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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 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.

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.

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.

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 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.

The global repercussions of the COVID-19 pandemic on economies and public health worldwide have been profound. This study aims to examine the developmental trends of the COVID-19 pandemic, establish predictive models, and provide insights for effective control measures against potential future disease outbreaks. Considering the coexistence of both linear and nonlinear factors in COVID-19 data, conventional single-machine learning and traditional forecasting models encounter challenges in accurately predicting pandemic trends. To enhance the precision of COVID-19 pandemic predictions by integrating linear and nonlinear factors, this study proposes three combined forecasting models: CNN-LSTM-ARIMA, TCN-LSTM-ARIMA, and SSA-LSTM-ARIMA. These models leverage the strengths of deep learning in capturing nonlinear factors and the capabilities of the traditional ARIMA model in handling linear factors. Initially, LSTM and ARIMA models are used to model and predict the COVID-19 pandemic in Quebec, Canada. Subsequently, CNN models, TCN models, and the Sparrow Search Algorithm are employed to integrate predictions from the LSTM and ARIMA models. Comparative analyses of the three combined models, it was found that the CNN-LSTM-ARIMA model exhibits the highest predictive accuracy, with an MSE of 7048.26, RMSE of 83.95, MAE of 61.18, MAPE of 0.16, and $R^{2}$ of 0.95. To validate the applicability and stability of the CNN-LSTM-ARIMA model in predicting COVID-19 pandemics, Italian COVID-19 pandemic data was employed. The three combined forecasting models are established and evaluated using model evaluation metrics. The results affirm that the CNN-LSTM-ARIMA model remains the optimal choice, underscoring its high stability and suitability for COVID-19 pandemic forecasting endeavors.

The Three Gorges hydropower station in China creates a large reservoir by diverting water from the Yangtze River, increasing the risk of geological disasters, especially massive landslides along the reservoir shoreline. To mitigate these risks, improving geological monitoring and early warning systems is crucial. Interferometric Synthetic Aperture Radar (InSAR) is widely used to monitor reservoir bank landslides. However, its potential in early warning systems is limited due to temporal resolution constraints, preventing timely warnings. To address this, we propose integrating daily hydrological data (precipitation and water level observations) with historical InSAR deformation sequences using our deep learning-based multivariate united state estimation network, “MUSEnet.” This approach generates customized daily landslide deformation products for high-risk areas, greatly enhancing early warning capabilities by providing timely and accurate information on landslide occurrence and magnitude. We validated our method using 161 Sentinel-1 A images of the Xinpu landslide in the Three Gorges Reservoir area. Through statistical analysis, we identified different degrees of influence from rainfall and reservoir water level on the deformation of the Xinpu landslide at various locations. Additionally, we observed distinct lag times between deformation and corresponding rainfall and reservoir water level events. By utilizing deep learning, our method estimates nonlinear states by considering hysteresis and intelligently accounts for the impact of rainfall and reservoir water level, resulting in more accurate estimations compared to traditional models.

Abstract Background Screening for Tuberculosis (TB) is a critical tactic for minimizing the prevalence of illness within schools. Tuberculosis Preventive Therapy (TPT), in turn, effectively staves off the development of TB from latent tuberculosis infection (LTBI). Unfortunately, there is limited research on LTBI and TPT among students. This study aimed to assess LTBI among freshmen in Changping District and advocate for the implementation of TPT. Methods The prospective study collected data from 12 educational institutions within the Changping District of Beijing. The Kolmogorov − Smirnov test and other statistical methods were used for statistical analysis, $${x}^{2}$$ x 2 was obtained using the formula $${x}^{2}=$$ x 2 = nΣA2/nRnC-1, df = (C-1) (R-1). We analyzed potential factors impacting the LTBI rate, and scrutinized the possible causes behind the low application of TPT and its efficacy for LTBI treatment, China. Results Among 19,872 freshmen included in this study, 18 active TB cases (91 per 10,0000) and 2236 LTBI cases (11.6% of 19,223) were identified, respectively. Furthermore, of those with LTBI, 1045 (5.4% of 19,223) showed a strong positive for purified protein derivative (PPD), but only 312 opted for TB preventive treatment. There appeared to be no significant difference in the prevalence of LTBI and TPT rate between male and female students. Concurrently, 11 (71 per 100,000) and 7 (158 per 100,000) cases of active tuberculosis were identified in 6 universities and 6 higher vocational colleges, respectively. Interestingly, almost all freshmen who underwent TPT came from universities, suggesting a statistically significant disparity in TPT rate (χ2 = 139.829, P

Sulfur dioxide (SO2) is a typical pollutant that affects human health, climate, and environmental and ecological conditions. China has been experiencing high concentrations of SO2, particularly in urban areas, since the 1990s. In 2010, a “joint prevention and control” (JPC) policy was issued to address air pollution problems and strengthen the regulation of SO2 emissions. This study aimed to describe the mitigation effects of this policy on SO2 emissions in 116 Chinese cities from 2003 to 2017. We applied global and local Moran's I indices to confirm the presence of significant spatial autocorrelation in SO2 emissions and constructed four spatial models to assess the effect of the JPC policy in reducing SO2 emissions and its transmission mechanism. We found that the policy decreased SO2 emissions by 1.89 × 104 tons, SO2 intensity by 1.70 tons per km2, and SO2 per capita of 158.49 tons per 10,000 people in each city, on average, all of which are significant changes. The empirical results also show that population growth, economic structure, and environmental protection significantly decrease SO2 emissions. Finally, we recommended policies to encourage regional cooperation under the JPC policy, with the aim of promoting further reductions in SO2 emissions.

In this study, an in-depth analysis of the microstructure and hardness of 6082 aluminum alloy under a novel solution-forging integrated process was conducted by performing a series of isothermal uniaxial compression tests at various strain rates and aging durations. The results indicated that the highest hardness was 125.0 ± 1.2 HV at peak aging with a forming strain rate of 10 s−1; a 16.1% improvement compared to the conventional T6 forming process. The deformation reduced the subsequent peak aging time from 8 h in the conventional process to 6 h. In addition, the composite phases, including short-range disordered B'/U2 phase and composite phase with multiple structures, were also observed under a strain rate of 10 s−1 with 6 h of aging. As the strain rate increased, the grain size increased, accompanied by an increase in dislocation density. For the integrated process, the deformation microstructure would inherit to the aging state and affect the precipitation kinetics during aging, including grain morphology, dislocation density, and the aging precipitated phase, especially for the formation of composite phase; these were the main reasons for the higher hardness after ageing when compared to the hardness of the alloy under traditional T6 state.

China has abundant straw resources, but challenges in utilization persist. Utilization rates need improvement, and environmental pollution from straw burning remains a significant issue. Accurate and intelligent remote sensing classification of straw types is crucial for enhancing straw utilization and preventing straw burning. This paper proposed a new approach for the intelligent classification of maize straw types, using the DenseNet201 deep transfer learning algorithm based on RGB images captured by Unmanned Aerial Vehicle (UAV). The sample labels dataset was established for maize straw types, utilizing DenseNet201 deep transfer learning algorithm to pre-train the sample set. This pre-training facilitated model transfer and parameter initialization. Subsequently, the second round of deep transfer learning was performed to construct the final maize straw type remote sensing classification models using DenseNet201 deep transfer learning algorithm. This model and results were subsequently compared with maize straw type classification by the ResNet50 and GoogLeNet deep transfer learning algorithms, as well as maize straw type classification using DenseNet201, ResNet50, and GoogLeNet deep learning algorithms. The results showed that the accuracy of the pre-trained maize straw type deep transfer learning remote sensing classification model surpassed that of the untrained maize straw type deep learning remote sensing classification model, resulting in an enhancement of accuracy by 8.59%, 7.38%, and 1.28%, respectively. The DenseNet201 deep transfer learning model for maize straw types exhibited the highest accuracy with the overall accuracy of 95.57%, and the kappa coefficient of 0.9410. Hence, the DenseNet201 deep transfer learning classification of maize straw types enabled the attainment of intelligent remote sensing recognition of maize straw types. The classification methodology, model, and results presented in this paper can serve as valuable technical references, offering essential information support for agricultural and environmental protection departments actively involved in the comprehensive utilization of straw resources and atmospheric environmental protection efforts.

Natural environments play a crucial role in transmission of antimicrobial resistance (AMR). Development of methods to manage antibiotic resistance genes (ARGs) in natural environments are usually limited to the laboratory or field scale, partially due to the complex dynamics of transmission between different environmental compartments. Here, we conducted a nine-year longitudinal profiling of ARGs at a watershed scale, and provide evidence that restrictions on livestock farms near water bodies significantly reduced riverine ARG abundance. Substantial reductions were revealed in the relative abundance of genes conferring resistance to aminoglycosides (42%), MLSB (36%), multidrug (55%), tetracyclines (53%), and other gene categories (59%). Additionally, improvements in water quality were observed, with distinct changes in concentrations of dissolved reactive phosphorus, ammonium, nitrite, pH, and dissolved oxygen. Antibiotic residues and other pharmaceuticals and personal care products (PPCPs) maintain at a similarly low level. Microbial source tracking demonstrates a significant decrease in swine fecal indicators, while human fecal pollution remains unchanged. These results suggest that the reduction in ARGs was due to a substantial reduction in input of antibiotic resistant bacteria and genes from animal excreta. Our findings highlight the watershed as a living laboratory for understanding the dynamics of AMR, and for evaluating the efficacy of environmental regulations, with implications for reducing environmental risks associated with AMR on a global scale.

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.

Abstract Objective To describe a novel method of medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction and to compare the reconstruction outcome of orbital floor reconstruction with modified and traditional methods. Methods The data of 23 patients who underwent maxillectomy and orbital floor defect reconstruction by individualized titanium mesh in Peking University School and Hospital of Stomatology between 2018 and 2021 were retrospectively reviewed. While eight patients received modified orbital floor reconstruction with titanium mesh and angled screwdriver (group A), 15 patients received traditional orbital floor reconstruction (group B). The contact area with buccal flap for titanium mesh in groups A and B was calculated. Titanium mesh deformation, fracture or exposure was recorded. Postoperative ophthalmic function and success of esthetic restoration were assessed. Results Mean follow‐up was for 15.7 months (range, 9–22 months). The contact area with buccal flap for the modified titanium mesh in group A (13.11 ± 1.41 cm2) was significantly less than that of the traditional titanium mesh in group B (21.83 ± 1.23 cm2; p .05). No specific complications were reported. Conclusion We propose a novel method of zygomatic medial fixation of titanium mesh with a right‐angled screwdriver for orbital floor and maxillary reconstruction, which has the potential to prevent the postoperative exposure of titanium mesh. Level of Evidence Level III (Retrospective comparative study).

Abstract Background To identify the disease-causing gene in a Chinese family affected with congenital aniridia. Methods Patients underwent systematic ophthalmic examinations such as anterior segment photography, fundus photography, optical coherence tomography, and fundus fluorescein angiography. The proband was screened for pathogenic variants by whole exome sequencing (WES) and copy number variant (CNV) analysis. Real-time quantitative PCR (RT-qPCR) was applied to confirm the CNV results. Breakpoints were identified by long-range PCR followed by Sanger sequencing. Results All seven members of this Chinese family, including four patients and three normal individuals, were recruited for this study. All patients showed bilateral congenital aniridia with nystagmus, except the son of the proband, who presented with bilateral partial coloboma of the iris. A novel heterozygous deletion (chr11:31,139,019–31,655,997) containing the 3’ regulatory enhancers of the PAX6 gene was detected in this family. We also reviewed the reported microdeletions downstream of PAX6 in patients with aniridia. Conclusions We identified a novel microdeletion, 517 kb in size located about 133 kb downstream of the PAX6 gene, responsible for congenital aniridia in this Chinese family, which expands the spectrum of aniridia-associated mutations in PAX6.

Abstract Introduction Low serum selenium and altered tumour RNA expression of certain selenoproteins are associated with a poor breast cancer prognosis. Selenoprotein expression stringently depends on selenium availability, hence circulating selenium may interact with tumour selenoprotein expression. However, there is no matched analysis to date. Methods This study included 1453 patients with newly diagnosed breast cancer from the multicentric prospective Sweden Cancerome Analysis Network – Breast study. Total serum selenium, selenoprotein P and glutathione peroxidase 3 were analysed at time of diagnosis. Bulk RNA-sequencing was conducted in matched tumour tissues. Fully adjusted Cox regression models with an interaction term were employed to detect dose-dependent interactions of circulating selenium with the associations of tumour selenoprotein mRNA expression and mortality. Results 237 deaths were recorded within ~ 9 years follow-up. All three serum selenium biomarkers correlated positively (p

ABSTRACT Purpose: To compare the effectiveness and safety of marketed oral drugs for overactive bladder based on a systematic review and network meta-analysis approach. Methods: Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. Result: A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Conclusion: Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel targeting LAG-3 drugs have also been approved in clinical application. With the widespread use of the drug, we must deeply analyze the dilemma of the agents and seek a breakthrough in the treatment prospect. Over the past decades, these agents have demonstrated dramatic efficacy, especially in patients with melanoma and non-small cell lung cancer (NSCLC). Nonetheless, in the field of a broad concept of solid tumours, non-specific indications, inseparable immune response and side effects, unconfirmed progressive disease, and complex regulatory networks of immune resistance are four barriers that limit its widespread application. Fortunately, the successful clinical trials of novel ICB agents and combination therapies, the advent of the era of oncolytic virus gene editing, and the breakthrough of the technical barriers of mRNA vaccines and nano-delivery systems have made remarkable breakthroughs currently. In this review, we enumerate the mechanisms of each immune checkpoint targets, associations between ICB with tumour mutation burden, key immune regulatory or resistance signalling pathways, the specific clinical evidence of the efficacy of classical targets and new targets among different tumour types and put forward dialectical thoughts on drug safety. Finally, we discuss the importance of accurate triage of ICB based on recent advances in predictive biomarkers and diagnostic testing techniques.

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.

BackgroundIsocitrate dehydrogenase-wildtype glioblastoma (IDH-wildtype GBM) and IDH-mutant astrocytoma have distinct biological behaviors and clinical outcomes. The location of brain tumors is closely associated not only with clinical symptoms and prognosis but also with key molecular alterations such as IDH. Therefore, we hypothesize that the key brain regions influencing the prognosis of glioblastoma and astrocytoma are likely to differ. This study aims to (1) identify specific regions that are associated with the Karnofsky Performance Scale (KPS) or overall survival (OS) in IDH-wildtype GBM and IDH-mutant astrocytoma and (2) test whether the involvement of these regions could act as a prognostic indicator.MethodsA total of 111 patients with IDH-wildtype GBM and 78 patients with IDH-mutant astrocytoma from the Cancer Imaging Archive database were included in the study. Voxel-based lesion-symptom mapping (VLSM) was used to identify key brain areas for lower KPS and shorter OS. Next, we analyzed the structural and cognitive dysfunction associated with these regions. The survival analysis was carried out using Kaplan–Meier survival curves. Another 72 GBM patients and 48 astrocytoma patients from Harbin Medical University Cancer Hospital were used as a validation cohort.ResultsTumors located in the insular cortex, parahippocampal gyrus, and middle and superior temporal gyrus of the left hemisphere tended to lead to lower KPS and shorter OS in IDH-wildtype GBM. The regions that were significantly correlated with lower KPS in IDH-mutant astrocytoma included the subcallosal cortex and cingulate gyrus. These regions were associated with diverse structural and cognitive impairments. The involvement of these regions was an independent predictor for shorter survival in both GBM and astrocytoma.ConclusionThis study identified the specific regions that were significantly associated with OS or KPS in glioma. The results may help neurosurgeons evaluate patient survival before surgery and understand the pathogenic mechanisms of glioma in depth.

Ficus carica L. (dioecious), the most significant commercial species in the genus Ficus, which has been cultivated for more than 11,000 years and was one of the first species to be domesticated. Herein, we reported the most comprehensive F. carica genome currently. The contig N50 of the Orphan fig was 9.78 Mb, and genome size was 366.34 Mb with 13 chromosomes. Based on the high-quality genome, we discovered that F. carica diverged from Ficus microcarpa ~34 MYA, and a WGD event took place about 2─3 MYA. Throughout the evolutionary history of F. carica, chromosomes 2, 8, and 10 had experienced chromosome recombination, while chromosome 3 saw a fusion and fission. It is worth proposing that the chromosome 9 experienced both inversion and translocation, which facilitated the emergence of the F. carica as a new species. And the selections of F. carica for the genes of recombination chromosomal fragment are compatible with their goal of domestication. In addition, we found that the F. carica has the FhAG2 gene, but there are structural deletions and positional jumps. This gene is thought to replace the one needed for female common type F. carica to be pollinated. Subsequently, we conducted genomic, transcriptomic, and metabolomic analysis to demonstrate significant differences in the expression of CHS among different varieties of F. carica. The CHS playing an important role in the anthocyanin metabolism pathway of F. carica. Moreover, the CHS gene of F. carica has a different evolutionary trend compared to other Ficus species. These high-quality genome assembly, transcriptomic, and metabolomic resources further enrich F. carica genomics and provide insights for studying the chromosomes evolution, sexual system, and color characteristics of Ficus.

BackgroundParkinson’s disease (PD) is a neurodegenerative disease with high incidence rate. Resting state functional magnetic resonance imaging (rs-fMRI), as a widely used method for studying neurodegenerative diseases, has not yet been combined with two important indicators, amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF), for standardized analysis of PD.MethodsIn this study, we used seed-based d-mapping and permutation of subject images (SDM-PSI) software to investigate the changes in ALFF and CBF of PD patients. After obtaining the regions of PD with changes in ALFF or CBF, we conducted a multimodal analysis to identify brain regions where ALFF and CBF changed together or could not synchronize.ResultsThe final study included 31 eligible trials with 37 data sets. The main analysis results showed that the ALFF of the left striatum and left anterior thalamic projection decreased in PD patients, while the CBF of the right superior frontal gyrus decreased. However, the results of multimodal analysis suggested that there were no statistically significant brain regions. In addition, the decrease of ALFF in the left striatum and the decrease of CBF in the right superior frontal gyrus was correlated with the decrease in clinical cognitive scores.ConclusionPD patients had a series of spontaneous brain activity abnormalities, mainly involving brain regions related to the striatum-thalamic-cortex circuit, and related to the clinical manifestations of PD. Among them, the left striatum and right superior frontal gyrus are more closely related to cognition.Systematic review registrationhttps://www.crd.york.ac.uk/ PROSPERO (CRD42023390914).

AbstractThe safety of the Three Gorges Reservoir, the world’s largest hydraulic project, has attracted significant attention. Among the landslides in the area, the Xinpu landslide complex stands out as one of the largest. However, accurately detecting and interpreting the timing and magnitude of its movement remains a challenge. This study introduces a framework using interferometric synthetic aperture radar (InSAR) for investigating the Xinpu landslide complex. In areas with dense vegetation like Xinpu, estimating landslide movement has traditionally been problematic. The proposed method, based on independent component analysis-assisted intermittent multi-temporal InSAR, overcomes this limitation by retrieving complete and reliable time-series deformation without prior deformation models. Through an analysis of Sentinel-1 datasets covering a period of 4 years, our approach significantly enhances deformation density and accuracy in comparison to other multi-temporal InSAR techniques. When contrasted with these methods, our proposed approach exhibits an average RMS improvement of up to 46.2% between GNSS measurements and the InSAR-derived results. The complete time-series deformation reveals diverse triggers at different sections of the Xinpu landslide complex. Precipitation, with a 45-day lag, primarily controls the landslide, while the toe of the landslide shows joint effects from precipitation and water level fluctuations, with a 14-day lag. Cross-correlation analysis estimates lag times for deformation responses to different triggers and enables discussion of the complex’s kinematic process. Overall, this approach enhances InSAR performance in vegetated areas and aids in uncovering landslide triggers for effective hazard mitigation.

BackgroundAlzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some possible mechanisms of comorbidity, the two diseases have been studied in combination by many researchers, and even some scholars call AD type 3 diabetes. But the relationship between the two is still controversial.MethodsThis study used seed-based d mapping software to conduct a meta-analysis of the whole brain resting state functional magnetic resonance imaging (rs-fMRI) study, exploring the differences in amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) between patients (AD or T2DM) and healthy controls (HCs), and searching for neuroimaging evidence that can explain the relationship between the two diseases.ResultsThe final study included 22 datasets of ALFF and 22 datasets of CBF. The results of T2DM group showed that ALFF increased in both cerebellum and left inferior temporal gyrus regions, but decreased in left middle occipital gyrus, right inferior occipital gyrus, and left anterior central gyrus regions. In the T2DM group, CBF increased in the right supplementary motor area, while decreased in the middle occipital gyrus and inferior parietal gyrus. The results of the AD group showed that the ALFF increased in the right cerebellum, right hippocampus, and right striatum, while decreased in the precuneus gyrus and right superior temporal gyrus. In the AD group, CBF in the anterior precuneus gyrus and inferior parietal gyrus decreased. Multimodal analysis within a disease showed that ALFF and CBF both decreased in the occipital lobe of the T2DM group and in the precuneus and parietal lobe of the AD group. In addition, there was a common decrease of CBF in the right middle occipital gyrus in both groups.ConclusionBased on neuroimaging evidence, we believe that T2DM and AD are two diseases with their respective characteristics of central nervous activity and cerebral perfusion. The changes in CBF between the two diseases partially overlap, which is consistent with their respective clinical characteristics and also indicates a close relationship between them.Systematic review registrationPROSPERO [CRD42022370014].

The ocular glymphatic system supports bidirectional fluid transport along the optic nerve, thereby removes metabolic wastes including amyloid-β. To better understand this biological process, we examined the distributions of intravitreally and intracisternally infused tracers in full-length optic nerves from different age groups of mice. Aging was linked to globally impaired ocular glymphatic fluid transport, similar to what has seen previously in the brain. Aging also reduced the pupillary responsiveness to light stimulation and abolished light-induced facilitation in anterograde ocular glymphatic flow. In contrast to normal aging, in the DBA/2 J model of glaucoma, we found a pathological increase of glymphatic fluid transport to the anterior optic nerve that was associated with dilation of the perivascular spaces. Thus, aging and glaucoma have fundamentally different effects on ocular glymphatic fluid transport. Manipulation of glymphatic fluid transport might therefore present a new target for the treatment of glaucoma.

Abstract Glioblastoma (GBM) is the most frequent malignant brain tumor, the relapse of which is unavoidable following standard treatment. However, the effective treatment for recurrent GBM is lacking, necessitating the understanding of key mechanisms driving tumor recurrence and the identification of new targets for intervention. Here, we integrated single-cell RNA-sequencing data spanning 36 patient-matched primary and recurrent GBM (pGBM and rGBM) specimens, with 6 longitudinal GBM spatial transcriptomics to explore molecular alterations at recurrence, with each cell type characterized in parallel. Genes involved in extracellular matrix (ECM) organization are preferentially enriched in rGBM cells, and MAFK is highlighted as a potential regulator. Notably, we uncover a unique subpopulation of GBM cells that is much less detected in pGBM and highly expresses ECM and mesenchyme related genes, suggesting it may contribute to the molecular transition of rGBM. Further regulatory network analysis reveals that transcription factors, such as NFATC4 and activator protein 1 members, may function as hub regulators. All non-tumor cells alter their specific sets of genes as well and certain subgroups of myeloid cells appear to be physically associated with the mesenchyme-like GBM subpopulation. Altogether, our study provides new insights into the molecular understanding of GBM relapse and candidate targets for rGBM treatment.

Abstract Objective To explore whether MRI‐visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. Methods A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case–control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi‐square or Fisher's exact tests to initially determine whether high‐grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high‐grade EPVS in migraine. Results The prevalence of high‐grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high‐grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136–4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534–6.935; P = 0.002) were more likely to suffer from migraine. Interpretation This case–control study showed that high‐grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.