to withstand cold temperatures, diseases, and arid conditions. Indeed, the Cabernet Sauvignon grape variety, predominantly cultivated in Shangri-La where the UV intensity reaches 21–22w/m2, has displayed remarkable resilience in recent decades. However, the specific impact of UV-B radiation on Cabernet Sauvignon grape leaves has yet to be fully understood. Consequently, our objective is to investigate the influence of UV radiation on grapes grown at high altitudes. To gain insights into the short-term effects on grape leaves, we conducted a comprehensive investigation involving anatomical and photosynthetic changes. Additionally, we analyzed the transcriptomic and proteomic regulation associated with these changes following exposure to UV-B radiation at intensities ranging from 15–20w/m2 for durations of 3 and 7 days.The findings of our study demonstrated that exposure to UV-B radiation, particularly at intensities surpassing 10w/m2, led to noticeable changes in the morphology of epidermal and palisade tissue cells. Furthermore, after a 3-day exposure to UV-B, we observed an upregulation of proteins responsible for cytoskeletal organization and cell wall synthesis. Conversely, following a 7-day treatment, proteins associated with disease resistance and antioxidants showed increased expression. Transcriptomic analysis revealed a significant enrichment of proteins and genes linked to pathogen infection, defense mechanisms, and antioxidant processes. Overall, our research highlighted the positive impact of intense UV radiation at high altitudes on enhancing disease resistance and environmental adaptability in Cabernet Sauvignon grape plants.

Distiller's grains, byproducts of the brewing process, represent a valuable resource for extracting natural phenolic compounds due to their significant global production. This study presents the first evidence of the protective effects of Moutai distiller's grain polyphenol extract (MDGP) on dextran sulfate sodium (DSS)-induced colitis in mice. These protective effects manifest predominantly through the amelioration of general colitis indices and histopathological improvements. Utilizing liquid chromatography-high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS), the main components of MDGP were identified as rutin, quercetin, naringenin, and dihydroquercetin. Moreover, a novel mechanism was elucidated by which rutin, the primary active component of MDGP, alleviates DSS-induced colitis. Assessment of intestinal barrier function, microbial sequencing, fecal transplantation, and antibiotic depletion experiments revealed that rutin suppresses the abundance of pathogenic bacteria (Helicobacter, Klebsiella, and Veillonella) while promoting the proliferation of beneficial bacteria (Ruminococcus_torques_group, Lachnoclostridium, and norank_f__Muribaculaceae). This modulation culminates in elevated butyric acid concentrations within short-chain fatty acids (SCFAs), amplified integrity of tight (ZO-1, occludin) and adherent (E-cadherin, β-catenin) junctional complexes, fortified intestinal barrier function, and diminished intestinal inflammation.This investigation accentuates the innovative therapeutic potential of MDGP and its main active component, rutin, in assuaging DSS-induced intestinal inflammation and fortifying the intestinal barrier through a mechanism predominantly mediated by the intestinal microbiota. Such insights potentially elevate the prominence of distiller's grains in the realm of functional food development.

Glucose oxidase (GOx) can specifically catalyze the conversion of β-d-glucose into gluconic acid and hydrogen peroxide (H2O2) in the presence of oxygen, making it promising for tumor starvation therapy and oxidative therapy. However, GOx's immunogenicity, poor in vivo stability, short half-life, and potential systemic toxicity, limit its application in cancer therapy. Nanocarriers are capable of improving the pharmacological properties of therapeutic drugs (e.g. stability, circulating half-life, and tumor accumulation) and lower toxicity, hence resolving GOx issues and enhancing its efficacy. Although the application of targeted nanocarriers based on GOx has recently flourished, this field has not yet been reviewed and evaluated. Herein, we initially examined the mechanism of GOx-based nanocarriers for enhanced tumor therapy. Also, we present a comprehensive and up-to-date review that highlights GOx-based nanocarriers for tumor targeting therapy. This review expands on GOx-based nano-targeted combination therapies from both passive and active targeting perspectives, meanwhile, active targeting is further classified into ligand-mediated targeting and physical-mediated targeting. Furthermore, this review also emphasizes the present challenges and promising advancements.

Economic resilience has been a popular issue in recent years. Along with the consideration of severe shocks caused by the financial crisis of 2007–2008 and globalization of industry and the upgradation of knowledge and technology, economic resilience has brought in much attention. About 50 years of development of planned industrial parks in Taiwan has resulted in considerable economic scale; however, due to changes in interior demands and the exterior environment with time, rearrangement and industrial transformation have made the development of industrial parks difficult. Accordingly, the resilience of planned industrial parks in Taiwan, when encountering a variety of shocks, need to be reviewed and examined. This study selects 12 planned industrial parks from Tainan and Kaohsiung, in southern Taiwan, as subjects and had a complete understanding of economic resilience and factors that influence economic resilience from literature reviews. Four quadrant model constituted by the indicators of economic resistance and recovery as well as discriminant analysis are implemented to analyze the resilience of industrial parks with different backgrounds and various shocks, as well as the elements influencing the resilience. Analytical results indicate that planned industrial parks with industrial structures based on specialized variety or with a steady input of knowledge and innovation to research and development benefited the industrial parks in better resilience, while complete infrastructure planning and governance are fundamental conditions for resilience.

White mold of pea caused by Sclerotinia sclerotiorum is a common disease in China. However, we discovered that the diverse Sclerotinia species could cause white mold on pea plants in Chongqing and Sichuan of China during recent disease surveys. Thus, the objective of this study was to confirm the causal agents from diseased pea plants. The obtained isolates of white mold from Chongqing and Sichuan were identified by morphological characters and molecular characterization to determine the pathogen species, and their pathogenicity was confirmed on pea through completing Koch's postulates. Fungal isolates of Sclerotinia-like were obtained from diseased plants or sclerotia. Based on morphological characteristics and molecular characterization, 30 isolates were identified to three species, six isolates as S. minor, seven as S. sclerotiorum, and 17 as S. trifoliorum. In pathogenicity tests on pea cultivars Zhongwan 4 and Longwan 1, all 30 isolates caused typical symptoms of white mold on the inoculated plants, and the inoculated pathogens were re-isolated from the diseased plants. This study confirmed that white mold of pea was caused by three Sclerotinia species, S. sclerotiorum, S. minor and S. trifoliorum in Chongqing and Sichuan. It is the first report that S. minor and S. trifoliorum cause white mold of pea in Southwest China.

In this research, micro Coix lacryma-jobi L. vertical flow constructed wetlands (VFCWs) were set up using domestic sewage (DWS) and 1/2 Hoagland nutrient solution (HNS) as VFCWs water sources. 0, 20 mg L−1 and 40 mg L−1 of Cr6+ (in the form of K2Cr7O2) were added into the water sources separately in order to study the response of Coix lacryma-jobi L. under Cr6+ stress. The results showed that the inhibition rates of Cr6 + on plant height, stem diameter, shoot and root dry weight treated with HNS were 2.88~10.16%, 5.12~11.86%, 3.53~6.51% and 2.89~6.34% higher than those in DWS treatment. SEM analysis showed that the nuclear bilayer membrane was slightly damaged, the chromatin decreased and the number of mitochondrial cristae decreased when treated with 20 mg L−1 of Cr6+, however, organelle damage was more severe under 40 mg L−1 of Cr6+exposure. The X-ray energy spectrum analysis results indicated that the accumulation of chromium in epidermis and endodermis were higher than those in stele. The contents of total Cr in roots, stems and leaves treated with HNS were higher than those of DWS treatment. The highest content of Cr was observed in cell wall (32.12–188.1 mg kg-1), followed by vacuole (5.0–38.14 mg kg-1). The contents of Cr in each subcellular component in roots, stems, and leaves treated with HNS were higher than those of DWS, except for organelle components in the 14th week. DWS was used as water influent, the contents of easily migrated combined Cr (ETM) in roots, stems and leaves were significantly lower than those in HNS treatment. Improving the nutritional conditions of constructed wetlands might be beneficial to the improvement of their ability to purify chrome-containing waste water.

Rationale: Myocardial infarction (MI) is a leading cause of cardiovascular mortality globally. The improvement of microvascular function is critical for cardiac repair after MI. Evidence now points to long non-coding RNAs (lncRNAs) as key regulators of cardiac remodelling processes. The lncRNA Malat1 is involved in the development and progression of multiple cardiac diseases. Studies have shown that Malat1 is closely related to the regulation of endothelial cell regeneration. However, the potential molecular mechanisms of Malat1 in repairing cardiac microvascular dysfunction after MI remain unreported. Methods and results: The present study found that Malat1 is upregulated in the border zone of infarction in mouse hearts, as well as in isolated cardiac microvascular endothelial cells (CMECs). Targeted knockdown of Malat1 in endothelial cells exacerbated oxidative stress, attenuated angiogenesis and microvascular perfusion, and as a result decreased cardiac function in MI mice. Further studies showed that silencing Malat1 obviously inhibited CMEC proliferation, migration and tube formation, which was at least in part attributed to disturbed mitochondrial dynamics and activation of the mitochondrial apoptosis pathway. Moreover, bioinformatic analyses, luciferase assays and pull-down assays indicated that Malat1 acted as a competing endogenous RNA (ceRNA) for miR-26b-5p and formed a signalling axis with Mfn1 to regulate mitochondrial dynamics and endothelial functions. Overexpression of Mfn1 markedly reversed the microvascular dysfunction and CMEC injuries that were aggravated by silencing Malat1 via inhibition of excessive mitochondrial fragments and mitochondria-dependent apoptosis. Conclusions: The present study elucidated the functions and mechanisms of Malat1 in cardiac microcirculation repair after MI. The underlying mechanisms of the effects of Malat1 could be attributed to its blocking effects on miR-26b-5p/Mfn1 pathway-mediated mitochondrial dynamics and apoptosis.

Background: Our previous studies have showed that p-Hydroxylcinnamaldehyde (CMSP) could induce the differentiation of ESCC cells via the cAMP-RhoA-MAPK signalling pathway, which suggests a new potential strategy for ESCC treatment. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent inducer of apoptosis in several tumour cells by binding to the death receptors DR4 and DR5. However, TRAIL has little effect on oesophageal squamous cell carcinoma (ESCC) cells due to the loss of the receptors. The present study determined the effect of CMSP, the firstly found chemical constituent of Cochinchinamomordica seed (CMS), on TRAIL-induced apoptosis and its mechanism in ESCC cells. Methods: MTS assays were performed to examine the CMSP- and TRAIL-mediated inhibition of ESCC cell growth. Flow cytometry and Hoechst 33258 staining assays were used to detect apoptosis in ESCC cells treated with CMSP combined with TRAIL. Western blotting was used to determine the effect of CMSP on the expression of p38, p-p38, DR4, DR5, Bid and caspase-3/8 in ESCC cells treated with CMSP combined with TRAIL. Additionally, immunodeficient Balb-c/null mouse model was used to determine the chemotherapeutic efficacy of CMSP and TRAIL against ESCC tumour xenograft growth in vivo. Results: We found that the combination of CMSP and TRAIL had a greater inhibitory effect on ESCC cell viability in vitro than CMSP or TRAIL alone. CMSP enhanced the TRAIL-induced apoptosis in ESCC cells by upregulating the expression of DR4 and DR5 via the p38 MAPK signalling pathway. Furthermore, the increased expression of DR4 and DR5 upon TRAIL-induced apoptosis in ESCC cells was mediated at least in part by subsequent caspase-3 and caspase-8 activation. Moreover, the in vivo model showed that tumour growth was significantly slower in CMSP and TRAIL combination-treated mice than in mice treated with CMSP or TRAIL alone. Conclusion: Taken together, our findings indicate that CMSP as an extract from TCM, might be as a potential sensitizer of TRAIL and thus provide a novel strategy for the clinical treatment of ESCC.

Good crop stand establishment and root system development are essential for optimum grain yield of dryland wheat (Triticum aestivum L.). At present, little is known about the effect of tillage and straw mulch on the root system of wheat under dryland areas in southwestern China. The aim of this study was to evaluate the effect of three tillage treatments (no-till, NT; rotary till, RT; conventional till, CT) and two crop residue management practices (straw mulch, ML; non-straw mulch, NML) on stand establishment, root growth and grain yield of wheat. NT resulted in lower soil cover thickness for the wheat seed, higher number of uncovered seeds, lower percentage of seedling-less ridges and lower tiller density compared to RT and CT; ML resulted in higher tiller density compared to NML. Straw mulching resulted in more soil water content and root length density (RLD) at most of the growth stages and soil depths. The maximum RLD, root surface area density and root dry matter density were obtained under NT. In the topmost 10 cm soil layer, higher RLD values were found under NT than those under RT and CT. There were no significant differences in the yield or yield components of wheat among the tillage treatments in 2011–2012, but NT resulted in a significant higher yield compared to RT and CT in 2012–2013. Grain yield was significantly higher in ML compared to in NML. A strong relationship was observed between the water-use efficiency and the grain yield. Both NT and ML proved beneficial for wheat in term of maintaining higher tiller density, better soil water status and root growth, leading to a higher grain yield and enhanced water-use efficiency, especially in a low rainfall year.

Specific recognition and selective extraction of mycotoxin in environmental and food matrixes is significant to guarantee public health. Covalent organic frameworks (COFs) are promising adsorbents with tailorable functionality, but their low binding affinity and poor selectivity hamper their wide application for selective extraction of trace mycotoxin from complex matrix. Herein, we report calixarene incorporated molecular imprinting on COF to prepare molecularly imprinted calix[4]arene-containing COF (MICOF-CX4) for supramolecular recognition and specific adsorption of citrinin. Calixarene with host-guest chemistry was used as a functional monomer, while amine units with different topologies and function groups were selected to regulate MICOF-CX4 to match with citrinin. The complementary shape and supramolecular interactions of MICOF-CX4 gave highly selective recognition for citrinin. Moreover, MICOF-CX4 with vast accessible surface and plentiful imprinting sites exhibited faster adsorption kinetics and 4-fold higher adsorption capacity for citrinin adsorption than no-imprinted COF-CX4. Combination of MICOF-CX4 based solid-phase extraction with high-performance liquid chromatography-mass spectrometry allowed interference free determination of trace citrinin in real samples with a low detection limit of 0.03 ng mL -1 , good precision of 4.5 % and quantitative recovery of 88.2 %-101.4 %. The cooperative functions of calixarene and molecular imprinting make COF promising adsorbent for specific adsorption of trace targets in complex matrixes., 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 B.V. All rights reserved.)

Lappanolides A-N (1-14), 14 undescribed sesquiterpenoids, along with 23 known ones (15-37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC 50 values ranging from 5.2 to 45.7 μM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC 50 values of 5.28 and 5.30 μM, and CC 50 values of 9.85 and 6.37 μM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Covalent organic frameworks (COFs) are attractive materials for sample pretreatment due to their tunable structures and functions. However, the precise recognition of contaminant in complex environmental matrices by COFs remains challenging owing to their insufficient specific active sites. Herein, we report Co 2+ coordination-assisted molecularly imprinted flexible COF (MI-COF@Co 2+ ) for selective recognition of ochratoxin A (OTA). The MI-COF@Co 2+ was prepared via one-step polymerization of 3,3-dihydroxybenzidine, 2,4,6-tris(4-formylphenoxy)- 1,3,5-triazine, Co 2+ and template. The flexible units endowed COFs with the self-adaptable ability to regulate the molecular conformation and coordinate with Co 2+ to locate the imprinted cavities. The coordination interaction greatly improved the adsorption capacity and selectivity of MI-COF@Co 2+ for OTA. The prepared MI-COF@Co 2+ was used as solid phase extraction adsorbent for high-performance liquid chromatography determination of OTA with the detection limit of 0.03 ng mL -1 and the relative standard deviation of < 2.5 %. In addition, this method permitted interference-free determination of OTA in real samples with recovery from 89.5 % to 102.8 %. This work provides a simple way to improve the selectivity of COFs for the determination of hazardous compounds in complex environments., 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 B.V. All rights reserved.)

Purpose: To evaluate the efficacy of intravesical (IVe) Bacillus Calmette-Guerin (BCG) to treat non-muscle invasive bladder cancer (NMIBC) recurrences in patients who have previously undergone nephroureterectomy for upper tract urothelial carcinoma (UTUC)., Methods: We performed a single institution retrospective review of patients who underwent nephroureterectomy for UTUC from 2009 to 2021. Patients who subsequently developed NMIBC treated with transurethral resection followed by IVe BCG were included in the study group. A control cohort was formed by retrospective review of patents with primary NMIBC treated with BCG during the same period. Patients in the control cohort were matched by stage of bladder cancer at a 2:1 ratio of control to study subjects. Demographic data, pathology of bladder tumors prior to and following BCG, use of maintenance BCG (mBCG), time to recurrence, time to progression, progression to cystectomy, and progression to metastatic disease were collected on all patients. Descriptive statistics were utilized to compare the 2 groups. The primary outcome was progression to muscle invasive disease. Secondary outcomes included intravesical recurrence free survival, disease free survival, and progression to metastatic disease. Univariable and multivariable logistic regression analysis was performed to elucidate independent variables associated with bladder tumor recurrence. Multivariable Cox regression analysis was used to assess the impact of prior UTUC on time to bladder tumor recurrence., Results: One-hundred and ninety-one patients underwent nephroureterectomy at our institution from 2009 to 2021 for UTUC. Twenty-five patients were identified to have subsequently developed NMIBC recurrences treated with inductions BCG. The control group was comprised of 50 patients with primary NMIBC matched by stage of bladder cancer for which BCG was indicated in the study group. Median (interquartile range [IQR]) follow-up was significantly longer in the control group relative to the study group (64.8 [50.1-85.6] vs 25 months [17-35]; P = 0.001). There were no significant differences in demographics between the study and control groups. The rate of progression to muscle invasive disease was 17% vs 0% in the study group and control group respectively (P = 0.0521). History of UTUC was associated with increased risk of intravesical bladder tumor recurrence post BCG on multivariable analysis (HR 2.5; P = 0.017) and Kaplan Meier survival analysis (P = 0.039). The mean time to bladder tumor recurrence after treatment with BCG was significantly worse in the study group at (7.9 vs. 23.9 months; P = 0.0322). Similarly, the rate of progression to metastatic disease was worse in the study group (24% vs 2%; P = 0.0047). Overall disease-free survival was also noted to be significantly worse on Kaplan Meier survival analysis in the study group (P = 0.0074). No statistically significant differences in the stage grade of bladder tumor recurrence, grade of bladder tumor recurrence, or rate of progression to cystectomy were identified., Conclusions: Our study suggests reduced efficacy of BCG for NMIBC in patients with a history of UTUC. Patients in this population should be counseled accordingly. Research into alternative treatments for bladder tumor recurrence and more aggressive prophylactic regimens after nephroureterectomy for prevention of bladder tumor recurrence in this population is encouraged., Competing Interests: Declaration of competing interest None of the authors have a conflict of interest with the submitted research. There were no funding sources for the research submitted. All listed authors have contributed significantly to the published research and reviewed the above manuscript. There was no use of artificial intelligence software in the writing or editing of the submitted research., (Copyright © 2024 Elsevier Inc. All rights reserved.)