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Abstract Genes involved in drug absorption, distribution, metabolism, and excretion (ADME) are named ADME genes. However, the comprehensive role of ADME genes in kidney renal clear cell carcinoma (KIRC) remains unclear. Using the clinical and gene expression data of KIRC patients downloaded from The Cancer Genome Atlas (TCGA), ArrayExpress, and the Gene Expression Omnibus (GEO) databases, we cluster patients into two patterns, and the population with a relatively poor prognosis demonstrated higher level of immunosuppressive cell infiltration and higher proportion of glycolytic subtypes. Then, 17 ADME genes combination identified through the least absolute shrinkage and selection operator algorithm (LASSO, 1000 times) was utilized to calculate the ADME score. The ADME score was found to be an independent predictor of prognosis in KIRC and to be tightly associated with the infiltration level of immune cells, metabolic properties, tumor-related signaling pathways, genetic variation, and responses to chemotherapeutics. Our work revealed the characteristics of ADME in KIRC. Assessing the ADME profiles of individual patients can deepen our comprehension of tumor microenvironment (TME) features in KIRC and can aid in developing more personalized and effective therapeutic strategies.

Abstract Background There is an association between migraine and dementia, however, their causal relationship remains unclear. This study employed bidirectional two-sample Mendelian randomization (MR) to investigate the potential causal relationship between migraine and dementia and its subtypes: Alzheimer’s disease (AD), vascular dementia (VaD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods Summary-level statistics data were obtained from publicly available genome-wide association studies (GWAS) for both migraine and five types of dementia. Single nucleotide polymorphisms (SNPs) associated with migraine and each dementia subtype were selected. MR analysis was conducted using inverse variance weighting (IVW) and weighted median (WM) methods. Sensitivity analyses included Cochran’s Q test, MR pleiotropy residual sum and outlier (MR-PRESSO) analysis, the intercept of MR-Egger, and leave-one-out analysis. Results Migraine showed a significant causal relationship with AD and VaD, whereas no causal relationship was observed with all-cause dementia, FTD, or DLB. Migraine may be a potential risk factor for AD (odds ratio [OR]: 1.09; 95% confidence interval [CI]: 0.02–0.14; P = 0.007), while VaD may be a potential risk factor for migraine (OR: 1.04; 95% CI: 0.02–0.06; P = 7.760E-5). Sensitivity analyses demonstrated the robustness of our findings. Conclusion Our study suggest that migraine may have potential causal relationships with AD and VaD. Migraine may be a risk factor for AD, and VaD may be a risk factor for migraine. Our study contributes to unraveling the comprehensive genetic associations between migraine and various types of dementia, and our findings will enhance the academic understanding of the comorbidity between migraine and dementia.

Abstract Owing to its versatile roles in almost all aspects of plants, FERONIA (FER), a receptor-like kinase of the Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) subfamily, has received extensive research interests during the past decades. Accumulating evidence has been emerged that FER homologs in horticultural crops also play crucial roles in reproductive biology and responses to environmental stimuli (abiotic and biotic stress factors). Here, we provide a review for the latest advances in the studies on FER homologs in modulating stress responses in horticultural crops, and further analyze the underlying mechanisms maintained by FER. Moreover, we also envisage the missing links in current work and provide a perspective for future studies on this star protein.

Abstract Introduction As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. Method In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. Results We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. Conclusion Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA. Graphical Abstract

Abstract Objective To retrospectively analyze the risk factors for postoperative delirium (POD) after orthopedic surgery in elderly patients and establish an individualized nomogram to predict the risk of POD. Methods The data of 1011 patients who underwent orthopedic surgery from January 2019 to January 2022 were retrospectively analyzed. Univariate and multivariate logistic analyses were used to screen for independent risk factors. Stepwise regression was conducted to screen risk factors to construct a nomogram to predict the risk of POD after orthopedic surgery in elderly individuals, and nomogram validation analyses were performed. Results The logistic regression results showed that age (≥ 75 years old vs.

Background: Since the inception of the term “Biomimetics” in 1991, the concept of utilizing natural solutions or deriving inspiration from nature to address contemporary engineering challenges has gained significant attention within the scientific community. Organisms, in order to thrive in harsh environments, have evolved a wide range of micro/nanostructured surfaces, which serve as a rich source of inspiration for the development of artificial micro/nano-structured surfaces. These natural adaptations provide valuable insights and novel pathways for fabricating such surfaces. Aim: To conclude recent advances in micro/nano-structured surfaces from four aspects: biomimetic micro-structured surfaces of plants and animals, properties and applications of biomimetic surfaces, methods of preparations, and their limitation. Key Scientific Concepts:: Artificial micro/nano-structured surfaces inspired by animals and plants are classified and demonstrated according to their living environment. The performances, principles and preparation techniques of natural superhydrophobic surfaces, slippery liquid-infused porous surfaces (SLIPS), anisotropic surfaces, etc. are described in detail. Moreover, the pros and cons of each preparation measures are compared and the challenges developing large-scale, cost-effective surface microstructure preparation processes are pointed out. In the end, the development trends of artificial micro/nano-structured surface are forecasted.

Abstract Electroencephalography (EEG) microstate analysis is a neuroimaging analytical method that has received considerable attention in recent years and is widely used for analysing EEG signals. EEG is easily influenced by internal and external factors, which can affect the repeatability and stability of EEG microstate analysis. However, there have been few reports and publicly available datasets on the repeatability of EEG microstate analysis. In the current study, a 39-year-old healthy male underwent a total of 60 simultaneous electroencephalography and electrocardiogram measurements over a period of three months. After the EEG recording was completed, magnetic resonance imaging (MRI) was also conducted. To date, this EEG dataset has the highest number of repeated measurements for one individual. The dataset can be used to assess the stability and repeatability of EEG microstates and other analytical methods, to decode resting EEG states among subjects with open eyes, and to explore the stability and repeatability of cortical spatiotemporal dynamics through source analysis with individual MRI.

ABSTRACT: An attenuated vaccine against the Mycoplasma gallisepticum ts-11 strain has become an effective prevention and control method against MG infection. However, the ts-11 strain is usually difficult to distinguish from the non-ts-11 strain (including field isolates and other vaccine strains (F and 6/85)). Therefore, it is critical to establish a rapid and effective method to distinguish ts-11 strains from non-ts-11 strains. The gene sequences of the ts-11 strain (CP044225.1) and the non-ts-11 strain (including the wild-type (CP006916.3), 6/85 (CP044224.1), and F strains (NC_017503.1) were used to construct a conserved region containing a single point mutation in the potC gene in the ts-11 strain, after which a primer–probe combination method was designed. The primer–probe method was able to accurately and efficiently identify the ts-11 and non-ts-11 strains with minimum detection limits of 2.43 copies/μL and 1.65 copies/μL, respectively. Moreover, it could simultaneously distinguish the ts-11 strain from a non-ts-11 strain, and amplifications of avian influenza virus, infectious bronchitis virus, Newcastle disease virus, fowl adenovirus, infectious laryngotracheitis virus, infectious bursal disease virus, chicken anemia virus, Marek's disease virus, Mycoplasma synoviae, and Ornithobacter rhinotracheale were negative. The detection of clinical samples revealed that the established dual-probe fluorescence quantitative PCR method could be used to screen for mixed and single infections of the ts-11 strain and non-ts-11 strains effectively, with lower variation coefficients for intra- and interbatch repetition. The established cycleave dual-probe fluorescence quantitative PCR method showed good specificity, sensitivity, and repeatability and provides powerful technical support for the rapid and efficient differential diagnosis of the MG ts-11 strain from non-ts-11 strains.

Unsafe hoisting operations have been consistently associated with numerous safety incidents involving tower cranes. Currently, the predominant measures to mitigate these operations center around comprehensive training and education, emphasizing standardized protocols prior to hoisting activities. Despite concerted efforts in this direction, a conspicuous research gap persists in early-warning mechanisms during the construction phase. This paper aims to address this gap by proposing an innovative early-warning methodology, inspired by the principles of digital twin and knowledge graph. We firstly introduce a digital twin framework designed to mirror the real-time operational status of the tower crane. This framework enables the immediate detection of deviations or infractions as they occur. Subsequently, we develop a knowledge graph capable of promptly identifying unsafe hoisting operations by leveraging real-time data obtained from the digital twin. To validate the efficacy of our proposed methodology, we construct a scaled-down replica of a tower crane and establish a tailored digital twin system. The findings of a series of experimental trials prominently underscore the system's capability to generate timely alerts in response to unsafe hoisting operations while maintaining an impressively low rate of false alarms.

The fabrication of highly efficient yet stable noble-metal-free bifunctional electrocatalysts that can simultaneously catalyse both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) remains challenging. Herein, we employ the heterostructure coupling strategy, showcasing an aerosol-assisted chemical vapour deposition (AACVD) aided synthetic approach for the in-situ growth of cobalt molybdenum sulphide nanocomposites on carbon paper (CoMoS@CP) as a bifunctional electrocatalyst. The AACVD allows the rational incorporation of Co in the Mo–S binary structure, which modulates the morphology of CoMoS@CP, resulting in enhanced HER activity (ŋ10 = 171 mV in acidic and ŋ10 = 177 mV in alkaline conditions). Furthermore, the CoS2 species in the CoMoS@CP ternary structure extends the OER capability, yielding an ŋ100 of 455 mV in 1 M KOH. Lastly, we found that the synergistic effect of the Co–Mo–S interface elevates the bifunctional performance beyond binary counterparts, achieving a low cell voltage (1.70 V at 10 mA cm−2) in overall water splitting test and outstanding catalytic stability (∼90 % performance retention after 50-/30-h continuous operation at 10 and 100 mA cm−2, respectively). This work has opened up a new methodology for the controllable synthesis of self-supported transition metal-based electrocatalysts for applications in overall water splitting.

Abstract Targeting cancer‐specific metabolic processes is a promising therapeutic strategy. Here, this work uses a compound library that directly inhibits metabolic enzymes to screen the potential metabolic targets in lung adenocarcinoma (LUAD). SHIN1, the specific inhibitor of serine hydroxymethyltransferase 1/2 (SHMT1/2), has a highly specific inhibitory effect on LUAD cells, and this effect depends mainly on the overexpression of SHMT2. This work clarifies that mitogen‐activated protein kinase 1 (MAPK1)‐mediated phosphorylation at Ser90 is the key mechanism underlying SHMT2 upregulation in LUAD and that this phosphorylation stabilizes SHMT2 by reducing STIP1 homology and U‐box containing protein 1 (STUB1)‐mediated ubiquitination and degradation. SHMT2‐Ser90 dephosphorylation decreases S‐adenosylmethionine levels in LUAD cells, resulting in reduced N6‐methyladenosine (m6A) levels in global RNAs without affecting total protein or DNA methylation. Methylated RNA immunoprecipitation sequencing (MeRIP‐Seq) and RNA sequencing (RNA‐Seq) analyses further demonstrate that SHMT2‐Ser90 dephosphorylation accelerates the RNA degradation of oncogenic genes by reducing m6A modification, leading to the inhibition of tumorigenesis. Overall, this study elucidates a new regulatory mechanism of SHMT2 during oncogenesis and provides a theoretical basis for targeting SHMT2 as a therapeutic target in LUAD.

AbstractAs an autoimmune disease of the colon, the incidence of ulcerative colitis (UC) remains high. Carbon dots (CDs), a new type of nanomaterials, display excellent biological activity and are expected to inspire a new treatment for UC. A green method was used to carbonise rhei radix rhizoma (RRR) and extract CDs to study their anti-ulcer activity. The RRR-based carbon dots (RRR-CDs) were characterised by electron microscopy, optical techniques, and other techniques. The results indicated RRR-CDs have abundant chemical groups, excellent solubility and tiny size (1.374 nm–4.533 nm), which may be conducive to the exertion of inherent activity. Using a classic dextran sodium sulphate (DSS)-induced UC mouse model, for the first time, it was demonstrated RRR-CDs have significant anti-ulcerative activity in improving DAI score (from 2.8 to 1.6), colon length (4.15 to 6.08), and histopathology in mice. The underlying mechanisms of anti-ulcerative activity may be related to haemostatic, antioxidant, and anti-inflammatory activities to protect the mucosal barrier. RRR-CDs have symptomatic and potential mechanisms of treatment and are expected to become a candidate drug for the treatment of UC. This not only further expands the basis for the biological activity of CDs, but provides a potential treatment plan for solving thorny diseases in clinical practice.

Abstract Background To accelerate the clinical translation of tumor‐infiltrating lymphocytes (TILs) biomarkers for guiding chemotherapy de‐escalation in early‐stage triple‐negative breast cancer (TNBC), cost‐effectiveness evidence is essential but has not been investigated. We intend to evaluate the cost‐effectiveness of using TILs to guiding chemotherapy de‐escalation in patients with early‐stage TNBC from the perspective of the Chinese health service system. Methods The hybrid decision‐tree‐Markov model was designed to compare the cost‐effectiveness of cytotoxic chemotherapy guided by whether TILs assay was performed in 50‐year‐old female patients with early‐stage TNBC over a lifetime horizon. In Strategy (1), if TILs testing was performed, patients with TILs values exceeding 30% could be spared from chemotherapy. In Strategy (2), where no TILs testing was performed, all patients were administered chemotherapy following China's clinical practices. Based on the algorithm built by Guyot, the individual patient data were reconstructed from the published Kaplan–Meier curves, and the survival functions were calculated by parametric methods. Cost estimates were valued in Chinese yuan (as per rates in 2022). Results In 50‐year‐old female patients with early‐stage TNBC, Strategy (1), which employs TILs testing to guide cytotoxic chemotherapy yielded an additional 0.47 quality‐adjusted life years (QALYs) and saved 40,976 yuan, with an incremental cost‐effectiveness ratio (ICER) of −87,182.98 yuan per QALY gained compared with Strategy (2). This indicates that compared with Strategy (2), Strategy (1) is the dominant scheme. The results were sensitive to utility parameters, discount rates, and treatment costs after relapse. At a willingness‐to‐pay threshold of 85,700 yuan (based on GDP per capita) per QALY, the probability of TILs being cost‐effective was almost 100%. Conclusions The application of biomarkers (TILs) to guide decisions for chemotherapy de‐escalation is a cost‐effective strategy for early‐stage TNBC patients and deserves to be widely promoted in clinical practice.

In this study, indigo carmine (IC)-calcium carbonate lakes with different crystalline forms of calcium carbonate were prepared through co-precipitation methods, and the properties of these lakes and their formation mechanisms were investigated. The results showed that amorphous calcium carbonate (ACC) exhibited the smallest particle size and the largest specific surface area, resulting in the highest adsorption efficiency. Vaterite, calcite, and aragonite followed after ACC in decreasing order of adsorption efficiency. Kinetic analysis and isothermal analysis revealed the occurrence of chemisorption and multilayer adsorption during formation of the lakes. The FTIR and Raman spectra suggested participation of sulfonic acid groups in chemisorption. Appearance of IC significantly altered TGA curves by changing weight loss rate before decomposition of calcium carbonate. EDS analysis revealed the adsorption of IC predominantly happened on the surface of calcium carbonate particles rather than the interior.

This study aimed to elucidate responses of the bacterial structure and diversity of the rhizosphere in flowering broomcorn millet after rehydration following drought stress. In this study, the broomcorn millet varieties ‘Hequ red millet’ (A1) and ‘Yanshu No.10′ (A2), known for their different drought tolerance levels, were selected as experimental materials. The plants were subjected to rehydration after drought stress at the flowering stage, while normal watering (A1CK and A2CK) served as the control. Soil samples were collected at 10 days (A11, A21, A1CK1, and A2CK1) and 20 days (A12, A22, A1CK2, and A2CK2) after rehydration. High-throughput sequencing technology was employed to investigate the variations in bacterial community structure, diversity, and metabolic functions in the rhizosphere of the broomcorn millet at different time points following rehydration. The findings indicated that the operational taxonomic units (OTUs) of bacteria in the rhizosphere of broomcorn millet were notably influenced by the duration of treatment, with a significant decrease in OTUs observed after 20 days of rehydration. However, bacterial Alpha diversity was not significantly impacted by rehydration following drought stress. The bacterial community in the rhizosphere of broomcorn millet was mainly composed of Actinobacteria and Proteobacteria. After rewatering for 10 to 20 days after drought stress, the abundance of Sphingomonas and Aeromicrobium in the rhizosphere soil of the two varieties of broomcorn millet decreased gradually. Compared with Yanshu No.10, the abundance of Pseudarthrobacter in the rhizosphere of Hequ red millet gradually increased. A Beta diversity analysis revealed variations in the dissimilarities of the bacterial community which corresponded to different rehydration durations. The relative abundance of bacterial metabolic functions in the rhizosphere of broomcorn millet was lower after 20 days of rehydration, compared to measurements after 10 days of rehydration. This observation might be attributed to the exchange of materials between broomcorn millet and microorganisms during the initial rehydration stage to repair the effects of drought, as well as to the enrichment of numerous microorganisms to sustain the stability of the community structure. This study helps to comprehend the alterations to the bacterial structure and diversity in the rhizosphere of broomcorn millet following drought stress and rehydration. It sheds light on the growth status of broomcorn millet and its rhizosphere microorganisms under real environmental influences, thereby enhancing research on the drought tolerance mechanisms of broomcorn millet.

In order to clarify the effect of different fertilizers on foxtail millet quality under low nitrogen conditions, we used JGNo.21 and LZGNo.2 as experimental materials and set up five treatments, including non-fertilization, nitrogen, phosphorus, compound, and organic fertilizers, to study the regulation of different fertilizer types on agronomic traits, nutrient fractions, and pasting characteristics of foxtail millet under low nitrogen conditions. Compared with the control, all of the fertilizers improved the agronomic traits of JGNo.21 to a certain extent. Nitrogen and compound fertilizer treatments reduced the starch content of JGNo.21; the starch content was reduced by 0.55% and 0.07% under nitrogen and compound fertilizers treatments. Phosphorus and organic fertilizers increased starch content, and starch content increased by 0.50% and 0.56% under phosphorus and organic fertilizer treatments. The effect of each fertilizer treatment on protein content was completely opposite to that of starch; different fertilizer treatments reduced the fat content of JGNo.21 and increased the fiber content. Among them, nitrogen and phosphorus fertilizers increased the yellow pigment content; the yellow pigment content increased by 1.21% and 2.64% under nitrogen and phosphorus fertilizer treatments. Organic and compound fertilizers reduced the content of yellow pigment; the yellow pigment content was reduced by 3.36% and 2.79% under organic and compound fertilizer treatments. Nitrogen and organic fertilizers increased the fat content of LZGNo.2; the fat content increased by 2.62% and 1.98% under nitrogen, organic fertilizer treatment. Compound and phosphorus fertilizer decreased the fat content; the fat content decreased by 2.16% and 2.90% under compound and phosphorus fertilizer treatment. Different fertilizer treatments reduced the cellulose and yellow pigment content of LZGNo.2. The content of essential, non-essential, and total amino acids of JGNo.21 was increased under compound and nitrogen fertilizer treatments and decreased under organic and phosphorus fertilizer treatments. The content of essential, non-essential, and total amino acids of LZGNo.2 was significantly higher under compound, nitrogen, and organic fertilizer treatments compared with control and significantly decreased under phosphorus fertilizer treatments. Nitrogen and compound fertilizer treatments significantly reduced the values of peak viscosity, trough viscosity, breakdown viscosity, final viscosity, setback viscosity, and pasting time of each index of JGNo.21; phosphorus and organic fertilizer treatments improved the values of each index. In contrast, the pasting viscosity of LZGNo.2 increased under phosphorus fertilizer treatment and decreased under nitrogen fertilizer treatment. Reasonable fertilization can improve the quality of foxtail millet, which provides a scientific theoretical basis for improving the quality of foxtail millet.