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Abstract Metabolic-associated steatohepatitis (MASH) and ulcerative colitis (UC) exhibit a complex interconnection with immune dysfunction, dysbiosis of the gut microbiota, and activation of inflammatory pathways. This study aims to identify and validate critical butyrate metabolism-related shared genes between both UC and MASH. Clinical information and gene expression profiles were sourced from the Gene Expression Omnibus (GEO) database. Shared butyrate metabolism-related differentially expressed genes (sBM-DEGs) between UC and MASH were identified via various bioinformatics methods. Functional enrichment analysis was performed, and UC patients were categorized into subtypes using the consensus clustering algorithm based on sBM-DEGs. Key genes within sBM-DEGs were screened through Random Forest, Support Vector Machines-Recursive Feature Elimination, and Light Gradient Boosting. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) analysis on independent datasets. Additionally, the expression levels of characteristic genes were validated across multiple independent datasets and human specimens. Forty-nine shared DEGs between UC and MASH were identified, with enrichment analysis highlighting significant involvement in immune, inflammatory, and metabolic pathways. The intersection of butyrate metabolism-related genes with these DEGs produced 10 sBM-DEGs. These genes facilitated the identification of molecular subtypes of UC patients using an unsupervised clustering approach. ANXA5, CD44, and SLC16A1 were pinpointed as hub genes through machine learning algorithms and feature importance rankings. ROC analysis confirmed their diagnostic efficacy in UC and MASH across various datasets. Additionally, the expression levels of these three hub genes showed significant correlations with immune cells. These findings were validated across independent datasets and human specimens, corroborating the bioinformatics analysis results. Integrated bioinformatics identified three significant biomarkers, ANXA5, CD44, and SLC16A1, as DEGs linked to butyrate metabolism. These findings offer new insights into the role of butyrate metabolism in the pathogenesis of UC and MASH, suggesting its potential as a valuable diagnostic biomarker.

Abstract Risk prediction for subsequent cardiovascular events remains an unmet clinical issue in patients with coronary artery disease. We aimed to investigate prognostic metabolic biomarkers by considering both shared and distinct metabolic disturbance associated with the composite and individual cardiovascular events. Here, we conducted an untargeted metabolomics analysis for 333 incident cardiovascular events and 333 matched controls. The cardiovascular events were designated as cardiovascular death, myocardial infarction/stroke and heart failure. A total of 23 shared differential metabolites were associated with the composite of cardiovascular events. The majority were middle and long chain acylcarnitines. Distinct metabolic patterns for individual events were revealed, and glycerophospholipids alteration was specific to heart failure. Notably, the addition of metabolites to clinical markers significantly improved heart failure risk prediction. This study highlights the potential significance of plasma metabolites on tailed risk assessment of cardiovascular events, and strengthens the understanding of the heterogenic mechanisms across different events.

Iron is an essential nutrient for maintaining red blood cell metabolism and assisting bone marrow hematopoiesis. Iron deficiency can cause various diseases, such as anemia, stunted growth, and premature birth in pregnant women. As a new iron supplement product, peptide iron chelate has been used as a new ideal iron supplement in recent years because of its advantages of high absorption rate, safety, and no side effects. This paper mainly reviews the preparation of foodborne peptides and peptide iron chelates and the factors affecting their chelation activity, explored the iron-binding mechanism of peptides, summarizes their binding sites and chelation patterns, further analyzes their conformational changes and intermolecular forces, and summarizes how they promote iron bioavailability. The aim is to provide a reference for developing and applying iron peptide chelates in functional foods and new iron supplements.

To investigate the effects of different extraction processes on the physicochemical properties and volatile flavor compounds of chicken oil. This study used three different extraction processes, namely dry, wet and microwave to extract chicken oil. The physicochemical properties of chicken oil extracted by different processes were comprehensively compared. At the same time, the volatile substance composition was determined by headspace gas chromatography-mass spectrometry, and the key volatile flavor component composition differences in chicken oil extracted by different processes were established by combining relative odor activity values, principal component analysis, and cluster analysis. The results showed that the chicken oil cooked by dry method had the lowest brightness, a redder and yellower color, and a lower content of malondialdehyde. Wet cooking chicken oil had the highest brightness, a greenish or yellowish color, and a lower acid value. The chicken oil cooked by microwave had a slightly darker brightness, lighter yellow and red, higher extraction rate, better oxidation stability, and shorter cooking time. A total of 49 volatile flavor compounds were identified in chicken oil samples extracted using different extraction methods. Among them, 39, 41, and 44 volatile flavor compounds were extracted from chicken oil using dry, wet, and microwave methods, respectively, with a total of 30 volatile flavor compounds. By combining ROAV and PCA, (E,E)-2,4-heptadienal, 1-octen-3-ol, hexanal, (E)-2-deceenal, 1-pentanol, octanal, (E,E)-2,4-decadienal, and 3-methylbutanal were identified as the main characteristic flavor compounds of chicken oil. The characteristic flavor substances extracted from chicken oil by microwave method had a high content and a variety of types. This study indicated that microwave technology had the advantages of relatively short time consumption, high yield, good oxidation stability and high content with variety of characteristic flavor substances in chicken oil, making it a worthwhile approach for further research and exploration of chicken oil extraction.

To evaluate the degree of unsaturation of different varieties of Camellia oil, it was necessary to establish a rapid evaluation method with a narrow iodine value range (iodine value difference less than 10). In this study, a rapid quantitative prediction model for iodine value of oil in high-resolution Raman spectroscopy based on linear regression and gradient descent method was established. The Raman signals (785 nm) about 39 group of Camellia oil samples and 10 group of commercially oils were firstly collected. Then, the intensity ratio of peaks of 1656 cm−1 and 1440 cm−1 (I1656/1440) were selected through smoothing algorithm least squares smoothing filter (Savitzky-Golay), polynomial fitting and deconvolution algorithm Lorentzian. A credible model was obtained through correlation analysis with the iodine value of corresponding oil samples. The coefficient of determination (R2) of the test set of the constructed quantitative model was >0.82, the mean square error (MSE) was

To efficiently utilize chicken blood, one of the by-products of broiler chickens, the fresh chicken blood was as the main raw material in this study. The peak area of immobilized water in low field nuclear magnetic field was used as the evaluation standard. The effect of different varieties and concentrations of anti-freezing amendments was investigated in the peak area of immobilized water for the frozen chicken blood tofu. Moreover, the preparation process of frozen chicken blood tofu was optimized by response surface design. Furthermore, the water loss rate, texture and color index were analyzed in the optimized frozen chicken blood tofu, which could provide scientific basis for the development of frozen chicken blood tofu products. The results showed that the optimized preparation process of frozen chicken blood tofu was as follows, 0.1% (w/v) of sodium fatty acyllactate, 0.1% (w/v) of potassium alginate, and 2% (w/v) of cassava modified starch. Under this process condition, the low-field nuclear magnetic non-flowing water peak area of frozen chicken blood tofu was 2143, which was the largest compared with the blank group and other treated groups. Therefore, the water retention effect in this study was best. The hardness, chewability, gelability and brightness of the optimized frozen chicken blood tofu were significantly (P

Abstract Background Oral microbial dysbiosis contributes to the development of oral squamous cell carcinoma (OSCC). Our previous study showed that Prevotella intermedia (P. intermedia) were enriched in the oral mucosal surface, plaque, and saliva of patients with OSCC. Intratumoral microbiome could reshape the immune system and influence the development of various tumors. However, the invasion status of human OSCC tissues by P. intermedia and the pathway through which intratumoral P. intermedia potentiates tumor progression remain unexplored. Methods P. intermedia in human OSCC or normal tissues was detected by FISH. A mouse OSCC cell line SCC7 was adopted to investigate the effects of heat-killed P. intermedia treatment on cell proliferation, invasion, and cytokine release by using CCK-8 assay, transwell invasion assay and ELISA. Moreover, we established a mouse transplanted tumor model by using SCC7 cells, injected heat-killed P. intermedia into tumor tissues, and investigated the effects of heat-killed P. intermedia on tumor growth, invasion, cytokine levels, immune cell infiltrations, and expression levels by using gross observation, H&E staining, ELISA, immunohistochemistry, mRNA sequencing, and transcriptomic analysis. Results Our results indicated that P. intermedia were abundant in OSCC and surrounding muscle tissues. Heat-killed P. intermedia promoted SCC7 cell proliferation, invasion and proinflammatory cytokine secretions, accelerated transplanted tumor growth in mice, exacerbate muscle and perineural invasion of OSCC, elevated the serum levels of IL-17A, IL-6, TNF-α, IFN-γ, and PD-L1, induced Treg cells M2 type macrophages in mouse transplanted tumors. The data of transcriptomic analysis revealed that heat-killed P. intermedia increased the expression levels of inflammatory cytokines and chemokines while reduced the expression levels of some tumor suppressor genes in mouse transplanted tumors. Additionally, IL-17 signaling pathway was upregulated whereas GABAergic system was downregulated by heat-killed P. intermedia treatment. Conclusions Taken together, our results suggest that P. intermedia could inhibit the expression of tumor suppressors, alter the tumor microenvironment, and promote the progression of OSCC.

Abstract Vitiligo is an autoimmune disease characterized by epidermal melanocyte destruction, with abnormal autoimmune responses and excessive oxidative stress as two cardinal mechanisms. Human umbilical mesenchymal stem cells‐derived exosomes (hUMSCs‐Exos) are regarded as promising therapeutic choice for autoimmune diseases due to potent immunosuppressive and anti‐oxidative properties, which can be potentiated under 3D cell culture condition. Nevertheless, whether exosomes derived from 3D spheroids of hUMSCs (3D‐Exos) exhibit considerable therapeutic effect on vitiligo and the underlying mechanism remain elusive. In this study, systemic administration of 3D‐Exos showed a remarkable effect in treating mice with vitiligo, as revealed by ameliorated skin depigmentation, less CD8+T cells infiltration, and expanded Treg cells in skin, and 3D‐Exos exerted a better effect than 2D‐Exos. Mechanistically, 3D‐Exos can prominently facilitate the expansion of Treg cells in vitiligo lesion and suppress H2O2‐induced melanocytes apoptosis. Forward miRNA profile analysis and molecular experiments have demonstrated that miR‐132‐3p and miR‐125b‐5p enriched in 3D‐Exos greatly contributed to these biological effects by targeting Sirt1 and Bak1 respectively. In aggregate, 3D‐Exos can efficiently ameliorate vitiligo by simultaneously potentiating Treg cells‐mediated immunosuppression and suppressing oxidative stress‐induced melanocyte damage via the delivery of miR‐132‐3p and miR‐125b‐5p. The employment of 3D‐Exos will be a promising treament for vitiligo.

IntroductionPrimary central nervous system lymphoma (PCNSL) is a rare type of non-Hodgkin’s lymphoma that affects brain parenchyma, eyes, cerebrospinal fluid, and spinal cord. Diagnosing PCNSL can be challenging because imaging studies often show similar patterns as other brain tumors, and stereotactic brain lesion biopsy conformation is invasive and not always possible. This study aimed to validate a previous proteomic profiling (PMID: 32610669) of cerebrospinal fluid (CSF) and develop a CSF-based proteomic panel for accurate PCNSL diagnosis and differentiation.MethodsCSF samples were collected from patients of 30 PCNSL, 30 other brain tumors, and 31 tumor-free/benign controls. Liquid chromatography tandem-mass spectrometry targeted proteomics analysis was used to establish CSF-based proteomic panels.ResultsFinal proteomic panels were selected and optimized to diagnose PCNSL from tumor-free controls or other brain tumor lesions with an area under the curve (AUC) of 0.873 (95%CI: 0.723-0.948) and 0.937 (95%CI: 0.807- 0.985), respectively. Pathways analysis showed diagnosis panel features were significantly enriched in pathways related to extracellular matrices-receptor interaction, focal adhesion, and PI3K-Akt signaling, while prion disease, mineral absorption and HIF-1 signaling were significantly enriched with differentiation panel features.DiscussionThis study suggests an accurate clinical test panel for PCNSL diagnosis and differentiation with CSF-based proteomic signatures, which may help overcome the challenges of current diagnostic methods and improve patient outcomes.

Objectives: Bidirectional Mendelian randomization (MR) combined with clinical case analysis was used to elucidate the relationship between generalized anxiety disorder (GAD) caused by mental overload and the risk of weight-bearing joint (hip/knee) osteoarthritis (OA). Methods: We performed MR analyses using publicly released genome-wide association study summary statistics to measure the causal effects between mental overload and weight-bearing joint OA risk. The primary MR analysis utilized the inverse-variance weighted (IVW) method, complemented by additional methods, including simple mode, weighted mode, MR-Egger regression, and weighted median. The leave-one-out method was used for sensitivity analysis. Concurrently, data from patients with OA (Kellgren–Lawrence grades III–IV) who needed total knee/hip arthroplasty were collected. Patient assessments were conducted utilizing the Western Ontario and McMaster Universities arthritis index, Penn State worry questionnaire, and visual analogue scale. Results: Genetically predisposed GAD did not correlate with the risk of weight-bearing joint OA (IVW odds ratio [OR] = 0.840, 95 % confidence interval = 0.128, 5.50, P = 0.855). In reverse MR analyses, we detected no causal effect of weight-bearing OA on GAD (IVW OR = 1.00, 95 % CI = 0.985, 1.03, P = 0.687). In the clinical case evaluation, weight overload joint OA and GAD were highly correlated. Conclusion: MR analysis indicated no bidirectional causal effect of GAD caused by mental overload on weight-bearing joint (hip or knee) OA. Clinical studies support the finding that GAD is highly correlated with weight-bearing joint OA. However, whether there is a causal relationship between GAD caused by mental overload and weight-overloading joint OA requires further investigation.

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with motor rehabilitative training or delivered before motor training. The necessity of concurrently applying taVNS with motor training for post-stroke motor rehabilitation remains unclear. We aimed to investigate the necessity and advantages of applying the taVNS concurrently with motor training by an electromyography (EMG)-triggered closed-loop system for post-stroke rehabilitation.MethodsWe propose a double-blinded, randomized clinical trial involving 150 stroke patients assigned to one of three groups: concurrent taVNS, sequential taVNS, or sham control condition. In the concurrent group, taVNS bursts will synchronize with upper extremity motor movements with EMG-triggered closed-loop system during the rehabilitative training, while in the sequential group, a taVNS session will precede the motor rehabilitative training. TaVNS intensity will be set below the pain threshold for both concurrent and sequential conditions and at zero for the control condition. The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Secondary measures include standard upper limb function assessments, as well as EMG and electrocardiogram (ECG) features.Ethics and disseminationEthical approval has been granted by the Medical Ethics Committee, affiliated with Zhujiang Hospital of Southern Medical University for Clinical Studies (2023-QX-012-01). This study has been registered on ClinicalTrials (NCT05943431). Signed informed consent will be obtained from all included participants. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings.DiscussionThis study represents a pioneering effort in directly comparing the impact of concurrent taVNS with motor training to that of sequential taVNS with motor training on stroke rehabilitation. Secondly, the incorporation of an EMG-triggered closed-loop taVNS system has enabled the automation and individualization of both taVNS and diverse motor training tasks—a novel approach not explored in previous research. This technological advancement holds promise for delivering more precise and tailored training interventions for stroke patients. However, it is essential to acknowledge a limitation of this study, as it does not delve into examining the neural mechanisms underlying taVNS in the context of post-stroke rehabilitation.

Out-of-hospital cardiac arrest is a major public health problem worldwide due to its high burden and poor outcomes. Despite progress in treatment, patient outcomes remain unsatisfactory, particularly in low-resource settings. The establishment of a registry is the first step towards gaining a comprehensive understanding of prevailing local conditions and identifying potential opportunities for improving patient survival. Here, we provide a narrative review of the BASeline Investigation of Out-of-hospital Cardiac Arrest (BASIC-OHCA), the first national OHCA registry in China, to introduce its development history, current state, challenges and future directions. We aim to enhance cross-cultural understanding by providing insights from China, while also serving as a reference for the implementation of large-scale registries in low-resource settings.

Drought stress limits agricultural productivity worldwide. Identifying and characterizing genetic components of drought stress-tolerance networks may improve crop resistance to drought stress. We show that the regulatory module formed by miR166 and its target gene, ATHB14-LIKE, functions in the regulation of drought tolerance in soybean (Glycine max). Drought stress represses the accumulation of miR166, leading to upregulation of its target genes. Optimal knockdown of miR166 in the stable transgenic line GmSTTM166 conferred drought tolerance without affecting yield. Expression of ABA signaling pathway genes was regulated by the miR166-mediated regulatory pathway, and ATHB14-LIKE directly activates some of these genes. There is a feedback regulation between ATHB14-LIKE and MIR166 genes, and ATHB14-LIKE inhibits MIR166 expression. These findings reveal that drought-triggered regulation of the miR166-mediated regulatory pathway increases plants drought resistance, providing new insights into drought stress regulatory network in soybean.

Abstract Concentrations of arsenic (As), cadmium (Cd), mercury (Hg) and lead (Pb) in crayfish from Jiangsu province, China, were measured and their health risks were evaluated. For crayfish from both crayfish-rice culture system (CRCS) and crayfish intensive culture system (CICS), concentrations of As, Cd and Pb in whole body of crayfish (WB) were significantly higher than those in abdominal muscle of crayfish (AM), while concentration of Hg in WB was significantly lower than that in AM. No significant difference in concentrations of the heavy metals was found between CRCS and CICS. Concentrations of the heavy metals in AM from both systems were below the limit set by the national standard of China. Estimated daily intake values of the heavy metals were far below the provisional tolerable daily intakes set by Joint FAO/WHO committee on Food Additives, and the corresponding hazard quotient and hazard index were below one. Therefore, consumption of crayfish with the average daily consumption rate (DCR) could be generally regarded as safe. For the consumption with two more times of average DCR during peak season, there might be a potential health risk from intakes of As and Hg in abdominal muscle of crayfish. Graphical Abstract

In this study, the study on physicochemical, rheological properties and water-holding capacity of gelatin of chicken lungs was investigated to replace bovine and porcine gelatin. The extraction rates of chicken, bovine and porcine lung gelatin by ultrasound assisted alkaline protease were 52.12 %, 69.06 % and 70 %, respectively. Three lung gelatins had similar molecular weight distribution in SDS-PAGE with low content of high molecular weight subunits. The amino acid content of bovine lung gelatin (18.03 %) was higher than in chicken (16.62 %) and porcine lung (15.30 %). The highest intensity of 2θ = 7.5° diffraction peak in bovine lung gelatin was observed, which indicated that the triple helix content of bovine lung gelatin was higher than that of chicken and porcine lung gelatin. The lowest apparent viscosity of chicken lung gelatin was 0.253 mPa·s, but the highest water holding capacity of chicken lung gelatin was 331.72 %. Therefore, chicken lung gelatin can be used as a substitute for bovine and porcine gelatin in some functional properties.

Objectives To investigate the relationships among caregiver burden, family resilience, and caregiver capacity in the care of stroke survivors. We hypothesised that family resilience would mediate the relationship between caregiver burden and caregiver capacity.Design A cross-sectional study design was used.Setting The study was conducted in a tertiary care setting in Ningbo City, Zhejiang Province, China.Participants The study involved 413 stroke survivors and their primary caregivers.Outcome measures The primary caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale, Zarit Caregiver Burden Interview and Family Caregiver Task Inventor and provided their sociodemographic information. Stroke survivors were assessed for activities of daily living, and their sociodemographic information was provided. Data were analysed, controlling for sociodemographic variables and focusing on the mediating effect of family resilience.Results Caregiver burden was influenced by the activities of daily living of stroke survivors, caregiver age and caregiver health status (p

Background: As a scaffold protein, calcium/calmodulin-dependent serine protein kinase (CASK) has been extensively studied in a variety of tissues throughout the body. The Cask gene is ubiquitous in several tissues, such as the neurons, islets, heart, kidneys and sperm, and is mostly localised in the cytoplasm adjacent to the basement membrane. CASK binds to a variety of proteins through its domains to exerting its biological activity. Scope of review: Here, we discuss the role of CASK in multiple tissues throughout the body. The role of different CASK domains in regulating neuronal development, neurotransmitter release and synaptic vesicle secretion was emphasised; the regulatory mechanism of CASK on the function of pancreatic islet β cells was analysed; the role of CASK in cardiac physiology, kidney and sperm development was discussed; and the role of CASK in different tumours was compared. Finally, we clarify the importance of the Cask gene in the body, and how deletion or mutation of the Cask gene can have adverse consequences. Major conclusions: CASK is a conserved gene with similar roles in various tissues. The function of the Cask gene in the nervous system is mainly involved in the development of the nervous system and the release of neurotransmitters. In the endocrine system, an involvement of CASK has been reported in the process of insulin vesicle transport. CASK is also involved in cardiomyocyte ion channel regulation, kidney and sperm development, and tumour proliferation. CASK is an indispensable gene for the whole body, and CASK mutations can cause foetal malformations or death at birth. In this review, we summarise the biological functions and pathological mechanisms of CASK in various systems, thereby providing a basis for further in-depth studies of CASK functions.

Gastric cancer is a highly metastatic malignant tumor with high morbidity and mortality globally. Recent studies reported that sulfonamide derivatives such as indisulam exhibited inhibitory effects on the viability and migration of cancer cells. However, multiple clinical trials revealed that indisulam did not significantly prevent cancer progression due to metastasis and drug resistance. Therefore, it is necessary to discover new potent derivatives to explore alternative therapeutic strategies. Here, we synthesize multiple indisulam derivatives and examine their inhibitory effects on the viability and migration of gastric cancer cells. Among them, compounds SR‐3‐65 and WXM‐1‐170 exhibit better inhibitory effects on the migration of gastric cancer cells than indisulam. Mechanistically, we discover that they could attenuate the PI3K/AKT/GSK-3β/β-catenin signaling pathway and lead to the suppression of epithelial-to-mesenchymal transition (EMT)-related transcription factors. The influence of SR‐3‐65 on the migration of gastric cancer cells is blocked by the PI3K inhibitor LY294002 while SR‐3‐65 and WXM‐1‐170 reverse the effect of PI3K activator 740 Y-P on the migration of gastric cancer cells. Molecular docking and molecular dynamics simulation further confirm that PI3K is the target of SR‐3‐65. Our study unveils a novel mechanism by which SR‐3‐65 and WXM‐1‐170 inhibit the migration of gastric cancer cells. Together with the previous discovery, we reveal that subtle structural change in indisulam results in a striking switch on the molecular targets and their associated signaling pathways for the inhibition of the migration of gastric cancer cells. These findings might provide informative insights for the development of targeted therapy for gastric cancer.

To evaluate the potential of chicken blood for dietary iron supplementation, chicken blood and ferrous chloride were used as raw materials to prepare iron-chelating peptides from chicken blood in this paper. The structure of iron-chelating peptides from chicken blood was characterized by scanning electron microscopy and differential scanning calorimetry. The stability of iron-chelating peptides from chicken blood was analyzed at different temperatures (30~80 ℃) and pH (2~9), and its in vitro stability was also discussed. The study confirmed that it had good thermal stability (iron retention rate above 73.76%) and acid and alkali resistance. The digestive stability of iron-chelating peptides from chicken blood (iron retention of 86.01%) was found to be better than that of ferrous sulfate and ferrous gluconate by simulated digestion in vitro. In addition, under the influence of three dietary factors, namely 1% phytic acid, 1% oxalic acid, and 8% dietary fiber, iron-chelating peptides from chicken blood showed better bioaccessibility than ferrous sulfate and ferrous gluconate.

Abstract. Background:. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC. Methods:. We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25. Results:. USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo. Conclusions:. In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.

The Yellow River Basin (YB) acts as a key barrier to ecological security and is an important experimental region for high-quality development in China. There is a growing demand to assess the ecological status in order to promote the sustainable development of the YB. The eco-environmental quality (EEQ) of the YB was assessed at both the regional and provincial scales utilizing the remote sensing-based ecological index (RSEI) with Landsat images from 2000 to 2020. Then, the Theil–Sen (T-S) estimator and Mann–Kendall (M-K) test were utilized to evaluate its variation trend. Next, the optimal parameter-based geodetector (OPGD) model was used to examine the drivers influencing the EEQ in the YB. Finally, the geographically weighted regression (GWR) model was utilized to further explore the responses of the drivers to RSEI changes. The results suggest that (1) a lower RSEI value was found in the north, while a higher RSEI value was found in the south of the YB. Sichuan (SC) and Inner Mongolia (IM) had the highest and the lowest EEQ, respectively, among the YB provinces. (2) Throughout the research period, the EEQ of the YB improved, whereas it deteriorated in both Henan (HA) and Shandong (SD) provinces. (3) The soil-available water content (AWC), annual precipitation (PRE), and distance from impervious surfaces (IMD) were the main factors affecting the spatial differentiation of RSEI in the YB. (4) The influence of meteorological factors (PRE and TMP) on RSEI changes was greater than that of IMD, and the influence of IMD on RSEI changes showed a significant increasing trend. The research results provide valuable information for application in local ecological construction and regional development planning.

Abstract Aim This study aimed to measure pandemic fatigue, physical and mental health, and job status of front‐line medical staff in Ningbo. And to identify factors associated with pandemic fatigue. Background There was an acute increase in fatigue symptoms at the COVID‐19 pandemic onset. The front‐line medical staff is particularly vulnerable to fatigue due to their high‐intensity work. Design This was a descriptive, cross‐sectional study conducted using an online survey that included demographic data, investigation of COVID‐19 history and job status. The Fatigue Assessment Scale, GAD‐7 score and Sleep Quality Scale were used to collect data from 479 front‐line medical staff. Methods The study involved 479 front‐line medical staff in Ningbo, China. The survey was conducted using an online questionnaire that included demographic data, investigation of COVID‐19 history and job status. The Fatigue Assessment Scale, GAD‐7 score and Sleep Quality Scale were used to collect data. Results The results showed that of the 479 participants, 393 (82%) reported pandemic fatigue, 393 (82%) reported job satisfaction and 433 (90.4%) identified with their sense of job value. Sleep quality, work with a fever, economic subsidies for fighting COVID‐19 and recognizing professional value were significantly correlated with pandemic fatigue. Conclusions As the COVID‐19 pandemic challenges front‐line medical workers, implementing measures is essential. Health policy implementers could provide sufficient front‐line medical staff to ensure rest in case of infection, promote sleep quality and foster professional value and financial subsidies in units. Relevance to clinical practice The study shows how pandemic fatigue affects front‐line medical staff during the COVID‐19 pandemic and suggests measures to support them, including promoting sleep quality, providing rest for infected staff, fostering professional value and financial subsidies. The recommendations are relevant to clinical practice as they help support medical staff and ensure high‐quality care for patients during the pandemic. Patient or Public Contribution No Patient or Public Contribution. Not applicable.

Purpose To determine the effect of auricular acupuncture on preoperative blood pressure (BP) elevation in different age groups. Materials and methods Auricular acupuncture treats elevated BP among patients before surgery. This prospective, randomized clinical trial was performed at Li Huili Hospital of Ningbo Medical Center, China, from January to June 2021. We prospectively enrolled 120 patients with elevated BP aged 45 to 75 and observed them in the inpatient department. Patients were randomly assigned in a 1:1 ratio to undergo auricular acupuncture or sham control groups. In addition to usual care, the study group underwent auricular acupuncture bilaterally at HX6 7i–Ear apex, TF4–Shen men, TF1–Superior triangular fossa, and CO15–Heart. Results A total of 120 patients completed the study, 60 in the study group and 60 in the control group. Of these, 76 (63.3%) were men, and the mean (standard deviation) was 64.55 (9.48) years. The differences in systolic BP comparisons after intervention were significant (7.88 mmHg; 95% confidence interval [CI], 2.94 to 12.81; P = .002). Diastolic BP also showed statistical significance (5.85 mmHg; 95% CI, 3.05 to 8.64; P < .01. Neither AA-related adverse events nor serious adverse events occurred. Stratified by age, the differences comparisons of systolic BP (−10.13 mmHg; 95% confidence interval [CI], −16.69 to −3.57; P

ABSTRACTIntroduction An effective salvage regimen for the reinduction of remission is lacking for refractory or relapsed primary central nervous system lymphoma (r/r PCNSL). This study aimed to evaluate the efficacy and safety of cytarabine plus temozolomide in treating r/r PCNSL and to explore the associated prognostic factors.Methods A single-center retrospective cohort study was conducted to assess the efficacy and safety of cytarabine and temozolomide (AT) in r/r PCNSL patients. KIR and HLA genotyping was performed on peripheral blood samples.Results Thirty PCNSL patients receiving an AT regimen (cytarabine 3 g/m2 for 2 days combined with temozolomide 150 mg/m2 for 5 days) in our institution were analyzed. The median age was 65 years (range 25–79 years). A total of 43.4% of patients (13/30) achieved an overall response within a median follow-up of 16 months (95% confidence interval [CI]: 11–23 months). The median PFS and OS of the cohort were 1.5 months (95% CI: 1–4 months) and 19.5 months (95% CI: 11 months to not calculable), respectively. Patients harboring KIR3DL1/HLA-B genotypes predicting low affinity had a higher response rate (p = 0.042) and longer median PFS (3 months) than those with KIR3DL1/HLA-B genotypes predicting high affinity (1 month) (p = 0.0047). Cox regression analysis indicated that KIR/HLA-B genotypes were independently associated with PFS (p = 0.043). However, KIR/HLA-B genotypes had no impact on the OS of the cohort. The toxicity of AT treatment was mild and manageable.Conclusion The AT regimen was well tolerated, and patients with specific KIR-HLA genotypes may benefit from this regimen.

ABSTRACTBackground Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients.Methods Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups.Results The PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374–0.926, P = 0.024).Conclusion PNI would be a simple and immediately available tool for predicting the prognosis of MDS.

In the study, variations of physicochemical factors, lipoxygenase (LOX) and hydroxyl octadecanodienoic acid (HODEs) were investigated during manufacturing of traditional salted meat, and the relationship between LOX and HODEs was studied and the evolution of lipids oxidation was tentatively discussed. The results indicated that LOX activity increased at salting stage, followed by decreasing continuously during the salted meat manufacturing. The total amount of HODEs increased slowly, while the ratio of 13-HODEs/9-HODEs decreased from 1.31 to 1.13. There was a significantly positive correlation between LOX activity and the ratio of 13-HODEs/9-HODEs (r=0.942, P

Abstract STAG2, an important subunit in cohesion complex, is involved in the segregation of chromosomes during the late mitosis and the formation of sister chromatids. Mutational inactivation of STAG2 is a major cause of the resistance of BRAF-mutant melanomas to BRAF/MEK inhibitors. In the present study, we found that STAG2 was frequently down-regulated in thyroid cancers compared with control subjects. By a series of in vitro and in vivo studies, we demonstrated that STAG2 knockdown virtually had no effect on malignant phenotypes of BRAF-mutant thyroid cancer cells such as cell proliferation, colony formation and tumorigenic ability in nude mice compared with the control. In addition, unlike melanoma, STAG2 knockdown also did not affect the sensitivity of these cells to MEK inhibitor. However, we surprisingly found that STAG2-knockdown cells exhibited more sensitive to glutamine deprivation or glutaminase inhibitor BPTES compared with control cells. Mechanistically, knocking down STAG2 in BRAF-mutant thyroid cancer cells decreases the protein stability of c-Myc via the ERK/AKT/GSK3β feedback pathway, thereby impairing glutamine metabolism of thyroid cancer cells by down-regulating its downstream targets such as SCL1A5, GLS and GLS2. Our data, taken together, demonstrate that STAG2 inactivation reprograms glutamine metabolism of BRAF-mutant thyroid cancer cells, thereby improving their cellular response to glutaminase inhibitor. This study will provide a potential therapeutic strategy for BRAF-mutant thyroid cancers.

Calcium is an essential nutrient and plays an important role in life and health. Insufficient calcium intake in the body can lead to kinds of diseases, such as rickets and osteoporosis. As more and more calcium chelated peptides are prepared from food in recent years, the advantages of calcium chelated peptides like good stability and high bioavailability have attracted much attention and calcium chelated peptides have been reported to be a kind of ideal calcium supplements. In this paper, the research progress of calcium chelted peptide is summarized, the preparation, separation and purification methods of calcium chelted peptide are introduced, the factors affecting its chelating ability are analyzed, and the ways to promote the bioavailability of calcium are also discussed, in order to provide help for the development and utilization of calcium chelted peptide in functional foods in the future.

Bile salt hydrolase (BSH) is an intracellular enzyme which is produced by intestinal flora during the period of growth and reproduction. This enzyme has been suggested to be involved in the host's bile acid balance, lipid metabolism and metabolic responses. Therefore, BSH has always been a research hotspot. Detailed knowledge of BSH structure and substrate preferences is a solid foundation for the development of BSH related products. This review explains the source and distribution of BSH, test method for BSH activity. It also introduces enzymatic properties and genetic organization. Finally, the potential applications of BSH research are briefly discussed. This review would provide theoretical basis for the in-depth research of BSH, developments of related functional foods, and other industry applications.

Abstract Background Aberrant epigenetic remodeling events contribute to progression and metastasis of breast cancer (Bca). The specific mechanims that epigenetic factors rely on to mediate tumor aggressiveness remain unclear. We aimed to elucidate the roles of epigenetic protein PHF6 in breast tumorigenesis. Methods Published datasets and tissue samples with PHF6 staining were used to investigate the clinical relevance of PHF6 in Bca. CCK-8, clony formation assays were used to assess cell growth capacity. Cell migration and invasion abilities were measured by Transwell assay. The gene mRNA and protein levels were measured by quantitative real-time PCR and western blot. Chromatin immunoprecipitation (ChIP)-qPCR assays were used to investigate transcriptional relationships among genes. The Co-immunoprecipitation (Co-IP) assay was used to validate interactions between proteins. The CRISPR/Cas9 editing technology was used to construct double HIF knockout (HIF-DKO) cells. The subcutaneous xenograft model and orthotopic implantation tumor model were used to asess in vivo tumor growth. Results In this study, we utilized MTT assay to screen that PHF6 is required for Bca growth. PHF6 promotes Bca proliferation and migration. By analyzing The Cancer Genome Atlas breast cancer (TCGA-Bca) cohort, we found that PHF6 was significantly higher in tumor versus normal tissues. Mechanistically, PHF6 physically interacts with HIF-1α and HIF-2α to potentiate HIF-driven transcriptional events to initiate breast tumorigenesis. HIF-DKO abolished PHF6-mediated breast tumor growth, and PHF6 deficiency in turn impaired HIF transcriptional effects. Besides, hypoxia could also rely on YAP activation, but not HIF, to sustain PHF6 expressions in Bca cells. In addition, PHF6 recuits BPTF to mediate epigenetic remodeling to augment HIF transcriptional activity. Targeting PHF6 or BPTF inhibitor (AU1) is effective in mice models. Lastly, PHF6 correlated with HIF target gene expression in human breast tumors, which is an independent prognostic regulator. Conclusions Collectively, this study identified PHF6 as a prognostic epigenetic regulator for Bca, functioning as a HIF coactivator. The fundamental mechanisms underlying YAP/PHF6/HIF axis in breast tumors endowed novel epigenegtic targets for Bca treatment.

Abstract Melanoma is the most lethal type of skin cancer, originating from the malignant transformation of melanocyte. While the development of targeted therapy and immunotherapy has gained revolutionary advances in potentiating the therapeutic effect, the prognosis of patients with melanoma is still suboptimal. During tumor progression, melanoma frequently encounters stress from both endogenous and exogenous sources in tumor microenvironment. SIRT7 is a nuclear-localized deacetylase of which the activity is highly dependent on intracellular nicotinamide adenine dinucleotide (NAD+), with versatile biological functions in maintaining cell homeostasis. Nevertheless, whether SIRT7 regulates tumor cell biology and tumor immunology in melanoma under stressful tumor microenvironment remains elusive. Herein, we reported that SIRT7 orchestrates melanoma progression by simultaneously promoting tumor cell survival and immune evasion via the activation of unfolded protein response. We first identified that SIRT7 expression was the most significantly increased one in sirtuins family upon stress. Then, we proved that the deficiency of SIRT7 potentiated tumor cell death under stress in vitro and suppressed melanoma growth in vivo. Mechanistically, SIRT7 selectively activated the IRE1α-XBP1 axis to potentiate the pro-survival ERK signal pathway and the secretion of tumor-promoting cytokines. SIRT7 directly de-acetylated SMAD4 to antagonize the TGF-β-SMAD4 signal, which relieved the transcriptional repression on IRE1α and induced the activation of the IRE1α-XBP1 axis. Moreover, SIRT7 up-regulation eradicated anti-tumor immunity by promoting PD-L1 expression via the IRE1α-XBP1 axis. Additionally, the synergized therapeutic effect of SIRT7 suppression and anti-PD-1 immune checkpoint blockade was also investigated. Taken together, SIRT7 can be employed as a promising target to restrain tumor growth and increase the effect of melanoma immunotherapy.

Distributed wind power has the potential to contribute significantly to China's carbon neutrality goals. However, the recent policy shift away from wind power subsidies necessitates a thorough examination of alternative revenue streams, such as carbon emission reduction benefits. In response to this need, our paper aims to assess the impact of carbon reduction revenue on the investment viability of distributed wind power projects. Employing the Monte Carlo method, we construct investment models for a case study based in Shanghai, incorporating variables like feed-in tariffs and carbon trading prices. Our analysis reveals that, although distributed wind power investments are generally feasible, optimal investment should be deferred until 2031 according to real options analysis. We further note that carbon reduction revenue can enhance the investment value and shorten the dynamic payback period of these projects; however, current low trading volumes and prices for carbon credits do not sufficiently compensate for the absence of subsidies.

Evodiamine (EVO) is a quinazoline carboline alkaloid isolated from the fruits of the traditional Chinese herb Evodiae fructus. In the present study, we synthesized thirty EVO derivatives (9–38) with various benzenesulfonyl groups by sulfonylation of the amino group of 3-NH-EVO and thirty benzenesulfonyl chloride substituents. The results of the MTT assay showed that most of the compounds had good antitumor activity on H460, PC9, PC9/GR, H1299 and SW620 cancer cells as well as on normal LO2 cells. Among them, compounds 9, 18 and 28 were more potent than other compounds on H460 cell lines with an IC50 value of 9.1 M, 10.5 M and 9.5 M, respectively, even more potent than the positive PGMI-004A with one IC50 of 31.1 M. The enzymatic activity of representative compounds was further evaluated against phosphoglycerate mutase 1 (PGAM1). The results showed that compound 11 with an IC50 of 0.062 μM and compound 34 with an IC50 of 0.059 μM were similar to the positive drug’s IC50 of 0.052 μM. These results indicated that these compounds could be developed into potential PGAM1 inhibitors. In addition, compounds 9, 18, and 28 could induce apoptosis, block the cell cycle at the G2/M stage, lead to bursting of reactive oxygen species, and induce mitochondrial dysfunction. Overall, the present work showed that the benzenesulfonyl chloride-substituted evodiamine derivatives have good antitumor activity against tumor cells and show promise as anticancer agents.

Background: Due to the poor prognosis and rising occurrence, there is a crucial need to improve the diagnosis of Primary Central Nervous System Lymphoma (PCNSL), which is a rare type of non-Hodgkin’s lymphoma. This study utilized targeted metabolomics of cerebrospinal fluid (CSF) to identify biomarker panels for the improved diagnosis or differential diagnosis of primary central nervous system lymphoma (PCNSL).Methods: In this study, a cohort of 68 individuals, including patients with primary central nervous system lymphoma (PCNSL), non-malignant disease controls, and patients with other brain tumors, was recruited. Their cerebrospinal fluid samples were analyzed using the Ultra-high performance liquid chromatography - tandem mass spectrometer (UHPLC-MS/MS) technique for targeted metabolomics analysis. Multivariate statistical analysis and logistic regression modeling were employed to identify biomarkers for both diagnosis (Dx) and differential diagnosis (Diff) purposes. The Dx and Diff models were further validated using a separate cohort of 34 subjects through logistic regression modeling.Results: A targeted analysis of 45 metabolites was conducted using UHPLC-MS/MS on cerebrospinal fluid (CSF) samples from a cohort of 68 individuals, including PCNSL patients, non-malignant disease controls, and patients with other brain tumors. Five metabolic features were identified as biomarkers for PCNSL diagnosis, while nine metabolic features were found to be biomarkers for differential diagnosis. Logistic regression modeling was employed to validate the Dx and Diff models using an independent cohort of 34 subjects. The logistic model demonstrated excellent performance, with an AUC of 0.83 for PCNSL vs. non-malignant disease controls and 0.86 for PCNSL vs. other brain tumor patients.Conclusion: Our study has successfully developed two logistic regression models utilizing metabolic markers in cerebrospinal fluid (CSF) for the diagnosis and differential diagnosis of PCNSL. These models provide valuable insights and hold promise for the future development of a non-invasive and reliable diagnostic tool for PCNSL.

Abstract Background Magnolia, a traditional and important ornamental plant in urban greening, has been cultivated for about 2000 years in China for its elegant flower shape and gorgeous flower color. Most varieties of Magnolia bloom once a year in spring, whereas a few others, such as Magnolia liliiflora Desr. ‘Hongyuanbao’, also bloom for the second time in summer or early autumn. Such a twice flowering trait is desirable for its high ornamental value, while its underlying mechanism remains unclear. Methods Paraffin section was used to show the flowering time and phenotypic changes of M. liliiflora ‘Hongyuanbao’ during the twice flowering periods from March 28 to August 25, 2018. Gas chromatography-mass spectrometry (GC-MS) was then performed to explore the chemical metabolites through the twice flower bud differentiation process in ‘Hongyuanbao’, and the metabolites were screened and identified by orthogonal projection to latent structures discriminant analysis (OPLS-DA). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was used to reveal the relationship between the sugar metabolites and twice-flowering characteristic. To further investigate the potential role of sucrose and trehalose on flowering regulation of ‘Hongyuanbao’, the plants once finished the spring flowering were regularly sprayed with sucrose and trehalose solutions at 30 mM, 60 mM, and 90 mM concentrations from April 22, 2019. The flower bud differentiation processes of sprayed plants were observed and the expression patterns of the genes involved in sucrose and trehalose metabolic pathways were studied by quantitative reverse transcription PCR (qRT-PCR). Results It showed that ‘Hongyuanbao’ could complete flower bud differentiation twice in a year and flowered in both spring and summer. The metabolites of flower bud differentiation had a significant variation between the first and second flower buds. Compared to the first flower bud differentiation process, the metabolites in the sucrose and trehalose metabolic pathways were significantly up-regulated during the second flower bud differentiation process. Besides that, the expression levels of a number of trehalose-6-phosphate synthase (TPS) genes including MlTPS1, MlTPS5, MlTPS6, MlTPS7 and MlTPS9 were substantially increased in the second flower differentiation process compared with the first process. Exogenous treatments indicated that compared to the control plants (sprayed with water, CK), all three concentrations of trehalose could accelerate flowering and the effect of 60 mM concentration was the most significant. For the sucrose foliar spray, only the 60 mM concentration accelerated flowering compared with CK. It suggested that different concentration of trehalose and sucrose might have different effects. Expression analysis showed that sucrose treatment increased the transcription levels of MlTPS5 and MlTPS6, whereas trehalose treatment increased MlTPS1, showing that different MlTPS genes took part in sucrose and trehalose metabolic pathways respectively. The expression levels of a number of flowering-related genes, such as MlFT, MlLFY, and MlSPL were also increased in response to the sprays of sucrose and trehalose. Conclusions We provide a novel insight into the effect of sucrose and trehalose on the flowering process in Magnolia. Under the different sugar contents treatments, the time of flower bud differentiation of Magnolia was advanced. Induced and accelerated flowering in response to sucrose and trehalose foliar spray, coupled with elevated expression of trehalose regulatory and response genes, suggests that secondary flower bud formation is a promoted by altered endogenous sucrose and trehalose levels. Those results give a new understanding of sucrose and trehalose on twice-flowering in Magnolia and provide a preliminary speculation for inducing and accelerating the flowering process in Magnolia.

Context Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases.Objective To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases.Materials and methods Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01–1 mg/mL) on ACh/BaCl2-induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248–992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice.Results Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p

Soil total nitrogen content (TN) is a crucial factor in boosting the growth of crops. Its surplus or scarcity will alter the quality and yield of crops to a certain extent. Traditional methods such as chemical analysis is complicated, laborious and time-consuming. A faster and more efficient method to detect TN should be explored to address this problem. The hyperspectral technology integrates conventional energy and spectroscopy which aids in the simultaneous collection of spatial and spectral information from an object. It has gradually proved its significance and gained popularity in the analysis of soil composition. This study discussed the possibility of using hyperspectral technology to detect TN, analyzed six spectral data preprocessing methods and five modeling methods: partial least squares (PLS), back-propagation (BP) neural network, radial basis function (RBF) neural network, extreme learning machine (ELM) and support vector regression (SVR) with evaluation index R2 and RMSE. Setting the content of chemical analysis as the control and comparing the errors from spectral analysis. According to the results, all five models can be used for TN detection, and the SVR model with R2 0.912 1 and RMSE 0.758 1 turned to the best method. The study showed that the spectral model can detect TN quickly, providing a reference for the detection of elements in soil with favorable research significance.

Context Suchilactone, a lignan compound extracted from Monsonia angustifolia E.Mey. ex A.Rich. (Geraniaceae), has little research on pharmacological activity; whether suchilactone has inhibitory effect on acute myeloid leukaemia (AML) is unclear. Objective To investigate the antitumor effect of suchilactone and its mechanism in AML. Materials and methods The effects of suchilactone on cell growth were detected by CCK-8 and flow cytometry. Network pharmacology was conducted to explore target of suchilactone. Gene expression was detected by western blot and RT-PCR. SHI-1 cells (1 × 106 cell per mouse) were subcutaneously inoculated into the female SCID mice. Suchilactone (15 and 30 mg/kg) was dissolved in PBS with 0.5% carboxymethylcellulose sodium and administered (i.g.) to mice once a day for 19 days, while the control group received PBS with 0.5% carboxymethylcellulose sodium. Tumour tissues were stained with Ki-67 and TUNEL. Results Suchilactone exerted an effective inhibition on the growth of SHI-1 cells with IC50 of 17.01 μM. Then, we found that suchilactone binds to the SHP2 protein and inhibits its activation, and suchilactone interacted with SHP2 to inhibit cell proliferation and promote cell apoptosis via blocking the activation of SHP2. Moreover, Suchilaction inhibited tumour growth of AML xenografts in mice, as the tumour weight decreased from 0.618 g (control) to 0.35 g (15 mg/kg) and 0.258 g (30 mg/kg). Suchilactone inhibited Ki-67 expression and increased TUNEL expression in tumour tissue. Discussion and conclusions Our study is the first to demonstrate suchilactone inhibits AML growth, suggesting that suchilactone is a candidate drug for the treatment of AML.

A series of Zn salts were used as catalysts for the reaction of glycerol and urea to produce glycerol carbonate and it was found that ZnSO4 showed the highest catalytic activity. Furthermore, the effects of reaction parameters on the glycerol conversion and glycerol carbonate yield were studied in detail. The results indicated that the glycerol conversion and glycerol carbonate yield were increased with the reaction temperature, reaction time, and catalyst amount while the optimal reaction conditions were 140 °C, 240 min, catalyst amount of 5 wt% (based on the glycerol weight), and urea-to-glycerol molar ratio of 1.1:1. During the reaction, the ZnSO4 catalyst is transformed into Zn(NH3)2SO4 at the initial stage of the reaction and then further transformed into Zn(C3H6O3). Zn(C3H6O3) and (NH4)2SO4 may be the true active species for the activation of urea and glycerol, respectively. The reaction mechanism is proposed in this article. Based on the experimental results, a reaction kinetics model considering the change in volume of the reaction system was also established, and the model parameters were obtained by fitting the experimental data. The statistical results showed that the established kinetics model is accurate.

Remote sensing (RS) scene classification has always attracted much attention as an elemental and hot topic in the RS community. In recent years, many methods using convolutional neural networks (CNNs) and other advanced machine-learning techniques have been proposed. Their performance is excellent; however, they are disabled when there are noisy labels (i.e., RS scenes with incorrect labels), which is inevitable and common in practice. To address this problem, some specific RS classification models have been developed. Although feasible, their behavior is still limited by the complex contents of RS scenes, excessive noise filtering schemes, and intricate noise-tolerant learning strategies. To further enhance the RS classification results under the noisy scenario and overcome the above limitations, in this paper we propose a multiscale information exploration network (MIEN) and a progressive learning algorithm (PLA). MIEN involves two identical sub-networks whose goals are completing the classification and recognizing possible noisy RS scenes. In addition, we develop a transformer-assistive multiscale fusion module (TAMSFM) to enhance MIEN’s behavior in exploring the local, global, and multiscale contents within RS scenes. PLA encompasses a dual-view negative-learning (DNL) stage, an adaptively positive-learning (APL) stage, and an exhaustive soft-label-learning (ESL) stage. Their aim is to learn the relationships between RS scenes and irrelevant semantics, model the links between clean RS scenes and their labels, and generate reliable pseudo-labels. This way, MIEN can be thoroughly trained under the noisy scenario. We simulate noisy scenarios and conduct extensive experiments using three public RS scene data sets. The positive experimental results demonstrate that our MIEN and PLA can fully understand RS scenes and resist the negative influence of noisy samples.

Understanding the effects of natural and human disturbance factors on fractional vegetation coverage (FVC) is significant in the promotion of ecological and environmental protection. However, most of the relevant studies neglect to consider differences in the effect of driving factors on areas with different vegetation change characteristics. In this paper, we have combined Theil-Sen median trend analysis and Mann-Kendall testing to identify degraded and restored areas. Differences in the impact of various factors on FVC in terms of degradation, restoration, and the whole region were distinguished quantitatively using the geodetector model. Additionally, the constraint line approach was used to detect the influence thresholds of factors on FVC. The results are shown as below: (1) FVC showed an overall improving trend, and vegetation restoration and degradation areas accounted for 69.2% and 22.0%, respectively. (2) The two dominant factors affecting FVC were Digital Elevation Model (DEM) and temperature for both degraded and restored regions. However, the explanatory power of precipitation was noticeably different between regions. (3) Most natural factors had a “convex” constraint effect on FVC, which gradually weakened with an increase in the variable below the threshold and vice versa. Human disturbance factors negatively constrained FVC, and the constraint effect increased with increased human activity. This study can help decision-makers optimize specific implementation policies relating to ecological restoration and sustainable development.

Objective This study assessed the association between sleep duration, perceived organisational support (POS), personal resilience and anxiety among non-hospitalised residents during the COVID-19 pandemic in Ningbo, China.Methods In this cross-sectional study, an online survey was conducted from 27 January 2023 to 5 February 2023, involving non-hospitalised residents over 14 years old in Ningbo. We received 1938 valid responses. The study used the General Demographic Characteristics Scale, the Generalised Anxiety Disorder Scale, Brief Resilient Coping Scale and the POS questionnaire.Results Among the 1938 valid questionnaires, 1068 (55.1%) participants reported anxiety. Multivariate logistic regression analysis revealed that high organisational support (β=–0.34, adjusted OR (aOR) 0.71, 95% CI 0.51 to 0.98, p=0.038), moderate resilience (β=–0.26, aOR 0.77, 95% CI 0.63 to 0.95, p=0.013), high resilience (β=–0.67, aOR 0.51, 95% CI 0.36 to 0.73, p

IntroductionHuntington’s disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) and is characterized by late-onset neurodegeneration that primarily affects the striatum. Several studies have shown that mutant HTT can also affect neuronal development, contributing to the late-onset neurodegeneration. However, it is currently unclear whether mutant HTT impairs the development of glial cells, which is important for understanding whether mutant HTT affects glial cells during early brain development.MethodsUsing HD knock-in mice that express full-length mutant HTT with a 140 glutamine repeat at the endogenous level, we analyzed the numbers of astrocytes and oligodendrocytes from postnatal day 1 to 3 months of age via Western blotting and immunocytochemistry. We also performed electron microscopy, RNAseq analysis, and quantitative RT-PCR.ResultsThe numbers of astrocytes and oligodendrocytes were not significantly altered in postnatal HD KI mice compared to wild type (WT) mice. Consistently, glial protein expression levels were not significantly different between HD KI and WT mice. However, at 3 months of age, myelin protein expression was reduced in HD KI mice, as evidenced by Western blotting and immunocytochemical results. Electron microscopy revealed a slight but significant reduction in myelin thickness of axons in the HD KI mouse brain at 3 months of age. RNAseq analysis did not show significant reductions in myelin-related genes in postnatal HD KI mice.ConclusionThese data suggest that cytoplasmic mutant HTT, rather than nuclear mutant HTT, mediates myelination defects in the early stages of the disease without impacting the differentiation and maturation of glial cells.

BackgroundPrimary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma with a poor prognosis. We aimed to evaluate the prognostic impact of circulating NK cells in PCNSL.Materials and methodsPatients diagnosed with PCNSL who were treated at our institution between December 2018 and December 2019 were retrospectively screened. Patient variables including age, sex, Karnofsky performance status, diagnostic methods, location of lesions, lactate dehydrogenase, cerebrospinal fluids (CSF), and vitreous fluids involvement or not were documented. NK cell count and NK cell proportion (NK cell count/lymphocyte count) in the peripheral blood were evaluated by flow cytometry. Some patients underwent two consecutive NK cell tests before and three weeks after chemotherapy (before the next chemotherapy). The fold change in NK cell proportion and NK cell counts were calculated. CD56-positive NK cells in tumor tissue were assessed by immunohistochemistry. NK cell cytotoxicity assay was performed using flow cytometry.ResultsA total of 161 patients with PCNSL were included in this study. The median NK cell count of all NK cell tests was 197.73/μL (range 13.11–1889.90 cells/μL). The median proportion of NK cells was 14.11% (range 1.68–45.15%) for all. Responders had a higher median NK cell count (p165 cells/μL) appeared to have a longer median overall survival than those with a low NK cell count (p=0.0054). A high fold change in the proportion of NK cells (>0.1957; p=0.0367) or NK cell count (>0.1045; p=0.0356) was associated with longer progression-free survival. Circulating NK cells from newly-diagnosed PCNSL demonstrated an impaired cytotoxicity capacity compared to those from patients with PCNSL in complete remission or healthy donors.ConclusionOur study indicated that circulating NK cells had some impact on the outcome of PCNSL.

Conductive polymers in combination with carbon matrix are an effective way for the confinement of lithium polysulfides and improved conductivity of sulfur. It can advance the commercial application of lithium-sulfur batteries to optimize preparation methods of conductive polymers in combination with carbon matrix in the process of loading sulfur. Here, a S/C@PANI composite is synthesized via an in situ one-step synthesis method using graphite as a conductive carrier and polyaniline as a conductive polymer. The effect of different preparation methods on the property of the as-prepared S/C@PANI composite is investigated. The S/C@PANI composite prepared via the one-step method delivers a specific capacity of 984 mA h g−1 at 0.1 C, especially 404 mA h g−1 at a high rate of 3 C, and maintains a discharge capacity of 465 mA h g−1 after 200 cycles at 0.5 C, responding to a capacity retention of 77.3%, showing excellent rate capability and good cycling performance. These exceptional performances are attributed to the booted electron transport pathways and suppressed shuttle effect of polysulfides resulting from the strengthening covalent coupling between polyaniline and graphite via one-step assembly synthesis. The one-step synthesis method used in this work offers a facile and efficient route for applying Li/S batteries.

Abstract Background Long non-coding RNAs (lncRNAs) are implicated in the development of multiple cancers. In our previous study, we demonstrated that HDAC1/4-mediated silencing of microRNA-200b (miR-200b) enhances docetaxel (DTX)-resistance of human lung adenocarcinoma (LAD) cells. Methods and results Herein, we probed the function of LncRNA MARCKSL1–2 (MARCKSL1-transcript variant 2, NR_052852.1) in DTX resistance of LAD cells. It was found that MARCKSL1–2 expression was markedly reduced in DTX-resistant LAD cells. Through gain- or loss- of function assays, colony formation assay, EdU assay, TUNEL assay, and flow cytometry analysis, we found that MARCKSL1–2 suppressed the growth and DTX resistance of both parental and DTX-resistant LAD cells. Moreover, we found that MARCKSL1–2 functioned in LAD through increasing miR-200b expression and repressing HDAC1. Mechanistically, MARCKSL1–2 recruited the suppressor of zeste 12 (SUZ12) to the promoter of histone deacetylase 1 (HDAC1) to strengthen histone H3 lysine 27 trimethylation (H3K27me3) of HDAC1 promoter, thereby reducing HDAC1 expression. MARCKSL1–2 up-regulated miR-200b by blocking the suppressive effect of HDAC1 on the histone acetylation modification at miR-200b promoter. Furthermore, in vivo analysis using mouse xenograft tumor model supported that overexpression of MARCKSL1–2 attenuated the DTX resistance in LAD tumors. Conclusions We confirmed that MARCKSL1–2 alleviated DTX resistance in LAD cells by abolishing the inhibitory effect of HDAC1 on miR-200b via the recruitment of SUZ12. MARCKSL1–2 could be a promising target to improve the chemotherapy of LAD. Graphical abstract

Abstract Background There are different degrees of flaws in the knowledge structure of humanistic medicine of medical staff. The level of emotional intelligence of medical staff affects their career development as well as their relationship with patients. Currently, the research on humanistic care ability (HCA) and emotional intelligence of medical staff in China and other countries is rare. This study aimed to investigate the correlation between the level of HCA and level of emotional intelligence of the whole hospital staff. Methods The questionnaire survey employed contained self-designed questions on the hospital staff members’ socio-demographic background, Caring Ability Inventory, and Wong and Law Emotional Intelligence Scale. The survey was conducted with the staff of West China Second University Hospital, Sichuan University in April 2020. Results The hospital staff’s average CAI score was 197.77 ± 20.30, and their average WLEIS score was 84.21 ± 13.48. The CAI and WLEIS scores of the hospital staff who chose their college majors on their own interests were higher than those who chose their majors for other reasons (employability, suggestions from family or others, etc.). The CAI and WLEIS scores of the hospital staff who had received more comprehensive and in-depth humanistic care training were higher than those who did not. The CAI score of the hospital staff who had participated in volunteer service activities was higher than those who did not. The WLEIS score of the Pediatrics Department staff was higher than that of the Outpatient and Emergency Department staff, and the difference was statistically significant (P