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Abstract Background The association of a combination of the TyG index and obesity markers, specifically waist circumference (WC), with cognitive function is unknown. This research investigated the relationship between TyG-WC measurements and cognitive impairment in a low-income population in China; moreover, this study evaluated the role of diabetes mellitus and body mass index (BMI) in modulating this relationship. Methods 1125 eligible individuals aged ≥ 60 years participated in this study. The TyG index and obesity indicators (BMI, WC, and waist-to-height ratio) were calculated for individual participants and categorized into quartiles. Multivariate logistic regression analysis was used to evaluate the correlation between TyG-WC values and cognitive impairment; the possibility of a nonlinear relationship was explored using constrained cubic spline analysis. The participants were divided into different groups according to their diabetes status and BMI category for subgroup analyses. Linear regression was used to investigate the correlation between TyG-WC values and MMSE scores. Results The prevalence of cognitive impairment in the study participants was 47.3%, with a significant negative association between TyG-WC values and cognitive impairment, (odds ratio [OR] = 0.999; 95% confidence interval [CI], 0.997–1.00, P = 0.009). A U-shaped correlation was observed between the TyG-WC values and cognitive impairment (P = 0.008). Subgroup analyses showed that the inverse association between TyG-WC values and cognitive impairment was stronger in non-diabetic individuals (OR = 0.998; 95% CI, 0.997–0.999; P = 0.002) and in those with a lower BMI (

In order to solve the problem of poor performance of welded joints of steel and aluminum dissimilar materials, this study proposes the use of ceramic particle-reinforced aluminum alloy as an alternative to traditional aluminum alloy for welding, effectively overcoming this problem. In this paper, the laser welding of stainless steel/6061 aluminum alloy (SA) and stainless steel/TiC–TiB2 duplex nanoparticle-reinforced 6061 aluminum alloy (SRA) was realized. The effect of ceramic nanoparticles on the microstructure and mechanical properties of SRA joint was systematically studied, and the strengthening mechanism of nanoparticles was revealed. Under the same process parameters, the melting zone of SRA joint is larger and the intermetallic compound (IMCs) layer is narrower. Moreover, the grain size of the brittle Fe–Al compound phase in the IMCs layer is significantly reduced, which effectively inhibits the initiation of cracks at the steel/aluminum interface. The study shows that ceramic particles have a pinning effect on the dislocations, limiting the grain growth, reducing the thickness of the intermetallic compound layer, and decreasing the content of the brittle FeAl3 phase. Moreover, ceramic nanoparticles promote the formation of Mg2Si strengthened phase at the grain boundary, further hinder the dislocation movement and improve the strength of the joint. Under the welding power of 3400 W and welding speed of 31 mm/s, SRA joint achieves the maximum tensile shear of 1718 N, which is 15% higher than the strength of SA joint.

Abstract Glycosphingolipids (GSLs) are abundantly expressed in cancer cells. The effects of GSL-targeted immunotherapies are not fully understood. Here, we show that the inhibition of GSL synthesis with the UDP-glucose ceramide glucosyltransferase inhibitor eliglustat can increase the exposure of the major histocompatibility complex (MHC) and tumour antigen peptides, enhancing the antitumour response of CD8+ T cells in a range of tumour models. We therefore conducted a proof-of-concept phase I trial on the combination of eliglustat and an anti-PD-1 antibody for the treatment of advanced cancers (NCT04944888). The primary endpoints were safety and feasibility, and the secondary endpoint was antitumor activity. All prespecified endpoints were met. Among the 31 enrolled patients, only 1 patient experienced a grade 3 adverse event (AE), and no grade 4 AEs were observed. The objective response rate was 22.6% and the disease control rate reached 71%. Of the 8 patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) colorectal cancer, one achieved complete response and two each had partial response and stable disease. In summary, inhibiting the synthesis of GSLs might represent an effective immunotherapy approach.

AimThe Triglyceride-Glucose (TyG) index, an indicator of insulin resistance, has been proposed as a predictor of cardiovascular diseases. However, its role in predicting stroke risk, particularly in low-income populations, is not well understood. This study aimed to investigate the predictive value of the TyG index for stroke incidence in a low-income Chinese population, with a focus on gender and age-specific differences.MethodsThis 10-year prospective cohort study included 3,534 participants aged ≥45 years from rural areas in northern China. Baseline data on demographic characteristics, lifestyle factors, and clinical measurements were collected. Participants were followed for stroke incidence, categorized into ischemic and hemorrhagic stroke. Multivariate logistic regression models were used to assess the association between the TyG index and stroke incidence, adjusting for potential confounders.ResultsDuring the follow-up period, 368 participants (10.4%) experienced a stroke, with 327 ischemic and 31 hemorrhagic strokes. TyG index was significantly associated with total and ischemic stroke incidence but not hemorrhagic stroke. After adjusting for confounding factors, for every one standard deviation increase in TyG index, the risk of stroke increased by 32% for overall stroke (RR: 1.32; 95% CI: 1.08-1.61; P=0.006) and 39% for ischemic stroke (RR: 1.39; 95% CI: 1.12-1.73; P=0.003). The risk of stroke in the highest TyG tertile levels (tertile 3) increased by 49% (RR: 1.49; 95% CI 1.11-1.99; P=0.007) for overall stroke, compared to those in the lowest tertile levels (tertile 1). For ischemic stroke, the risk of stroke increased by 53% (RR: 1.53; 95% CI 1.12-2.11; P=0.008) in the highest TyG tertile levels (tertile 3) compared to those in the lowest tertile levels (tertile 1).ConclusionThis 10-year prospective cohort study has established the TyG index as an independent predictor of both total and ischemic stroke incidence in a low-income Chinese population. The findings indicate that the TyG index is particularly effective in predicting stroke risk among women and older adults (≥60 years), but not for hemorrhagic stroke. These insights are crucial for improving clinical practice and stroke prevention strategies.

Abstract Background This study aimed to evaluate the efficacy of radiomics signatures derived from polyenergetic images (PEIs) and virtual monoenergetic images (VMIs) obtained through dual-layer spectral detector CT (DLCT). Moreover, it sought to develop a clinical-radiomics nomogram based on DLCT for predicting cancer stage (early stage: stage I-II, advanced stage: stage III-IV) in pancreatic ductal adenocarcinoma (PDAC). Methods A total of 173 patients histopathologically diagnosed with PDAC and who underwent contrast-enhanced DLCT were enrolled in this study. Among them, 49 were in the early stage, and 124 were in the advanced stage. Patients were randomly categorized into training (n = 122) and test (n = 51) cohorts at a 7:3 ratio. Radiomics features were extracted from PEIs and 40-keV VMIs were reconstructed at both arterial and portal venous phases. Radiomics signatures were constructed based on both PEIs and 40-keV VMIs. A radiomics nomogram was developed by integrating the 40-keV VMI-based radiomics signature with selected clinical predictors. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and decision curves analysis (DCA). Results The PEI-based radiomics signature demonstrated satisfactory diagnostic efficacy, with the areas under the ROC curves (AUCs) of 0.92 in both the training and test cohorts. The optimal radiomics signature was based on 40-keV VMIs, with AUCs of 0.96 and 0.94 in the training and test cohorts. The nomogram, which integrated a 40-keV VMI-based radiomics signature with two clinical parameters (tumour diameter and normalized iodine density at the portal venous phase), demonstrated promising calibration and discrimination in both the training and test cohorts (0.97 and 0.91, respectively). DCA indicated that the clinical-radiomics nomogram provided the most significant clinical benefit. Conclusions The radiomics signature derived from 40-keV VMI and the clinical-radiomics nomogram based on DLCT both exhibited exceptional performance in distinguishing early from advanced stages in PDAC, aiding clinical decision-making for patients with this condition.

Nanofiltration (NF) membrane technology has been widely used in the removal of salts and trace organic pollutants, such as pharmaceuticals and personal care products (PPCPs), due to its superiority. A positive-charged composite NF membrane with an active skin layer was prepared by polyethyleneimine (PEI), trimethyl benzene chloride, and quaternate chitosan (HTCC) through second interfacial polymerization on the polyethersulfone ultrafiltration membrane. The physicochemical properties of the nanocomposite membrane were investigated using surface morphology, hydrophilicity, surface charge, and molecular weight cut-off (MWCO). The influence of the concentration and reaction time of PEI and HTCC was documented. The optimized membrane had a MWCO of about 481 Da and possessed a pure water permeability of 25.37 L·m−2·h−1·MPa−1. The results also exhibited salt rejection ability as MgCl2 > CaCl2 > MgSO4 > Na2SO4 > NaCl > KCl, showing a positive charge on the fabricated membrane. In addition, the membrane had higher rejection to atenolol, carbamazepine, amlodipine, and ibuprofen at 89.46, 86.02, 90.12, and 77.21%, respectively. Moreover, the anti-fouling performance and stability of the NF membrane were also improved. HIGHLIGHTS A positive-charged nanofiltration (NF) membrane was modified by quaternate chitosan (HTCC) via second interfacial polymerization.; HTCC, containing quaternarized chitosan, was prepared with natural chitosan.; Anti-fouling performance and stability were improved.; The NF membrane surface was positively charged.; Salts and trace organic pollutants, such as pharmaceuticals and personal care products, were removed.;

Abstract Background This study aimed to evaluate whether inosine enhances the efficacy of immune‐checkpoint inhibitors in human malignant solid tumors. Methods This single‐center, prospective, randomized, open‐label study was conducted, from January 2021 to December 2022, in Beijing Friendship Hospital, Capital Medical University, and participants were randomly assigned (1:1) to either the inosine (trial) or non‐inosine (control) group that received inosine (dosage: 0.2 g, three times/day) + PD‐1/PD‐L1 inhibitor or only PD‐1/PD‐L1 inhibitor ± targeted ± chemotherapy, respectively. Efficacy was assessed every 6 weeks (i.e., after every two–three treatment cycles). The primary endpoint was the objective response rate (ORR); the secondary endpoints were disease control rate, overall survival (OS), and progression‐free survival (PFS). The trial was registered at ClinicalTrials.gov (NCT05809336). Results Among the 172 participants with advanced malignant solid tumors, 86 each were assigned to the inosine and non‐inosine groups, wherein the median PFS (95% CI) was 7.00 (5.31–8.69) and 4.40 (3.10–5.70) months, respectively (hazard ratio [HR] 0.63; 95% CI 0.44–0.90, p = 0.011), and the ORR was 26.7% and 15.1%, respectively (p = 0.061). In the inosine and non‐inosine groups, the median OS was not reached and was 29.67 (95% CI 17.40–41.94) months, respectively (HR 1.05 [95% CI 0.59–1.84], p = 0.874). Compared with the non‐inosine group, the median PFS and ORR of the inosine group were significantly prolonged and improved in the multiple exploratory subgroup analyses. The safety analysis showed that Grades 3 and 4 adverse reactions occurred in 25 (29%) and 31 (36%) patients in the inosine and non‐inosine groups, respectively, and tended to decrease in the inosine group compared with the non‐inosine group. Conclusion Inosine had a tendency to enhance the efficacy of immune‐checkpoint inhibitors and reduced immunotherapy‐related adverse reactions.

BackgroundIn China, mitral valve regurgitation (MR) is the most common cardiovascular valve disease. However, patients in China typically experience a high incidence of this condition, coupled with a low level of health knowledge and a relatively low rate of surgical treatment. TikTok hosts a vast amount of content related to diseases and health knowledge, providing viewers with access to relevant information. However, there has been no investigation or evaluation of the quality of videos specifically addressing MR. ObjectiveThis study aims to assess the quality of videos about MR on TikTok in China. MethodsA cross-sectional study was conducted on the Chinese version of TikTok on September 9, 2023. The top 100 videos on MR were included and evaluated using quantitative scoring tools such as the modified DISCERN (mDISCERN), the Journal of the American Medical Association (JAMA) benchmark criteria, the Global Quality Score (GQS), and the Patient Education Materials Assessment Tool for Audio-Visual Content (PEMAT-A/V). Correlation and stepwise regression analyses were performed to examine the relationships between video quality and various characteristics. ResultsWe obtained 88 valid video files, of which most (n=81, 92%) were uploaded by certified physicians, primarily cardiac surgeons, and cardiologists. News agencies/organizations and physicians had higher GQS scores compared with individuals (news agencies/organizations vs individuals, P=.001; physicians vs individuals, P=.03). Additionally, news agencies/organizations had higher PEMAT understandability scores than individuals (P=.01). Videos focused on disease knowledge scored higher in GQS (P

ObjectivesThis study aimed to observe the intervention of Weizhuan’an prescription on rats with precancerous lesions of gastric cancer (PLGC) as well as its regulation on gastric mucosal microflora and inflammatory factors and explore the pharmacodynamic mechanisms of Weizhuan’an Formula.MethodsThe rats were classified into the blank control group (BCG); low-, medium-, and high-dose groups of Weizhuan’an prescription (LDG, MDG, and HDG, respectively); and natural recovery group (NRG) at random. The rats in the traditional Chinese medicine (TCM) group were given corresponding doses of Weizhuan’an formula, while the rats in the NRG and BCG were given an equivalent volume of distilled water for 12 weeks. After that, gastric mucosa samples of rats were collected to observe the general and pathological changes in the gastric mucosa; the changes in gastric mucosal microflora were detected by 16S rDNA amplicon sequencing, and the inflammatory factors were analyzed by cytokine antibody microarray and Western blotting.ResultsThe results suggest that compared with the BCG, the pathology of gastric mucosa and gastric mucosal microflora and inflammatory factors in rats with PLGC have changed significantly, while Weizhuan’an formula effectively improved them, especially in the MDG and HDG (p < 0.05). Compared with the NRG, the abundance of probiotics such as Lactobacillus and Veillonella were increased, while the abundance of pathogens such as Proteobacteria and Pseudomonas was decreased (p < 0.05, p < 0.01), and the relative contents of IL-2, IL-4, IL-13, and MCP-1 in gastric mucosa were decreased (p < 0.05). Moreover, it can upregulate the DNA-binding transcriptional regulator, ABC type multidrug transport system, and related enzymes and affect the signaling pathways such as viral protein interaction with cytokine and cytokine receptor and T cell receptor signaling pathway significantly (p < 0.05, p < 0.01), which can promote drug absorption and utilization and repair damaged gastric mucosa.ConclusionThe study confirmed that Weizhuan’an prescription can treat rats with PLGC by regulating gastric mucosal microflora and inflammatory factors.

The deterioration depth (D) is a relatively simple index used to evaluate the deterioration degree of solidified soil. Based on the equivalent relationship between the accelerated deterioration tests and the conventional deterioration tests and the power function form of the D prediction equation, a rapid prediction method is proposed in this study for predicting the D of cement solidified marine soft soil. Deterioration test results of the cement solidified marine soft soil showed that increases in the concentration of seawater accelerated the rate of cement soil deterioration. Deterioration test results of the cement solidified marine soft soil showed that increases in the concentration of seawater accelerated the rate of cement soil deterioration. Additionally, the D obtained from indoor and in-site conventional deterioration tests is almost the same. A rapid prediction method for the D of cement stabilized marine soft soil was established with the equivalent relationship between the accelerated and conventional deterioration tests and a power function form of the deterioration depth prediction equation. The predicted D and the development trend were more consistent with the results of the indoor and in-site conventional deterioration tests.

This paper proposes a virtual position-offset injection based permanent magnet temperature estimation approach for permanent magnet synchronous machines (PMSMs). The concept of virtual position-offset injection is mathematically transforming the machine model to a virtual frame with a position-offset. The virtual frame temperature estimation model is derived to calculate the permanent magnet temperature (PMT) directly from the measurements with computation efficiency. The estimation model involves a combined inductance term, which can simplify the establishment of saturation compensation model with less measurements. Moreover, resistance and inverter distorted terms are cancelled in the estimation model, which can improve the robustness to the winding temperature rise and inverter distortion. The proposed approach can achieve simplified computation in temperature estimation and reduced memory usage in saturation compensation. While existing model-based approaches could be affected by either the need of resistance and inverter information or complex saturation compensation. Experiments are conducted on the test machine to verify the proposed approach under various operating conditions.

Abstract Traumatic brain injuries (TBI) and stroke are major causes of morbidity and mortality in both developing and developed countries. The complex and heterogeneous pathophysiology of TBI and cerebral ischemia‐reperfusion injury (CIRI), in addition to the blood‐brain barrier (BBB) resistance, is a major barrier to the advancement of diagnostics and therapeutics. Clinical data showed that the severity of TBI and stroke is positively correlated with the number of neutrophils in peripheral blood and brain injury sites. Furthermore, neutrophil extracellular traps (NETs) released by neutrophils correlate with worse TBI and stroke outcomes by impairing revascularization and vascular remodeling. Therefore, targeting neutrophils to deliver NETs inhibitors to brain injury sites and reduce the formation of NETs can be an optimal strategy for TBI and stroke therapy. Herein, the study designs and synthesizes a reactive oxygen species (ROS)‐responsive neutrophil‐targeting delivery system loaded with peptidyl arginine deiminase 4 (PAD4) inhibitor, GSK484, to prevent the formation of NETs in brain injury sites, which significantly inhibited neuroinflammation and improved neurological deficits, and improved the survival rate of TBI and CIRI. This strategy may provide a groundwork for the development of targeted theranostics of TBI and stroke.

Pyrrolizidine alkaloids (PAs) and their N-oxide (PANOs), as emerging environmental pollutants and chemical hazards in food, have become the focus of global attention. PAs/PANOs enter crops from soil and reach edible parts, but knowledge about their uptake and transport behavior in crops is currently limited. In this study, we chose tea (Camellia sinensis L.) as a representative crop and Sp/SpNO as typical PAs/PANOs to analyze their root uptake and transport mechanism. Tea roots efficiently absorbed Sp/SpNO, utilizing both passive and active transmembrane pathways. Sp predominantly concentrated in roots and SpNO efficiently translocated to above-ground parts. The prevalence of SpNO in cell-soluble fractions facilitated its translocation from roots to stems and leaves. In soil experiment, tea plants exhibited weaker capabilities for the uptake and transport of Sp/SpNO compared to hydroponic conditions, likely due to the swift degradation of these compounds in the soil. Moreover, a noteworthy interconversion between Sp and SpNO in tea plants indicated a preference for reducing SpNO to Sp. These findings represent a significant stride in understanding the accumulation and movement mechanisms of Sp/SpNO in tea plants. The insights garnered from this study are pivotal for evaluating the associated risks of PAs/PANOs and formulating effective control strategies.

Abstract Although chimeric antigen receptor (CAR) T cells have become an important treatment option for patients with relapsed/refractory B-cell malignancies, more than 60% of patients with diffuse large B-cell lymphoma (DLBCL) treated with CAR-T cell therapies fail to achieve a durable response. To reveal changes in CAR-T cell therapy and identify response biomarkers, we conducted a retrospective analysis of pre-manufacture source T cells and CAR-T cell products and their association with outcome in 58 patients with r/rDLBCL who received tandem CD19/CD20 CAR-T cell therapy. We performed bulk RNA-Seq, single-cell RNA-Seq, and paired T cell receptor sequencing on CAR-T cell products and pre-manufacture T cells from DLBCL patients. We note that a CD8+ stem cell-like memory T cell population with a higher proportion and enhanced activating capacity of the CAR-T cell products was key to achieving durable clinical response. By analysing autologously-derived, pre-manufacture T cells, our data suggest that heterogeneity in the cellular and molecular features of pre-manufacture T cells contribute to the variation in efficacy after CAR-T cell therapy in DLBCL. The differences in anti-tumour efficacy of CAR-T cells among patients with different clinical outcomes appear to be due to the loss of CCR7 gene expression, coupled with increased expression of activation- and inhibitor-related genes in the CD8+ naïve-T cell populations among the apheresis T cells from patients with a poor molecular response. These findings significantly advance our understanding of the underlying molecular determinants of pre-manufacture T cell function.

Transformers have recently gained significant attention in low-level vision tasks, particularly for remote sensing image super-resolution (RSISR). The vanilla vision transformer aims to establish long-range dependencies between image patches. However, its global receptive field leads to a quadratic increase in computational complexity with respect to spatial size, rendering it inefficient for addressing RSISR tasks that involve processing large-sized images. In an effort to mitigate computational costs, recent studies have explored the utilization of local attention mechanisms, inspired by convolutional neural networks (CNNs), focusing on interactions between patches within small windows. Nevertheless, these approaches are naturally influenced by smaller participating receptive fields, and the utilization of fixed window sizes hinders their ability to perceive multi-scale information, consequently limiting model performance. To address these challenges, we propose a hierarchical transformer model named the Multi-Scale and Global Representation Enhancement-based Transformer (MSGFormer). We propose an efficient attention mechanism, Dual Window-based Self-Attention (DWSA), combining distributed and concentrated attention to balance computational complexity and the receptive field range. Additionally, we incorporated the Multi-scale Depth-wise Convolution Attention (MDCA) module, which is effective in capturing multi-scale features through multi-branch convolution. Furthermore, we developed a new Tracing-Back Structure (TBS), offering tracing-back mechanisms for both proposed attention modules to enhance their feature representation capability. Extensive experiments demonstrate that MSGFormer outperforms state-of-the-art methods on multiple public RSISR datasets by up to 0.11–0.55 dB.

Abstract Objective To develop a nomogram for predicting the occurrence of sepsis-associated delirium (SAD). Materials and methods Data from a total of 642 patients were retrieved from the Medical Information Mart for Intensive Care (MIMIC III) database to build a prediction model. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of SAD. The performance of the nomogram was assessed in terms of discrimination and calibration by bootstrapping with 1000 resamples. Results Multivariate logistic regression identified 4 independent predictors for patients with SAD, including Sepsis-related Organ Failure Assessment(SOFA) (p = 0.004; OR: 1.131; 95% CI 1.040 to 1.231), mechanical ventilation (P

Abstract Background Perioperative sleep disorders (PSD) are an independent risk factor for postoperative delirium (POD), which is a common complication after surgery. Elderly patients who undergo robot-assisted radical prostatectomy (RARP) often experience perioperative sleep disorders (PSD). Dexamethasone, a medication that works by inhibiting the hypothalamic-pituitary-suprarenal cortical axis, can reduce the negative effects of surgical stress. The objective of this study was to determine whether intravenous administration of dexamethasone at the time of anesthesia induction could improve postoperative sleep quality in elderly patients, thereby indirectly reducing the risk of postoperative cognitive impairment and accelerating postoperative rehabilitation. Methods/design This study is a randomized, double-blind, placebo-controlled trial that was conducted at a single center. A sample size of 116 patients was determined through calculation, and these patients were randomly assigned to either the dexamethasone group (group D, n = 58) or the blank control group (group C, n = 58). On the day of surgery, the anesthesia nurse prepared either diluted dexamethasone or saline in advance, according to the patient's assigned group. The blinded anesthesiologist administered the medication during induction, and a dedicated person followed up with the patient for three consecutive postoperative days. All other aspects of care were managed equally between the two groups. The primary outcome measure was sleep quality, while secondary outcome measures included postoperative sleep time, postoperative delirium (POD), pain scores, and other complications. Relevant test measures were recorded for analysis. Discussion This study aims to investigate the impact of intravenous dexamethasone on sleep quality and duration of patients undergoing robot-assisted radical prostatectomy (RARP). If the findings of this study protocol are affirmative, it could enhance the sleep quality of elderly patients after surgery, thereby minimizing the risk of postoperative delirium (POD), and providing substantial evidence for the perioperative enhanced recovery management of elderly patients. Trial registration Chinese clinical trial registry: ChiCTR2200063488, Registered on 5 October 2022.

Self-constructed water-in-oil emulsions can be stabilized by a natural pentacyclic triterpenoid, betulin. A higher betulin concentration (3%) results in smaller emulsion droplet sizes. Microscopy, confocal laser scanning microscopy and rheology indicate that the stabilizing mechanism is attributed to betulin crystals on the emulsion interface and within the continuous phase, thereby enabling excellent freeze/thaw and thermal stability. The betulin Pickering emulsion (1%) significantly increased betulin bioaccessibility (22.4%) compared to betulin alone (0.2%) and betulin-oil physical mixture (7.9%). A higher level of betulin at 3% leads to smaller emulsion particle size, potentially resulting in a greater surface area. This, in return, promotes a higher release of free fatty acids (FFA), contributing to the release and solubilization of betulin from emulsions. Additionally, it leads to the formation of micelles, further increasing betulin bioaccessibility (29.3%). This study demonstrates Pickering emulsions solely stabilized by phytochemical betulin provides an innovative way to improve its bioaccessibility.

The establishment of ecological security patterns (ESPs) has emerged as a significant approach to address the inherent conflict between ecological preservation and economic advancement. Existing studies commonly only focus on the supply of ecosystem services (ESs) but pay little attention to the demand for ESs and less attention to ecosystem service flow (ESF), which leads to the limited satisfaction of ecological space planning with the needs of human society. This study takes the West Liao River basin as an example to design a comprehensive ecological security pattern construction and optimization method. This study quantified the supply and demand of soil conservation (SC), carbon fixation (CF), water purification (WP), windbreak and sand fixation (WS) and water provision (FW) five key ESs in the study area from 2000 to 2020, and discussed the construction and optimization strategy of the ESPs from the perspective of “supply-flow-demand”. The results indicated that a total of 25 ecological source areas have been identified, with an optimized total area of 3.57×104km2, with 53 ecological corridors, including 15 primary corridors, 38 secondary corridors, 31 ecological checkpoints, and 16 ecological obstacle points. Based on the spatial distribution of ecological sources, an ecological security pattern of “four zones, three belts, and multiple branches” has been constructed. The distribution of ecological sources in the watershed is mainly on the forest and grassland in the northern, central, eastern, and southwestern regions, ecological pinch points is predominantly observed in the central and western regions, and the first-class ecological corridors are predominantly located in the western region. Research has shown that there is a mismatch between the supply and demand of ecosystem services within the study area. The use of the “supply-flow-demand” framework can more accurately identify ecological sources that traditional methods have not been able to identify. This research finding will contribute to enhancing the comprehension of the ecosystems within the West Liao River basin. This study aims to explore and optimize the construction methods of ESPs, which have certain universality and reference value, and can provide new paths and decision support for the construction of future regional ecological security patterns.

IntroductionTubulin epsilon and delta complex 2 (TEDC2) is widely expressed in various human tissues and primarily governs centriole stability. However, the biological significance of TEDC2 in pan-cancer is unclear.MethodsIn this study, we employed R software and various online bioinformatics analysis tools to investigate the functional attributes of TEDC2 in human tumours and its potential involvement in immune response. The status of TEDC2 expression was evaluated in samples from the TCGA and GEO datasets, as well as in tumour and corresponding normal samples from the TCGA database. Subsequently, Kaplan-Meier estimates, clinical correlations, and univariate Cox regressions were used to analyze the 33 types of tumors from TCGA and determine the prognostic significance of TEDC2. Moreover, nomogram models were formulated using three distinct tumours, namely kidney renal clear cell carcinoma (KIRC), lung adenocarcinoma (LUAD), and liver hepatocellular carcinoma (LIHC), to evaluate the prognostic significance of TEDC2 in tumours. Furthermore, TEDC2 was investigated for its correlation with the levels of immune cell infiltration, and a functional enrichment analysis was conducted to identify potential signalling pathways involving TEDC2. ResultsDifferential analysis revealed that 16 tumour types expressed TEDC2 to a greater extent than normal tissues. The abnormal expression of TEDC2 can predict survival outcomes in patients with adrenocortical carcinoma (ACC), KIRC, kidney renal papillary cell carcinoma (KIRP), LUAD, LIHC, lower grade glioma (LGG), and thymoma (THYM). Subsequent results indicated that TEDC2 has the ability to influence ECM regulators, cell cycle, and Immune checkpoint-associated signalling pathways, which could potentially lead to a poor prognosis and tumour progression.DiscussionTEDC2 has been identified as a potential therapeutic target that could predict the prognosis of multiple tumour types, making it a promising target for reversing tumour development.

Inhaling silica causes the occupational illness silicosis, which mostly results in the gradual fibrosis of lung tissue. Previous research has demonstrated that hypoxia-inducible factor-1α (HIF-1α) and glycolysis-related genes are up-regulated in silicosis. The role of 2-deoxy-D-glucose (2-DG) as an inhibitor of glycolysis in silicosis mouse models and its molecular mechanisms remain unclear. Therefore, we used 2-DG to observe its effect on pulmonary inflammation and fibrosis in a silicosis mouse model. Furthermore, in vitro cell experiments were conducted to explore the specific mechanisms of HIF-1α. Our study found that 2-DG down-regulated HIF-1α levels in alveolar macrophages induced by silica exposure and reduced the interleukin-1β (IL-1β) level in pulmonary inflammation. Additionally, 2-DG reduced silica-induced pulmonary fibrosis. From these findings, we hypothesize that 2-DG reduced glucose transporter 1 (GLUT1) expression by inhibiting glycolysis, which inhibits the expression of HIF-1α and ultimately reduces transcription of the inflammatory cytokine, IL-1β, thus alleviating lung damage. Therefore, we elucidated the important regulatory role of HIF-1α in an experimental silicosis model and the potential defense mechanisms of 2-DG. These results provide a possible effective strategy for 2-DG in the treatment of silicosis.

(1) Background: To assess the efficacy of the quantitative parameters of intravoxel incoherent motion (IVIM) diffusion-weighted imaging for hepatocellular carcinoma (HCC) diagnosis after transarterial chemoembolization (TACE). (2) Methods: Fifty HCC patients after TACE were included and underwent MRI. All of the patients were scanned with the IVIM-DWI sequence and underwent TACE retreatment within 1 week. Referring to digital subtraction angiography (DSA) and MR enhanced images, two readers measured the f, D, and D* values of the tumor active area (TAA), tumor necrotic area (TNA), and adjacent normal hepatic parenchyma (ANHP). Then, the distinctions of the TAA, TNA, and ANHP were compared and we analyzed the differential diagnosis of the parameters in three tissues. (3) Results: For values of f and D, there were significant differences between any of the TAA, TNA, and ANHP (p < 0.05). The values of f and D were the best indicators for identifying the TAA and TNA, with AUC values of 0.959 and 0.955, respectively. The values of f and D performed well for distinguishing TAA from ANHP, with AUC values of 0.835 and 0.753, respectively. (4) Conclusions: Quantitative IVIM-DWI was effective for evaluating tumor viability in HCC patients treated with TACE and may be helpful for non-invasive monitoring of the tumor viability.

Background: While radiotherapy has been studied in the treatment of locally advanced pancreatic ductal adenocarcinoma (PDAC), few studies have analyzed the effects of radiotherapy on PDAC in patients with liver metastases. This study aimed to determine whether PDAC patients with liver metastases have improved survival after radiotherapy treatment. Methods: The data of 8535 patients who were diagnosed with PDAC with liver metastases between 2010 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Survival analysis and Cox proportional hazards regression analysis of cancer-specific mortality and overall survival were performed, and propensity score matching (PSM) was used to reduce selection bias. Results: After PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the radiotherapy group were longer than those in the nonradiotherapy group (OS: 6 months vs. 4 months; mCSS: 6 months vs. 5 months, both p < 0.05), respectively. The multivariate analysis showed that cancer-specific mortality rates were higher in the nonradiotherapy group than in the radiotherapy group (HR: 1.174, 95% CI: 1.035–1.333, p = 0.013). The Cox regression analysis according to subgroups showed that the survival benefits (OS and CSS) of radiotherapy were more significant in patients with tumor sizes greater than 4 cm (both p < 0.05). Conclusions: PDAC patients with liver metastases, particularly those with tumor sizes greater than 4 cm, have improved cancer-specific survival (CSS) rates after receiving radiotherapy.

China introduced the ''agricultural water conversion policy'' in 2012 to efficiently utilize agricultural water resources and improve production technology in different regions of the Country to increase sustainable agriculture production. To this end, for Policy impact evaluation, our study employed slack-based measure data envelopment analysis, Meta frontier Analysis, and the Malmquist productivity index to measure the agriculture water usage efficiency, agriculture Production technology heterogeneity, and total factor productivity change in pre- and post-agriculture water policy (2012) implementation in different regions of China. Data for 31 provinces and cities were taken for efficiency and productivity estimation from 2000 to 2020. Results revealed that agriculture water usage efficiency significantly increased after the policy implementation. The average agricultural water usage efficiency score for the 2000–2012pre–policy period is 0.6763, whereas the average AWUE score for the 2013–2020 post–policy period is 0.7522, showing an increase of 11.22%. Further results show that the eastern region maintains superior agriculture production technology compared to the western and central regions, with an average technology gap ratio of 0.8941 during the study period. The average total factor productivity change for the study period is 1.0769. Technological change is the primary determinant of productivity growth. There was a marginal decline in average Productivity change after policy implementation. Mann-Whitney and Kruskal Wallis test strengthens the study's results by providing statistically significant differences among different periods and regions.

Throughout the coronavirus (COVID-19) pandemic, the sanitizing products benzethonium chloride (BEC) and polyhexamethylene guanidine hydrochloride (PHMG-H) were widely used; however, few studies have investigated their combined toxicity to organisms. In the present study, acute toxicity and genotoxicity of BEC, PHMG-H, and the combination of the two were investigated as endpoints using Daphnia carinata as the model organism. For individual reagents, PHMG-H was found to be more toxic than BEC in terms of both mortality and genotoxicity. DNA damage and survival rate were used as toxicity endpoints. The interaction was evaluated with the concentration addition (CA) model via toxic unit (TU) approach and additive index (AI) method in mixtures at different ratios in TU. Only the binary mixture BEC + PHMG-H at the ratio 1:9 in TU was regarded as synergistic, while all others indicated increased antagonistic effects as the proportion of BEC increased over the PHMG-H concentration. The findings here benefit understanding surrounding precisely how BEC and PHMG-H interact at different mixing ratios, and can assist with the evaluation of risk assessments for binary mixtures in aquatic ecosystems.

Objectivegastrointestinal stromal tumors (GISTs) with KIT exon 11 deletions have more malignant clinical outcomes. A radiomics model was constructed for the preoperative prediction of KIT exon 11 deletion in GISTs.MethodsOverall, 126 patients with GISTs who underwent preoperative enhanced CT were included. GISTs were manually segmented using ITK-SNAP in the arterial phase (AP) and portal venous phase (PVP) images of enhanced CT. Features were extracted using Anaconda (version 4.2.0) with PyRadiomics. Radiomics models were constructed by LASSO. The clinical-radiomics model (combined model) was constructed by combining the clinical model with the best diagnostic effective radiomics model. ROC curves were used to compare the diagnostic effectiveness of radiomics model, clinical model, and combined model. Diagnostic effectiveness among radiomics model, clinical model and combine model were analyzed in external cohort (n=57). Statistics were carried out using R 3.6.1.ResultsThe Radscore showed favorable diagnostic efficacy. Among all radiomics models, the AP-PVP radiomics model exhibited excellent performance in the training cohort, with an AUC of 0.787 (95% CI: 0.687-0.866), which was verified in the test cohort (AUC=0.775, 95% CI: 0.608-0.895). Clinical features were also analyzed. Among the radiomics, clinical and combined models, the combined model showed favorable diagnostic efficacy in the training (AUC=0.863) and test cohorts (AUC=0.851). The combined model yielded the largest AUC of 0.829 (95% CI, 0.621–0.950) for the external validation of the combined model. GIST patients could be divided into high or low risk subgroups of recurrence and mortality by the Radscore.ConclusionThe radiomics models based on enhanced CT for predicting KIT exon 11 deletion mutations have good diagnostic performance.

Abstract Ischemic stroke is a refractory disease that endangers human health and safety owing to cerebral ischemia. Brain ischemia induces a series of inflammatory reactions. Neutrophils migrate from the circulatory system to the site of cerebral ischemia and accumulate in large numbers at the site of inflammation across the blood–brain barrier. Therefore, hitchhiking on neutrophils to deliver drugs to ischemic brain sites could be an optimal strategy. Since the surface of neutrophils has a formyl peptide receptor (FPR), this work modifies a nanoplatform surface by the peptide cinnamyl‐F‐(D)L‐F‐(D)L‐F (CFLFLF), which can specifically bind to the FPR receptor. After intravenous injection, the fabricated nanoparticles effectively adhered to the surface of neutrophils in peripheral blood mediated by FPR, thereby hitchhiking with neutrophils to achieve higher accumulation at the inflammatory site of cerebral ischemia. In addition, the nanoparticle shell is composed of a polymer with reactive oxygen species (ROS)‐responsive bond breaking and is encased in ligustrazine, a natural product with neuroprotective properties. In conclusion, the strategy of hitching the delivered drugs to neutrophils in this study could improve drug enrichment in the brain, thereby providing a general delivery platform for ischemic stroke or other inflammation‐related diseases.

Bacterial infections can lead to the formation of chronic wounds and delay the wound-healing process. Therefore, it is important to explore safe and efficient antimicrobial agents that have wound-healing and biocompatible properties. In this study, novel starch-fabricated silver nitroprusside nanoparticles (S-AgNP NPs) were prepared for biocompatible wound-healing applications. The study showed that S-AgNP NPs are spherical, with an average size of 356 ± 22.28 d. nm and zeta potential of −27.8 ± 2.80 mV, respectively. Furthermore, the FTIR and XRD results showed that S-AgNP NPs have functional groups and crystal structures from the silver nitroprusside nanoparticles (AgNP NPs) and starch. Additionally, S-AgNP NPs showed excellent bacterial and biofilm inhibition on B. cereus (15.6 μg/mL), L. monocytogenes (15.6 μg/mL), S. aureus (31.3 μg/mL), E. coli (31.3 μg/mL) and S. enterica (62.5 μg/mL). Moreover, S-AgNP NPs promoted cell migration and proliferation at a concentration of 62.5 μg/mL compared to AgNP NPs. Meanwhile, S-AgNP NPs had good biocompatibility and low cytotoxicity compared to AgNP NPs. Therefore, this study provided new ideas for the development of wound-healing agents with bacteriostatic properties in chronic wounds.

Banana (Musa acuminate) has been popular among consumers worldwide due to its rich nutrients and minerals. However, bananas are highly susceptible to the physical and biological factors that lead to postharvest loss during transportation and storage. In this work, novel sodium alginate (SA) films incorporated with silver nitroprusside nanoparticles (AgNNPs) were prepared to extend the shelf life of bananas through antibacterial and antioxidant coating. The results exhibited that AgNNPs were cubical and that their size was L. monocytogenes, S. enterica, and E. coli at the concentration of 500 µg/mL. Moreover, during the storage of bananas, SA-AgNNPs nanocomposite coatings act as a barrier to microbial contamination and slow down the ripening of bananas. As a result, compared with SA-coated and uncoated bananas, SA-AgNNPs-coated bananas exhibited the lowest weight loss and lowest total bacterial colonies, thus greatly extending their shelf life. Particularly when coated with SA-AgNNPs films, total bacterial colonies (TBC) in the banana peel and pulp were as low as 1.13 × 103 and 51 CUF/g on the ninth day of storage, respectively. Our work offers an efficient strategy to improve the quality of bananas during the postharvest period, with extensive applications in fruit preservation and food packing.

The co-crystal berberine-ibuprofen is an effective agent for treating obesity through a reduction of the activity of the non-canonical I κB kinases, IKKε and TBK1.

Abstract The gut microbiota have long been recognized to play a key role in human health and disease. Currently, several lines of evidence from preclinical to clinical research have gradually established that the gut microbiota can modulate antitumor immunity and affect the efficacy of cancer immunotherapies, especially immune checkpoint inhibitors (ICIs). Deciphering the underlying mechanisms reveals that the gut microbiota reprogram the immunity of the tumor microenvironment (TME) by engaging innate and/or adaptive immune cells. Notably, one of the primary modes by which the gut microbiota modulate antitumor immunity is by means of metabolites, which are small molecules that could spread from their initial location of the gut and impact local and systemic antitumor immune response to promote ICI efficiency. Mechanistic exploration provides novel insights for developing rational microbiota-based therapeutic strategies by manipulating gut microbiota, such as fecal microbiota transplantation (FMT), probiotics, engineered microbiomes, and specific microbial metabolites, to augment the efficacy of ICI and advance the age utilization of microbiota precision medicine.

The interactions between active pharmaceutical ingredients (APIs) and excipients may lead to API degradation, thereby affecting the safety and efficacy of drug products. Cbf-14 is a synthetic peptide derived from Cathelicidin-BF, showing potential for bacterial and fungal infections. In order to assess impurities in Cbf-14 gel, we developed a two-dimensional liquid chromatography coupled with quadrupole/time-of-flight mass spectrometric method. A total of eleven peptide degradation impurities were identified and characterized. Furthermore, the compatibility tests were conducted to evaluate the interactions of Cbf-14 with glycerol and methylcellulose, respectively. The results revealed that the impurities originated from condensation reactions between Cbf-14 and aldehydes caused by glycerol degradation. Several aldehydes were employed to validate this hypothesis. The formation mechanisms were elucidated as Maillard reactions between primary amino groups of Cbf-14 and aldehydes derived from glycerol degradation. Additionally, the compatibility of Cbf-14 with glycerol from different sources and with varying storage times was investigated. Notably, the interaction products in the gel increased with extended storage time, even when fresh glycerol for injection was added. This study offers unique insights into the compatibility study of peptides and glycerol, contributing to the ongoing quality study of Cbf-14 gel. It also serves as a reference for the design of other peptide preparations and excipients selections.

Considering Inner Mongolia as the study area, the ecological theory of climate change, and human activities affecting a wide range of biodiversity patterns, MODIS multi-timeseries remote sensing image data were used and the interannual variation index was obtained by the method of fitting the curve to obtain the annual phenological and seasonal indicators. At the same time, the Landsat 8 standard deviation image was calculated to obtain the spatial variation index and generate spatial–temporal remote sensing indices to quantify the threat of climate change to biodiversity. In addition, the impact of human activities on biodiversity was quantified by generating a map of the human footprint in Inner Mongolia. The spatial–temporal remote sensing index and the human footprint index were integrated to identify areas protected from climate change and human activities, respectively. Eventually, the hotspot areas of biodiversity conservation in Inner Mongolia were obtained and priority protected area planning was based on the hotspot identification results. In this study, remote sensing technology was used to identify biodiversity conservation hotspots, which can overcome the limitations of insufficient species data from the past, improve the reliability of large-scale biodiversity conservation analyses, and be used for targeted management actions that have practical significance for biodiversity conservation planning.

Abstract Background Fish is favored by consumers, while amino acids and fatty acids are the main nutrients of muscle. At present, it has been found that the gut microbial community may be involved in the regulation of host material anabolism. Juvenile and adult bighead carp (A. nobilis) from Chagan lake and Xinlicheng reservoir were selected, and divided into four groups to compare the differences of gut microbial communities, free amino acid and fatty acids in muscle. Results The results showed that fish in different lakes or ages contained specific microbiota, the gut microbial structure was similar, but the microbial content was significantly different. Gut microbial abundance of juvenile fish in Chagan lake was significantly higher than that of other groups. Phylum level analysis Proteobacteria was the dominant gut bacteria of fish in both adult and juvenile fish from two separate lakes. Actinobacteria was another dominant bacterial phylum in juvenile fish in both lakes. Contents of free amino acids and fatty acids in muscle were detected, and the relationships between them and gut microbial communities were analyzed. Bighead carp grew from juvenile to adult, Actinobacteria abundance decreased (P

ABSTRACT: Lung cancer has the highest incidence and mortality rate worldwide. Immunotherapy is a universal treatment for lung cancer, but its overall treatment remains a challenge. Tumor immunoediting is a process in which the immune system restricts or promotes tumor development through elimination, equilibrium, and escape to change tumor immunogenicity and obtain an immunosuppressive mechanism to promote disease progression. An increasing number of immunotherapy drugs, including monoclonal antibody-targeting drugs and chimeric antigen (Ag) receptor-modified T cells (CAR-T cells), have been used in clinical therapy. Additionally, cancer vaccine development and new clustered regularly spaced short palindromes (CRISPR)- based combination therapies against cancer open up new avenues for immunotherapy. However, these immunotherapies cause autoimmune induction and non-specific inflammation, with many limitations. The development and study of nanoparticle systems have shown the possibility of localization, pharmacokinetic programming, and immunomodulator co-delivery. Rapid advances in nanotechnology over the past decade have provided a strategic impetus for cancer immunotherapy improvements. Nanotechnology advancements in various aspects, such as virus-like size, high surface-volume ratio, and surface modifications to precisely target specific cell types, can be investigated through cancer vaccine and immunomodulator delivery system development. This review presents the current immunotherapy approaches for lung cancer and emphasizes the current process and prospects of the fusion of cancer immunotherapy, nanotechnology, bioengineering, and drug delivery.

ABSTRACT: Nanodiamonds (NDs) are emerging as a promising platform for theranostic particles since they offer a single platform that possesses multiple important properties. These include a simple mechanism of synthesis, small size, chemical inertness, a variety of available surface functional groups, good biocompatibility, stable fluorescence, and a long fluorescence lifetime. The use of NDs to deliver anticancer drugs has been an important ND application since NDs can increase chemosensitivity, sustain drug release, and minimize drug side effects. These unique properties have stimulated the application of NDs to cancer imaging and therapy. In this review, we offer a brief introduction of ND structure and their functional properties. This is followed by a summary of recent uses of NDs for imaging purposes, including fluorescent imaging, magnetic resonance imaging (MRI), and other imaging technologies. Special concern is given to studies focusing on NDs use for anticancer drug delivery, anticancer gene delivery, photothermal and photodynamic therapies, and multifunctional combination therapy. We then discuss ND biocompatibility and toxicity in various cells and animal models. Finally, we also discuss the main problems to be solved by future research before NDs can be put to clinical use. The purpose of this review is to provide a side-by-side comparison of studies reporting ND-mediated cancer imaging therapy so that readers can assess the potential clinical applications of ND and have the background necessary to understand the clinical test results associated with ND-related therapy in animals and humans.

This review explored the potential of edible insects to address the challenges of malnutrition and food security. Although grain production in China has met the Food and Agriculture Organization standards, the shortage of protein supply is still a big issue. Moreover, expanding livestock farming is considered unsustainable and environmentally unfriendly. Edible insects have become an alternative with higher sustainable and ecological properties. There are 324 species of insects currently consumed in China, and they have high nutritional value, with a rich source of protein and unsaturated fatty acids. Insect farming provides numerous benefits, including green feeds for livestock, poultry, and aquaculture, sustainable organic waste management, as well as industrial and pharmaceutical raw materials. The food toxicological evaluations conducted in China indicated that edible insects are safe for general consumption by the Chinese, but allergies and other related food safety issues should not be ignored. Consumer acceptance is another barrier to overcome, with different schemas between China and Western countries. More research on the potential functions of edible insects and their product development may enhance their acceptance in China. Overall, incorporating edible insects into our diet is a promising solution to address challenges related to protein supply and food security. To ensure safety and sustainability, appropriate legislation, quality regulations, large-scale insect farms, and acceptable processing techniques are necessary. Moreover, more scientific research and social awareness are required to promote the culture and utilization of edible insects in China.

Abstract Introduction Programmed death 1 (PD‐1)/programmed death‐ligand 1 (PD‐L1) inhibitors are proved to be promising and are applied for the treatment of a variety of solid tumors. This retrospective study evaluated the efficacy of PD‐1/PD‐L1 inhibitors in patients with advanced solid tumors and explore the effect of clinical characteristics on it. Materials and Methods From October 2017 to April 2020, a total of 90 patients from Capital Medical University Affiliated Beijing Friendship Hospital were enrolled. Results At a median follow‐up of 10.55 months, objective response was observed in 23 patients and the objective response rate was 25.6%. The median progression‐free survival (PFS) was 5.5 months (95% confidence interval [CI], 3.69–7.37). The 6m‐PFS was 45.8% and 12m‐PFS was 25.1%. The median overall survival (OS) was 16.9 months (95% CI, not reached [NR]‐NR). The 12m‐OS was 58.1% and 18m‐OS was 48.1%. Conclusion The efficacy of PD‐1/PD‐L1 inhibitors in the treatment of advanced solid tumors was comparable to previous studies. ECOG performance status, smoking status, liver metastasis, neutrophil‐to‐lymphocyte ratio were independently correlated with PFS while liver metastasis and lactate dehydrogenase level were independently correlated with OS.

ABSTRACT: Stroke is a serious acute cerebrovascular disease attributable to disruptions in the blood supply to the brain tissue as a result of vascular obstruction or sudden rupture of blood vessels in the brain, which further result in hypoxia of the brain and reduction of necessary nutrients, apoptosis of neurons, and damage to brain tissue. The majority of stroke patients are ischemic stroke. The main clinical treatments for ischemic stroke include medical thrombolysis in the early stage of onset and surgical thrombectomy or stent implantation in the late stage of onset, all of which have their own indications, advantages, and disadvantages, and show limited clinical application. For cerebral ischemia-reperfusion injury with an extremely poor prognosis, there is currently no effective prevention and treatment method in the clinic. Therefore, timely and effective treatment is needed to treat cerebral ischemia-reperfusion injury. An increasing number of studies have shown that natural products have a good curative effect on cerebral ischemia-reperfusion injury. However, due to their low solubility, low bioavailability, and short half-life, many natural products cannot optimally exert their curative effects on cerebral ischemia-reperfusion injury. Natural products-based nanoparticles modified with specific ligands have attracted much attention because of their high-efficiency permeation through the blood–brain barrier, targeted delivery abilities, and the protection of the active components from degradation. Therefore, this review focused on the prevention and treatment of cerebral ischemia-reperfusion injury in the natural product-based nanoparticles.

Seed germination is the most sensitive stage of plant life history. Studying its response to drought and salinity can analysis the response and adaptation characteristics of desert plants to the environment. In this experiment, the seeds of four common desert ephemeral plants in Xinjiang (Ixiolirion tataricum, Nepeta micrantha, Lepidium apetalum, and Plantago minuta) were used as materials. To study the germination characteristics of seeds under drought, we used salt stress, and coupled salt-drought stress under treatments and explored the germination recovery ability of rehydrated seeds after salt and drought stress treatments. The results showed that: (1) Under salt stress, the germination ability of four plant seeds was inhibited in different degrees. Overall, the degree of inhibition was proportional to the concentration of NaCl solution. (2) Drought stress slowed the seed germination process, and the greater the degree of stress, the more pronounced the slowdown; PEG treatment showed no significant effect on the germination of the four seeds at low concentrations and significant inhibition at medium and high concentrations. (3) The coupled salt-drought treatment significantly alleviated the stress effect of one factor and improved the germination characteristics of seeds. (4) Seeds that did not germinate under different concentrations of salt stress, drought stress, and coupled stresses rapidly recover germination when the stress was relieved or lifted. Ephemeral plants are sensitive to environmental changes, and this study aims to provide a reference basis for vegetation restoration and ecological rehabilitation in arid and semi-arid areas.

Polygoni Multiflori Radix (PM) and Rhei radix et rhizoma (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components’ similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice. Nine groups of mice with 28 days of oral administration of these herbal extracts or 2,3,5,4′-tetrahydroxystilbene-2-O-β-D-glucoside (TSG, major and unique characteristic component in PM)-herb combinations were set as follows: Group-1, control; Group-2, PM ethanol-extract (PME); Group-3, PM praeparata ethanol-extract (PMPE); Group-4, Rhubarb ethanol-extract (RME); Group-5, Steamed rhubarb ethanol-extract (RMPE); Group-6, TSG; Group-7, PMPE-TSG combination; Group-8, RME-TSG combination; Group-9, RMPE-TSG combination. Each experimental group received an equivalent emodin dose of 29 mg/kg except for the TSG group, and an equivalent TSG dose of 1,345 mg/kg except for the PMPE, RME and RMPE groups. The results showed that PME, PMPE-TSG and RME-TSG induced liver lesions and biochemical abnormalities of liver function compared with the control. In contrast, PMPE, RME, RMPE, TSG and RMPE-TSG caused no liver lesions and fewer biochemical abnormalities. Considering the related components, only the co-administration of high doses of TSG and emodin-8-O-β-D-glucoside (EMG, major anthraquinone glycoside in PM) in these groups could cause liver lesions. According to tissue distribution and correlation analysis, EMG dose was positively correlated with the high hepatic emodin and TSG exposure, and the hepatic emodin and TSG exposure were positively correlated with the biochemical abnormalities of liver function. Cell viability test in vitro showed emodin was more hepatotoxic than TSG and EMG, and mainly emodin and TSG of the three had synergistic hepatotoxic effects. Therefore, creatively using rhubarb as a reference, this study revealed that PM hepatotoxicity in mice mainly came from the integrative contribution of TSG, EMG and emodin.

BackgroundBiotin is a water-soluble vitamin acting as a covalently bound coenzyme in regulating energy production. Previous studies have reported that biotin supplementation may influence blood glucose and lipid level in patients with type 2 diabetes mellitus (T2DM).MethodsWe searched Pubmed, Embase, and Cochrane library databases up to 8th August 2022 for studies examining the effects of biotin supplementation in T2DM patients. Pooled effects were measured by weighted mean differences (WMDs) with 95% confidence intervals (CI) using random effects models. Inter-study heterogeneity was assessed and quantified.ResultsA total of five random controlled trials (RCT), involving 445 participants were included. It was suggested that biotin supplementation for 28 to 90 days significantly decreased the level of fasting blood glucose (FBG) (MD: −1.21 mmol/L, 95% CI: −2.73 to 0.31), total cholesterol (TC) (MD: −0.22 mmol/L, 95% CI: −0.25 to −0.19) and triglycerides (TG) (MD: −0.59 mmol/L, 95% CI: −1.21 to 0.03). No significant beneficial effects were observed on insulin (MD: 1.88 pmol/L 95% CI: −13.44 to 17.21). Evidence for the impact of biotin supplementation on the levels of glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and very low-density lipoprotein cholesterol (VLDL-C) was limited to draw conclusion.ConclusionsBiotin supplementation may decrease FBG, TC and TG levels. However, its influence on insulin is not significant and further studies on the effects of biotin on HbA1c, LDL-C, HDL-C and VLDL-C are expected.

This paper focuses on the problems of inaccurate extraction of winter wheat edges from high-resolution images, misclassification and omission due to intraclass differences as well as the large number of network parameters and long training time of existing classical semantic segmentation models. This paper proposes a lightweight winter wheat planting area extraction model that combines the DeepLabv3+ model and a dual-attention mechanism. The model uses the lightweight network MobileNetv2 to replace the backbone network Xception of DeepLabv3+ to reduce the number of parameters and improve the training speed. It also introduces the lightweight Convolutional Block Attention Module (CBAM) dual-attention mechanism to extract winter wheat feature information more accurately and efficiently. Finally, the model is used to complete the dataset creation, model training, winter wheat plantation extraction, and accuracy evaluation. The results show that the improved lightweight DeepLabv3+ model in this paper has high reliability in the recognition extraction of winter wheat, and its recognition results of OA, mPA, and mIoU reach 95.28%, 94.40%, and 89.79%, respectively, which are 1.52%, 1.51%, and 2.99% higher than those for the original DeepLabv3+ model. Meanwhile, the model’s recognition accuracy was much higher than that of the three classical semantic segmentation models of UNet, ResUNet and PSPNet. The improved lightweight DeepLabv3+ also has far fewer model parameters and training time than the other four models. The model has been tested in other regions, and the results show that it has good generalization ability. The model in general ensures the extraction accuracy while significantly reducing the number of parameters and satisfying the timeliness, which can achieve the fast and accurate extraction of winter wheat planting sites and has good application prospects.

As the lakes located in the Qinghai-Tibet Plateau are important carriers of water resources in Asia, dynamic changes to these lakes intuitively reflect the climate and water resource variations of the Qinghai-Tibet Plateau. To address the insufficient performance of the Convolutional Neural Network (CNN) in learning the spatial relationship between long-distance continuous pixels, this study proposes a water recognition model for lakes on the Qinghai-Tibet Plateau based on U-Net and ViTenc-UNet. This method uses Vision Transformer (ViT) to replace the continuous Convolutional Neural Network layer in the encoder of the U-Net model, which can more accurately identify and extract the continuous spatial relationship of lake water bodies. A Convolutional Block Attention Module (CBAM) mechanism was added to the decoder of the model enabling the spatial information and spectral information characteristics of the water bodies to be more completely preserved. The experimental results show that the ViTenc-UNet model can complete the task of lake water recognition on the Qinghai-Tibet Plateau more efficiently, and the Overall Accuracy, Intersection over Union, Recall, Precision, and F1 score of the classification results for lake water bodies reached 99.04%, 98.68%, 99.08%, 98.59%, and 98.75%, which were, respectively, 4.16%, 6.20% 5.34%, 4.80%, and 5.34% higher than the original U-Net model. Compared to FCN, the DeepLabv3+, TransUNet, and Swin-Unet models also have different degrees of advantages. This model innovatively introduces ViT and CBAM into the water extraction task of lakes on the Qinghai-Tibet Plateau, showing excellent water classification performance of these lake bodies. This method has certain classification advantages and will provide an important scientific reference for the accurate real-time monitoring of important water resources on the Qinghai-Tibet Plateau.

This paper focuses on the problems of omission, misclassification, and inter-adhesion due to overly dense distribution, intraclass diversity, and interclass variability when extracting winter wheat (WW) from high-resolution images. This paper proposes a deep supervised network RAunet model with multi-scale features that incorporates a dual-attention mechanism with an improved U-Net backbone network. The model mainly consists of a pyramid input layer, a modified U-Net backbone network, and a side output layer. Firstly, the pyramid input layer is used to fuse the feature information of winter wheat at different scales by constructing multiple input paths. Secondly, the Atrous Spatial Pyramid Pooling (ASPP) residual module and the Convolutional Block Attention Module (CBAM) dual-attention mechanism are added to the U-Net model to form the backbone network of the model, which enhances the feature extraction ability of the model for winter wheat information. Finally, the side output layer consists of multiple classifiers to supervise the results of different scale outputs. Using the RAunet model to extract the spatial distribution information of WW from GF-2 imagery, the experimental results showed that the mIou of the recognition results reached 92.48%, an improvement of 2.66%, 4.15%, 1.42%, 2.35%, 3.76%, and 0.47% compared to FCN, U-Net, DeepLabv3, SegNet, ResUNet, and UNet++, respectively. The superiority of the RAunet model in high-resolution images for WW extraction was verified in effectively improving the accuracy of the spatial distribution information extraction of WW.

Diabetes, which is mainly characterized by increased apoptosis and dysfunction of beta (β) cells, is a metabolic disease caused by impairment of pancreatic islet function. Previous studies have demonstrated that death-associated protein kinase-related apoptosis-inducing kinase-2 (Drak2) is involved in regulating β cell survival. Since natural products have multiple targets and often are multifunctional, making them promising compounds for the treatment of diabetes, we identified Drak2 inhibitors from a natural product library. Among the identified products, luteolin, a flavonoid, was found to be the most effective compound. In vitro, luteolin effectively alleviated palmitate (PA)-induced apoptosis of β cells and PA-induced impairment of primary islet function. In vivo, luteolin showed a tendency to lower blood glucose levels. It also alleviated STZ-induced apoptosis of β cells and metabolic disruption in mice. This function of luteolin partially relied on Drak2 inhibition. Furthermore, luteolin was also found to effectively relieve oxidative stress and promote autophagy in β cells, possibly improving β cell function and slowing the progression of diabetes. In conclusion, our findings show the promising effect of Drak2 inhibitors in relieving diabetes and offer a potential therapeutic target for the protection of β cells. We also reveal some of the underlying mechanisms of luteolin’s cytoprotective function.

Long-term coal dust exposure triggers complex inflammatory processes in the coal workers’ pneumoconiosis (CWP) lungs. The progress of the inflammation is reported to be affected by disordered cell metabolism. However, the changes in the metabolic reprogramming associated with the pulmonary inflammation induced by the coal dust particles are unknown. Herein, we show that coal dust exposure causes glycogen accumulation and the reprogramming of glucose metabolism in the CWP lung. The glycogen accumulation caused by coal dust is mainly due to macrophages, which reprogram glycogen metabolism and trigger an inflammatory response. In addition, 2-deoxy-D-glucose (2-DG) reduced glycogen content in macrophages, which was accompanied by mitigated inflammation and restrained NF-κB activation. Accordingly, we have pinpointed a novel and crucial metabolic pathway that is an essential regulator of the inflammatory phenotype of coal dust-exposed macrophages. These results shed light on new ways to regulate CWP inflammation.