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Abstract Whole-genome duplication (WGD) in plants triggers profound morphological and physiological changes, with DNA modification being a key epigenetic factor that helps neo-polyploids overcome challenges and gain adaptive advantages. Tetraploids were previously mined from diploid citrus seedlings, showing enhanced environmental adaptability and potential as rootstocks. These tetraploids exhibited increased leaf and cell wall thickness compared to their diploid counterparts. To explore the impact of WGD, transcriptomic and whole-genome bisulfite sequencing (WGBS) were conducted on two pairs of citrus tetraploids and their diploid controls, revealing significant molecular changes. Notably, tetraploid citrus displayed lower CG methylation levels in gene and transposable element (TE) bodies relative to diploids. Differentially methylated genes (DMGs) between tetraploids and diploids were primarily associated with immune stress, organ development, metabolic pathways, and secondary metabolism. In Trifoliate orange (Poncirus trifoliata L. Raf.) and Ziyang Xiangcheng (Citrus junos Sieb. ex Tanaka), only 150 and 58 differentially expressed genes (DEGs) were identified, respectively, with enrichment in critical cellular processes such as cell wall synthesis, plastid development, and pathways modulating chloroplasts and plasma membranes. A total of 70 genes showed both differential methylation and expression, including ACN1, Nac036, and ASMT1, which are involved in stomatal development, leaf morphology, and melatonin synthesis, respectively, offering insight into the regulatory mechanisms of phenotype alterations after polyploidization. These findings reveal the epigenetic modifications in polyploid citrus and highlight the role of polyploidization-induced methylation in driving phenotypic changes.

Abstract Purpose The task faced by surgeons becomes significantly more challenging when they encounter lower extremity bone defects due to a variety of causes requiring lengthening. The most discussed and successful approach is the Illizarov technique, or lengthening over a nail (LON):distraction osteogenesis is also widely performed with monoliteral external fixators and intramedullarylengthening nails have increasingly been used in the last decade. Methods The data were collected from PubMed, Cochrane Library, Embase, and the Web of Science for all available studies comparing the outcomes of Ilizarov technique alone and LON technique (from January 1, 1997, to November 30, 2023). The outcomes of interest encompassed the external fixation index (EFI) (month/cm), mean duration of follow-up (MFT) (month), length gained (LG) (cm), consolidation index (CIx) (month/cm), and bone healing index (BHI) (month/cm).Complications include pin tract infection rate (PTI), axial deviation rate (AD), occurrence of intramedullary infection (II), delayed consolidation rate (DC), as well as data categorized into three levels of problems, obstacles, and sequelae based on the severity of complications.Two reviewers independently assessed each study for quality and extracted data. The case–control or respective cohort studies were evaluated using the Newcastle–Ottawa scale (NOS) to determine their techniqueological rigor.The Cochrane Collaboration’s risk assessment tool was employed to perform quality evaluations for randomized controlled trials. Results This review included thirteen studies comprising a total of 629 patients.The external fixation index (month/cm) was significantly smaller in the LON technique compared to the Ilizarov technique alone [Mean Difference(MD) = -29.59, 95% CI -39.68–-19.49, P

Abstract Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a significant global health challenge, with limited therapeutic options for patients with KRAS-mutated tumors. Herein, a copper-based metal-organic framework (Cu-MOF) was applied as a novel cuproptosis-mediated nanoplatform for lung cancer therapy. Cu-MOF would disassemble and liberate copper ions under the acidic microenvironment of lysosomes of cancer cells, initiating a cascade of cellular events. The released copper ions catalyzes the Fenton reaction, generating hydroxyl radicals that induce oxidative damage, leading to cytoskeletal disruption and activation of caspase-3, ultimately triggering apoptosis. Simultaneously, with the mediation of the key regulatory factor FDX1, we found that the copper ions binding to the mitochondrial protein DLAT could result in the loss of iron-sulfur cluster proteins and aggregation of lipoylated proteins, which culminated in proteotoxic stress-induced cuproptosis. The pronounced anti-tumor effects of Cu-MOF with apoptosis and cuproptosis were confirmed both in vitro and in vivo experiments. Such dual induction of apoptosis and cuproptosis by Cu-MOF presents a promising therapeutic strategy for NSCLC, particularly for KRAS-mutated tumors, and expands potential applications of Cu-based nanomateirals for other cancers.

Abstract We retrospectively investigated the correlation between the spinal cord compression angle and increased signal intensity (ISI) in 118 patients with ossification of the posterior longitudinal ligament (OPLL). Patients were analyzed based on the presence and shape of ISI on magnetic resonance imaging. Various indicators, including the spinal cord compression angle, were measured through imaging examinations. Spearman’s correlation and logistic regression were used for analyses. Significant positive correlations were observed between the ISI grade and the spinal cord compression angle, maximum spinal canal occupying rate, cervical range of motion, and segmental range of motion. The spinal cord compression ratio and Japanese Orthopaedic Association (JOA) score were negatively correlated with the ISI grade. Regression analysis revealed that the spinal cord compression angle and JOA scores were independent factors that significantly influenced ISI grade. The odds ratio of ISI was 3.858 (95% confidence interval: 0.974–15.278) when comparing the highest and lowest quartiles of the spinal cord compression angle. Patients with a spinal cord compression angle > 35° had more severe imaging manifestations. Thus, a spinal cord compression angle > 35° could serve as a significant indicator of OPLL severity, and greater attention should be focused on treating patients with larger spinal cord compression angles.

Abstract Background Rice is one of the major staples that feeds about one half of the global populations, and it is important to identify the genetic loci for the traits related to yield improvement. Lodging will cause severe yield loss when it happens, and stem diameter has been characterized as an important trait for lodging resistance. However, most QTLs for stem diameter have not been finely dissected due to their sensitivity to environmental fluctuation. Result In this study, we performed QTL analysis for stem diameter using populations derived from Nipponbare (NIP) and strong culm variety YYP1, and confirmed the single and combined effect of three major QTLs by recombinant inbred lines (RILs). Based on the QTL location, we found that qWS5 is a novel QTL not well characterized before. To finely dissect the novel locus, several recombinant heterogeneous inbred families (HIFs) were selected from the RILs for linkage analysis and their derived nearly isogenic lines (NILs) were subjected to detailed trait investigation throughout different years. The HIF-NILs strategy confined the QTL to about 380 kb region supported by repeated genotype and phenotype data, and it lays the foundation for QTL cloning in the future. In addition, introgression of the QTL to an elite japonica variety SD785 was performed by successive backcrossing, and it confirmed the value of qWS5 in increasing stem diameter and other agronomic traits during rice breeding. Conclusions We prove that qWS5 is a novel QTL with relatively stable effect for stem diameter and the QTL can be finely mapped to small region by the HIF-NILs strategy. The result will facilitate the improvement of rice lodging resistance by molecular marker assisted selection breeding.

Resveratrol (RES), a type of stilbenoid, is known for its significant role in enhancing meat quality by virtue of activating SIRT1. Against this backdrop, this study explored the impact of resveratrol on various parameters influencing flesh quality in adult grass carp. Over a span of 9 weeks, adult grass carp were fed diets with five different levels of RES (0, 40, 80, 160 and 320 mg/kg). Our findings demonstrated that resveratrol supplementation had no adverse effects on the growth performance of adult grass carp. Notably, adding the right amount of resveratrol to the diets caused the protein and amino acid levels, pH24 h, and shear force of grass carp muscle to rise. Additionally, it led to a reduction in cooking loss and lactic acid content. Moreover, Addition of appropriate levels of resveratrol to the feed promoted myofiber hyperplasia in adult grass carp, which may be achieved by stimulating adult myoblast proliferation and differentiation. Subsequent studies have found that appropriate levels of resveratrol inhibit endoplasmic reticulum stress (ERS), which promotes muscle fiber development. Additionally, resveratrol was found to lead to an increase in unsaturated fatty acid (UFA) content in grass carp muscle. This alteration in fatty acid composition could be attributed to changes in fatty acid transport, synthesis, and catabolism. According to muscle protein carbonyl level, muscle protein content and frequency of muscle fibers smaller than 20 μm, the optimum resveratrol supplementations of grass carp were 178.33, 198.33 and 226.67 mg/kg.

Fair-faced concrete is green concrete that is directly decorated by its texture. For a more stunning visual impact, pigmented fair-faced concrete with more colors on the surface is prepared. However, the effects of different pigments and service environments on pigmented fair-faced concrete need to be explored. Therefore, four iron oxide inorganic pigments were employed to prepare pigmented fair-faced concrete, and the changes in its fresh properties and mechanical properties were studied through slump, slump flow, and compressive strength tests. Meanwhile, camera analysis and colorimetry were utilized to evaluate the changes in its apparent properties and color stability under four different distinct service environments in this experiment. Results indicate that incorporating pigments reduces both the slump and slump flow of the fresh mixture, and its fresh properties gradually decrease as the pigment content increases. The slump and slump flow of concrete with 6 % iron oxide yellow (IOY) were 30.00 % and 44.00 % lower than the control. Adding IOY and iron oxide red (IOR) can improve the 7-d and 28-d compressive strength of concretes. The 28-d compressive strength of concrete with 2 %-6 % IOY increased by 7.72 %, 11.78 % and 15.09 % over the control. Meanwhile, the surface pore area of concrete with IOY is the lowest and that of concrete containing 2 % IOY is 3.97 cm2/m2. Additionally, the color stability of concrete performs best in water immersion environments and worst in natural environments. It is noteworthy that the concrete added with IOY exhibits excellent color stability under all four service environments. This study aims to evaluate the effects of different pigments on concrete properties and investigate the color stability of four types of concrete under diverse service conditions. The findings will promote the application of pigmented fair-faced concrete in construction and provide technical insights for future research.

Hepatopancreatic necrosis syndrome (HPNS) has recently become a major epidemic in shrimp farms, resulting in enormous economic loss. However, its etiology remains controversial. Diseased Litopenaeus vannamei (L. vannamei), collected from shrimp farms, were analyzed for pathological diagnosis, bacterial isolation, and identification. After that, the effects of the three plant extracts on the primary pathogens of HPNS were analyzed in vitro and in vivo. The results revealed that the primary pathogens of HPNS were Vibrio parahaemolyticus (V. parahaemolyticus) with ToxR and TLH gene, V. cholerae with ompW gene, and Proteus vulgaris (P. vulgaris) with rpoA gene. These three bacterial strains exhibited extensive antibiotic resistance. The “Chaiyinhugan” mixture, the “Sanhuanglian” mixture, and the Polygonum hydropiper flavonoid extract inhibited the growth of all three dominant strains. Additionally, the three plant extracts reduced HPNS shrimp mortality, improved shrimp immunity, and attenuated hepatopancreatic pathology. Among them, the Polygonum hydropiper flavonoid extract displayed better effects and could be applied to prevent and treat HPNS in producing and breeding L. vannamei. In conclusion, V. parahaemolyticus, V. cholerae, and P. vulgaris are the major pathogens causing HPNS. Herbal extracts such as Polygonum hydropiper flavonoid extract can be applied to prevent and treat HPNS.

Abstract Objective To develop a nomogram based on tumor and peritumoral edema (PE) radiomics features extracted from preoperative multiparameter MRI for predicting brain invasion (BI) in atypical meningioma (AM). Methods In this retrospective study, according to the 2021 WHO classification criteria, a total of 469 patients with pathologically confirmed AM from three medical centres were enrolled and divided into training (n = 273), internal validation (n = 117) and external validation (n = 79) cohorts. BI was diagnosed based on the histopathological examination. Preoperative contrast-enhanced T1-weighted MR images (T1C) and T2-weighted MR images (T2) for extracting meningioma features and T2-fluid attenuated inversion recovery (FLAIR) sequences for extracting meningioma and PE features were obtained. The multiple logistic regression was applied to develop separate multiparameter radiomics models for comparison. A nomogram was developed by combining radiomics features and clinical risk factors, and the clinical usefulness of the nomogram was verified using decision curve analysis. Results Among the clinical factors, PE volume and PE/tumor volume ratio are the risk of BI in AM. The combined nomogram based on multiparameter MRI radiomics features of meningioma and PE and clinical indicators achieved the best performance in predicting BI in AM, with area under the curve values of 0.862 (95% CI, 0.819–0.905) in the training cohort, 0.834 (95% CI, 0.780–0.908) in the internal validation cohort and 0.867 (95% CI, 0.785–0.950) in the external validation cohort, respectively. Conclusions The nomogram based on tumor and PE radiomics features extracted from preoperative multiparameter MRI and clinical factors can predict the risk of BI in patients with AM.

Abstract Chloroplast genomes, pivotal for understanding plant evolution, remain unexplored in Rutaceae, a family with key perennial crops like citrus. Leveraging next-generation sequencing data from 509 Rutaceae accessions across 15 species, we conducted a de novo assembly of 343 chloroplast genomes, unveiling a chloroplast variation map highlighting the heterogeneous evolution rates across genome regions. Notably, differences in chloroplast genome size primarily originate from large single-copy and small single-copy regions. Structural variants predominantly occurred in the single-copy region, with two insertions located at the single-copy and inverted repeat region boundary. Phylogenetic analysis, principal component analysis, and population genetic statistics confirmed the cohesive clustering of different Citrus species, reflecting evolutionary dynamics in Citrus diversification. Furthermore, a close chloroplast genetic affinity was revealed among Atalantia (previously regarded as primitive citrus), Clausena, and Murraya. Zanthoxylum formed a distinct group with heightened genetic diversity. Through expanding our analysis to include 34 published chloroplast genomes, we explored chloroplast gene selection, revealing divergent evolutionary trends in photosynthetic pathways. While Photosystem I and Photosystem II exhibited robust negative selection, indicating stability, the Nicotinamide adenine dinucleotide (NADH) dehydrogenase pathway demonstrated rapid evolution, which was indicative of environmental adaptation. Finally, we discussed the effects of gene length and GC content on chloroplast gene evolution. In conclusion, our study reveals the genetic characterization of chloroplast genomes during Rutaceae diversification, providing insights into the evolutionary history of this family.

Abstract Objectives Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. Methods Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer–specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. Results In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157–5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). Conclusions Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Abstract Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and enpp1 deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.

IntroductionTriple-negative breast cancer (TNBC) is the most malignant type of breast cancer, and its prognosis is still the worst. It is necessary to constantly explore the pathogenesis and effective therapeutic targets of TNBC. Formononetin is an active ingredient with anti-tumor effects that we screened earlier. The main purpose of this study is to elucidate mechanism of the inhibitory effect of Formononetin on TNBC.MethodsWe conducted experiments through both in vivo and in vitro methodologies. The in vivo experiments utilized a nude mice xenotransplantation model, while the in vitro investigations employed two breast cancer cell lines, MDA-MB-231 and MDA-MB-468. Concurrently, ferroptosis associated proteins, lipid peroxide levels, and proteins related to the rapamycin complex 1 were analyzed in both experimental settings.ResultsIn our study, Formononetin exhibits significant inhibitory effects on the proliferation of triple TNBC, both in vivo and in vitro. Moreover, it elicits an increase in lipid peroxide levels, downregulates the expression of ferroptosis-associated proteins GPX4 and xCT, and induces ferroptosis in breast cancer cells. Concurrently, Formononetin impedes the formation of the mammalian target of rapamycin complex 1 (mTORC1) and suppresses the expression of downstream Sterol regulatory element-binding protein 1(SREBP1). The utilization of breast cancer cells with SREBP1 overexpression or knockout demonstrates that Formononetin induces ferroptosis by modulating the mTORC1-SREBP1 signaling axis.DiscussionIn conclusion, this study provides evidence that Formononetin exerts an anti-proliferative effect on triple-negative breast cancer by inducing ferroptosis. Moreover, the mTORC1-SREBP1 signal axis is identified as the primary mechanism through which formononetin exerts its therapeutic effects. These findings suggest that formononetin holds promise as a potential targeted drug for clinical treatment of TNBC.

The sharing of pathological data is highly important in various applications, such as remote diagnosis, graded diagnosis, illness treatment, and specialist system development. However, ensuring reliable, secure, privacy-preserving, and efficient sharing of pathological data poses significant challenges. This paper presents a novel solution that leverages blockchain technology to ensure reliability in pathological data sharing. Additionally, it employs conditional proxy re-encryption (C-PRE) and public key encryption with equality test technology to control the scope and preserve the privacy of shared data. To assess the practicality of our solution, we implemented a prototype system using Hyperledger Fabric and conducted evaluations with various metrics. We also compared the solution with relevant schemes. The results demonstrate that the proposed solution effectively meets the requirements for pathological data sharing and is practical in production scenarios.

Objective: To validate the predictive power of newly developed magnetic resonance (MR) morphological and clinicopathological risk models in predicting low anterior resection syndrome (LARS) 6 months after anterior resection of middle and low rectal cancer (MLRC). Methods: From May 2018 to January 2021, 236 patients with MLRC admitted to two hospitals (internal and external validation) were included. MR images, clinicopathological data, and LARS scores (LARSS) were collected. Tumor morphology data included longitudinal involvement length, maximum tumor diameter, proportion of tumor to circumference of the intestinal wall, tumor mesorectal infiltration depth, circumferential margin status, and distance between the tumor and anal margins. Pelvic measurements included anorectal angle, mesenterial volume (MRV), and pelvic volume. Univariate and multivariate logistic regression was used to obtain independent risk factors of LARS after anterior resection Then, the prediction model was constructed, expressed as a nomogram, and its internal and external validity was assessed using receiver operating characteristic curves. Results: The uni- and multivariate analysis revealed distance between the tumor and anal margins, MRV, pelvic volume, and body weight as significant independent risk factors for predicting LARS. From the nomogram, the area under the curve (AUC), sensitivity, and specificity were 0.835, 75.0 %, and 80.4 %, respectively. The AUC, sensitivity, and specificity in the external validation group were 0.874, 83.3 %, and 91.7 %, respectively. Conclusion: This study shows that MR imaging and clinicopathology presented by a nomogram can strongly predict LARSS, which can then individually predict LARS 6 months after anterior resection in patients with MLRC and facilitate clinical decision-making. Clinical relevance statement: We believe that our study makes a significant contribution to the literature. This method of predicting postoperative anorectal function by preoperative measurement of MRV provides a new tool for clinicians to study LARS.

The ceiling radiant cooling panel (CRCP) with air layer based on serpentine shaped flow channel was proposed to solve condensation risk, however, the performance of CRCP was weakened owing to the serpentine shaped flow channel with high-pressure drop. Hence, the parallel shaped type CRCP with air layer was proposed in this work. The effects of both structural and operational parameters on surface temperature distribution and the cooling performance were evaluated. Results showed the cooling capacity was increased with the increase of chilled water velocity and tube diameter, while decreased with the increase in the air layer thickness, cooling panel thickness, tube spacing and chilled water temperature. Considering that condensation risk, it is recommended to set tube spacing, tube diameter, air layer thickness and cooling panel thickness above 125 mm, 10 mm, 12 mm and 1.5 mm, respectively. In the structure parameters of the CRCP, the cooling panel thickness exhibits the maximum impact on cooling capacity with relational grade of 0.87, and the air layer thickness has the maximum impact on surface temperature uniformity with relational grade of 0.82. The findings could serve as guideline for better practical applications of parallel shaped type CRCP with an air layer in different scenarios.

Copper-mediated cell death presents distinct pathways from established apoptosis processes, suggesting alternative therapeutic approaches for colon cancer. Our research aims to develop a predictive framework utilizing long-noncoding RNAs (lncRNAs) related to cuproptosis to predict colon cancer outcomes while examining immune interactions and intercellular signaling. We obtained colon cancer-related human mRNA expression profiles and clinical information from the Cancer Genome Atlas repository. To isolate lncRNAs involved in cuproptosis, we applied Cox proportional hazards modeling alongside the least absolute shrinkage and selection operator technique. We elucidated the underlying mechanisms by examining the tumor mutational burden, the extent of immune cell penetration, and intercellular communication dynamics. Based on the model, drugs were predicted and validated with cytological experiments. A 13 lncRNA–cuproptosis-associated risk model was constructed. Two colon cancer cell lines were used to validate the predicted representative mRNAs with high correlation coefficients with copper-induced cell death. Survival enhancement in the low-risk cohort was evidenced by the trends in Kaplan–Meier survival estimates. Analysis of immune cell infiltration suggested that survival was induced by the increased infiltration of naïve CD4+ T cells and a reduction of M2 macrophages within the low-risk faction. Decreased infiltration of naïve B cells, resting NK cells, and M0 macrophages was significantly associated with better overall survival. Combined single-cell analysis suggested that CCL5–ACKR1, CCL2–ACKR1, and CCL5–CCR1 pathways play key roles in mediating intercellular dialogues among immune constituents within the neoplastic microhabitat. We identified three drugs with a high sensitivity in the high-risk group. In summary, this discovery establishes the possibility of using 13 cuproptosis-associated lncRNAs as a risk model to assess the prognosis, unravel the immune mechanisms and cell communication, and improve treatment options, which may provide a new idea for treating colon cancer.

Abstract Background The data of the prognostic role of V‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations in early‐stage lung adenocarcinoma (LUAD) patients is scarce. This study aimed to investigate the proportion, clinicopathological features, and prognostic significance of patients with stage I LUAD carrying BRAF mutations. Methods We collected 431 patients with pathological stage I LUAD from cBioPortal for Cancer Genomics and 1604 LUAD patients tested for BRAF V600E and epidermal growth factor receptor (EGFR) mutations from Shanghai Pulmonary Hospital. Survival curves were drawn by the Kaplan–Meier method and compared by log‐rank test. Cox proportional hazard models, propensity‐score matching (PSM), and overlap weighting (OW) were performed in this study. The primary endpoint was recurrence‐free survival (RFS). Results The proportion of BRAF mutations was estimated at 5.6% in a Caucasian cohort. BRAF V600E mutations were detected in six (1.4%) patients in Caucasian populations and 16 (1.0%) patients in Chinese populations. Two BRAF V600E‐mutant patients were detected to have concurrent EGFR mutations, one for 19‐del and one for L858R. For pathological stage I LUAD patients, BRAF mutations were not significantly associated with worse RFS than wild‐type BRAF patients (HR = 1.111; p = 0.885). After PSM and OW, similar results were presented (HR = 1.352; p = 0.742 and HR = 1.246; p = 0.764, respectively). BRAF V600E mutation status also lacked predictive significance for RFS (HR, 1.844; p = 0.226; HR = 1.144; p = 0.831 and HR = 1.466; p = 0.450, respectively). Conclusions In this study, we demonstrated that BRAF status may not be capable of predicting prognosis in stage I LUAD patients. There is a need for more data to validate our findings.

Abstract Background Intervertebral disc calcification (IDC) combined with calcification in children has been sporadically reported, while ossification of the posterior longitudinal ligament (OPLL) in the cervical spine in pediatric patients is exceedingly rare. The aim of this study is to investigate the potential prognosis and outcomes associated with this condition. Case presentation We present an unusual case involving a 10-year-old Chinese child diagnosed with calcified cervical disc herniation and ossification of the posterior longitudinal ligament. Conservative treatment measures were implemented, and at the 1-month and 6-month follow-up, the patient's pain exhibited significant improvement. Subsequent cervical MRI and CT scans revealed the complete disappearance of OPLL and substantial absorption of the calcified disc. During the three-month follow-up, CT demonstrated slight residual disc calcification, however, the patient remained asymptomatic with no discernible limitation in cervical motion. Conclusions We conducted a comprehensive review of several cases presenting with the same diagnosis. It is noteworthy that IDC combined with OPLL in children constitutes a rare clinical entity. Despite imaging indications of potential spinal canal occupation, the majority of such cases demonstrate complete absorption following conservative treatment, with OPLL exhibiting a faster absorption rate than calcified discs.

Abstract Background For complete revascularization, patients with diffuse coronary artery disease should have a coronary endarterectomy and a coronary artery bypass graft (CE-CABG). Sadly, CE can lead to a lack of endothelium, which raises the risk of thrombotic events. Even though daily dual antiplatelet therapies (DAPT) have been shown to reduce thrombotic events, the risk of perioperative thrombotic events is high during the high-risk period after CE-CABG, and there is no consistent protocol to bridge DAPT. This trial aims to compare safety and efficacy between tirofiban and heparin as DAPT bridging strategies after CE-CABG. Methods In phase I, 266 patients undergoing CE-CABG will be randomly assigned to tirofiban and heparin treatment groups to compare the two treatments in terms of the primary safety endpoint, chest tube drainage in the first 24 h. If the phase I trial shows tirofiban non-inferiority, phase II will commence, in which an additional 464 patients will be randomly assigned. All 730 patients will be studied to compare major cardiovascular and cerebrovascular events (MACCEs) between the groups in the first 30 days after surgery. Discussion Given the possible benefits of tirofiban administration after CE-CABG, this trial has the potential to advance the field of adult coronary heart surgery. Trial registration chictr.org.cn, ChiCTR2200055697. Registered 6 January 2022. https://www.chictr.org.cn/com/25/showproj.aspx?proj=149451 . Current version: 20,220,620.

Abstract Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism.

In this paper, the gas-liquid flow pattern and CO2 dissolution transport process of microalgae solution in an air-lift photobioreactor (PBR) are investigated by numerical simulations. In order to promote the gas-liquid mass transfer efficiency to enhance the carbon fixation, we propose different optimization schemes for the structure. Firstly, a two-phase flow model and a mass transfer model are employed to investigate the fluid flow characteristics. The flow state is evaluated by velocity in light direction, turbulent kinetic energy (TKE), gas hold-up and CO2 mass transfer coefficient. The results show that the gas flow rate of 0.2 V/V/min is the optimum value for the inlet. Secondly, CO2 mass transfer and carbon fixation rates are analyzed for different inlet CO2 volume fractions. With the increase of CO2 volume fraction, the carbon fixation rate first increases and then decreases, the highest fixation rate reaching 2.21 × 10−4 mol m−3 s−1 at 6 %. Finally, based on numerical simulations, three optimized structures with different spacing of baffles are proposed and evaluated the performance in comparison with the original. The results show that the gas distribution and CO2 mass transfer are significantly improved, with the one-sided baffle structure is the best. In summary, this study provides a new and useful reference to evaluate the gas-liquid mixing and improve the microalgae carbon fixation rate.

BackgroundIncomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells.MethodsIn this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

Tripartite interactions play a fundamental role in the quantum information processing and quantum technology. However, it is generally difficult to realize strong tripartite coupling. We investigate the estimation of a tripartite coupling strength in a hybrid setup composed of a single nitrogen-vacancy (NV) center and a micromagnet. A time-independent parametric drive can be utilized to increase the estimation precision of the tripartite coupling strength. By calculating the quantum Fisher information (QFI), we can obtain the optimal estimation precision by measuring the eigenstate of the tripartite system. At the critical position, the QFI is divergent due to that the preparation time of the eigenstate is divergent. When the system is subjected to a dissipation, the QFI near the critical point of the driven-dissipation phase transition is analytically obtained. The direct intensity measurement is the optimal measurement near the dissipation phase transition point. In addition, we quantify the robustness of an imperfect measurement operator by the measurement noise susceptibility based on the error propagation formula. We find that the direct intensity measurement is robust enough against small measurement disturbance from a coherent drive. But it can be disturbed by the nonlinear anti-harmonic measurement noise, especially near the critical point.

Objectives: To develop and validate a risk prediction model by identifying the preoperative factors associated with an increased risk of pneumonia after spinal surgery. Methods: This study included patients with spinal disease from two hospitals between January 2021 and June 2023. The patients were divided into the training and validation sets, which were categorized as postoperative pneumonia (POP) or non-POP, respectively. This study identified the independent risk variables for POP using a multivariate logistic regression analysis. A nomogram prediction model was developed and validated using risk factors, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) to assess predictive performance. Results: Following exclusion, 2223 patients from Changzheng Hospital were enrolled in the training set and 357 patients from the No. 905 Hospital of PLA Navy were enrolled in the validation set. Univariate and multivariate logistic regression analyses revealed that operation time, American Society of Anesthesiologists (ASA) grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, chronic obstructive pulmonary disease (COPD), underlying diseases, and spinal section were risk factors for POP development in patients with spinal diseases. The area under the ROC curve of the training set was 0.950, whereas that of the validation set was 0.879. The model calibration curves demonstrated good agreement, and the DCA indicated a high expected net benefit value. Conclusion: The POP risk prediction model has high accuracy and efficiency in predicting POP in patients with spinal diseases. POP development is influenced by factors such as operation length, ASA grade, smoking, non-wearing of medical masks, lack of preoperative respiratory training, COPD, underlying diseases, and lumbar surgery.

Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro, comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.

Abstract Background Gene expression profiles have important significance for gene expression characteristics and further functional studies. More attention has been given to the expression databases in humans and mice, but less attention has been given to rats, while rat models also play an irreplaceable role in biomedical experiments. Results To depict the rat gene expression profiles in mRNA expression levels, we analyzed over 2,700 RNA sequencing (RNA-Seq) samples from 48 tissues, 40 primary cell types and 25 cell lines; and then mapped them to the latest version of the rat genome reference, mRatBN7.2. Based on these datasets and reanalysis, we constructed a new database, the Omic Horizon Expression Database ( http://immudb.bjmu.edu.cn/expression.html ), which allows expressional profile query of over 25,000 rat genes based on non-redundant gene symbols. The database supports requests using gene symbols (or alias), Ensemble and Entrez gene IDs. Gene expression profiles can be queried in three categories: tissues, primary cells and cell lines. Application examples including expression profiling and comparison, as well as identification of novel rat genes, were illustrated to show the utility of the database. Conclusions As an omic resource, the Omic Horizon Expression Database provides horizons of gene expression profiles across various tissues and cells, which greatly facilitates the identification of rat genes as well as functional clues.

Abstract The objective of this study was to coat negatively charged polymer brushes by a covalent bond onto the surface of polyvinylchloride using a simple conventional surface free radical polymerisation technique. The coated surfaces were assessed with contact angle, protein adsorption, cell adhesion, and bacterial adhesion. Bovine serum albumin and bovine fibrinogen were used for protein adsorption evaluation. Mouse fibroblast (NIH‐3T3) cells and Pseudomonas aeruginosa were used to assess surface adhesion. Results show that the surface modified with all the attached polymers exhibited significantly reduced contact angle, protein adsorption, and cell as well as bacterial adhesion among which the negatively charged polymers showed extremely low values in all the tests. The negatively charged polymer shows its contact angle at 5° as compared to 70° for original polyvinylchloride. Its bovine serum albumin, bovine fibrinogen, 3T3 adhesion, and P. aeruginosa adhesion were 93%, 84%, 92%, and 92% lower than the original PVC, respectively. Furthermore, the polyvinylchloride surface coated with negatively charged polymer brushes exhibited a hydrogel‐like property. The results indicate that coating a polyvinylchloride surface with acrylic acids using a simple surface‐initiated free radical polymerisation and then converting those to negatively charged salts can be an effective and efficient route for fouling‐resistant applications.

Abstract Occult nodal metastasis (ONM) plays a significant role in comprehensive treatments of non-small cell lung cancer (NSCLC). This study aims to develop a deep learning signature based on positron emission tomography/computed tomography to predict ONM of clinical stage N0 NSCLC. An internal cohort (n = 1911) is included to construct the deep learning nodal metastasis signature (DLNMS). Subsequently, an external cohort (n = 355) and a prospective cohort (n = 999) are utilized to fully validate the predictive performances of the DLNMS. Here, we show areas under the receiver operating characteristic curve of the DLNMS for occult N1 prediction are 0.958, 0.879 and 0.914 in the validation set, external cohort and prospective cohort, respectively, and for occult N2 prediction are 0.942, 0.875 and 0.919, respectively, which are significantly better than the single-modal deep learning models, clinical model and physicians. This study demonstrates that the DLNMS harbors the potential to predict ONM of clinical stage N0 NSCLC.

Distributed drive electric vehicles improve steering response and enhance overall vehicle stability by independently controlling each motor. This paper introduces a control framework based on Adaptive Model Predictive Control (AMPC) for coordinating handling stability, consisting of three layers: the dynamic supervision layer, online optimization layer, and low-level control layer. The dynamic supervision layer considers the yaw rate and maneuverability limits when establishing the β−β˙ phase plane stability boundary and designs variable weight factors based on this stability boundary. The online optimization layer constructs the target weight-adaptive AMPC strategy, which can adjust the control weights for maneuverability and lateral stability in real time based on the variable weight factors provided by the dynamic supervision layer. The low-level control layer precisely allocates the driver’s requested driving force and additional yaw moment by using torque distribution error and tire utilization as the cost function. Finally, experiments are conducted on a Simulink-CarSim co-simulation platform to assess the performance of AMPC. Simulation results show that, compared to the traditional MPC strategy, this control strategy not only enhances maneuverability under normal conditions but also improves lateral stability control under extreme conditions.

Providing safe, smooth, and efficient trajectories for autonomous vehicles has long been a question of great interest in the field of autopiloting. In dynamic and ever-changing urban environments, safe and efficient trajectory planning is fundamental to achieving autonomous driving. Nevertheless, the complexity of environments with multiple constraints poses challenges for trajectory planning. It is possible that behavior planners may not successfully obtain collision-free trajectories in complex urban environments. Herein, this paper introduces spatio–temporal joint optimization-based trajectory planning (SJOTP) with multi-constraints for complex urban environments. The behavior planner generates initial trajectory clusters based on the current state of the vehicle, and a topology-guided hybrid A* algorithm applied to an inflated map is utilized to address the risk of collisions between the initial trajectories and static obstacles. Taking into consideration obstacles, road surface adhesion coefficients, and vehicle dynamics constraints, multi-constraint multi-objective coordinated trajectory planning is conducted, using both differential-flatness vehicle models and point-mass vehicle models. Taking into consideration longitudinal and lateral coupling in trajectory optimization, a spatio–temporal joint optimization solver is used to obtain the optimal trajectory. The simulation verification was conducted on a multi-agent simulation platform. The results demonstrate that this methodology can obtain optimal trajectories safely and efficiently in complex urban environments.

Improving the measurement precision of low temperature is significant in fundamental science and advanced quantum technology application. However, the measurement precision of temperature T usually diverges as T tends to zero. Here, by utilizing a heavy impurity to measure the temperature of a Bose gas, we obtain the Landau bound to precision δ^{2}T∝T^{2} to avoid the divergence. When the initial momentum of the heavy impurity is close to be fixed and nonzero, the measurement precision can be δ^{2}T∝T^{3} to break the Landau bound. We derive the momentum distribution of the heavy impurity at any moment and obtain the optimal measurement precision of the temperature by calculating the Fisher information. As a result, we find that increasing the expectation value P_{0} and reducing the variance Δ/2 of the initial momentum can help to improve the measurement precision. Moreover, under certain conditions, sqrt[Δ]/P_{0} is a relevant parameter, the smallness of which helps improve the thermometric precision of the probe. In addition, the momentum measurement is the optimal measurement of the temperature in the case that the initial momentum is close to be fixed and not equal to zero. The kinetic energy measurement is the optimal measurement in the case that the expectation value of the initial momentum is close to zero. Finally, we obtain that the temperatures of two Bose gases can be measured simultaneously. The simultaneous measurement precision is proportional to T^{2} when two temperatures are close to T.

Abstract Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment. Graphical Abstract

Lung ischemia–reperfusion injury (IRI) stands as the primary culprit behind primary graft dysfunction (PGD) after lung transplantation, yet viable therapeutic options are lacking. In the present study, we used a murine hilar clamp (1 h) and reperfusion (3 h) model to study IRI. The left lung tissues were harvested for metabolomics, transcriptomics, and single-cell RNA sequencing. Metabolomics of plasma from human lung transplantation recipients was also performed. Lung histology, pulmonary function, pulmonary edema, and survival analysis were measured in mice. Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase (ALOX12) and its metabolite 12-hydroxyeicosatetraenoic acid (12-HETE), which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap (NET) formation during lung IRI. Additionally, single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells. Importantly, Alox12-knockout (KO) mice exhibited a notable decrease in ferroptosis, NET formation, and tissue injury. To investigate the interplay between endothelial ferroptosis and NET formation, a hypoxia/reoxygenation (HR) cell model using 2 human endothelial cell lines was established. By incubating conditioned medium from HR cell model with neutrophils, we found that the liberation of high mobility group box 1 (HMGB1) from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway. Last, the administration of ML355, a targeted inhibitor of Alox12, mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models. Collectively, our study indicates ALOX12 as a promising therapeutic strategy for lung IRI.

Blockchain is commonly employed in access control to provide safe medical data exchange because of the characteristics of decentralization, nontamperability, and traceability. Patients share personal health data by granting access rights to users or medical institutions. The major purpose of the existing access control techniques is to identify users who are permitted to access medical data. They hardly ever recognize internal assailants from legitimate entities. Medical data will involve multilayer access within the authorized organizations. Considering the cost of permissions management and the problem of insider malicious node attacks, users hope to implement authorization constraints within the authorized institutions. It can prevent their data from being maliciously disclosed by end-users from different authorized healthcare domains. For the purpose to achieve the fine-grained permissions propagation control of medical data in sharing institutions, a trust-based authorization access control mechanism is suggested in this study. Trust thresholds are assigned to different privileges based on their sensitivity and used to generate zero-knowledge proof to be broadcasted among blockchain nodes. This method evaluates the trust of each user through the dynamic trust calculation model. And meanwhile, smart contract is employed to verify whether the user’s trust can activate some permissions and ensure the privacy of the user’s trust in the process of authorization verification. In addition, the authorization transaction between users and institutions is recorded on the blockchain for patient traceability and accountability. The feasibility and effectiveness of the scheme are demonstrated through comprehensive comparisons and extensive experiments.

The issues of energy accessibility and vulnerability have garnered significant attention in recent research. However, previous studies have tended to emphasize access-based energy justice while neglecting vulnerability-based energy justice, particularly in emergency scenarios. This study aims to address this gap by examining the conceptual differences between the two concepts through practical examples and exploring the profile of energy-vulnerable individuals. In this study, a dataset comprising 1650 buildings in Los Angeles was selected. A spatial regression model was employed to investigate the factors influencing energy use intensity (EUI) in the years 2019 and 2020, as well as the rate of change in EUI between these two years. This analysis was conducted within the framework of the two-tier model of energy justice combining energy accessibility and vulnerability proposed in this article. The results revealed that, considering the impact of the COVID-19 pandemic on the urban energy environment, more demographic types experienced adverse effects, indicating energy-vulnerable populations. Among these groups, older adults were impacted adversely most, followed by the Asian population and the unemployed population. The two-tier framework of energy justice proposed in this article compensates for the shortcomings of traditional energy justice perspectives and confirms the typology of energy-vulnerable populations more objectively. The findings also confirm the spatial dependence and heterogeneity of these impacts. The findings will prompt a reevaluation of energy equity in urban settings and offer a theoretical foundation for energy policy decision-making.

Antimicrobial AgO/Ag/carboxymethyl chitosan-graphene oxide (AgO/Ag/CGO) films were synthesized by UV-light-assisted reduction followed by ionic crosslinking method. The structure of the AgO/Ag/CGO films were explored by X-ray diffraction (XRD), field-emission scanning electron microscope (FE-SEM), Transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), ultraviolet–visible spectroscopy (UV–vis), and Fourier-transform infrared (FTIR) analysis. We have also tested the cytotoxicity and cell viability of AgO/Ag/CGO3. The results of cytotoxicity of AgO/Ag/CGO3 on HepG2 cells suggests that the nanocomposite is not cytotoxic. Additionally, thermal stability, swelling ratio, antimicrobial activity of the AgO/Ag/CGO films were evaluated in detail, which revealed that the addition of GO improves the thermal stability and swelling ratio of AgO/Ag/CGO films. Of the three AgO/Ag/CGO films, the AgO/Ag/CGO3 exhibited better antimicrobial activity and higher inhibition rate against E. coli (89.2%) and S. aureus (93.4%). Therefore, the simple and green method is potential candidate for prepare of Ag-based antimicrobial film materials.

Abstract Background The current nodal (pN) classification still has limitations in stratifying the prognosis of small cell lung cancer (SCLC) patients with pathological classifications T1-2N0-2M0. Thus. This study aimed to develop and validate a modified nodal classification based on a multicenter cohort. Materials and methods We collected 1156 SCLC patients with pathological classifications T1-2N0-2M0 from the Surveillance, Epidemiology, and End Results database and a multicenter database in China. The X-tile software was conducted to determine the optimal cutoff points of the number of examined lymph nodes (ELNs) and lymph node ratio (LNR). The Kaplan-Meier method, the Log-rank test, and the Cox regression method were used in this study. We classified patients into three pathological N modification categories, new pN#1 (pN0-#ELNs > 3), new pN#2 (pN0-#ELNs ≤ 3 or pN1-2-#LNR ≤ 0.14), and new pN#3 (N1-2-#LNR > 0.14). The Akaike information criterion (AIC), Bayesian Information Criterion, and Concordance index (C-index) were used to compare the prognostic, predictive ability between the current pN classification and the new pN component. Results The new pN classification had a satisfactory effect on survival curves (Log-rank P

Abstract The incidence of stroke and neurodegenerative diseases is gradually increasing in modern society, but there is still no treatment that is effective enough. Stem cells are cells that can reproduce (self‐renew) and differentiate into the body, which have shown significance in basic research, while doctors have also taken them into clinical trials to determine their efficacy and safety. Existing clinical trials mainly include middle‐aged and elderly patients with stroke or Parkinson's disease (mostly 40–80 years old), mainly involving injection of mesenchymal stem cells and bone marrow mesenchymal stem cells through the veins and the putamen, with a dosage of mostly 106–108 cells. The neural and motor functions of the patients were restored after stem cell therapy, and the safety was found to be good during the follow‐up period of 3 months to 5 years. Here, we review all clinical trials and the latest advances in stroke, Alzheimer's disease, and Parkinson's disease, with the hope that stem cell therapy will be used in the clinic in the future to achieve effective treatment rates and benefit patients.

Abstract Background The efficacy of monotherapy of AMG-510 is limited. This study explored whether the AMG-510 and cisplatin combination increases the anti-tumor effect in lung adenocarcinoma with the mutation of Kirsten rat sarcoma viral oncogene (KRAS) G12C. Methods Patients’ data were used to analyze the proportion of KRAS G12C mutation. Besides, the next-generation sequencing data was used to uncover information about co-mutations. The cell viability assay, the concentration inhibiting 50% of cell viability (IC50) determination, colony formation, and cell-derived xenografts were conducted to explore the anti-tumor effect of AMG-510, Cisplatin, and their combination in vivo. The bioinformatic analysis was conducted to reveal the potential mechanism of drug combination with improved anticancer effect. Results The proportion of KRAS mutation was 2.2% (11/495). In this cohort with KRAS mutation, the proportion of G12D was higher than others. Besides, KRAS G12A mutated tumors had the likelihood of concurrent serine/threonine kinase 11 (STK11) and kelch-like ECH-associated protein 1 (KEAP1) mutations. KRAS G12C and tumor protein p53 (TP53) mutations could appear at the same time. In addition, KRAS G12D mutations and C-Ros oncogene 1 (ROS1) rearrangement were likely to be present in one tumor simultaneously. When the two drugs were combined, the respective IC50 values were lower than when used alone. In addition, there was a minimum number of clones among all wells in the drug combination. In in vivo experiments, the tumor size reduction in the drug combination group was more than twice that of the single drug group (p

In order to deeply explore the utilization value of Quezui tea, the antioxidant activity and tyrosinase inhibitory activity of its three phenolic compounds including 6'-O-caffeoylarbutin (CA), β-arbutin, and chlorogenic acid were analyzed in this study. The results indicated that all three phenolic compounds of Quezui tea had excellent antioxidation activity. The IC50 values of CA, β-arbutin, and chlorogenic acid on DPPH radical scavenging were 13.56±0.14, 104.41±6.52 and 8.42±0.21 μg/mL, respectively. The IC50 values of ABTS+ radical scavenging were 18.01±0.06, 50.60±1.25 and 26.93±0.38 µg/mL, respectively. The IC50 values of OH radical scavenging were 2.64±0.06, >10.00 and CA>β-arbutin. In addition, the inhibitory activities of all three phenolic compounds of Quezui tea were significantly different. CA had inhibitory effects on both monophenolase and diphenolase activities with IC50 values of 1.114±0.035 and 95.198±1.117 μmol/L, respectively. β-arbutin only had inhibitory effects on monophenolase activities with IC50 value of 681.335±17.975 μmol/L, and chlorogenic acid had no inhibitory effect on either monophenolase activity or diphenolase activity. The results would provide an important foundation for the development and utilization of the active compounds from Quezui tea.

Abstract Long-term observations have shown that many plants and aboveground animals have changed their phenology patterns due to warmer temperatures over the past decades. However, empirical evidence for phenological shifts in alpine organisms, particularly belowground organisms, is scarce. Here, we investigate how the activities and phenology of plants, soil microbes, and soil fauna will respond to warming in an alpine meadow on the Tibetan Plateau, and whether their potential phenological changes will be synchronized. We experimentally simulate an increase in soil temperature by 2–4 °C according to future projections for this region. We find that warming promotes plant growth, soil microbial respiration, and soil fauna feeding by 8%, 57%, and 20%, respectively, but causes dissimilar changes in their phenology during the growing season. Specifically, warming advances soil faunal feeding activity in spring and delays it in autumn, while their peak activity does not change; whereas warming increases the peak activity of plant growth and soil microbial respiration but with only minor shifts in their phenology. Such phenological asynchrony in alpine organisms may alter ecosystem functioning and stability.

Abstract Background Colorectal cancer (CRC) is one of the most prevalent types of malignant tumours. Metastasis is the leading cause of cancer-related mortality, with lung metastases accounting for 32.9% of all metastatic CRCs. However, since the biological mechanism of lung metastatic CRC is poorly understood, limited therapeutic targets are available. In the present study, we aimed to identify the key genes and molecular processes involved in CRC lung metastasis. Methods The differentially expressed genes (DEGs) between primary and lung metastatic CRC patients were obtained from the Gene Expression Omnibus (GEO) database via the GEO2R tool. The enriched biological processes and pathways modulated by the DEGs were determined with Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome Gene Sets analyses. The search tool Retrieval of Interacting Genes (STRING) and Cytoscape were used to construct a protein–protein interaction (PPI) network among DEGs. Results The DEGs were enriched in surfactant metabolism, cell–cell communication and chemokine signaling pathways. The defined hub genes were included CLU, SFTPD, CCL18, SPP1, APOE, BGN and MMP3. Among them, CLU, SFTPD and CCL18 might be associated with the specific lung tropism metastasis in CRC. In addition, the expression and prognostic values of the hub genes in CRC patients were verified in database of The Cancer Genome Atlas (TCGA) and GEO. Moreover, the protein levels of the hub genes were detected in primary and lung metastatic CRC cells, serum or tissues. Furthermore, SFTPD was confirmed to facilitate cellular proliferation and lung metastasis in CRC. Conclusion This bioinformatics study may provide a better understanding of the candidate therapeutic targets and molecular mechanisms for CRC lung metastasis.

There is no targeted therapy for KRAS proto‐oncogene, GTPase (KRAS)‐mutant metastatic colorectal cancer (mCRC) because the underlying mechanism remains obscure. Based on bioinformatic analysis, this study aims to elucidate a potential gene target for which an approved drug is available, and to reveal the function as well as the underlying mechanism of the candidate gene. Here, we identified that ryanodine receptor 2 (RyR2) expression was upregulated in KRAS‐mutant mCRC, and that this promoted cancer cell metastasis. S107, an approved drug to inhibit calcium release from RyR2 in the clinic, inhibited cancer cell metastasis both in vitro and in vivo. High expression of RyR2 predicts poor survival in our patient cohort. CRC patients with serosa invasion and vascular tumor thrombus are characterized by high RyR2 expression. Analysis of expression profiles upon RyR2 knockdown and inhibition, revealed a set of metastasis‐related molecules, and identified BTB domain and CNC homolog 1 (BACH1) as the main transcription factor regulated by RyR2. RyR2 regulates cellular reactive oxygen species (ROS) levels, which activates nuclear factor erythroid 2‐related factor 2 (Nrf2; also known as NFE2L2) and HMOX1 expression, and thus BACH1 accumulation. Collectively, this study provides evidence that the RyR2/ROS/BACH1 axis may be a potential intervention target for CRC metastasis.

To investigate the dissolution mechanism of Ti metal, ab initio calculations were conducted to observe the impact of Ti vacancy defects on the O-adsorbed Ti(0001) surface, focusing on the formation energies of Ti vacancy, geometric structures, and electronic structures. The surface structures subsequent to Ti dissolution were simulated by introducing a Ti cavity on both clean and O-adsorbed Ti(0001) surfaces. Our findings indicated that Ti vacancy formation energies and electrochemical dissolution potential on the O-adsorbed Ti(0001) surface surpassed those on the clean surface, and they increased with increasing O coverage. This suggested that O adsorption inhibited Ti dissolution and enhanced O atom interaction with the Ti surface as O coverage increased. Furthermore, at higher O coverage, Ti vacancies contributed to the strengthening of Ti-O bonds on the O-adsorbed Ti(0001) surface, indicating that Ti dissolution aided in stabilizing the Ti surface. The formation of Ti vacancies brought the atomic ratio of Ti to O on the Ti surface closer to that of TiO2, potentially explaining the increased stability of the structure with Ti vacancies.

AbstractThe conventional treatment methods used for the management of autoimmune diseases (ADs) have limited efficacy and also exhibit significant side effects. Thus, identification of novel strategies to improve the efficacy and safety of ADs treatment is urgently required. Overactivated immune response and oxidative stress are common characteristics associated with ADs. Polydopamine (PDA), as a polymer material with good antioxidant and photothermal conversion properties, has displayed useful application potential against ADs. In addition, PDA possesses good biosafety, simple preparation, and easy functionalization, which is conducive for the pharmacological development of PDA nanomaterials with clinical transformation prospects. Here, we have first reviewed the preparation of PDA, the different functional integration strategies of PDA-based biomaterials, and their potential applications in ADs. Next, the mechanism of action of PDA in ADs has been elaborated in detail. Finally, the application opportunities and challenges linked with PDA nanomaterials for ADs treatment are discussed. This review is contributed to design reasonable and effective PDA nanomaterials for the diagnosis and treatment of ADs.

Background: The objective of the present study was to identify patients with pathologic stage I lung adenocarcinoma (LUAD) who are at high risk of recurrence and assess the efficacy of adjuvant chemotherapy (ACT) in these individuals. Methods: A retrospective study was conducted on 1504 patients with pathologic stage I LUAD who underwent surgical resection at Shanghai Pulmonary Hospital and Sun Yat-sen University Cancer Center. Cox proportional hazard regression analyses were performed to identify indicators associated with a high risk of recurrence, while the Kaplan-Meier method and Log-rank test were employed to compare recurrence-free survival (RFS) and overall survival (OS) between patients with ACT and those without it. Results: Four independent indicators, including age (≥62 years), visceral pleural invasion (VPI), predominant pattern (micropapillary/solid), and lymphovascular invasion (LVI), were identified to be significantly related with RFS. Subsequently, patients were classified into high-risk and low-risk groups by LVI, VPI, and predominant pattern. The administration of ACT significantly increased both RFS (P