Search

Abstract Background The role of tumor inflammatory microenvironment in the advancement of cancer, particularly prostate cancer, is widely acknowledged. ELL-associated factor 2 (EAF2), a tumor suppressor that has been identified in the prostate, is often downregulated in prostate cancer. Earlier investigations have shown that mice with EAF2 gene knockout exhibited a substantial infiltration of inflammatory cells into the prostatic stroma. Methods A cohort comprising 38 patients who had been diagnosed with prostate cancer and subsequently undergone radical prostatectomy (RP) was selected. These patients were pathologically graded according to the Gleason scoring system and divided into two groups. The purpose of this selection was to investigate the potential correlation between EAF2 and CD163 using immunohistochemistry (IHC) staining. Additionally, in vitro experimentation was conducted to verify the relationship between EAF2 expression, macrophage migration and polarization. Results Our study demonstrated that in specimens of human prostate cancer, the expression of EAF2 was notably downregulated, and this decrease was inversely associated with the number of CD163-positive macrophages that infiltrated the cancerous tissue. Cell co-culture experiments revealed that the chemotactic effect of tumor cells towards macrophages was intensified and that macrophages differentiated into tumor-associated macrophages (TAMs) when EAF2 was knocked out. Additionally, the application of cytokine protein microarray showed that the expression of chemokine macrophage migration inhibitory factor (MIF) increased after EAF2 knockout. Conclusions Our findings suggested that EAF2 was involved in the infiltration of CD163-positive macrophages in prostate cancer via MIF. Graphical abstract

Abstract Limited studies have triangulated the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and systolic blood pressure (SBP), diastolic blood pressure (DBP) or hypertension risk utilizing both observational and Mendelian randomization (MR) approaches. We employed data from the Norwegian Trøndelag Health Study (HUNT) to conduct cross-sectional (n = 5854) and prospective (n = 3592) analyses, as well as one-sample MR (n = 86,324). We also used largest publicly available data for two-sample MR. Our cross-sectional analyses showed a 25 nmol/L increase in 25(OH)D was associated with a 1.73 mmHg decrease in SBP (95% CI − 2.46 to − 1.01), a 0.91 mmHg decrease in DBP (95% CI − 1.35 to − 0.47) and 19% lower prevalence of hypertension (OR 0.81, 95% CI 0.74 to 0.90) after adjusting for important confounders. However, these associations disappeared in prospective analyses. One-sample and two-sample MR results further suggested no causal relationship between serum vitamin D levels and blood pressure or hypertension risk in the general population.

Objective: To study the relationships of serum 25-hydroxyvitamin D [25(OH)D] with dental caries and periodontitis in a general Norwegian adult population. Methods: We analysed a subsample of 1605 participants from the Trøndelag Health Study (HUNT) in Norway that had serum 25(OH)D levels measured in HUNT3 (2006-08) and oral health assessed in the HUNT4 Oral Health Study (2017-19). Negative binomial and Poisson regression models were used to estimate the ratios of means (RMs; for count oral outcomes) and prevalence ratios (PRs; for dichotomous oral outcomes). Results: Serum 25(OH)D was inversely associated with the number of decayed teeth in a dose-response gradient (

Abstract We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.

Abstract Objective Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. Materials and methods The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. Results According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2–3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. Conclusion In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

Abstract Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4’s function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.

Abstract Background There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Methods We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. Results The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids (n = 78; MTX group) or corticosteroids alone (n = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group (p = .005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group (p = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group (p = .002). There were no differences in treatment-related adverse events between the two groups. Conclusions In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. Trial registration The trial was registered with clinicaltrials.gov (NCT04960644).

In this paper, we studied a Hadamard-type fractional Riemann-Stieltjes integral boundary value problem. The existence of nontrivial solutions was obtained by using the fixed-point method when the nonlinearities can be superlinear, suberlinear, and have asymptotic linear growth. Our results improved and generalized some results of the existing literature.

In this work, we investigate a Riemann-Liouville-type impulsive fractional integral boundary value problem. Using the fixed point index, we obtain two existence theorems on positive solutions under some conditions concerning the spectral radius of the relevant linear operator. Our method improves and generalizes some results in the literature.

Cellular traction forces (CTFs) are generated by adherent cells and involved in regulating migration, morphology, and homeostasis. Accurate measurement of CTFs is crucial for understanding fundamental biological processes such as morphogenesis, angiogenesis, and wound healing. However, directly measuring CTFs, which typically range in the nanonewton scale, is challenging. Cellular traction force microscopy (TFM) has been developed to quantify CTFs, but detailed operational procedures and complex data analysis limit its applicability. In this study, hydrogels embedded with fluo-spheres serve as the substrate for TFM measurement under a detailed TFM protocol. Additionally, we designed a user-friendly program for easy parameter setting. An open-source program called Python Fourier transform traction cytometry (pyFTTC) is introduced for data analysis, utilizing particle image velocimetry (PIV) to calculate the traction force from a batch of images. Cross-correlation based PIV and L2-regularized FTTC are applied to all images for data analysis. This article provides a straightforward protocol for quantifying CTFs in standard laboratories, facilitating both cell biology studies and biomaterials development.

Abstract Background Green tea has been reported to be potentially protective against the development of cardiovascular disease (CVD). This study aimed to investigate the association between green tea consumption and incident CVD in type 2 diabetes (T2D) patients with overweight/obesity. Methods A total of 4756 Chinese overweight/obese T2D patients were recruited and followed up for 6.27 years. Information on green tea consumption was collected at baseline using interviewer-administered questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD according to green tea consumption were estimated using the Cox proportional hazards model. Results Compared with non-habitual consumers, participants who consumed > 5 g/day of green tea leaves reduced the risk of CVD by 29% (95%CI: 0.55–0.92), stroke by 30% (95%CI: 0.51–0.95) and coronary heart disease (CHD) by 40% (95%CI: 0.40–0.89). Similarly, participants who consumed green tea for ≥ 40 years reduced the risk of CVD by 31% (95%CI: 0.54–0.88), stroke by 33% (95%CI: 0.50–0.90) and CHD by 39% (95%CI: 0.42–0.88). Among participants with 5 g/day of tea leaves and > 40 years of tea consumption were associated with 59% (95%CI: 0.23–0.72) and 57% (95%CI: 0.26–0.74) reduced risk of stroke, respectively. However, among participants with ≥ 5-year history of T2D, > 5 g/day of tea leaves and > 40 years of tea consumption were associated with a 50% (95%CI: 0.30–0.82) and 46% (95%CI: 0.35–0.85) reduced risk of CHD, respectively. Conclusions Green tea consumption is associated with reduced risk of CVD, stroke, and CHD in overweight/obese T2D patients.

Abstract Background Human health is seriously threatened by antibiotic-induced intestinal disorders. Herein, we aimed to determine the effects of Autoinducer-2 (AI-2) combined with Lactobacillus rhamnosus GG (LGG) on the intestinal barrier function of antibiotic-induced intestinal dysbiosis neonatal mice. Methods An antibiotic-induced intestinal dysbiosis neonatal mouse model was created using antibiotic cocktails, and the model mice were randomized into the control, AI-2, LGG, and LGG + AI-2 groups. Intestinal short-chain fatty acids and AI-2 concentrations were detected by mass spectrometry and chemiluminescence, respectively. The community composition of the gut microbiota was analyzed using 16S rDNA sequencing, and biofilm thickness and bacterial adhesion in the colon were assessed using scanning electron microscopy. Transcriptome RNA sequencing of intestinal tissues was performed, and the mRNA and protein levels of HCAR2 (hydroxycarboxylic acid receptor 2), claudin3, and claudin4 in intestinal tissues were determined using quantitative real-time reverse transcription PCR and western blotting. The levels of inflammatory factors in intestinal tissues were evaluated using enzyme-linked immunosorbent assays (ELISAs). D-ribose, an inhibitor of AI-2, was used to treat Caco-2 cells in vitro. Results Compared with the control, AI-2, and LGG groups, the LGG + AI-2 group showed increased levels of intestinal AI-2 and proportions of Firmicutes and Lacticaseibacillus, but a reduced fraction of Proteobacteria. Specifically, the LGG + AI-2 group had considerably more biofilms and LGG on the colon surface than those of other three groups. Meanwhile, the combination of AI-2 and LGG markedly increased the concentration of butyric acid and promoted Hcar2, claudin3 and claudin4 expression levels compared with supplementation with LGG or AI-2 alone. The ELISAs revealed a significantly higher tumor necrosis factor alpha (TNF-α) level in the control group than in the LGG and LGG + AI-2 groups, whereas the interleukin 10 (IL-10) level was significantly higher in the LGG + AI-2 group than in the other three groups. In vitro, D-ribose treatment dramatically suppressed the increased levels of Hcar2, claudin3, and claudin4 in Caco-2 cells induced by AI-2 + LGG. Conclusions AI-2 promotes the colonization of LGG and biofilm formation to improve intestinal barrier function in an antibiotic-induced intestinal dysbiosis neonatal mouse model.

BackgroundSince the outbreak of COVID-19, China has implemented a series of non-pharmaceutical interventions (NPIs), effectively containing the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as various respiratory pathogens. With the continuous relaxation of restrictions, China has entered a new phase of the post-pandemic era. However, the epidemiological differences of Mycoplasma pneumoniae (MP) between the two phases in Ningbo and even in China remain unclear.MethodsData of children aged 0–14 years who visited the Ningbo Medical Center LiHuiLi Hospital due to acute respiratory tract infections from January 2020 to December 2023 were collected. PCR was used to detect 13 respiratory pathogens and the macrolide-resistance of Mycoplasma pneumoniae.ResultsAmong 10,206 children, 2,360 were infected with MP (23.12%). Among the total, the MP positive rate during the NPI phase (6.35%) was significantly lower than that during the non-NPI phase (34.28%), while the macrolide resistance rate increased from 62.5% (NPI phase) to 81.1% (non-NPI phase). The rate of MP co-infection increased from 11.2% (NPI phase) to 30.3% (non-NPI phase). MP infection exhibited obvious seasonality, with the highest prevalence in autumn (30.0%) followed by summer (23.6%). There were differences in MP positivity rates among different age groups, with the highest among school-age children at 39.5%. During the NPI phase, all age groups were less susceptible to MP, while during the non-NPI phase, the susceptible age for MP was 4–12 years, with 8 years being the most susceptible. The susceptible age for MP co-infection was 0–6 years. MP exhibited antagonistic effects against numerous pathogens. Compared to MP single infection, the proportion of pneumonia was higher in MP co-infection cases.ConclusionThe removal of NPIs significantly impacted the spread of MP, altering population characteristics including age, seasonality, macrolide resistance, and MP co-infection rates.

BackgroundPostoperative delirium (POD) is a common anesthetic side effect in cardiac surgery. However, the role of oxygen saturation monitoring in reducing postoperative delirium has been controversial. Therefore, this meta-analysis aimed to analyze whether NIRS monitoring during cardiac surgery under cardiopulmonary bypass could reduce the incidence of postoperative delirium.MethodsPubMed, Web of Science, Cochrane Library, Embase and China National Knowledge Infrastructure (CNKI) databases were systematically searched using the related keywords for randomized-controlled trials (RCTs) published from their inception to March 16, 2024. This review was conducted by the Preferred Reporting Project and Meta-Analysis Statement (PRISMA) guidelines for systematic review. The primary outcome was postoperative delirium, and the second outcomes included the length of ICU stay, the incidence of kidney-related adverse outcomes, and the incidence of cardiac-related adverse outcomes.ResultsThe incidence of postoperative delirium could be reduced under the guidance of near-infrared spectroscopy monitoring (OR, 0.657; 95% CI, 0.447–0.965; P = 0.032; I2 = 0%). However, there were no significant differences in the length of ICU stay (SMD, 0.005 days; 95% CI, −0.135–0.146; P = 0.940; I2 = 39.3%), the incidence of kidney-related adverse outcomes (OR, 0.761; 95% CI, 0.386–1.500; P = 0.430; I2 = 0%), and the incidence of the cardiac-related adverse outcomes (OR, 1.165; 95% CI, 0.556–2.442; P = 0.686; I2 = 0%) between the two groups.ConclusionNear-infrared spectroscopy monitoring in cardiac surgery with cardiopulmonary bypass helps reduce postoperative delirium in patients.Systematic Review RegistrationPROSPERO, identifier, CRD42023482675

Abstract Purpose Lung cancer (LC) and breast cancer (BC) are the most common causes of brain metastases (BMs). Time from primary diagnosis to BM (TPDBM) refers to the time interval between initial LC or BC diagnosis and development of BM. This research aims to identify clinical, molecular, and therapeutic risk factors associated with shorter TPDBM. Methods We retrospectively reviewed all diagnosed LC and BC patients with BM at Harbin Medical University Cancer Hospital from 2016 to 2020. A total of 570 patients with LC brain metastasis (LCBM) and 173 patients with breast cancer brain metastasis (BCBM) patients who met the inclusion criteria were enrolled for further analysis. BM free survival time curves were generated using Kaplan–Meier analyses. Univariate and multivariate Cox regression analyses were applied to identify risk factors associated with earlier development of BM in LC and BC, respectively. Results The median TPDBM was 5.3 months in LC and 44.4 months in BC. In multivariate analysis, clinical stage IV and M1 stage were independent risk factors for early development of LCBM. LC patients who received chemotherapy, targeted therapy, pulmonary radiotherapy, and pulmonary surgery had longer TPDBM. For BC patients, age ≥ 50 years, Ki67 ≥ 0.3, HER2 positive or triple‐negative breast cancer subtype, advanced N stage, and no mastectomy were correlated with shorter TPDBM. Conclusions This single‐institutional study helps identify patients who have a high risk of developing BM early. For these patients, early detection and intervention could have clinical benefits.

Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) ( n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III–IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67–3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%–72.2%) and 55.4% (95% CI = 44.3%–69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%–29.5%) and 33.8% (95% CI = 21.8%–45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.

BackgroundCuprizone (CPZ)-treated mice show significant demyelination, altered gut microbiome, and depressive-like behaviors. However, the effects of venlafaxine (Ven) on the gut microbiome and depressive-like behavior of CPZ-treated mice are largely unclear.MethodsMale C57BL/6J mice were fed a chow containing 0.2% cuprizone (w/w) for 5 weeks to induce a model of demyelination. Meanwhile, the gut microbiota and depressive-like behaviors were assessed after the mice were fed with Ven (20 mg/kg/day) or equal volumes of distilled water for 2 weeks by oral gavage from the third week onward during CPZ treatment.ResultsCPZ treatment decreased the sucrose preference rate in the sucrose preference test and increased the immobility time in the tail-suspension test, and it also induced an abnormality in β-diversity and changes in microbial composition. Ven alleviated the depressive-like behavior and regulated the composition of the gut microbiota, such as the increase of Lactobacillus and Bifidobacterium in CPZ-treated mice.ConclusionThe anti-depressant effects of Ven might be related to the regulation of gut microbiota in the CPZ-treated mice.

Abstract High‐entropy alloys (HEAs) materials, as promising nanomaterials, have garnered significant attention from researchers due to their excellent performance in the field of hydrogen evolution reaction (HER). The four core effects of HEAs, including the high‐entropy effect, severe lattice distortion effect, sluggish diffusion effect, and cocktail effect, are pivotal in underpinning their remarkable mechanical and thermodynamic properties. Nevertheless, the intricate geometric and electronic structures of HEAs make their catalytic mechanisms exceptionally complex and challenging to decipher. In particular, a thorough analysis of the underlying factors responsible for the outstanding catalytic activity, selectivity, and the ability to maintain stable hydrogen production, even at high current densities, in HEAs is lacking. To provide a systematic exploration of the design and application of HEAs in HER systems, this review commences with an examination of the physicochemical properties of HEAs. It covers a wide range of topics, including the synthesis methods of HEAs, and the major reaction mechanisms of HERs, and presents innovative methods and approaches for designing HEAs specifically in the context of HERs.

Objectives To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework.Design Mendelian randomisation analyses of two prospective population-based cohorts.Setting Individuals of European ancestries living in Norway or the UK.Participants 56 150 participants from the Trøndelag Health Study (HUNT) in Norway and 366 385 participants from UK Biobank recruited by postal invitation.Outcomes All-cause mortality and cause-specific mortality (cardiovascular, cancer, non-cardiovascular non-cancer).Results A previously published non-linear Mendelian randomisation analysis of these data using the residual stratification method suggested a J-shaped association between genetically predicted BMI and mortality outcomes with the lowest mortality risk at a BMI of around 25 kg/m2. However, the ‘constant genetic effect’ assumption required by this method is violated. The reanalysis of these data using the more reliable doubly-ranked stratification method provided some indication of a J-shaped relationship, but with much less certainty as there was less precision in estimates at the lower end of the BMI distribution. Evidence for a harmful effect of reducing BMI at low BMI levels was only present in some analyses, and where present, only below 20 kg/m2. A harmful effect of increasing BMI for all-cause mortality was evident above 25 kg/m2, for cardiovascular mortality above 24 kg/m2, for cancer mortality above 30 kg/m2 and for non-cardiovascular non-cancer mortality above 26 kg/m2. In UK Biobank, the association between genetically predicted BMI and mortality at high BMI levels was stronger in women than in men.Conclusion This research challenges findings from previous conventional observational epidemiology and Mendelian randomisation investigations that the lowest level of mortality risk is at a BMI level of around 25 kg/m2. Our results provide some evidence that reductions in BMI will increase mortality risk for a small proportion of the population, and clear evidence that increases in BMI will increase mortality risk for those with BMI above 25 kg/m2.

Leukemia caused by environmental chemical pollutants has attracted great attention, the malignant leukemic transformation model of TK6 cells induced by hydroquinone (HQ) has been previously found in our team. However, the type of leukemia corresponding to this malignant transformed cell line model needs further study and interpretation. Furthermore, the molecular mechanism of malignant proliferation of leukemic cells induced by HQ remains unclear. This study is the first to reveal the expression of aberrant genes in leukemic cells of HQ-induced malignant transformation, which may correspond to chronic lymphocytic leukemia (CLL). The expression of Linc01588, a long non-coding RNA (lncRNA), was significantly up-regulated in CLL patients and leukemic cell line model which previously described. After gain-of-function assays and loss-of-function assays, feeble cell viability, severe apoptotic phenotype and the increased secretion of TNF-α were easily observed in malignant leukemic TK6 cells with Linc01588 deletion after HQ intervention. The tumors derived from malignant TK6 cells with Linc01588 deletion inoculated subcutaneously in nude mice were smaller than controls. In CLL and its cell line model, the expression of Linc01588 and miR-9–5p, miR-9–5p and SIRT1 were negative correlation respectively in CLL and cell line model, while the expression of Linc01588 and SIRT1 were positive correlation. The dual-luciferase reporter assay showed that Linc01588 & miR-9–5p, miR-9–5p & SIRT1 could bind directly, respectively. Furthermore, knockdown of miR-9–5p successfully rescued the severe apoptotic phenotype and the increased secretion of TNF-α caused by the Linc01588 deletion, the deletion of Linc01588 in human CLL cell line MEC-2 could also inhibit malignant biological characteristics, and the phenotype caused by the deletion of Linc01588 could also be rescued after overexpression of SIRT1. Moreover, the regulation of SIRT1 expression in HQ19 cells by Linc01588 and miR-9–5 P may be related to the Akt/NF-κB pathway. In brief, Linc01588 deletion inhibits the malignant biological characteristics of HQ-induced leukemic cells via miR-9–5p/SIRT1, and it is a novel and hopeful clue for the clinical targeted therapy of CLL.

In order to improve the efficiency of energy utilization, the integrated energy system (IES) has emerged. The IES typically acts as a whole system during operations, the subsystems are separated, and the interests of each system are independent. In this paper, considering the relationship between the various energy systems, non-cooperative game theory is used to establish the optimal dispatch model. The proposed model mainly relies on the relationship between the cooperation and competition among various subsystems to obtain the maximum benefit they can accept. Furthermore, the basic definition is combined with the particle swarm optimization algorithm to solve the problem. The results show that the optimization strategy proposed in this paper can operate safely and reliably, and effectively distribute the benefits of each energy system.

Abstract Background Research focusing on the association between serum vitamin D and oral health outcomes in children, such as dental caries and molar incisor hypomineralisation (MIH), shows inconsistent results. Previous studies have predominantly investigated dental caries and MIH as dichotomized outcomes, which limits the information on their distribution. In addition, the methods used for analysing serum vitamin D have varied. The present study aimed to investigate potential associations between serum vitamin D status measured by Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS) and the prevalence, as well as the number of teeth, affected by dental caries or MIH among 7–9-year-old Norwegian children. Methods The study had a cross-sectional design and included 101 children aged 7–9 years. Serum 25-hydroxyvitamin D (25(OH)D) was measured and included as continuous (per 25 nmol/l) and categorised (insufficient (

Abstract Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), and prolonged ER stress leads to cell apoptosis. Despite increasing research in this area, the underlying molecular mechanisms remain unclear. Here, we discover that ER stress upregulates the UPR signaling pathway while downregulating E2F target gene expression and inhibiting the G2/M phase transition. Prolonged ER stress decreases the mRNA levels of E2F2, which specifically regulates the expression of F-Box Protein 5(FBXO5), an F-box protein that functions as an inhibitor of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase complex. Depletion of FBXO5 results in increased ER stress-induced apoptosis and decreased expression of proteins related to PERK/IRE1α/ATF6 signaling. Overexpression of FBXO5 wild-type (not its ΔF-box mutant) alleviates apoptosis and the expression of the C/EBP Homologous Protein (CHOP)/ATF. Mechanistically, we find that FBXO5 directly binds to and promotes the ubiquitin-dependent degradation of RNF183, which acts as a ubiquitin E3 ligase in regulating ER stress-induced apoptosis. Reversal of the apoptosis defects caused by FBXO5 deficiency in colorectal cancer cells can be achieved by knocking down RNF183 in FBXO5-deficient cells. Functionally, we observed significant upregulation of FBXO5 in colon cancer tissues, and its silencing suppresses tumor occurrence in vivo. Therefore, our study highlights the critical role of the FBXO5/RNF183 axis in ER stress regulation and identifies a potential therapeutic target for colon cancer treatment.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%–26.1%), 22.8% (95% CI 14.2%–31.4%) and 32.8% (95% CI 24.1%–41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%–84.9%), 72.7% (95% CI 63.7%–81.7%), and 62.3% (95% CI 53.5%–71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

ABSTRACTCRISPR-Cas technology has widely been applied to detect single-nucleotide mutation and is considered as the next generation of molecular diagnostics. We previously reported the combination of nucleic acid amplification (NAA) and CRISPR-Cas12a system to distinguish major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. However, the mixture of NAA and CRISPR-Cas12a reagents in one tube could interfere with the efficiency of NAA and CRISPR-Cas12a cleavage, which in turn affects the detection sensitivity. In the current study, we employed a novel photoactivated CRISPR-Cas12a strategy integrated with recombinase polymerase amplification (RPA) to develop one-pot RPA/CRISPR-Cas12a genotyping assay for detecting SARS-CoV-2 Omicron sub-lineages. The new system overcomes the potential inhibition of RPA due to early CRISPR-Cas12a activation and cleavage of the target template in traditional one-pot assay using photocleavable p-RNA, a complementary single-stranded RNA to specifically bind crRNA and precisely block Cas12a activation. The detection can be finished in one tube at 39℃ within 1 h and exhibits a low limit of detection of 30 copies per reaction. Our results demonstrated that the photocontrolled one-pot RPA/CRISPR-Cas12a assay could effectively identify three signature mutations in the spike gene of SARS-CoV-2 Omicron variant, namely, R346T, F486V, and 49X, and distinguish Omicron BA.1, BA.5.2, and BF.7 sub-lineages. Furthermore, the assay achieved a sensitivity of 97.3% and a specificity of 100.0% and showed a concordance of 98.3% with Sanger sequencing results.IMPORTANCEWe successfully developed one-pot recombinase polymerase amplification/CRISPR-Cas12a genotyping assay by adapting photocontrolled CRISPR-Cas technology to optimize the conditions of nucleic acid amplification and CRISPR-Cas12a-mediated detection. This innovative approach was able to quickly distinguish severe acute respiratory syndrome coronavirus 2 Omicron variants and can be readily modified for detecting any nucleic acid mutations. The assay system demonstrates excellent clinical performance, including rapid detection, user-friendly operations, and minimized risk of contamination, which highlights its promising potential as a point-of-care testing for wide applications in resource-limiting settings.

BackgroundAn insufficient number of intratumoral CD8+ T lymphocytes is a major barrier to antitumor immunity and immunotherapy. High endothelial venules (HEVs) are the major sites through which lymphocytes enter tumors; however, the molecular mechanism through which HEVs mediate CD8+ T lymphocyte infiltration remains poorly understood.MethodsForty-two patients with stage IIIA lung adenocarcinoma, who underwent surgery, were recruited. Multiplex immunohistochemical staining was conducted on tumor tissues to detect the immune checkpoint ligands (ICLs) expressed in the HEVs, blood vessels, and lymphatics. A new ICL score model was constructed to evaluate ligand expression. The relationship between ICL score, tumor-infiltrating CD8+ T cell frequency, and survival of patients was investigated.ResultsMature HEVs, but not blood vessels or lymphatics, mediated CD8+ T cell infiltration. However, the ICLs expressed on mature HEVs could negatively regulate CD8+ T cell entry into tertiary lymphoid structures (TLSs). In addition, according to the results obtained using our ICLtotal score model, the expression of ICLs on HEVs was observed to be a predictor of both CD8+ T cell infiltration and survival, in which a high ICLtotal score > 1 represent a weak CD8+ T cell infiltration and a high ICLtotal score > 2 predicts poor survival.ConclusionUsing the ICL score model, we discovered that ICLs expressed on HEVs are indicative of CD8+ T cell subset infiltration in TLSs, as well as of patient survival with lung cancer.

BackgroundThe infiltration and activation of immune cells in the tumor microenvironment (TIME) affect the prognosis of patients with cancer. Tertiary lymphoid structure (TLS) formation favors tumour- infiltrating-lymphocyte (TIL) recruitment and is regarded as an important indicator of good prognosis associated with immunotherapy in patients with tumors. Chemotherapy is currently one of the most commonly used clinical treatment methods. However, there have been no clear report to explore the effects of different types of chemotherapy on TLS formation in the TIME. This study examined the effects of immunogenic cell death (ICD)-inducing chemotherapeutics on immune cells, high-endothelial venules (HEV), and TLSs in mouse melanomas.MethodsDoxorubicin (an ICD inducer), gemcitabine (non-ICD inducer), and a combination of the two drugs was delivered intra-peritoneally to B16F1-loaded C57BL/6 mice. The infiltration of immune cells into tumor tissues was evaluated using flow cytometry. HEV and TLS formation was assessed using immunohistochemistry and multiple fluorescent immunohistochemical staining.ResultsDoxorubicin alone, gemcitabine alone, and the two-drug combination all slowed tumor growth, with the combined treatment demonstrating a more pronounced effect. Compared with the control group, the doxorubicin group showed a higher infiltration of CD8+ T cells and tissue-resident memory T cells (TRM) and an increase in the secretion of interferon-γ, granzyme B, and perforin in CD8+ T subsets and activation of B cells and dendritic cells. Doxorubicin alone and in combination with gemcitabine decreased regulatory T cells in the TIME. Moreover, doxorubicin treatment promoted the formation of HEV and TLS. Doxorubicin treatment also upregulated the expression of programmed cell death protein (PD)-1 in CD8+ T cells and programmed cell death protein ligand (PD-L)1 in tumor cells.ConclusionsThese results indicate that doxorubicin with an ICD reaction promotes TLS formation and increases PD-1/PD-L1 expression in tumor tissues. The results demonstrate the development of a therapeutic avenue using combined immune checkpoint therapy.

Bovine colostrum provides newborn calves with strong passive immunity, which will further affect the immunity of their offspring. Compared with other commercial dairy products, bovine colostrum emphasizes the limit of aflatoxin M1, pathogenic bacteria, microorganisms, antibiotics, stimulants, and other items, so it is safe to use. There are many reports that the use of bovine colostrum as a breast milk fortifier for preterm infants provides necessary immune support for premature infants, but the selection of bovine colostrum products chosen must be free of Bacillus cereus because they are very dangerous for premature infants. This also emphasizes that for the bovine colostrum that is used in preterm infants, more clinical research support is needed. At the same time, it should also be emphasized that the composition of BC is different from that of human colostrum, in particular, the main protein of BC is casein, while the main protein in breast milk is whey protein, especially α-lactalbumin, which together with ovalbumin is still the reference protein with the best biological value, especially for muscles. Therefore, bovine colostrum is currently not a complete substitute for breast milk. In recent years, in addition to reports of bovine colostrum use in preterm infants, studies have also found that bovine colostrum has immunomodulatory and promoting effects in adolescents, adults, and the elderly. This suggests that bovine colostrum has the potential to provide appropriate immune support for people of all ages. Therefore, this study aimed to evaluate the quality of nutritional characteristics of bovine colostrum on three dimensions. The effects of bovine colostrum on people of all ages is a narrative review of the effects of bovine colostrum on immunity in people of all ages. This review identified several classes of immunoactive substances in bovine colostrum, including immunoglobulins, cytokines, and enzymes, and compared the nutritional composition of bovine colostrum with mature milk, colostrum and mature milk in full-term breast milk, and colostrum and mature milk in preterm breast milk, to demonstrate that bovine colostrum provides a rich range of immunoactive components. In addition, the influencing factors affecting the quality of bovine colostrum (immunoglobulin) were reviewed, and it was found that individual differences, environmental factors, and processing methods had a great impact on the quality of BC. More importantly, the immunomodulatory effects of bovine colostrum in people of all ages were reviewed in detail (with an emphasis on preterm infants and immunocompromised children in neonates) as evidence to support the immunity effects of colostrum in people of all ages. This review hopes to use the above evidence to make people understand the health role of bovine colostrum as having a human immunomodulatory effect, and at the same time, when seeing the potential value of bovine colostrum in the future, the limitations of its application should also be deeply re-explored, such as lactose intolerance, allergies, etc., to provide effective solutions for the wide application of bovine colostrum.

Convolutional neural network (CNN)-based and Transformer-based methods for hyperspectral image (HSI) classification have rapidly advanced due to their unique characterization capabilities. However, the fixed kernel sizes in convolutional layers limit the comprehensive utilization of multi-scale features in HSI land cover analysis, while the Transformer’s multi-head self-attention (MHSA) mechanism faces challenges in effectively encoding feature information across various dimensions. To tackle this issue, this article introduces an HSI classification method, based on multi-scale convolutional features and multi-attention mechanisms (i.e., MSCF-MAM). Firstly, the model employs a multi-scale convolutional module to capture features across different scales in HSIs. Secondly, to enhance the integration of local and global channel features and establish long-range dependencies, a feature enhancement module based on pyramid squeeze attention (PSA) is employed. Lastly, the model leverages a classical Transformer Encoder (TE) and linear layers to encode and classify the transformed spatial–spectral features. The proposed method is evaluated on three publicly available datasets—Salina Valley (SV), WHU-Hi-HanChuan (HC), and WHU-Hi-HongHu (HH). Extensive experimental results have demonstrated that the MSCF-MAM method outperforms several representative methods in terms of classification performance.

Prior literature finds senior executives can influence auditor decision making. However, few studies have discussed the impact of employee's personal characteristics. Our research aims to fill the above research gaps by examining the impact of employee level education on audit costs. Taking A-share listed companies in Shanghai and Shenzhen from 2006 to 2021 as the research object, this paper examines the impact of employee education on audit fees. It is found that highly educated employees can effectively reduce the audit fees borne by the company, but the implementation of the Labor Protection Law weakens this inhibitory effect. In the case of low marketization level and weak Confucian culture intensity, employee education level has a more significant inhibitory effect on audit fees of listed companies. This study provides a basis for empirical research on the impact of employee attributes on auditor decision making, provides a new research perspective on the impact of labor protection law at the corporate micro level, and enriches the theoretical research on corporate governance rooted in traditional Chinese culture. We contribute to the practice that implications for evaluating the effectiveness of adopting labor protection.

Multi-horizontal submerged jets stilling basins have been utilized in large-scale water conservancy and hydropower projects due to its stable flow pattern, high energy dissipation rate and less atomization. This study employs vorticity criterion, Q criterion, λ2 criterion and Ω criterion to investigate the characteristics of vortex formation and turbulent dissipation in multi-horizontal submerged jets stilling basins with various configurations, including crest overflowing orifice alone (COO), combination of crest overflowing orifice and mid-discharge orifice (COO-MO) and mid-discharge orifice alone (MO). The results indicate that the Q criterion and λ2 criterion are effective in identifying vortex structure within multi-horizontal submerged jets stilling basin. Specifically, the stronger intensity of vortex structure and vortex dissipation are mainly distributed in the vicinity of the vertical drop, which gradually weakens for the increasing distance to the vertical drop. Furthermore, the intensity and number of vortexes with COO-MO are the largest. This conclusion can provide guidance for energy dissipation and bottom protection of stilling pool.

[This corrects the article DOI: 10.1371/journal.pone.0302631.].

With the rapid progress of urbanization in China, the real estate industry, characterized by a long industrial chain, has become a pillar industry for economic development. Therefore, we inspect the nexus between land finance, housing prices, and economic growth. For this purpose, we use the panel data of 277 cities at the prefecture level or above in China from 2011 to 2019, and empirically examine it by using the Panel Vector Auto Regression (PVAR) model. The results show that there is a causal relationship between housing prices and economic growth. Housing prices promote economic growth in the short term and inhibit it in the long term. Both economic growth and housing prices have a significant impact on land finance. The economic growth show a significantly positive impact, while housing prices promote land finance in the short term with a long-term trend from positive to negative. This is the first study that tries to probe the relationship between urban housing prices, land finance, and economic growth by considering 277 prefecture-level and above cities in China. To promote the stable development of the regional economy, local governments need to overcome their dependence on the housing market and land finance and promote the healthy development of the housing market.

Large constellations, especially at low-Earth orbit, have become a popular solution for global telecommunication. With the proliferation of prospective constellations, more and more satellites will be launched and deployed in the future, which challenges the regulatory framework from several aspects. In the last decades, the International Telecommunication Union (ITU) has established a regulatory framework of space radiocommunication systems for the purpose of securing rights and protection from technical harmful interference of subsequent networks. The well-known steps in the Radio Regulations include the advance publication of information, coordination, notification, and recording of frequency assignments in the Master International Frequency Register. The network registration procedure ran well with the conventional geostationary-satellite orbit (GSO) and non-GSO satellites until the emergence of large constellations. The scope of this paper is to introduce the current approach for ITU to regulate the registration of large constellations and point out the underlying issues. Three issues come from unclear provisions. The first one is whether a non-GSO network can be kept active with fewer satellites on orbit after bringing into use and the milestone requirement. The second issue is whether a non-GSO satellite can be used for bringing into use of different networks. The third issue is whether there should be an error tolerance for the notified orbital parameters in practice. Possible solutions such as postmilestone procedure and tolerance of orbital parameters are discussed. The chance for both ITU and Committee on Peaceful Uses of Outer Space (COPUOS) to explore the potential was also analyzed to implement mutual reference for constellation registration. Furthermore, if the collaboration of the 2 regimes going deep, it could also explore to build up a one-to-one mapping database to figure out the relationship between Master International Frequency Register fillings with actual deployment of large constellations in space.

IntroductionIntestinal health is very important to the health of livestock and poultry, and is even a major determining factor in the performance of livestock and poultry production. Spermidine is a type of polyamine that is commonly found in a variety of foods, and can resist oxidative stress, promote cell proliferation and regulate intestinal flora.MethodsIn this study, we explored the effects of spermidine on intestinal health under physiological states or oxidative stress conditions by irrigation with spermidine and intraperitoneal injection of 3-Nitropropionic acid (3-NPA) in Sichuan white goose.Results and discussionOur results showed that spermidine could increase the ratio of intestinal villus to crypt and improve intestinal morphology. In addition, spermidine can also reduce malondialdehyde (MDA) accumulation caused by 3-NPA by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) enzyme activity, thus alleviating intestinal damage. Furthermore, spermidine can regulate intestinal digestive enzyme activities and affect intestinal digestion and absorption ability. Spermidine can also promote an increase in intestinal microbial diversity and abundance and alleviate the change of microflora structure caused by 3-NPA. In conclusion, spermidine promotes the production of beneficial intestinal metabolites such as Wikstromol, Alpha-bisabolol and AS 1–5, thus improving the level of intestinal health. Taken together, these results indicate that spermidine can improve intestinal health by improving intestinal morphology, increasing antioxidant capacity and regulating intestinal flora structure.

Hyperspectral image classification (HSIC) has garnered increasing attention among researchers. While classical networks like convolution neural networks (CNNs) have achieved satisfactory results with the advent of deep learning, they are confined to processing local information. Vision transformers, despite being effective at establishing long-distance dependencies, face challenges in extracting high-representation features for high-dimensional images. In this paper, we present the multiscale efficient attention with enhanced feature transformer (MEA-EFFormer), which is designed for the efficient extraction of spectral–spatial features, leading to effective classification. MEA-EFFormer employs a multiscale efficient attention feature extraction module to initially extract 3D convolution features and applies effective channel attention to refine spectral information. Following this, 2D convolution features are extracted and integrated with local binary pattern (LBP) spatial information to augment their representation. Then, the processed features are fed into a spectral–spatial enhancement attention (SSEA) module that facilitates interactive enhancement of spectral–spatial information across the three dimensions. Finally, these features undergo classification through a transformer encoder. We evaluate MEA-EFFormer against several state-of-the-art methods on three datasets and demonstrate its outstanding HSIC performance.

In this study, an overview of two years of research findings concerning the 2022 Hunga Tonga–Hunga Ha’apai (HTHH) volcanic eruption in the stratospheric environment is provided, focusing on water vapor, aerosols, and ozone. Additionally, the potential impacts of these changes on aviation equipment materials are discussed. The HTHH volcanic eruption released a large amount of particles (e.g., ash and ice) and gases (e.g., H2O, SO2, and HCl), significantly affecting the redistribution of stratospheric water vapor and aerosols. Stratospheric water vapor increased by approximately 140–150 Tg (8–10%), with a concentration peak observed in the height range of 22.2–27 km (38–17 hPa). Satellite measurements indicate that the HTHH volcano injected approximately 0.2–0.5 Tg of sulfur dioxide into the stratosphere, which was partially converted into sulfate aerosols. In-situ observations revealed that the volcanic aerosols exhibit hygroscopic characteristics, with particle sizes ranging from 0.22–0.42 μm under background conditions to 0.42–1.27 μm. The moist stratospheric conditions increased the aerosol surface area, inducing heterogeneous chlorine chemical reactions on the aerosol surface, resulting in stratospheric ozone depletion in the HTHH plume within one week. In addition, atmospheric disturbances and ionospheric disruptions triggered by volcanic eruptions may adversely affect aircraft and communication systems. Further research is required to understand the evolution of volcanic aerosols and the impact of volcanic activity on aviation equipment materials.

Over the past several decades, deep neural networks have been extensively applied to medical image segmentation tasks, achieving significant success. However, the effectiveness of traditional deep segmentation networks is substantially limited by the small scale of medical datasets, a limitation directly stemming from current medical data acquisition capabilities. To this end, we introduce AttEUnet, a medical cell segmentation network enhanced by edge attention, based on the Attention U-Net architecture. It incorporates a detection branch enhanced with edge attention and a learnable fusion gate unit to improve segmentation accuracy and convergence speed on small medical datasets. The AttEUnet allows for the integration of various types of prior information into the backbone network according to different tasks, offering notable flexibility and generalization ability. This method was trained and validated on two public datasets, MoNuSeg and PanNuke. The results show that AttEUnet significantly improves segmentation performance on small medical datasets, especially in capturing edge details, with F1 scores of 0.859 and 0.888 and Intersection over Union (IoU) scores of 0.758 and 0.794 on the respective datasets, outperforming both convolutional neural networks (CNNs) and transformer-based baseline networks. Furthermore, the proposed method demonstrated a convergence speed over 10.6 times faster than that of the baseline networks. The edge attention branch proposed in this study can also be added as an independent module to other classic network structures and can integrate more attention priors based on the task at hand, offering considerable scalability.

Despite notable advancements achieved on Hyperspectral (HS) pansharpening tasks through deep learning techniques, previous methods are inherently constrained by convolution or self-attention intrinsic defects, leading to limited performance. In this paper, we proposed an Attention-Interactive Dual-Branch Convolutional Neural Network (AIDB-Net) for HS pansharpening. Our model purely consists of convolutional layers and simultaneously inherits the strengths of both convolution and self-attention, especially the modeling of short- and long-range dependencies. Specially, we first extract, tokenize, and align the hyperspectral image (HSI) and panchromatic image (PAN) by Overlapping Patch Embedding Blocks. Then, we specialize a novel Spectral-Spatial Interactive Attention which is able to globally interact and fuse the cross-modality features. The resultant token-global similarity scores can guide the refinement and renewal of the textural details and spectral characteristics within HSI features. By deeply combined these two paradigms, our AIDB-Net significantly improve the pansharpening performance. Moreover, with the acceleration by the convolution inductive bias, our interactive attention can be trained without large scale dataset and achieves competitive time cost with its counterparts. Compared with the state-of-the-art methods, our AIDB-Net makes 5.2%, 3.1%, and 2.2% improvement on PSNR metric on three public datasets, respectively. Comprehensive experiments quantitatively and qualitatively demonstrate the effectiveness and superiority of our AIDB-Net.

Landslides are a common geological disaster, which cause many economic losses and casualties in the world each year. Drawing up a landslide list and monitoring their deformations is crucial to prevent landslide disasters. Interferometric synthetic aperture radar (InSAR) can obtain millimeter-level surface deformations and provide data support for landslide deformation monitoring. However, some landslides are difficult to detect due to the low-coherence caused by vegetation cover in mountainous areas and the difficulty of phase unwrapping caused by large landslide deformations. In this paper, a method based on multi-direction phase gradient stacking is proposed. It employs the differential interferograms of small baseline sets to directly obtain the abnormal region, thereby avoiding the problem where part of landslide cannot be detected due to a phase unwrapping error. In this study, the Sentinel-1 satellite ascending and descending data from 2018 to 2020 are used to detect landslides around Zhouqu County, China. A total of 26 active landslides were detected in ascending data and 32 active landslides in the descending data using the method in this paper, while the SBAS-InSAR detected 19 active landslides in the ascending data and 25 active landslides in the descending data. The method in this paper can successfully detect landslides in areas that are difficult for the SBAS-InSAR to detect. In addition, the proposed method does not require phase unwrapping, so a significant amount of data processing time can be saved.