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Abstract The incidence of autoimmune diseases has significantly increased over the past 20 years. Excessive host immunoreactions and disordered immunoregulation are at the core of the pathogenesis of autoimmune diseases. The traditional anti-tumor chemotherapy drug CPT-11 is associated with leukopenia. Considering that CPT-11 induces leukopenia, we believe that it is a promising drug for the control of autoimmune diseases. Here, we show that CPT-11 suppresses T cell proliferation and pro-inflammatory cytokine production in healthy C57BL/6 mice and in complete Freund’s adjuvant-challenged mice. We found that CPT-11 effectively inhibited T cell proliferation and Th1 and Th17 cell differentiation by inhibiting glycolysis in T cells. We also assessed CPT-11 efficacy in treating autoimmune diseases in models of experimental autoimmune encephalomyelitis and psoriasis. Finally, we proved that treatment of autoimmune diseases with CPT-11 did not suppress long-term immune surveillance for cancer. Taken together, these results show that CPT-11 is a promising immunosuppressive drug for autoimmune disease treatment.

[Objective] To explore the effects of degradable mulch film mulching on runoff and loss of dissolved nitrogen and phosphorus. [Methods] Polyethylene film mulching (PF) with a thickness of 0.003 mm, degradable film mulching with a thickness of 0.006 mm (BF1), 0.008 mm (BF2), 0.010 mm (BF3) and 0.012 mm (BF4), and no mulch (CK) were set up. In in-situ runoff plots, using mulching on ridge tillage peanut planting as the study object, the runoff and concentration of ammonium nitrogen (NH4+—N), nitrate nitrogen (NO3-—N), and available phosphorus (PO43-—P) in runoff under natural rainfall conditions were measured, and the runoff and nutrient loss characteristics under different thickness of degradable mulch film were analyzed. [Results] (1) The degradation time of degradable film increased with the increase of film thickness. (2) The order of cumulative runoff was BF1

Background: Colon cancer is one of the most prevalent digestive cancers worldwide. Results of epidemiological, experimental, and clinical studies suggest that aspirin inhibits the development of colon cancer. This study aimed to systematically elucidate the molecular mechanisms by which aspirin prevents colon carcinogenesis. Methods: We determined the global protein expression profiles of colorectal cancer and aspirin-treated cells using quantitative proteomic analysis. We analyzed the proteomic results using bioinformatics (including differential proteins, protein annotation, Kyoto Encyclopedia of Genes and Genomes [KEGG] pathways, and protein–protein interaction [PPI] network). The viability of the colon cancer cell line and HT29 ​cells treated with aspirin was determined using the cell counting kit-8 assay. The differentially expressed proteins, such as p53 and cyclin-dependent kinase 1 (CDK1), were quantified using real-time polymerase chain reaction (PCR) and Western blotting. We measured cell cycle distribution and apoptosis in HT29 ​cells exposed to aspirin using fluorescence-activated cell sorting (FACS). Results: We found that 552 proteins were significantly dysregulated, of which 208 and 334 were upregulated and downregulated, respectively, in colon cancer cells exposed to 10 ​mmol/L of aspirin (95% confidence interval [CI]: -1.269 to -0.106, P ​

Summary: The avidity between immune cells and target cells is crucial for effective immune responses. Here, we present a protocol to measure single-cell avidity between cord blood-derived natural killer (NK) cells and the human acute myelocytic leukemia cell line KG-1a. We describe the steps for isolating cord blood mononuclear cells, purifying NK cells, and culturing KG-1a cells. We then detail the procedures for detecting cell avidity between NK cells and KG-1a cells using the acoustic force-based z-Movi cell avidity analyzer.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Allelopathy is the main chemical means in the invasion process of exotic plants and one of the key factors in grassland degradation. In this experiment, we investigated the effects of ethyl acetate phase extract (EAE), n-butanol phase extract (BE) and aqueous phase extract (AE) from the aboveground (stems and leaves) and roots of Ligularia sagitta on seed germination and seedling growth of four Gramineae forages (Poa pratensis L. Festuca ovina L. Elymus nutans Griseb. Agropyron cristatum (L.) Gaertn.) in their sympatric domains and one Legosuminae forage (Medicago sativa L.). The chemical components in each phase extract of L. sagitta were determined with UHPLC-MS/MS non-targeted metabolomics, and the differential compounds were screened using Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). Within a set concentration range, EAE significantly inhibited seed germination and seedling growth of four Gramineae forages. BE and AE acted mainly in the seedling growth stage and did not significantly inhibit forage seed germination. P. pratensis was most sensitive to L. sagitta extracts; at 2.0 mg/mL of EAE from roots, germination energy and germination rate of P. pratensis seeds were 0. L. sagitta extracts inhibited the growth of M. sativa seedlings and did not inhibit its seed germination. A total of 904 compounds were identified with UHPLC-MS/MS, among which 31, 64, 81 and 66 metabolites displayed different accumulation patterns in the four comparison groups (R.EAE vs. R.BE, R.EAE vs. R.AE, SL.EAE vs. SL.BE, SL.EAE vs. SL.AE), respectively. In particular, 9 compounds were found to be common up-regulated differential metabolites in the four comparison groups and were enriched in EAE. Additionally, N,N-dimethylaniline, Caffeic acid, 4-Hydroxybenzoic acid, 4-Hydroxybenzaldehyde and cis-9-Octadecenoic acid as potential allelochemicals in L. sagitta. The results of this study support efforts at finding alternative control plants for the restoration of poisonous grass-type degraded grasslands.

Abstract Background Microcirculatory perfusion disorder and inflammatory response are critical links in acute kidney injury (AKI). We aim to construct anti‐vascular cell adhesion molecule‐1(VCAM‐1) targeted microbubbles (TM) to monitor renal microcirculatory perfusion and inflammatory response. Methods TM carrying VCAM‐1 polypeptide was constructed by biological coupling. The binding ability of TM to human umbilical vein endothelial cells (HUVECs) was detected. Bilateral renal ischemia–reperfusion injury (IRI) models of mice were established to evaluate microcirculatory perfusion and inflammatory response using TM. Thirty‐six mice were randomly divided into six groups according to the different reperfusion time (0.5, 2, 6, 12, and 24 h) and sham‐operated group (Sham group). The correlation of TM imaging with serum and histopathological biomarkers was investigated. Results TM has advantages such as uniform distribution, regular shape, high stability, and good biosafety. TM could bind specifically to VCAM‐1 molecule expressed by tumor necrosis factor‐alpha (TNF‐α)‐treated HUVECs. In the renal IRI‐AKI model, the area under the curve (AUC) of TM significantly decreased both in the renal cortical and medullary after 2 h of reperfusion compared with the Sham group (p

Abstract The engineering of ferroic orders, which involves the evolution of atomic structure and local ferroic configuration in the development of next‐generation electronic devices. Until now, diverse polarization structures and topological domains are obtained in ferroelectric thin films or heterostructures, and the polarization switching and subsequent domain nucleation are found to be more conducive to building energy‐efficient and multifunctional polarization structures. In this work, a continuous and periodic strain in a flexible freestanding BaTiO3 membrane to achieve a zigzag morphology is introduced. The polar head/tail boundaries and vortex/anti‐vortex domains are constructed by a compressive strain as low as ≈0.5%, which is extremely lower than that used in epitaxial rigid ferroelectrics. Overall, this study c efficient polarization structures, which is of both theoretical value and practical significance for the development of next‐generation flexible multifunctional devices.

For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7–T11 injuries than in T2–T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Objective: To investigate the effect of pelvic floor electromyography Biofeedback and “four sacral needles” on pelvic floor muscle strength and quality of life in mild to moderate female stress Urinary incontinence (UI) patients. Methods: A total of 96 patients with mild to moderate female stress UI who were treated in Qingpu District Hospital of Traditional Chinese Medicine from June 2021 to May 2023 were randomly divided into a control group and a test group, with 48 cases in each group. The control group was given pelvic floor myoelectric stimulation combined with Biofeedback, and the treatment group was given “four sacral needles” on the basis of the control group. Record the Glazer electromyography assessment and 1-hour urine pad test leakage at weeks 0, 4, and 8 of treatment, and compare the therapeutic differences between the two groups. Result: Compared with before treatment, after 4 and 8 weeks of treatment, the Glazer evaluation and 1 h urine pad test leakage in both groups were significantly reduced ([Formula: see text]), and the experimental group had better indicators than the control group at 4 and 8 weeks of treatment ([Formula: see text]). The total effective rate of the experimental group was 97.7%, significantly higher than the control group’s 90.9% ([Formula: see text]). Conclusion: Pelvic floor electromyography Biofeedback combined with “four sacral needles” and simple pelvic floor electromyography Biofeedback is effective for women with mild to moderate stress UI. Pelvic floor electromyography Biofeedback combined with “four sacral needles” is superior to simple pelvic floor Biofeedback in the treatment of mild to moderate stress UI.

To investigate the effect of different process parameters on the powder feeding behaviour in coaxial laser cladding stainless steel powder with a fibre laser, high-speed cameras with different resolution, image analysis software and FLUENT software were employed to study the behaviour of conic powder jet stream under the nozzle. The feasibility of the method was also evaluated in detail. The obtained results show that grey level is not directly the powder distribution in the jet but rather a projection of this distribution. The powder distribution is an almost symmetrical Gaussian distribution in specific regions. As the powder feeding rate increases, the concentration of the convergence point increases; the carrier gas flow affects the gas and powder flow speed and concentration. The larger the carrier gas flow is, the greater the gas and powder flow speed are, but the concentration decreases, which is consistent with the grey image change law. The change of powder flow behaviour can be mainly attributed to the effect of gas flow rate on the movement tracks of powder particles. [ABSTRACT FROM AUTHOR]

This paper develops a new analytical model to predict the chip back-flow angle in machining with restricted contact grooved tools. The model is derived from a recently established universal slip-line model for machining with restricted contact cutaway tools. A comprehensive definition of the chip back-flow angle is presented first, and based on this, a quantitative analysis of the chip back-flow effect is established for a given set of cutting conditions, tool geometry, and variable tool-chip interfacial stress state. The model also predicts the cutting forces, the chip thickness, and the chip up-curl radius. A full experimental validation of the analytical predictive model involving the use of high speed filming technique is then presented for the chip back-flow angle. This validation provides a range of feasible/prevalent tool-chip interfacial frictional conditions for the given set of input conditions. [DOI: 10.1115/1.1559159]

ABSTRACT: Small peptides are nutrients and bioactive molecules that have dual regulatory effects on nutrition and physiology. They are of great significance for maintaining the intestinal health and production performance of broilers. We here cultured the primary small intestinal epithelial cells (IEC) of chicken in a medium containing L-Leu (Leu) and L-Leu-L-Leu (Leu-Leu) for 24 h. The untreated cells were considered as the control group. The growth, proliferation, and apoptosis of IEC were examined. By combining RNA-seq and label-free sequencing technology, candidate genes, proteins, and pathways related to the growth, proliferation, and apoptosis of IEC were screened. Immunofluorescence detection revealed that the purity of the isolated primary IEC was >90%. The Leu-Leu group significantly promoted IEC growth and proliferation and significantly inhibited IEC apoptosis, and the effect was better than those of the Leu and control groups. Using transcriptome sequencing, four candidate genes, CCL20, IL8L1, IL8, and IL6, were screened in the Leu group, and one candidate gene, IL8, was screened in the Leu-Leu group. Two candidate genes, IL6 and RGN, were screened in the Leu-Leu group compared with the Leu group. Nonquantitative proteomic marker sequencing results revealed that through the screening of candidate proteins and pathways, found one growth-related candidate protein PGM3 and three proliferation-related candidate proteins RPS17, RPS11, and RPL23, and two apoptosis-related candidate proteins GPX4 and PDPK1 were found in the Leu-Leu group compared with Leu group. In short, Leu-Leu could promote IEC growth and proliferation and inhibit IEC apoptosis. On combining transcriptome and proteome sequencing technologies, multiple immune- and energy-related regulatory signal pathways were found to be related to IEC growth, proliferation, and apoptosis. Three candidate genes of IL8, IL6, and RGN were identified, and six candidate proteins of PGM3, RPS17, RPS11, RPL23, GPX4, and PDPK1 were involved in IEC growth, proliferation, and apoptosis. The results provide valuable data for preliminarily elucidating small peptide-mediated IEC regulation pathways, improving the small peptide nutrition theoretical system, and establishing small peptide nutrition regulation technology.

Background Little is known about how well trial participants with chronic kidney disease (CKD) represent real‐world adults with CKD. We assessed the population representativeness of clinical trials supporting the 2021 Kidney Disease: Improving Global Outcomes blood pressure (BP) guidelines in real‐world adults with CKD. Methods and Results Using a cross‐sectional analysis, we identified patients with CKD who met the guideline definition of hypertension based on use of antihypertensive medications or sustained systolic BP ≥120 mm Hg in 2019 in the Veterans Affairs and Kaiser Permanente of Southern California. We applied the eligibility criteria from 3 BP target trials, SPRINT (Systolic Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and AASK (African American Study of Kidney Disease), to estimate the proportion of adults with a systolic BP above the guideline‐recommended target and the proportion who met eligibility criteria for ≥1 trial. We identified 503 480 adults in the Veterans Affairs and 73 412 adults in Kaiser Permanente of Southern California with CKD and hypertension in 2019. We estimated 79.7% in the Veterans Affairs and 87.3% in the Kaiser Permanente of Southern California populations had a systolic BP ≥120 mm Hg; only 23.8% [23.7%–24.0%] in the Veterans Affairs and 20.8% [20.5%–21.1%] in Kaiser Permanente of Southern California were trial‐eligible. Among trial‐ineligible patients, >50% met >1 exclusion criteria. Conclusions Major BP target trials were representative of fewer than 1 in 4 real‐world adults with CKD and hypertension. A large proportion of adults who are at risk for cardiovascular morbidity from hypertension and susceptible to adverse treatment effects lack relevant treatment information.

ABSTRACT: This research examined the impact of incorporating Angelica sinensis's aerial components (APA), commonly referred to as “female ginseng”, into broilers' diet. Two hundred eighty-eight 1-day-old Cobb 500 broilers were randomly assigned to the 4 experimental groups with 6 replications and 12 birds/replicate. The 4 groups were fed the diets included 4 concentrations of APA (0, 1, 2, and 3%, respectively). The study spanned 42 d, categorized as the starter phase (1–21 d) and the finisher phase (22–42 d). Notably, broilers fed with 3% APA demonstrated a pronounced surge in feed consumption and weight gain during the 22 to 42 d and over the full 42-d period (P < 0.05). Furthermore, when examining the broilers' intestinal structure, there was a notable increase in the villus height and villi ratio across the duodenum, jejunum, and ileum, with a decrease in crypt depth upon 3% APA inclusion (P < 0.05). On a molecular note, certain genes connected to the intestinal mechanical barrier, such as Zona Occludens 1 and Claudin-2, saw significant elevation in the jejunum (P < 0.05). The jejunum also displayed heightened levels of antimicrobial peptides like lysozyme, mucin 2, sIgA, IgG, and IgM, showcasing an enhanced chemical and immune barrier (P < 0.05). Delving into the 16SrDNA sequencing of intestinal content, a higher microbial diversity was evident with a surge in beneficial bacteria, particularly Firmicutes, advocating a resilient and balanced microecosystem. The findings imply that a 3% APA dietary addition bolsters growth metrics and fortifies the intestinal barrier's structural and functional integrity in broilers.

Pancreatic cancer is a malignant tumor of the digestive system that is highly malignant, difficult to treat, and confers a poor prognosis for patients. BRAF-activated noncoding RNA (BANCR) has been proven to play an important role in the invasion and metastasis of pancreatic cancer. In this study, we focused on BANCR as a potential therapeutic target for human pancreatic cancer. The BANCR level in pancreatic cancer tissues and cells is affected by m6A methylation. Based on this, the aim of our study was to investigate the effect of a highly potent and selective first-in-class catalytic inhibitor of METTL3 (STM2457) on BANCR m6A methylation and its malignant biological behaviors in pancreatic cancer. The relationship between BANCR expression and BANCR m6A modification was detected with RT-qPCR and MeRIP-PCR. The expression of methyltransferase-like 3 (METTL3), the key enzyme involved in m6A methylation, in pancreatic cancer tissues was detected using a Western blot. STM2457 was used in vitro to investigate its resistance to the proliferation, invasion, and metastasis of pancreatic cancer cells. BANCR was overexpressed in pancreatic cancer tissues and cells, which was associated with poor clinical outcomes and validated in pancreatic cancer cell lines. m6A modification was highly enriched within BANCR and enhanced its expression. Remarkably, STM2457 inhibited the proliferation, invasion, and metastasis of pancreatic cancer cells by down-regulating BANCR m6A modifications. This study demonstrates the promise of BANCR as a new diagnostic and therapeutic target for pancreatic cancer and reveals the therapeutic effect that STM2457 exerts on pancreatic cancer by down-regulating BANCR m6A modifications.

Abstract Background The exact pathophysiology of TS is still elusive. Previous studies have identified default mode networks (DMN) abnormalities in patients with TS. However, these literatures investigated the neural activity during the tic suppression, not a true resting-state. Therefore, this study aimed to reveal the neural mechanism of Tourette's syndrome (TS) from the perspective of topological organization and functional connectivity within the DMN by electroencephalography (EEG) in resting-state. Methods The study was conducted by analyzing the EEG data of TS patients with graph theory approaches. Thirty children with TS and thirty healthy controls (HCs) were recruited, and all subjects underwent resting-state EEG data acquisition. Functional connectivity within the DMN was calculated, and network properties were measured. Results A significantly lower connectivity in the neural activity of the TS patients in the β band was found between the bilateral posterior cingulate cortex/retrosplenial cortex (t = -3.02, p

To break the narrow diversity bottleneck of the wheat D genome, a set of Aegilops tauschii-wheat introgression (A-WI) lines was developed by crossing Ae. tauschii accession T015 with common wheat elite cultivar Zhoumai 18 (Zhou18). A high-density genetic map was constructed based on Single Nucleotide Polymorphism (SNP) markers and 15 yield-related traits were evaluated in 11 environments for detecting quantitative trait loci (QTL). A total of 27 environmentally stable QTL were identified in at least five environments, 20 of which were derived from Ae. tauschii T015, explaining up to 24.27% of the phenotypic variations. The major QTL for kernel length (KL), QKl-2D.5, was delimited to a physical interval of approximately 2.6 Mb harboring 52 candidate genes. Three Kompetitive Allele Specific PCR (KASP) markers were successfully developed based on nonsynonymous nucleotide mutations of candidate gene AetT093_2Dv1G100900.1 and showed that A-WI lines with the T015 haplotype had significantly longer KL than the Zhou18 haplotype across all 11 environments. Four primary valuable A-WIs with good trait performance and carrying yield-related QTL were selected for breeding improvement. The results will facilitate the efficient transfer of beneficial genes from Ae. tauschii into wheat cultivars to improve wheat yield and other traits.

Abstract Background Influenza is a common illness for its high rates of morbidity and transmission. The implementation of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic to manage its dissemination could affect the transmission of influenza. Methods A retrospective analysis, between 2018 and 2023, was conducted to examine the incidence of influenza virus types A and B among patients in sentinel cities located in North or South China as well as in Wuhan City. For validations, data on the total count of influenza patients from 2018 to 2023 were collected at the Central Hospital of Wuhan, which is not included in the sentinel hospital network. Time series methods were utilized to examine seasonal patterns and to forecast future influenza trends. Results Northern and southern cities in China had earlier outbreaks during the NPIs period by about 8 weeks compared to the 2018–2019. The implementation of NPIs significantly reduced the influenza-like illness (ILI) rate and infection durations. Influenza B Victoria and H3N2 were the first circulating strains detected after the relaxation of NPIs, followed by H1N1 across mainland China. The SARIMA model predicted synchronized H1N1 outbreak cycles in North and South China, with H3N2 expected to occur in the summer in southern cities and in the winter in northern cities over the next 3 years. The ILI burden is expected to rise in both North and South China over the next 3 years, with higher ILI% levels in southern cities throughout the year, especially in winter, and in northern cities mainly during winter. In Wuhan City and the Central Hospital of Wuhan, influenza levels are projected to peak in the winter of 2024, with 2 smaller peaks expected during the summer of 2023. Conclusions In this study, we report the impact of NPIs on future influenza trends in mainland China. We recommend that local governments encourage vaccination during the transition period between summer and winter to mitigate economic losses and mortality associated with influenza.

Purpose: To evaluate the safety and efficacy of different power modes(constant power and variable power) percutaneous microwave ablation (MWA) for treating hepatocellular carcinoma (HCC) and to predict the risk factors of recurrence after MWA. Materials and methods: In this retrospective study, a total of 112 patients with solitary HCC were included from January 2015 to January 2021. All patients received MWA through a percutaneous approach that was guided by ultrasound, 45 patients received variable power MWA, and the remaining 67 were treated with constant power MWA. The complete ablation rates, local recurrence rates, complications, and short-term survival were analyzed. Possible risk factors for tumor recurrence were analyzed. Results: The complete ablation rates were 95.9% for the first ablation and 100% for the second ablation for ≤3 cm lesions. The complete ablation rates were 84.2%(95.9% versus 84.2%, p = 0.039) for the first ablation and 94.7% (100% versus 94.7%, p = 0.113) for the second ablation for 3–5 cm lesions. Local and distant recurrence rates were 18.7%(21/112) and 14.3%(16/112). The 1-, 2-year survival rates were 86.3 and 66.3%, respectively. Subgroup analysis showed that 1-, 2-year survival rates were 91.1% and 78.5% in ≤3 cm group, and were 74.4% and 40.9% in 3–5 cm group, respectively. Univariate analysis revealed that a positive correlation existed between the HBV DNA replication(p = 0.007), AFP level of pre-MWA(p = 0.001) and post-MWA(p