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Spatial functionalization of hierarchically mesoporous metal–organic frameworks (HMMOFs) in a controllable manner is highly desirable yet challenging. Herein, microporous and mesoporous spaces as well as the external surface of nanoscale hierarchically mesoporous UiO-66-NH2 MOFs were site-separately modified to endow them with additional functionalities. Given the pore-filling effect of soft templates, the folic acid ligand was successfully grafted on the outer surface without reducing the pore size and available pore volumes, making the developed sensing nanoprobe competent to specifically identify cancer cells. The mesoporous support not only effectively protected the encapsulated enzymes but also facilitated the proximity between the substrates and enzymes by virtue of the spatial confinement effect. The Cu2+ ions introduced in microporous skeleton could synergistically activate the activity of horseradish peroxidase immobilized in mesopores. Thanks to such enhanced enzymatic activity and spatial functionalities, the designed nanoprobe could specifically and quantitatively check out FR-overexpressed cancer cells in a colorimetric and visible way. Through deliberately screening different functionalities in specific locations of HMMOFs, such a model is expected to set a guideline for the design of multiple-functional diagnostic platform for the detection of various cancers. [ABSTRACT FROM AUTHOR]

A rapid and simultaneous lateral flow immunochromatography (LFIC) method was established based on colloidal gold (CG) for testing three addictive drugs in milk tea, including methamphetamine (MET), ketamine (KET), and cocaine (COC).After optimizing the key parameters, such as the concentration of coated antigen, the combination position of the three analytes, and the immunoreaction time, the developed method could be used for the simultaneous identification of three target addictive drays in a milk tea sample with a lower concentration could be tested.The limits of detection of MET, KET, and COC were 1.60, 1.59, and 1.39 ng/mL, respectively.In milk tea samples, the mean recoveries of the three types of mixed reference analytes ranged from 90% to 109% with a relative standard deviation of less than 5%.Briefly, the multiple CG-LFIC method had the advantages of easy operation, fast analysis, high sensitivity, and good specificity.It can be an effective method for simultaneous screening addictive drugs in milk tea and provides promising applications in the bio-detection field. [ABSTRACT FROM AUTHOR]

Benthic δ18O stacks are the benchmarks by which paleoceanographic data are stratigraphically aligned and compared. However, a recent study found that between 1.8 and 1.9 million years ago (Ma) several Ceara Rise records differed substantially from the widely used LR04 global stack. Here, we use new Bayesian stacking software to construct regional stacks and demonstrate a geographical divergence in benthic δ18O features from 1.8 to 1.9 Ma. The pattern of isotopic stage features observed in the Ceara Rise is widespread throughout the Atlantic and differs notably from Pacific records. We propose that this regional difference in isotopic stages may be the result of relatively strong precession forcing and weaker obliquity forcing between 1.8 and 1.9 Ma. In accordance with the Antiphase Hypothesis, our results highlight a period of apparent sensitivity to regional precession forcing that is masked during most of the 41‐Kyr world due to the amplitude modulation of obliquity forcing. Plain Language Summary: To determine the age of deep‐sea sediments, often the oxygen isotope ratios of microfossils are measured and compared to a previously compiled global benchmark. Recently, one of the most widely used oxygen isotope benchmarks has been challenged based on a comparison with several Atlantic records. In this study we assess several lines of evidence including utilizing newly available data and software. We confirm the challenge to the global oxygen isotope benchmark and find that it is more widespread than originally realized. Particularly, we find that oxygen isotope records display different patterns between the Atlantic and Pacific Oceans from 1.8 to 1.9 million years ago (Ma). We propose that this difference is the result of the opposing seasonal solar radiation anomalies received by the northern and southern hemispheres, which exhibited particularly large amplitudes during this time. Our study adds supporting evidence to a hypothesis that explains the dominant frequency of oxygen isotopic cycles from 1.2 to 2.6 Ma. Key Points: New Atlantic and Pacific benthic δ18O stacks show different patterns between 1.8 and 1.9 MaThe Atlantic‐Pacific difference in this portion of the 41‐Kyr world may be caused by regional sensitivity to relatively strong precessionRegional benthic δ18O stacks are preferable to global stacks for stratigraphic alignment [ABSTRACT FROM AUTHOR]

Objective: The purpose of the study is to construct meaningful nomogram models according to the independent prognostic factor for metastatic pancreatic cancer receiving chemotherapy. Methods: This study is retrospective and consecutively included 143 patients from January 2013 to June 2021. The receiver operating characteristic (ROC) curve with the area under the curve (AUC) is utilized to determine the optimal cut‐off value. The Kaplan–Meier survival analysis, univariate and multivariable Cox regression analysis are exploited to identify the correlation of inflammatory biomarkers and clinicopathological features with survival. R software are run to construct nomograms based on independent risk factors to visualize survival. Nomogram model is examined using calibration curve and decision curve analysis (DCA). Results: The best cut‐off values of 966.71, 0.257, and 2.54 for the systemic immunological inflammation index (SII), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil‐to‐lymphocyte ratio (NLR) were obtained by ROC analysis. Cox proportional‐hazards model revealed that baseline SII, history of drinking and metastasis sites were independent prognostic indices for survival. We established prognostic nomograms for primary endpoints of this study. The nomograms' predictive potential and clinical efficacy have been evaluated by calibration curves and DCA. Conclusion: We constructed nomograms based on independent prognostic factors, these models have promising applications in clinical practice to assist clinicians in personalizing the management of patients. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is one of the most prevalent malignancies in women. Exosomes are important mediators of intercellular communication; however, their regulatory mechanisms in human umbilical vein endothelial cells (HUVECs) angiogenesis in breast cancer remain unknown. Methods: We isolated and characterized breast cancer cell-derived exosomes and investigated their functions. Exosomal sequencing and the TCGA database were used to screen long non-coding RNA (lncRNA). In vitro and in vivo experiments were performed to investigate the role of exosomal lncRNA in HUVEC angiogenesis and tumor growth. Molecular methods were used to demonstrate the molecular mechanism of lncRNA. Results: We demonstrated that breast cancer cell-derived exosomes promoted HUVEC proliferation, tube formation, and migration. Combining exosomal sequencing results with The Cancer Genome Atlas Breast Cancer database, we screened lncRNA small nucleolar RNA host gene 12 (SNHG12), which was highly expressed in breast cancer cells. SNHG12 was also upregulated in HUVECs co-cultured with exosome-overexpressed SNHG12. Moreover, overexpression of SNHG12 in exosomes increased HUVEC proliferation and migration, whereas deletion of SNHG12 in exosomes showed the opposite effects. In vivo experiments showed that SNHG12 knockdown in exosomes inhibited breast cancer tumor growth. Transcriptome sequencing identified MMP10 as the target gene of SNHG12. Functional experiments revealed that MMP10 overexpression promoted HUVEC angiogenesis. Mechanistically, SNHG12 blocked the interaction between PBRM1 and MMP10 by directly binding to PBRM1. Moreover, exosomal SNHG12 promoted HUVEC angiogenesis via PBRM1 and MMP10. Conclusions: In summary, our findings confirmed that exosomal SNHG12 promoted HUVEC angiogenesis via the PBRM1-MMP10 axis, leading to enhanced malignancy of breast cancer. Exosomal SNHG12 may be a novel therapeutic target for breast cancer. [ABSTRACT FROM AUTHOR]

Small molecules are significant risk factors for causing food safety issues, posing serious threats to human health. Sensitive screening for hazards is beneficial for enhancing public security. However, traditional detection methods are unable to meet the requirements for the field screening of small molecules. Therefore, it is necessary to develop applicable methods with high levels of sensitivity and specificity to identify the small molecules. Aptamers are short−chain nucleic acids that can specifically bind to small molecules. By utilizing aptamers to enhance the performance of recognition technology, it is possible to achieve high selectivity and sensitivity levels when detecting small molecules. There have been several varieties of aptamer target recognition techniques developed to improve the ability to detect small molecules in recent years. This review focuses on the principles of detection platforms, classifies the conjugating methods between small molecules and aptamers, summarizes advancements in aptamer−based conjugate recognition techniques for the detection of small molecules in food, and seeks to provide emerging powerful tools in the field of point−of−care diagnostics. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) antagonists are widely used for the treatment of prostate cancer (PCa), but their therapeutic efficacy is usually compromised by the rapid emergence of drug resistance. However, the lack of the detailed interaction between AR and its antagonists poses a major obstacle to the design of novel AR antagonists. Here, funnel metadynamics is employed to elucidate the inherent regulation mechanisms of three AR antagonists (hydroxyflutamide, enzalutamide, and darolutamide) on AR. For the first time it is observed that the binding of antagonists significantly disturbed the C‐terminus of AR helix‐11, thereby disrupting the specific internal hydrophobic contacts of AR‐LBD and correspondingly the communication between AR ligand binding pocket (AR‐LBP), activation function 2 (AF2), and binding function 3 (BF3). The subsequent bioassays verified the necessity of the hydrophobic contacts for AR function. Furthermore, it is found that darolutamide, a newly approved AR antagonist capable of fighting almost all reported drug resistant AR mutants, can induce antagonistic binding structure. Subsequently, docking‐based virtual screening toward the dominant binding conformation of AR for darolutamide is conducted, and three novel AR antagonists with favorable binding affinity and strong capability to combat drug resistance are identified by in vitro bioassays. This work provides a novel rational strategy for the development of anti‐resistant AR antagonists. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC). Methods: The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS). Results: 133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6–19.8) in combined therapy and 8.2 months (95% CI, 5.7–10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1–5 BMs (HR = 1.808, P = 0.012). Conclusions: Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1–5 BMs reduce the risk of extracranial recurrence. [ABSTRACT FROM AUTHOR]

Conductive grease has been considered as a potential solution in addressing electric erosion issue inside motor bearings. Understanding the conductive grease performance, especially the electric and tribological behaviour is crucial for its application. This paper combines bulk grease characterization and contact film study considering both electrical and tribological loading conditions. The results show that the electric performance for the selected conductive grease sample is electric field dependent, including both frequency and voltage amplitude. Its film impedance inside the contact area is closely related to the external electric field, running condition, and lubrication regime. The following film impedance calculation tells that not only bulk grease electric parameters, but the contact parameter, lubricant film contour and lubrication condition should be considered when performing the overall bearing electrical modelling. [ABSTRACT FROM AUTHOR]

The objective of this study is to explore the pharmacokinetics, tissue distribution, and excretion patterns of GL‐V9 and its glucuronide metabolite, 5‐O‐glucuronide GL‐V9, following the administration of GL‐V9 to Sprague–Dawley (SD) rats. In this research, we developed and validated rapid, sensitive, and selective ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) methods for quantifying GL‐V9 and 5‐O‐glucuronide GL‐V9 in various biological samples, including SD rat plasma, tissue homogenate, bile, urine, and feces. Quantification of GL‐V9 and 5‐O‐glucuronide GL‐V9 in plasma, tissue homogenate, bile, urine, and feces was performed using the validated LC–MS/MS methods. The bioavailability of GL‐V9 in SD rats ranged from 6.23% to 7.08%, and both GL‐V9 and 5‐O‐glucuronide GL‐V9 exhibited wide distribution and rapid elimination from tissues. The primary distribution tissues for GL‐V9 and 5‐O‐glucuronide GL‐V9 in rats were the duodenum, liver, and lung. GL‐V9 was predominantly excreted in urine, while 5‐O‐glucuronide GL‐V9 was primarily excreted in bile. GL‐V9 exhibited easy absorption and rapid conversion to its glucuronide metabolite, 5‐O‐glucuronide GL‐V9, following administration. [ABSTRACT FROM AUTHOR]

The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhancing mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes, with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10's UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. A comparative analysis demonstrated that TMSB10 UTR not only facilitated a higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by the increased secretion of IFN-γ and IL-4 and the proliferation of CD4+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and, potentially, other pathogens. [ABSTRACT FROM AUTHOR]

Carbon geological storage (CGS) is an important global practice implemented to mitigate the effects of CO2 emissions on temperature, climate, sea level, and biodiversity. The monitoring of CGS leakage and the impact of storage on hydrogeological properties is important for management and long-term planning. In this study, we show the value of passive monitoring methods based on measuring and modeling water-level responses to tides. We review how monitoring can be used to identify time-varying horizontal and vertical permeabilities as well as independently detect time-varying fracture distribution in aquifer–caprock systems. Methods based on water-level responses to Earth tides are minimally invasive, convenient, economic (since they use existing groundwater wells), and time-continuous. We show how measurements can be used to detect aquifer leakage (caprock confinement) and the distribution of surrounding faults and fractures, which are the two most important unsolved quantities in assessing geological CO2 storage strategies. [ABSTRACT FROM AUTHOR]

Multisensory integration and attention can interact in a way that attention to the visual constituent of a multisensory object results in an attentional spreading to its ignored auditory constituent, which can be either stimulus‐driven or representation‐driven depending on whether the object's visual constituent receives extra representation‐based selective attention. Previous research using simple unrelated audiovisual combinations has shown that the stimulus‐driven attentional spreading is contingent on audiovisual temporal simultaneity. However, little is known about whether this temporal constraint applies also to the representation‐driven attentional spreading, and whether it holds for the stimulus‐driven process elicited by real‐life multisensory objects. The current event‐related potential study investigated these questions by systematically manipulating the visual‐to‐auditory stimulus onset asynchrony (SOA: 0/100/300 ms) in an object‐selective visual recognition task wherein the representation‐driven and stimulus‐driven spreading processes, measured as two distinct auditory negative difference (Nd) components, could be isolated independently. Our results showed that both the representation‐driven and stimulus‐driven Nds decreased as the SOA increased. Interestingly, the representation‐driven Nd was completely absent, whereas the stimulus‐driven Nd was still robust, when the auditory constituents were delayed by 300 ms. These findings not only indicate that the role of audiovisual simultaneity in the representation‐driven attentional spreading has been underestimated, but also suggest that learned associations between the unisensory constituents of real‐life objects render the stimulus‐driven attentional spreading more tolerant of audiovisual asynchrony. By using two distinct auditory Nd components to track the representation‐driven and stimulus‐driven visual‐to‐auditory attentional spreading effects, this study is the first to demonstrate that: (a) the role of audiovisual temporal synchrony in the representation‐driven spreading has been underestimated in extant literature; (b) highly learned association between the unisensory constituents of a meaningful multisensory object can render the synchrony‐sensitive stimulus‐driven spreading still prominent even at a large audiovisual asynchrony. Thus, it provides novel insights into the multifaceted influences of low‐level temporal correspondence and high‐level semantic relevance on the interplay between attention and multisensory integration. [ABSTRACT FROM AUTHOR]

Environmental media affect the atmospheric oxidation processes of phenolic compounds (PhCs) released from biomass burning in the troposphere. Phenol (Ph), 4-hydroxybenzaldehyde (4-HBA), and vanillin (VL) are chosen as model compounds to investigate their reaction mechanism and kinetics at the air-water (A-W) interface, on TiO2 clusters, in the gas phase, and in bulk water using a combination of molecular dynamics simulation and quantum chemical calculations. Of them, Ph was the most reactive one. The occurrence percentages of Ph, 4-HBA, and VL staying at the A-W interface are ~72 %, ~68 %, and ~73 %, respectively. As the size of (TiO2)n clusters increases, the adsorption capacity decreases until n > 4, and beyond this, the capacity remains stable. A-W interface and TiO2 clusters facilitate Ph and VL reactions initiated by the O3 and HO•, respectively. However, oxidation reactions of 4-HBA are little affected by environmental media because of its electron-withdrawing group. The O3- and HO•-initiated reaction rate constant (k) values follow the order of PhA-W > VLTiO2 > VLA-W > 4-HBAA-W > 4-HBATiO2 > PhTiO2 and VLTiO2 > PhA-W > VLA-W > 4-HBATiO2 > PhTiO2 > 4-HBAA-W, respectively. Some byproducts are more harmful than their parent compounds, so should be given special attention. This work provides key evidence for the rapid oxidation observed in the O3/HO• + PhCs experiments at the A-W interface. More importantly, differences in oxidation of PhCs by different environmental media due to the impact of substituent groups were also identified. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have demonstrated a positive correlation between diet quality and cognitive performance, indicating that improving diet quality may be beneficial in preventing cognitive decline in older adults. However, few study has investigated the causal relationship between diet quality and cognitive performance. The purpose of this study is to evaluate the causal effects of diet quality on cognitive performance in Chinese adults aged 55 years and older. Particularly, we utilize the Chinese Diet Quality Index (CHEI), a dietary assessment tool tailored for Chinese populations, as a proxy for older adults' diet quality. Methods: Data were obtained from the China Health and Nutrition Survey (CHNS) ( N = 2337 , ≥ 55 years old) conducted in 2004 and 2006. Cognitive function was tested by a subset of items from the Telephone Interview for Cognitive Status-Modified (TICS-m). Data on dietary intake was retrieved from three consecutive 24 hour recalls by participants and its quality was assessed by the 17-items Chinese Healthy Eating Index (CHEI). An Instrumental Variable technique was used to deal with the potential endogeneity of dietary quality. The instrumental variable used in our study is the community mean of CHEI. Results: After adjusting for socio-demographic factors (age, gender, education, per capita household income), lifestyle habits (smoking, alcohol consumption, physical activity, BMI), and chronic diseases (hypertension, diabetes), our findings revealed that improving diet quality had a significant positive effect on cognitive performance ( P = 0.020 ), particularly in females aged 55-65 years ( P = 0.003 ) and females with primary education and below ( P < 0.001 ). Conclusion: Our study suggests that improving diet quality and adhering to the Dietary Guidelines for Chinese may enhance cognitive performance in Chinese adults aged 55 years and older. [ABSTRACT FROM AUTHOR]

Background: The ratio of non-high-density lipoprotein cholesterol (non-HDL-C) to high-density lipoprotein cholesterol (HDL-C) (NHHR) serves as a reliable lipid indicator associated with atherogenic characteristics. Studies have indicated a potential connection between suicidality and lipid metabolism. This research aims to investigate any possible association between the NHHR and the emergence of suicidal ideation within the confines of the study. Methods: This study examined the association between NHHR levels and suicidal ideation using data from the National Health and Nutrition Examination Survey (NHANES), conducted in the United States spanning 2005 and 2016. Calculation of the NHHR corresponds to the proportion of HDL-C to Non-HDL-C. The Patient Health Questionnaire-9's ninth question was implemented for assessing suicidal ideation. Using subgroup analysis, smooth curve fitting, and multivariate logistic regression analysis, the research was conducted. Results: Encompassing a cohort of 29,288 participants, the analysis identified that 3.82% of individuals reported suicidal ideation. After using multivariable logistic regression and thorough adjustments, elevated NHHR levels were significantly and positively associated with a heightened likelihood of suicidal ideation, according to the findings (odds ratio [OR] = 1.06; 95% confidence interval [CI]: 1.02–1.11; P = 0.0048). Despite extensive adjustment for various confounding factors, this relationship remained consistent. An inverted U-shaped curve was utilized to illustrate the link between NHHR and suicidal ideation among nonsmokers; the curve's inflection point was situated at 7.80. Subgroup analysis and interaction tests (all P for interaction > 0.05) demonstrated that there was no significant influence of the following variables on this positive relationship: age, sex, race, body mass index, education level, married status, hypertension, diabetes, and smoking status. Conclusion: Significantly higher NHHR levels were associated with an elevated likelihood of suicidal ideation. Based on these results, it is probable that NHHR may serve as a predictive indicator of suicidal ideation, emphasizing its potential utility in risk assessment and preventive strategies. [ABSTRACT FROM AUTHOR]

Background: Sedentary behaviour is considered to contribute to sarcopenia when combined with physical inactivity. Whether sedentary behaviour is independently associated with sarcopenia remains controversial. The aim of this study is to explore the association between sedentary behaviour and sarcopenia in older adults in community and long-term care facility settings. Methods: Eight electronic databases including MEDLINE, PsycINFO, Wanfang were searched from inception until August 2023. The review included cross-sectional and longitudinal studies concerning the association between sedentary behaviour and sarcopenia among participants over 60 years old. Evidence was pooled by both random-effects meta-analysis and narrative synthesis. Subgroup analyses explored variation according to adjustment of physical activity, settings, and measurements of sedentary behaviour and sarcopenia. Quality assessment for individual studies was performed with the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. Results: Seventeen articles (16 cross-sectional studies and 1 longitudinal study) of 25,788 participants from community or long-term care facility settings were included. The overall quality of the included studies was rated high. Meta-analysis of 14 cross-sectional studies showed that sedentary behaviour was independently positively associated with sarcopenia: pooled odd ratio 1.36 (95% confidence interval, 1.18–1.58). The independent positive association remained in subgroup analyses by adjustment of physical activity, settings, and measurements of sedentary behaviour and sarcopenia. The narrative analysis corroborated the findings of the meta-analysis and provided additional evidence suggesting that interruptions in sedentary periods were linked to a decreased likelihood of developing sarcopenia. Conclusions: The findings support the hypothesis that sedentary behaviour is independently positively associated with sarcopenia in older adults, providing vital indications for the development of strategies to prevent sarcopenia. Systematic review registration: The systematic review protocol has been registered with the PROSPERO database (CRD42022311399). [ABSTRACT FROM AUTHOR]

To solve the problem of hidden pattern recognition and high dimensional perception of geospatial sensor data, machine learning can build a model of the unknown relationship between associated data and characteristic variables. In recent years, clustering ensemble (CE) is a hot research area in machine learning, which has attracted much attention by combining multiple base clustering results into an ideal clustering solution and improving the robustness of clustering performance. To better solve the intelligent prediction of landslides in geological disasters, a novel CE method based on mountain monitoring text data is designed and implemented to analyze and predict landslide disasters. First, the effective information is extracted by preprocessing the original data. Then, the reliability weighting and weighted measure formulas were designed by combining the concepts of cosine similarity, information entropy and reliability. Accordingly, a novel clustering ensemble algorithm based on reliability weighted measure (RWMCE) was proposed to mine and analyze the effective information implicit in mountain monitoring text data. Furthermore, the method can reduce the attention to the poor clusters and improve the overall prediction performance by weighting from the cluster level and measuring the reliability of weighting. To test the diversity and robustness of RWMCE in the landslide monitoring data set, ten groups of schemes based on K-means, K-medoids, Fuzzy C-Means, and Gaussian Mixture Model were set up for performance evaluation. Experiments on nine publicly available datasets proves that RWMCE has better prediction performance for landslide geological disasters. [ABSTRACT FROM AUTHOR]

Fundamental differences in excitatory pyramidal cells across cortical areas and species highlight the implausibility of extrapolation from mouse to primate neurons and cortical networks. Far less is known about comparative regional and species‐specific features of neurochemically distinct cortical inhibitory interneurons. Here, we quantified the density, laminar distribution, and somatodendritic morphology of inhibitory interneurons expressing one or more of the calcium‐binding proteins (CaBPs) (calretinin [CR], calbindin [CB], and/or parvalbumin [PV]) in mouse (Mus musculus) versus rhesus monkey (Macaca mulatta) in two functionally and cytoarchitectonically distinct regions—the primary visual and frontal cortical areas—using immunofluorescent multilabeling, stereological counting, and 3D reconstructions. There were significantly higher densities of CB+ and PV+ neurons in visual compared to frontal areas in both species. The main species difference was the significantly greater density and proportion of CR+ interneurons and lower extent of CaBP coexpression in monkey compared to mouse cortices. Cluster analyses revealed that the somatodendritic morphology of layer 2–3 inhibitory interneurons is more dependent on CaBP expression than on species and area. Only modest effects of species were observed for CB+ and PV+ interneuron morphologies, while CR+ neurons showed no difference. By contrast to pyramidal cells that show highly distinctive area‐ and species‐specific features, here we found more subtle differences in the distribution and features of interneurons across areas and species. These data yield insight into how nuanced differences in the population organization and properties of neurons may underlie specializations in cortical regions to confer species‐ and area‐specific functional capacities. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy. Method: We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated. Results: We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06–0.39, I2 = 0.37%), 27% (95% CI 0.03–0.60, I2 = 60.43%) and 65% (95% CI 0.23–0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08–0.99, I2 = 85.20%), 47% (95% CI 0.14–0.81, I2 = 74.17%), 59% (95% CI 0.27–0.89, I2 = 60.23%), and 50% (95% CI 0.13–0.87, I2 = 73.89%), respectively. Conclusion: CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever. Registration: The protocol was registered in prospero, with the registration number CRD42022342647. [ABSTRACT FROM AUTHOR]

Recently, reconfigurable coding metasurfaces have attracted extensive attention due to their dynamic and flexible manipulation of electromagnetic (EM) waves, making them an effective solution to connect physical reality and information science. Nevertheless, most previously reported reconfigurable metasurfaces suffer from limited applications, as they solely possess either phase or amplitude modulation. In this article, we propose a reconfigurable coding metasurface that can regulate both phase and amplitude response independently. In the field of the metasurface, the phase response can tailor the wavefronts, and the amplitude response can adjust the redistribution of the energy of the EM waves. Specifically, by integrating a PIN diode into the meta-atom and controlling its bias voltage, the reflection phase can be switched between two opposite phases with a phase difference of about 180°, and the reflection amplitude can be manipulated from 0.02 to 0.98 continuously at 11 GHz. The unit element consists of simple multi-layer structures, reducing its production cost and processing difficulty. By loading 1-bit phase code and multi-bit amplitude code to each unit element severally, this metasurface can modulate the distribution of reflected EM waves in two-dimensional (2-D) space while simultaneously suppressing the sidelobes for any quantity of scattered beams over a wide operating band ranging from 10.5 to 11.5 GHz. This metasurface exhibits promising potential for manipulating the distribution of EM wave energy and shaping of EM beams, which can be expected to facilitate wireless communication technology. [ABSTRACT FROM AUTHOR]

Grylloprimevala jilina is a true cave insect living in the dark areas of caves. It has the characteristics of sparse skin pigmentation, degeneration of the compound eyes and monocular eyes, and obvious preference for high‐humidity and low‐temperature environments. Given the highly specialized, rare, and limited distribution, G. jilina is considered an endangered species and also a first‐level national protected insect in China. Cave creatures often undergo dramatic morphological changes in their sensory systems to adapt to the cave environment. Most previous studies mainly focused on morphological adaptive changes in cave insects, and only a few studied the changes at the gene level. In this study, we performed transcriptome analysis of G. jilina and constructed phylogenetic trees of genes that are related to environmental adaptation, including chemosensory, visual‐related, reproduction‐related, temperature adaptation‐related, and winged morph differentiation‐related genes. Besides, the expression levels of environmental adaption‐related genes in different tissues, including antennae, heads, thoraxes, abdomens, legs, and tails, were analyzed. The results showed the loss of chemosensory genes and vision‐related genes, the conservation of reproduction‐related genes and temperature adaptation‐related genes, and the conservation of wing‐related genes despite the loss of wings, and the results were consistent with other cave insects. The identification and expression study of genes possibly related to the environmental adaptability in G. jilina provided basic data for the protection of this endangered species and increased knowledge about insect evolution in general. [ABSTRACT FROM AUTHOR]

The distribution of phosphorus in permanent cropping systems such as orchards soil differs from that of other agricultural soils because of the developed root system with a large biomass and long-life cycle of fruit trees. However, our understanding of soil phosphorus in orchards remains poor. This study applied chemical and spectroscopic analyses to compare differences in soil phosphorus between different slope positions and soil horizons of a Pyrus bretschneideri orchard. The results suggested that soil phosphorus of the Pyrus bretschneideri orchard exceeded that in wasteland. Moderately labile organic phosphorus and orthophosphate are the main forms of soil phosphorus in Pyrus bretschneideri orchard and play an important role in phosphorus cycle of Pyrus bretschneideri orchard soil, the continuous supplementation of them can meet the phosphorus nutrient needs of Pyrus bretschneideri trees. Moreover, Pyrus bretschneideri trees mainly obtain nutrients from horizons AB to B, there should be further focus to the depth of 20–80 cm of fertilizer application approximately in Haplic Luvisols. [ABSTRACT FROM AUTHOR]

Background: Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy. Method: We searched PubMed, the Cochrane Library, Embase and Web of Science from January 2012 to August 2022 to find data reporting the results of CAR-T cells therapy combined with PD-1 in tumor patients. An updated search was conducted in October 2023. The partial response rate (PR), complete response rate (CR), objective response rate (ORR), mortality rate, and incidence of adverse reactions were calculated. Results: We analyzed 57 lymphoma patients from 5 clinical trials. The pooled partial, complete and overall response rates were 21% (95% CI 0.06–0.39, I2 = 0.37%), 27% (95% CI 0.03–0.60, I2 = 60.43%) and 65% (95% CI 0.23–0.98, I2 = 76.31%), respectively. The pooled incidence of cytokine release syndrome, neutropenia, fever, and fatigue was estimated to be 57% (95% CI 0.08–0.99, I2 = 85.20%), 47% (95% CI 0.14–0.81, I2 = 74.17%), 59% (95% CI 0.27–0.89, I2 = 60.23%), and 50% (95% CI 0.13–0.87, I2 = 73.89%), respectively. Conclusion: CAR-T-cell therapy combined with anti-PD-1 immunotherapy in the treatment of lymphoma patients has efficacy, and the most common adverse effect is fever. Registration: The protocol was registered in prospero, with the registration number CRD42022342647. [ABSTRACT FROM AUTHOR]

Paclitaxel, a natural anticancer drug, is widely recognized and extensively utilized in the treatment of breast cancer (BC). However, it may lead to certain side effects or drug resistance. Fortunately, combination therapy with another anti-tumor agent has been explored as an option to improve the efficacy of paclitaxel in the treatment of BC. Herein, we first evaluated the synergistic effects of paclitaxel and flubendazole through combination index (CI) calculations. Secondly, flubendazole was demonstrated to synergize paclitaxel-mediated BC cell killing in vitro and in vivo. Moreover, we discovered that flubendazole could reverse the drug resistance of paclitaxel-resistant BC cells. Mechanistically, flubendazole was demonstrated to enhance the inhibitory effect of paclitaxel via HIF1α/PI3K/AKT signaling pathways. Collectively, our findings demonstrate the effectiveness of flubendazole in combination with paclitaxel for treating BC, providing an insight into exploiting more novel combination therapies for BC in the future. [ABSTRACT FROM AUTHOR]

This study used a Mendelian randomization (MR) approach to investigate the causal relationship between genetically predicted endometriosis (EMS) and breast cancer risk. A total of 122,977 cases and 105,974 controls were included in the analysis, with gene-level summary data obtained from the Breast Cancer Association Consortium (BCAC). An inverse variance-weighting approach was applied to assess the causal relationship between EMS and breast cancer risk, and weighted median and MR-Egger regression methods were used to evaluate pleiotropy. Results showed a causal relationship between EMS and a decreased risk of overall breast cancer (odds ratio [OR] 0.95; 95% CI 0.90–0.99, p = 0.02). Furthermore, EMS was associated with a lower risk for estrogen receptor (ER)-positive breast cancer in a subgroup analysis based on immunohistochemistry type (OR 0.91; 95% CI 0.86–0.97, p = 0.005). However, there was no causal association between ER-negative breast cancer and survival (OR 1.00; 95% CI 0.94–1.06, p = 0.89). Pleiotropy was not observed. These findings provide evidence of a relationship between EMS and reduced breast cancer risk in invasive breast cancer overall and specific tissue types, and support the results of a previous observational study. Further research is needed to elucidate the mechanisms underlying this association. [ABSTRACT FROM AUTHOR]

Emerging multidrug resistance (MDR) in Clarireedia spp. is a huge challenge to the management of dollar spot (DS) disease on turfgrass. Insight into the molecular basis of resistance mechanisms may help identify key molecular targets for developing novel effective chemicals. Previously, a MDR isolate (LT586) of C. jacksonii with significantly reduced sensitivities to propiconazole, boscalid, and iprodione, and a fungicide-sensitive isolate (LT15) of the same species were isolated from creeping bentgrass (Agrostis stolonifera L.). The present study aimed to further explore the molecular mechanisms of resistance by using genome-wide transcriptional analyses of the two isolates. A total of 619 and 475 differentially expressed genes (DEGs) were significantly down and upregulated in the MDR isolate LT586, compared with the sensitive isolate LT15 without fungicide treatment. Three hundreds and six and 153 DEGs showed significantly lower and higher expression in the MDR isolate LT586 than those in the sensitive isolate LT15, which were commonly induced by the three fungicides. Most of the 153 upregulated DEGs were xenobiotic detoxification-related genes and genes with transcriptional functions. Fifty and 17 upregulated DEGs were also commonly observed in HRI11 (a MDR isolate of the C. jacksonii) compared with the HRS10 (a fungicide-sensitive isolate of same species) from a previous study without and with the treatment of propiconazole, respectively. The reliability of RNA-seq data was further verified by qRT-PCR method using a few select potentially MDR-related genes. Results of this study indicated that there were multiple uncharacterized genes, possibly responsible for MDR phenotypes in Clarireedia spp., which may have important implications in understanding the molecular mechanisms underlying MDR resistance. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is an aggressive and unstoppable malignancy. Natural killer T (NKT) cells, characterized by specific markers, play pivotal roles in many tumor-associated pathophysiological processes. Therefore, investigating the functions and complex interactions of NKT cells is great interest for exploring GBM. Methods: We acquired a single-cell RNA-sequencing (scRNA-seq) dataset of GBM from Gene Expression Omnibus (GEO) database. The weighted correlation network analysis (WGCNA) was employed to further screen genes subpopulations. Subsequently, we integrated the GBM cohorts from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases to describe different subtypes by consensus clustering and developed a prognostic model by least absolute selection and shrinkage operator (LASSO) and multivariate Cox regression analysis. We further investigated differences in survival rates and clinical characteristics among different risk groups. Furthermore, a nomogram was developed by combining riskscore with the clinical characteristics. We investigated the abundance of immune cells in the tumor microenvironment (TME) by CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms. Immunotherapy efficacy assessment was done with the assistance of Tumor Immune Dysfunction and Exclusion (TIDE) and The Cancer Immunome Atlas (TCIA) databases. Real-time quantitative polymerase chain reaction (RT-qPCR) experiments and immunohistochemical profiles of tissues were utilized to validate model genes. Results: We identified 945 NKT cells marker genes from scRNA-seq data. Through further screening, 107 genes were accurately identified, of which 15 were significantly correlated with prognosis. We distinguished GBM samples into two distinct subtypes and successfully developed a robust prognostic prediction model. Survival analysis indicated that high expression of NKT cell marker genes was significantly associated with poor prognosis in GBM patients. Riskscore can be used as an independent prognostic factor. The nomogram was demonstrated remarkable utility in aiding clinical decision making. Tumor immune microenvironment analysis revealed significant differences of immune infiltration characteristics between different risk groups. In addition, the expression levels of immune checkpoint-associated genes were consistently elevated in the high-risk group, suggesting more prominent immune escape but also a stronger response to immune checkpoint inhibitors. Conclusions: By integrating scRNA-seq and bulk RNA-seq data analysis, we successfully developed a prognostic prediction model that incorporates two pivotal NKT cells marker genes, namely, CD44 and TNFSF14. This model has exhibited outstanding performance in assessing the prognosis of GBM patients. Furthermore, we conducted a preliminary investigation into the immune microenvironment across various risk groups that contributes to uncover promising immunotherapeutic targets specific to GBM. [ABSTRACT FROM AUTHOR]

Understanding the microglial neuro-immune interactions in the primate brain is vital to developing therapeutics for cortical injury, such as stroke or traumatic brain injury. Our previous work showed that mesenchymal-derived extracellular vesicles (MSC-EVs) enhanced motor recovery in aged rhesus monkeys following injury of primary motor cortex (M1), by promoting homeostatic ramified microglia, reducing injury-related neuronal hyperexcitability, and enhancing synaptic plasticity in perilesional cortices. A focal lesion was induced via surgical ablation of pial blood vessels over lying the cortical hand representation of M1 of aged female rhesus monkeys, that received intravenous infusions of either vehicle (veh) or EVs 24 h and again 14 days post-injury. The current study used this same cohort to address how these injury- and recovery-associated changes relate to structural and molecular interactions between microglia and neuronal synapses. Using multi-labeling immunohistochemistry, high-resolution microscopy, and gene expression analysis, we quantified co-expression of synaptic markers (VGLUTs, GLURs, VGAT, GABARs), microglia markers (Iba1, P2RY12), and C1q, a complement pathway protein for microglia-mediated synapse phagocytosis, in perilesional M1 and premotor cortices (PMC). We compared this lesion cohort to age-matched non-lesion controls (ctr). Our findings revealed a lesion-related loss of excitatory synapses in perilesional areas, which was ameliorated by EV treatment. Further, we found region-dependent effects of EVs on microglia and C1q expression. In perilesional M1, EV treatment and enhanced functional recovery were associated with increased expression of C1q + hypertrophic microglia, which are thought to have a role in debris-clearance and anti-inflammatory functions. In PMC, EV treatment was associated with decreased C1q + synaptic tagging and microglia–spine contacts. Our results suggest that EV treatment may enhance synaptic plasticity via clearance of acute damage in perilesional M1, and thereby preventing chronic inflammation and excessive synaptic loss in PMC. These mechanisms may act to preserve synaptic cortical motor networks and a balanced normative M1/PMC synaptic function to support functional recovery after injury. [ABSTRACT FROM AUTHOR]

Background: The purpose of this paper was to systematically evaluate the application value of artificial intelligence in predicting mortality among COVID-19 patients. Methods: The PubMed, Embase, Web of Science, CNKI, Wanfang, China Biomedical Literature, and VIP databases were systematically searched from inception to October 2022 to identify studies that evaluated the predictive effects of artificial intelligence on mortality among COVID-19 patients. The retrieved literature was screened according to the inclusion and exclusion criteria. The quality of the included studies was assessed using the QUADAS-2 tools. Statistical analysis of the included studies was performed using Review Manager 5.3, Stata 16.0, and Meta-DiSc 1.4 statistical software. This meta-analysis was registered in PROSPERO (CRD42022315158). Findings: Of 2193 studies, 23 studies involving a total of 25 AI models met the inclusion criteria. Among them, 18 studies explicitly mentioned training and test sets, and 5 studies did not explicitly mention grouping. In the training set, the pooled sensitivity was 0.93 [0.87, 0.96], the pooled specificity was 0.94 [0.87, 0.97], and the area under the ROC curve was 0.98 [0.96, 0.99]. In the validation set, the pooled sensitivity was 0.84 [0.78, 0.88], the pooled specificity was 0.89 [0.85, 0.92], and the area under the ROC curve was 0.93 [1.00, 0.00]. In the subgroup analysis, the areas under the summary receiver operating characteristic (SROC) curves of the artificial intelligence models KNN, SVM, ANN, RF and XGBoost were 0.98, 0.98, 0.94, 0.92, and 0.91, respectively. The Deeks funnel plot indicated that there was no significant publication bias in this study (P > 0.05). Interpretation: Artificial intelligence models have high accuracy in predicting mortality among COVID-19 patients and have high prognostic value. Among them, the KNN, SVM, ANN, RF, XGBoost, and other models have the highest levels of accuracy. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to perform a Bayesian network meta‐analysis to evaluate the safety and efficacy of prophylactic bolus of different doses of ephedrine, phenylephrine, and norepinephrine for the prevention of spinal hypotension during cesarean section. Methods: The Web of Science, PubMed, EMBASE, Cochrane Library were searched until to May 20, 2022. The indicators included incidence of hypotension, reactive hypertension, bradycardia, nausea and vomiting, umbilical artery pH, and Apgar scores. Results: About 3125 related records were obtained and 17 RCTs met our eligibility criteria. Based on the results, prophylactic bolus injection of 21–30 mg ephedrine (82%) was the best efficacious option for preventing hypotension, followed by 13–16 μg norepinephrine and 81–120 mg phenylephrine; 121–150 μg phenylephrine had the highest probability (62%) caused reactive hypertension, followed by 11–30 mg ephedrine; phenylephrine was most likely to cause bradycardia in a dose‐dependent manner; 81–120 μg phenylephrine had the highest probability (37%) which associated with IONV; 6–12 μg norepinephrine (31%) had the lowest influence on IONV and had highest probability (34%) associated with improving umbilical arterial pH; 13–16 μg norepinephrine had highest probability (67% at 1 min, 49% at 5 min) which associated with improving Apgar scores. Conclusions: Based on this study, 5–10 mg ephedrine and 13–16 μg norepinephrine prophylactic bolus injection may be the optimum dosage of three drugs prevent spinal‐induced hypotension, which has the least impact on maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

To investigate the feasibility of developing litchi leaves as silage, we determined the fermentation quality of four varieties of litchi leaves (including "Wanpu", "Wuyejiu", "Tongzai" and "Zhuangyuanhong") ensiled with or without Lactobacillus plantarum on day 3, 7, 14 and 30. The in vitro dry matter digestibility and gas production of litchi leaves silages were also determined after 30 days of ensiling. The results showed that Lactobacillus plantarum significantly reduced pH value (p < 0.01), inhibited coliform bacteria, and reduced the production of ammonia nitrogen (p < 0.01) in all the four kinds of litchi leaves silage. Moreover, Lactobacillus plantarum treated litchi leaves ("Wanpu" and "Zhuangyuanhong") had lower yeasts than the untreated litchi leaves during ensiling. The number of molds in Lactobacillus plantarum treated groups ("Tongzai" and "Zhuangyuanhong") was below the detected level after 30 days ensiling, which was lower than that of the untreated groups. The addition of Lactobacillus plantarum also contributed to improving IVDMD and markedly reduced (p < 0.01) gas production of all litchi leaves silages. Conclusions: Lactobacillus plantarum can improve the fermentation quality and in vitro digestion characteristics of litchi leaves silage. Developing litchi leaves as silage material is a feasible way to recycle litchi leaves. [ABSTRACT FROM AUTHOR]

Background: Cuproptosis is a regulated cell death form associated with tumor progression, clinical outcomes, and immune response. However, the role of cuproptosis in pancreatic adenocarcinoma (PAAD) remains unclear. This study aims to investigate the implications of cuproptosis-related genes (CRGs) in PAAD by integrated bioinformatic methods and clinical validation. Methods: Gene expression data and clinical information were downloaded from UCSC Xena platform. We analyzed the expression, mutation, methylation, and correlations of CRGs in PAAD. Then, based on the expression profiles of CRGs, patients were divided into 3 groups by consensus clustering algorithm. Dihydrolipoamide acetyltransferase (DLAT) was chosen for further exploration, including prognostic analysis, co-expression analysis, functional enrichment analysis, and immune landscape analysis. The DLAT-based risk model was established by Cox and LASSO regression analysis in the training cohort, and then verified in the validation cohort. Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays were performed to examine the expression levels of DLAT in vitro and in vivo, respectively. Results: Most CRGs were highly expressed in PAAD. Among these genes, increased DLAT could serve as an independent risk factor for survival. Co-expression network and functional enrichment analysis indicated that DLAT was engaged in multiple tumor-related pathways. Moreover, DLAT expression was positively correlated with diverse immunological characteristics, such as immune cell infiltration, cancer-immunity cycle, immunotherapy-predicted pathways, and inhibitory immune checkpoints. Submap analysis demonstrated that DLAT-high patients were more responsive to immunotherapeutic agents. Notably, the DLAT-based risk score model possessed high accuracy in predicting prognosis. Finally, the upregulated expression of DLAT was verified by RT-qPCR and IHC assays. Conclusions: We developed a DLAT-based model to predict patients' clinical outcomes and demonstrated that DLAT was a promising prognostic and immunological biomarker in PAAD, thereby providing a new possibility for tumor therapy. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy has transformed cancer treatment patterns for advanced hepatocellular carcinoma (aHCC) in recent years. Therefore, the identification of predictive biomarkers has important clinical implications. Methods: We collected medical records from 117 aHCC patients treated with anti-PD-1 antibody. Kaplan-Meier analysis and Cox proportional hazard regression were used to evaluate the association between peripheral blood biomarkers and overall survival (OS) and progression-free survival (PFS). Finally, the prognostic nomogram was constructed. Results: The mPFS and mOS were 7.0 months and 18.7 months, respectively. According to Kaplan-Meier analysis and Cox regression analysis, we regarded the treatment regimen (p = 0.020), hemoglobin (Hb) at 6-week (p = 0.042), neutrophil-to-lymphocyte ratio (NLR) at 6-week (p < 0.001), system immune inflammation index (SII) at 6-week (p = 0.125) as predictors of PFS, and alpha fetoprotein (AFP) (p = 0.035), platelet-to-lymphocyte ratio (PLR) (p = 0.012), Hb at 6-week (p = 0.010) and NLR at 6-week (p = 0.020) as predictors of OS. Furthermore, the results suggest that the OS and PFS nomogram model were in agreement with actual observations. Conclusion: Biomarkers in peripheral blood can predict the prognosis of patients with aHCC treated with anti-PD-1 antibody. The development of nomogram models can help us to screen potential patients who can benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

GL-V9, a new synthetic flavonoid derived from wogonin, has shown beneficial biological functions. In this study, accurate and sensitive UPLC–MS/MS methods were developed and validated for the quantification of GL-V9 and its glucuronide metabolite (5-O-glucuronide GL-V9) in Beagle dog plasma. The chromatographic separation was performed on a C8 column (ACE Excel 5 C8 50×3.0 mm) using 0.1% formic acid and acetonitrile were used as mobile phase. Mass detection was performed on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization (ESI) interface operating in positive ion mode. Quantitative analysis was performed in multiple reaction monitoring (MRM) mode with the transitions of m/z 410.2→126.1 for GL-V9, m/z 586.3→410.0 for 5-O-glucuronide GL-V9 and m/z 180.0→110.3 for phenacetin (internal standard), respectively. The calibration curves for GL-V9 and 5-O-glucuronide GL-V9 showed excellent linearity over the concentration range of 0.5–500 ng/mL with correlation coefficient greater than 0.99. The intra- and inter-day accuracies were within 99.86% to 109.20% for GL-V9 and 92.55% to 106.20% for 5-O-glucuronide GL-V9, respectively. The mean recovery was 88.64% ± 2.70% for GL-V9, and 92.31% ± 6.28% for 5-O-glucuronide GL-V9, respectively. The validated method was successfully applied to the pharmacokinetic study in Beagle dogs after oral and intravenous administration. The oral bioavailability of GL-V9 was approximately 2.47%~4.35% in Beagle dogs and reached steady state on the fifth day after repeated dosing. [ABSTRACT FROM AUTHOR]

Background: Triple‐negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real‐world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real‐world setting and to explore possible correlates. Methods: The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed. Results: Eighty‐one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression‐free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later‐line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable. Conclusions: ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment. [ABSTRACT FROM AUTHOR]

In this work, magnetic barium phosphate (FBP) composites with different content of commercial Fe3O4 nanoparticles were easily prepared by a one-step hydrothermal method. FBP composites with a magnetic content of 3% (FBP3) were studied as the example for the removal of an organic pollutant (Brilliant Green, BG) from the synthetic medium. The adsorption study was executed under the variation of different experimental conditions, such as solution pH (5 ~ 11), dosage (0.02 ~ 0.20 g), temperature (293 ~ 323 K), and the contact time (0 ~ 60 min) on the removal of BG. For comparison purposes, the one-factor-at-a-time (OFAT) approach and Doehlert matrix (DM) were both employed to investigate the factor impacts involved. FBP3 showed a high adsorption capacity of 1419.3 ± 10.0 mg/g for at 25 °C and pH = 6.31. The kinetics study revealed the pseudo-second-order kinetic model as the best-fitted model, and the thermodynamic data fit well with the Langmuir model. The possible adsorption mechanisms involved are the electrostatic interaction and/or hydrogen bonding of PO43−...N+/C-H and HSO4−...Ba2+ between FBP3 and BG. Furthermore, FBP3 showed good easy reusability and high capacities for BG removal. Our results provide new insights for developing low-cost, efficient, and reusable adsorbent to remove BG from industrial wastewater. [ABSTRACT FROM AUTHOR]

Background: Clinical epidemiological studies have found that some patients with ulcerative colitis (UC) are prone to mental disorders. DSS-induced acute and chronic UC models are often used to evaluate the efficacy of anti-UC drugs. However, whether DSS has an effect on mouse behavior has not been reported. Methods: Acute and chronic UC models were induced by 3% DSS and 1.5% DSS, respectively. The bloody stool, the changes in the colon length, and histopathological changes in the colon were used to evaluate the success of the animal model. The behavior of mice was evaluated by open field experiment, tail suspension experiment and Sucrose preference test. Results: The weight of mice in 3% DSS group decreased significantly, the DAI score increased significantly, the colon length of mice was significantly shortened, and the structure of colonic crypts was abnormal, which showed inflammatory cell infiltration and shrinkage of crypts. Compared with the control group, the immobility time of 3%DSS group mice in the tail suspension test and forced swimming test had no effect, the number of running and grooming times was significantly reduced, and there was no significant difference in the number of standing times. No abnormality was observed in HE staining of the hippocampus. However, in 1.5% DSS-induced chronic UC model, behavioral and hippocampal abnormalities were observed not only UC symptoms. Conclusions: The acute UC model induced by 3% DSS has certain influence on the behavior of mice, but the mental state of mice is normal, which may be the abnormal behavior caused by UC symptoms; However, the chronic UC model induced by 1.5% DSS has a significant effect on the behavior of mice, and the mice have mental disorders, which are caused by mental disorders. [ABSTRACT FROM AUTHOR]

N,N-dihydroxyethyl-(5-methyl-[1,3,4] thiadiazol-2-sulfur)-carbonyl acetamide was synthesized and used as an inhibitor to protect Q235 carbon steel in a 1 M HCl solution. The results showed an increased inhibition efficiency with the increase in the concentration of this inhibitor, and an inhibition efficiency higher than 96% at 40 mg/L can be obtained from weight loss, electrochemical impedance spectroscopy, and potentiodynamic polarization results. The inhibition effect was determined by the adsorption film according to the surface morphology and elemental distribution of the carbon steel surface. The adsorption consists of physical adsorption and chemical adsorption in view of the free adsorption energy of −40.64 kJ/mol derived from the Langmuir adsorption isotherm line. The lone pair electrons of N, O and S and π electronics of double bonds in molecules form stable covalent coordination bonds with the empty d orbitals of iron atoms, which is beneficial to chemical adsorption of the inhibitor. The high inhibiton efficiency of this inhibitor is important for the potential application in pickling field. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is second cancer frequently occurring worldwide. Circular RNA hsa_circ_0000129 (circ_0000129) exerts a tumor‐promoting effect in BC. Nevertheless, the molecular mechanisms mediated by the upregulation of circ_0000129 during BC progression are not well understood. Methods: Forty‐five BC patients were recruited for the research. Changes in circ_0000129 levels were detected with quantitative reverse transcription‐polymerase chain reaction. Cell proliferation, apoptosis, migration, invasion, and angiopoiesis were determined by cell counting, 5‐ethynyl‐2′‐deoxyuridine (EdU), flow cytometry, transwell, and tube formation assays. Protein levels were detected by western blot analysis. The regulatory mechanism of circ_0000129 was predicted by bioinformatics analysis and validated by dual‐luciferase reporter and RNA immunoprecipitation assays. In vivo experiments were carried out to verify the function of circ_0000129. Results: Circ_0000129 was overexpressed in BC samples and cell lines. Functionally, circ_0000129 silencing reduced cell proliferation, migration, invasion, and promoted cell apoptosis, as well as induced HUVEC angiopoiesis in vitro. Furthermore, circ_0000129 knockdown decreased BC cell growth in mouse xenograft models. Mechanically, circ_0000129 interacted with miR‐485‐3p to mediate the inhibiting effect of miR‐485‐3p on SPIN1. Silenced miR‐485‐3p expression weakened the inhibiting effect of circ_0000129 knockdown on BC cell malignant behaviors. Also, forced SPIN1 expression weakened miR‐485‐3p upregulation mediated effects on BC cell malignant behaviors. Conclusion: Circ_0000129 acted as a miR‐485‐3p sponge molecular to mediate expression, thus promoting BC progression. Highlights: 1.Circ_0000129 was singularly increased in BC patients.2.Circ_0000129 silencing curbed BC cell malignant behaviors.3.Circ_0000129 regulated SPIN1 expression by sponging miR‐485‐3p. [ABSTRACT FROM AUTHOR]

Thermal runaway (TR) propagation of lithium-ion batteries (LIBs) in air may cause fire, and argon can effectively inhibit LIBs with TR propagation. The oxygen concentration and gas flow rate are the important factors affecting the TR propagation. Hence, an experimental device for LIBs with TR propagation in air and argon environments in a confined space was established, and a series of experiments were carried out. Subsequently, the critical conditions of oxygen concentration and gas flow rate that inhibit the TR propagation of the cell are investigated. The study found that LIBs with TR propagation occur in an air environment, while argon gas has a good effect on inhibiting LIBs with TR propagation. The critical oxygen concentration for LIBs with TR propagation in an argon environment is between 2.5 and 5%. The critical gas flow rates for LIBs with TR propagation are greater than 24 L min−1 under air and are between 18 and 24 L min−1 under argon. It is firmly believed that this work can provide useful inspirations for the TR suppression of LIBs. [ABSTRACT FROM AUTHOR]

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory effects on the wild-type strain and cross-inhibition activities against other mutant strains after two inactivated vaccine doses. However, the B.1.351, B.1.617.2 and B.1.1.529 mutants exhibit antibody resistance in the vaccine serum. Antibodies induced by homologous inactivated vaccines (n = 92) presented more effective inhibition against tested SARS-CoV-2 strains (p < 0.0001), especially B.1.351, B.1.617.2, and B.1.1.529 mutant strains, which had strong immune escape characteristics. In addition, a heterologous booster vaccination (n = 50) of a protein subunit vaccine ZifiVax (ZF2001) significantly restored humoral immune responses and even showed an increasing response against wild-type, B.1.351, B.1.617.2, and B.1.1.529 than homologous inactivated vaccines. Our analysis of the humoral immune response elicited by the different vaccine regimens, including inhibiting antibodies, indicated that a booster, whether homologous or heterologous, could be essential for achieving greater efficacy against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Undesirable side effects and multidrug tolerance are the main holdbacks to the treatment of cancer in conventional chemotherapy. Fortunately, targeted drug delivery can improve the enrichment of drugs at the target site and reduce toxicity to normal tissues and cells. A targeted drug delivery system is usually composed of a nanocarrier and a targeting component. The targeting component is called a "ligand". Aptamers have high target affinity and specificity, which are identified as attractive and promising ligands. Therefore, aptamers have potential application in the development of smart targeting systems. For instance, aptamers are able to efficiently recognize tumor markers such as nucleolin, mucin, and epidermal growth factor receptor (EGFR). Besides, aptamers can also identify glycoproteins on the surface of tumor cells. Thus, the aptamer-mediated targeted drug delivery system has received extensive attention in the application of cancer therapy. This article reviews the application of aptamers as smart ligands for targeted drug delivery in cancer therapy. Special interest is focused on aptamers as smart ligands, aptamer-conjugated nanocarriers, aptamer targeting strategy for tumor microenvironment (TME), and aptamers that are specified to crucial cancer biomarkers for targeted drug delivery. [ABSTRACT FROM AUTHOR]

This paper uses the provisions of the Soil Pollution Prevention and Control Action Plan for industrial and mining enterprises as a quasi-natural experiment and constructs a difference-in-differences (DID) model to study its effect on increasing the quantity and improving the quality of green innovation based on a panel of 453 industrial and mining enterprises in Shanghai and Shenzhen A-shares in China from 2011 to 2020. The results show that the Soil Plan can significantly promote the increase of green innovation and the quality of industrial and mining enterprises, and the results are still valid after a series of robustness tests. The mechanism test shows that the Soil Plan promotes the quality of green innovation by alleviating the financing constraints of industrial and mining enterprises, but the impact on their incremental quantity is not significant. The heterogeneity analysis shows that the effect of the Soil Plan on the quality of green innovation is stronger in the sample with a more independent board of directors and a digital mine transformation. This paper enriches the results in the field of soil pollution prevention and industrial and mining enterprises, and has important implications for the practice of promoting green innovation in Chinese enterprises. [ABSTRACT FROM AUTHOR]

The existing methods for multi-point harmonic contribution evaluation usually require some preconditions, such as the node harmonic current is equivalent to the harmonic emission current and the number of measurements is not less than the number of sources. However, these requirements may not be satisfied in practice. In this context, this paper proposes an improved sparse component analysis (SCA) method to solve the underdetermined blind source separation model, which is used to describe the harmonic state under incomplete measurements. The improved SCA adopts a new two-stage technique. First, the mixing matrix containing harmonic transfer impedances is estimated through the synchrosqueezing S-transform. Then, the source signal vector containing harmonic emission currents is reconstructed through the modified subspace projection. By matching the harmonic impedances and currents, the multi-point harmonic contribution evaluation is further achieved. The efficiency of the proposed method is verified by simulations and field case studies. The results demonstrate that the proposed method outperforms the existing methods in terms of accurately estimating the harmonic emission currents and quantifying the harmonic contributions under incomplete measurements. [ABSTRACT FROM AUTHOR]

Industrial hemp (Cannabis sativa L.), an annual herbaceous cash crop, is widely used for the remediation of heavy metal-contaminated soils due to its short growth cycle, high tolerance, high biomass, and lack of susceptibility to transfer heavy metals into the human food chain. In this study, a significant increase in proanthocyanidins was found in Yunnan hemp no. 1 after cadmium stress. Proanthocyanidins are presumed to be a key secondary metabolite for cadmium stress mitigation. Therefore, to investigate the effect of proanthocyanidins on industrial hemp under cadmium stress, four experimental treatments were set up: normal environment, cadmium stress, proanthocyanidin treatment, and cadmium stress after pretreatment with proanthocyanidins. The phenotypes from the different treatments were compared. The experimental results showed that pretreatment with proanthocyanidins significantly alleviated cadmium toxicity in industrial hemp. The transcriptome and metabolome of industrial hemp were evaluated in the different treatments. Proanthocyanidin treatment and cadmium stress in industrial hemp mainly affected gene expression in metabolic pathways associated with glutathione metabolism, phenylpropanoids, and photosynthesis, which in turn altered the metabolite content in metabolic pathways of phenylalanine, vitamin metabolism, and carotenoid synthesis. The combined transcriptomic and metabolomic analysis revealed that proanthocyanidins mitigated cadmium toxicity by enhancing photosynthesis, secondary metabolite synthesis, and antioxidant synthesis. In addition, exogenous proanthocyanidins and cadmium ions acted simultaneously on EDS1 to induce the production of large amounts of salicylic acid in the plant. Finally, overexpression of CsANR and CsLAR, key genes for proanthocyanidins synthesis in industrial hemp, was established in Arabidopsis plants. The corresponding plants were subjected to cadmium stress, and the results showed that CsLAR transgenic plants were more tolerant to cadmium than the CsANR transgenic and wild-type Arabidopsis plants. The results showed that salicylic acid and jasmonic acid were increased in Arabidopsis overexpressing CsLAR compared to AT wild-type Arabidopsis, and levels of secondary metabolites were significantly higher in Arabidopsis overexpressing CsLAR than in AT wild-type Arabidopsis. These results revealed how proanthocyanidins alleviated cadmium stress and laid the foundation for breeding industrial hemp varieties with higher levels of proanthocyanidins and greater tolerance. [ABSTRACT FROM AUTHOR]

The goal of the current study was to determine the appropriate spatial shapes for classroom occupants while saving energy. The research used parametric design and Genetic Algorithm (GA) to achieve this. Four recognized performance indicators, Energy Use Intensity (EUI), Useful Daylight Illuminance (UDI), Daylight Factor (DF), and Daylight Autonomy (DA), were used as the evaluation indexes for the research. The tests took place in six east–west-oriented classrooms at Shanghai University, China. The methodology was based on four steps: (1) parametric 3D modeling by Rhino and Grasshopper; (2) using building performance simulation tools; (3) running algorithm optimization; (4) outputting the useful results. The results proved that the methodology worked successfully in reducing energy consumption: optimized classrooms could be reduced by 7.5~14.5%, and classrooms with east directions were generally 4.8~8.3% more efficient than west-facing ones. The indoor lighting environment was also significantly improved, being slightly better than north–south-oriented classrooms in terms of the UDI index (60~75%) and inferior (but still high) in terms of the DF (4.0~7.0%) and DA (60~80%) indexes. The conclusion can help save design time in the early design process of teaching spaces. [ABSTRACT FROM AUTHOR]