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Abstract Recent research has explored the potential of the demethylating drug 5-azacytidine (Aza) as therapy for a range of diseases. However, the therapeutic efficacy of Aza for patients of atherosclerosis remains unclear. This study investigates the therapeutic application of Aza to atherosclerosis in order to elucidate the underlying mechanisms. We generated induced Tregs (iTregs) from CD4+ T cells by using Aza in vitro, and this was followed by the intravenous infusion of iTregs for the treatment of atherosclerosis. The adoptive transfer of Aza-iTreg significantly increased peripheral blood Treg cells, suppressed inflammation, and attenuated atherosclerosis in ApoE−/− mice. Furthermore, we observed a notable demethylation of the Forkhead box P3 (Foxp3)-regulatory T cell-specific demethylated region (TSDR) and an upregulation of Foxp3 expression in the CD4+ T cells in the spleen of the ApoE−/− mice following the transfer of Aza- iTregs. We also demonstrated that Aza converted naive CD4+ T cells into Tregs by DNA methyltransferase 1 (Dnmt1)-mediated Foxp3-TSDR demethylation and the upregulation of Foxp3 expression. Conversely, the overexpression of Dnmt1 in the CD4+ T cells attenuated the Aza-induced Foxp3-TSDR demethylation and upregulation of Foxp3 expression. Our results reveal that Aza converts naive CD4+ T cells into functional Tregs by inhibiting Dnmt1, and the transfer of Aza-iTregs suppresses atherosclerosis in mice.

Abstract Purpose One of the most frequent side effects of radical prostatectomy (RP) is urinary incontinence. The primary cause of urine incontinence is usually thought to be impaired urethral sphincter function; nevertheless, the pathophysiology and recovery process of urine incontinence remains unclear. This study aimed to identify potential risk variables, build a risk prediction tool that considers preoperative urodynamic findings, and direct doctors to take necessary action to reduce the likelihood of developing early urinary incontinence. Methods We retrospectively screened patients who underwent radical prostatectomy between January 1, 2020 and December 31, 2023 at the First People ‘s Hospital of Nantong, China. According to nomogram results, patients who developed incontinence within three months were classified as having early incontinence. The training group’s general characteristics were first screened using univariate logistic analysis, and the LASSO method was applied for the best prediction. Multivariate logistic regression analysis was carried out to determine independent risk factors for early postoperative urine incontinence in the training group and to create nomograms that predict the likelihood of developing early urinary incontinence. The model was internally validated by computing the performance of the validation cohort. The nomogram discrimination, correction, and clinical usefulness were assessed using the c-index, receiver operating characteristic curve, correction plot, and clinical decision curve. Results The study involved 142 patients in all. Multivariate logistic regression analysis following RP found seven independent risk variables for early urinary incontinence. A nomogram was constructed based on these independent risk factors. The training and validation groups’ c-indices showed that the model had high accuracy and stability. The calibration curve demonstrates that the corrective effect of the training and verification groups is perfect, and the area under the receiver operating characteristic curve indicates great identification capacity. Using a nomogram, the clinical net benefit was maximised within a probability threshold of 0.01–1, according to decision curve analysis (DCA). Conclusion The nomogram model created in this study can offer a clear, personalised analysis of the risk of early urine incontinence following RP. It is highly discriminatory and accurate, and it can help create efficient preventative measures and identify high-risk populations.

Highlights The stable periodic porous shielding materials were prepared by combining the strategies of 3D printing and metamaterial design. The relationship between porous material structure and electromagnetic interference shielding efficiency (EMI SE) effectiveness was deeply explored, revealing the important structural parameters for realizing tunable EMI SE property. The optimized design of the periodic porous shielding box achieves effective EMI shielding in a wide wavelength range (over 2.4 GHz).

Abstract During the progression of proliferative vitreoretinopathy (PVR) following ocular trauma, previously quiescent retinal pigment epithelial (RPE) cells transition into a state of rapid proliferation, migration, and secretion. The elusive molecular mechanisms behind these changes have hindered the development of effective pharmacological treatments, presenting a pressing clinical challenge. In this study, by monitoring the dynamic changes in chromatin accessibility and various histone modifications, we chart the comprehensive epigenetic landscape of RPE cells in male mice subjected to traumatic PVR. Coupled with transcriptomic analysis, we reveal a robust correlation between enhancer activation and the upregulation of the PVR-associated gene programs. Furthermore, by constructing transcription factor regulatory networks, we identify the aberrant activation of enhancer-driven RANK-NFATc1 pathway as PVR advanced. Importantly, we demonstrate that intraocular interventions, including nanomedicines inhibiting enhancer activity, gene therapies targeting NFATc1 and antibody therapeutics against RANK pathway, effectively mitigate PVR progression. Together, our findings elucidate the epigenetic basis underlying the activation of PVR-associated genes during RPE cell fate transitions and offer promising therapeutic avenues targeting epigenetic modulation and the RANK-NFATc1 axis for PVR management.

Due to the limited bandwidth and transmission congestion of the vehicle platoon's communication, it is inevitable to induce time delay, which significantly degrades the control performance of the vehicle platoon, even resulting in instability. This paper focuses on analyzing the internal stability under generic communication topologies and presents a method of computing the exact time delay margin (ETDM). The proposed method can offer a necessary and sufficient internal stability condition with no conservatism. Firstly, to reduce the analytical complexity and computational burden elegantly, we decompose the closed-loop platoon dynamics into a set of individual subsystems via similarity transformation and matrix factorization. This decomposition approach is applicable for any general communication topology. Secondly, an explicit formula is deduced to compute the ETDM by surveying the characteristic roots' distribution of all these individual subsystems. It is further demonstrated that only the positive purely imaginary roots need to be considered to compute the ETDM. Finally, simulations are conducted to demonstrate the effectiveness of the theoretical claims.

Abstract Background Colorectal cancer (CRC) ranks as the third most common malignancies in the world, and periodic examination of the patient is advantageous in reducing the mortality of CRC. The first blood-based Septin9 gene methylation assay which recognized by the US FDA for CRC examination was Epi proColon. However, this assay was not broadly applied in the current clinical guideline because of its relatively lower sensitivity in the detection of early-stage CRC. Methods This study aimed at developing a new multiplex Septin9 methylation assay (ColonUSK) which simultaneously evaluates two CpG-rich subregions in the promoter of the Septin9 gene and an internal control in a single reaction. ColonUSK proved increased sensitivity, with a detection limit as low as 12pg of the positive DNA compared with the Septin9 assay targeting one CpG-rich subregion. 1366 subjects were prospectively recruited from four comprehensive hospitals in China in an opportunistic screening study for assessing its value in CRC detection. Blind testing was developed to evaluate ColonUSK in comparison with clinical examination using clinical gold standard such as colonoscopy. Results The assay demonstrates clinical sensitivity for diagnosing colorectal cancer (CRC) and advanced adenoma at rates of 77.34% and 25.26%, respectively. Furthermore, ColonUSK exhibits a high degree of specificity for non-CRC cases (95.95%) clinically. Significantly, the detection rate of cases in high-grade intraepithelial neoplasia increased to 54.29%. The value for the assay in the Kappa test was 0.76, showing a high degree of consistency between ColonUSK and clinical gold standard. Conclusions ColonUSK indicated moderate diagnostic value and could become a non-invasive detection way for CRC. The implementation of the ColonUSK assay has the capacity to markedly enhance CRC screening practices.

Abstract Background Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. Methods Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. Results A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88–0.95, P = 2.92 × 10−7) and Europe (OR = 0.92, 95%CI 0.88–0.95, P = 4.61 × 10−6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. Conclusion Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

PurposeLefamulin is the first pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). However, the pharmacokinetic/pharmacodynamic (PK/PD) characteristics in Chinese CABP patients are not fully understood. This study aimed to evaluate its microbiological efficacy against Streptococcus pneumoniae and Staphylococcus aureus via PK/PD analysis.MethodsThe population PK (PopPK) model, established with foreign data was validated using data from Chinese CABP patients. PK/PD analysis was conducted for the intravenous administration of 150 mg q12 h for 1-h, 1.5-h and extended 2-h infusion. Oral administrations of 600 mg q12 h were assessed, considering original and higher plasma protein binding.ResultsLefamulin displayed similar PK characteristics in both Chinese and Western populations. The PopPK model effectively predicted lefamulin concentrations in Chinese CABP patients. Under the dosage regimen of 150 mg q12 h via intravenous infusion for 1/1.5/2 h, the probability of target attainments reached 98% at the minimum inhibitory concentration for both 90% S. pneumoniae and S. aureus, considering both original and higher protein binding rates. It is advisable to extend the infusion duration from 1/1.5 h–2 h to minimize the risk of adverse effects at the infusion site. Regardless of fasted or fed conditions, the PTAs for 600 mg q12 h lefamulin via oral administration proved comparable to those for intravenous administration.ConclusionThis study proved that intravenous and oral administrations of lefamulin can reach preclinical PK/PD targets of S. pneumoniae and S. aureus. These findings support the optimal use of lefamulin for the safe and effective treatment of Chinese CABP patients.

T-cell engagers (TCEs) represent a promising therapeutic strategy for various cancers and autoimmune disorders. These bispecific antibodies act as bridges, connecting T-cell receptors (TCRs) to target cells (either malignant or autoreactive) via interactions with specific tumour-associated antigens (TAAs) or autoantigens to form trimeric synapses, or trimers, that co-localise T-cells with target cells and stimulate their cytotoxic function. Bispecific TCEs are expected to exhibit a bell-shaped dose-response curve, with a defined optimal TCE exposure for maximizing trimer formation. The shape of the dose-response is determined by a non-trivial interplay of binding affinities, exposure and antigens expression levels. Furthermore, excessively low binding to the TCR may reduce efficacy, but mitigate risk of over-stimulating cytokine secretion or induce effector cell exhaustion. These inevitable trade-off highlights the importance of quantitatively understanding the relationship between TCE concentration, target expression, binding affinities, and trimer formation. We utilized a mechanistic target engagement model to show that, if the TCE design parameters are close to the recommended ranges found in the literature, relative affinities for TCR, TAA and target expression levels have qualitatively different, but predictable, effects on the resulting dose-response curve: higher expression levels shift the curve upwards, higher antigen affinity shifts the curve to the left, and higher TCR affinity shifts the curve upwards and to the left.

Abstract Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 phase. However, their practical applications are seriously obstructed by difficulties in thermodynamic phase regulation, complicated electrochemical phase transition, and unsatisfactory cycling life. Herein, we propose an efficient structural evolution strategy from biphase to monophase of Na0.766+xLixNi0.33−xMn0.5Fe0.1Ti0.07O2 through Li+ substitution. The role of Li+ substitution not only simplifies the unfavorable phase transition by altering the local coordination of transition metal (TM) cations but also stabilizes the cathode–electrolyte interphase to prevent the degradation of TM cations during battery cycling. As a result, the thermodynamically robust O3‐Na0.826Li0.06Ni0.27Mn0.5Fe0.1Ti0.07O2 cathode delivers a high capacity of 139.4 mAh g−1 at 0.1 C and shows prolonged cycling life at high rates, with capacity retention of 81.6% at 5 C over 500 cycles. This work establishes a solid relationship between the thermodynamic structure evolution and electrochemistry of layered cathode materials, contributing to the development of long‐life sodium‐ion batteries.

A contemporary world order is based on an increasingly complex system of interstate relations, which implies the need to thoroughly consider the international context, even when analyzing bilateral interactions. From this point of view, the concept of a ‘strategic triangle’, developed during the Cold War and applied primarily to analyze the dynamics of relationships between the USSR, the USA and the PRC, appears to have significant epistemological potential. In current conditions, it is of particular interest to use this concept to study the logic of relations in the ‘Russia–India–China’ (RIC) triangle. This research pursues two interrelated goals. On the one hand, it is aimed at identifying specific features of this new ‘strategic triangle’, its inner structure and logic of interactions between its participants. On the other hand, it assesses the applicability of the theoretical models developed during the Cold War to the relations within the framework of the RIC strategic triangle. The author examines the history, general dynamics and contemporary features of interaction within each pair of bilateral relations in this ‘triangle’. The research has confirmed the hypothesis that the relations between Russia, India, and China, indeed, form a specific subsystem of international relations, which can be described as a ‘strategic triangle’. At the same time, unlike the Sino-American-Soviet ‘strategic triangle’, it is the logic of cooperation, rather than rivalry, which generally prevails within the framework of the RIC.However, the RIC ‘triangle’ can also be described as an inherently inconsistent system. While China and Russia maintain close strategic cooperation in almost all areas, in the case of India and Russia, economic cooperation does not match the achieved level of political contacts, and Sino-Indian relations, despite the generally positive dynamics during the recent years, remain at a low level. All this points to the need to develop a new theoretical and methodological framework for analyzing trilateral relations between Russia, India and China as a special subsystem of the contemporary world politics, one that will be free from Cold War stereotypes.

Organic heterocyclic corrosion inhibitors play a crucial role in the non-destructive protection of excavated bronze relics exposed to the atmosphere. However, the current selection of corrosion inhibitors, additives, and dosage requires further investigation. This study involves a comprehensive preparation simulation of electrode materials and atmospheric corrosion electrolytes. The corrosion inhibition performance of 6-thioguanine (6-Tg) and traditional benzotriazole (BTA) inhibitors at pH = 7.5 is explored. Analytical techniques such as potentiodynamic polarization, EIS, XRD, XPS, and SEM-EDS were employed to analyze the characteristics of the research electrode materials. Surface analysis reveals that 6-Tg forms a protective corrosion inhibition film on the surface of the covered patina electrode, influencing the transition of Cu2(OH)3Cl to the more stable Cu2(OH)2CO3 crystal. Electrochemical results demonstrate that, after 600 h in the corrosion solution containing 0.1 g/L of 6-Tg, the corrosion potential and corrosion current reach 0.244 V and 4.9 μA cm−2, respectively. Upon adding 1.2 g/L of NaH2PO4, the polarization resistance and inhibiting efficiencies reach 15.6 kΩ cm2 and 99%, resulting in a synergistic corrosion inhibition effect and passivation potential shift from −0.6 V to 0.2 V region.

Background Spinal cord injury (SCI) poses a challenge due to limited treatment options. Recently, the effect and mechanism of Exo-loaded cannabinoid receptor type 2 (CB2) agonist AM1241(Exo + AM1241) have been applied in other inflammatory diseases but not in SCI.Methods The SCI model was set up using C57BL/6 mice, followed by the treatment of Exo, AM1241, and Exo + AM1241. We assessed the effects of the following treatments on motor function recovery using BMS, and evaluated histological changes, apoptosis activity, inflammation, and oxidative stress in the SCI mice model. Additionally, the effect of following treatments on spinal cord neural stem cells (NSCs) was evaluated under lipopolysaccharides (LPS) induced inflammatory and oxidative models and, glutamate (Gluts) induced cell apoptosis models.Result Our results demonstrated that Exo + AM1241 treatment significantly improved motor function recovery, after SCI by decreasing proinflammatory cytokines, and suppressing astrocyte/microglia (GFAP/Iba1) activation in the injury zone. Additionally, this treatment reduces pro-apoptotic proteins (Bax and caspase 3), increases the levels of the anti-apoptotic protein Bcl-2, enhances antioxidant defenses by boosting SOD and GSH, and lowers oxidative stress markers such as MDA. It also activates the Nuclear factor erythroid-2 (Nrf2) related factor 2 signaling pathway, thereby enhancing tissue protection against damage and cell death.

Background and aimThe prognosis of microsatellite stable (MSS)-colorectal cancer liver metastasis (CRCLM) following failure of multi-line therapy remains dismal. The aim of this study is to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus fruquintinib and tislelizumab (HAIC-F-T treatment) for MSS-CRCLM which failed from multiple-line therapy.MethodsFrom February 2021 to June 2023, 45 patients with MSS-CRCLM after failure of multiple-line therapy who received HAIC combined with fruquintinib and tislelizumab (HAIC-F-T triple treatment) were enrolled. The combination therapy included HAIC regimens with oxaliplatin and 5-fluorouracil or irinotecan, oxaliplatin, and 5-fluorouracil on days 1-2, intravenous tislelizumab (200 mg) before HAIC on day 1, and oral fruquintinb (3 mg/d) on day 3-21, every 4 weeks. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method.ResultsThe follow-up ended on June 22, 2024, with a median follow-up time of 17.5 months. The objective response rate was 42.2%, and the disease control rate was 82.2%. The median OS was 15.3 months (95% confidence interval [CI]:12.634-17.966), and the median PFS was 7.5 months (95% CI:5.318-9.682). The independent risk factors related to worse OS were previous PD-1 immunotherapy (P = 0.021) and the number of HAIC-F-T triple treatment cycles of ≤ 2 (P = 0.007). The incidence of grade 3 or higher adverse events (AEs) was 20%, with the most frequent grade 3 or higher AEs being abdominal pain (3/45, 6.7%).ConclusionHAIC combined with fruquintinib and tislelizumab may be an alternative salvage treatment for patients with MSS-CRCLM following failure of multiple-line therapy.

Abstract With a continually evolving society and increasing environmental energy concerns, green biomass materials are attracting considerable attention in the field of energy storage owing to their low cost, environmental friendliness, and excellent storage capacity. Biomass materials prepared by various methods have been used as electrodes in secondary batteries. In this review, we discuss the application scope of different types of biomass and biomass‐derived materials in zinc‐air, lithium‐ion, and lithium‐sulfur batteries. The application of biomass and biomass‐derived materials in batteries is gaining increasing attention and is expected to drive many exciting innovations in the field of sustainable energy storage technologies.

Choosing a suitable core loss model and accurately predicting energy loss are crucial in designing magnetic devices with high efficiency based on soft magnetic composites (SMCs). In this work, FeSiAl and FeSi SMCs with a uniform insulating layer were fabricated by a phosphating process. The effects of excitation waveform and DC bias field on core loss have been investigated in depth. The results show that different remagnetization rates of SMC under ideal sinusoidal and square waves result in different core losses at the same frequency and flux density. The improved general Steinmetz equation and the modified Steinmetz equation were shown to be suitable for calculating core loss under square excitation waves without DC bias field. When the DC bias field is applied, the core loss of FeSiAl and FeSi SMCs was found to increase significantly due to the magnetization state gradually approaching saturation. Interestingly, the variation tendency of core loss can be accurately predicted using the waveform coefficient Steinmetz equation under square excitation conditions with a DC bias environment. This work not only provides deep insights into core loss under different excitation waveforms and DC bias fields but also determines the application scope of different core loss models.

Abstract Background and aims Flavonoids are a class of secondary plant metabolites that have been shown to have multiple health benefits, including antioxidant and anti-inflammatory. This study was to explore the association between dietary flavonoid consumption and the prevalence of chronic respiratory diseases (CRDs) in adults. Methods and results The six main types of flavonoids, including isoflavones, anthocyanidins, flavan-3-ols, flavanones, flavones, and flavonols, were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007–2010 and 2017–2018 by the two 24-h recall interviews. The prevalence of CRDs, including asthma, emphysema, and chronic bronchitis, was determined through a self-administered questionnaire. The analysis included 15,753 participants aged 18 years or older who had completed a diet history interview. After adjustment for potential confounders, the inverse link was found with total flavonoids, anthocyanidins, flavanones, and flavones, with an OR (95%CI) of 0.86 (0.75–0.98), 0.84 (0.72–0.97), 0.80(0.69–0.92), and 0.85(0.73–0.98) for the highest group compared to the lowest group. WQS regression revealed that the mixture of flavonoids was negatively linked with the prevalence of CRDs (OR = 0.88 [0.82–0.95], P

Abstract. Background:. Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism. Methods:. We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments. Results:. The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 (ERAP1) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1. The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. Conclusion:. The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1. Trial Registration:. No. NCT00454519 (https://clinicaltrials.gov/)

Abstract Background Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. Methods RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. Results In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. Conclusions We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

IntroductionSoybean, as a globally significant crop, has garnered substantial attention due to its agricultural importance. The utilization of molecular approaches to enhance grain yield in soybean has gained popularity.MethodsIn this study, we conducted a genome-wide association study (GWAS) using 156 Chinese soybean accessions over a two-year period. We employed the general linear model (GLM) and the mixed linear model (MLM) to analyze three agronomic traits: pod number, grain number, and grain weight. ResultsOur findings revealed significant associations between qgPNpP-98, qgGNpP-89 and qgHGW-85 QTLs and pod number, grain number, and grain weight, respectively. These QTLs were identified on chromosome 16, a region spanning 413171bp exhibited associations with all three traits. DiscussionThese QTL markers identified in this study hold potential for improving yield and agronomic traits through marker-assisted selection and genomic selection in breeding programs.

This study aims to explore the potential application of hollow glass beads (HGB) compounded with graphene oxide (GO, HGB@GO) to improve the mechanical properties of rigid polyurethane foam (RPUF). This HGB@GO/RPUF composite is considered a potential filler for reinforcing aluminum honeycomb (AH). A characterization of the chemical structure and surface morphology of HGB@GO was conducted, as well as the analysis of its effect on the compression properties of the foam. The compressive strength of HGB@GO/RPUF (4 wt. %) is 146.17% higher than that of pure RPUF. This study also compared the deformation modes of AH and foam-filled honeycomb (F-AH) structure under axial crushing. The interaction effects between the foam and AH were also analyzed. The results indicated that the RPUF improves the compressive capacity and deformation stability of the AH through its good compression properties and interaction with the aluminum foil. The use of HGB@GO/RPUF further enhances the energy absorption characteristics of the F-AH. In comparison with the pure RPUF-AH, the total and specific energy absorption of the HGB@GO/RPUF (4 wt. %)-AH increase by 74.65% and 44.98%, respectively. This work demonstrates that the prepared HGB@GO can enhance the mechanical properties of RPUF, and HGB@GO/RPUF-AH is expected to be a desirable energy-absorbing device.

Summary: As the only cell type responsible for oxygen delivery, erythrocytes play a crucial role in supplying oxygen to hypoxic tissues, ensuring their normal functions. Hypoxia commonly occurs under physiological or pathological conditions, and understanding how erythrocytes adapt to hypoxia is fundamental for exploring the mechanisms of hypoxic diseases. Additionally, investigating acute and chronic mountain sickness caused by plateaus, which are naturally hypoxic environments, will aid in the study of hypoxic diseases. In recent years, increasingly developed proteomics and metabolomics technologies have become powerful tools for studying mature enucleated erythrocytes, which has significantly contributed to clarifying how hypoxia affects erythrocytes. The aim of this article is to summarize the composition of the cytoskeleton and cytoplasmic proteins of hypoxia-altered erythrocytes and explore the impact of hypoxia on their essential functions. Furthermore, we discuss the role of microRNAs in the adaptation of erythrocytes to hypoxia, providing new perspectives on hypoxia-related diseases.

Ethnopharmacological relevance: Murrayae Folium et Cacumen (MFC) is a plant considered to be a traditional Chinese medicine with culinary value as well. The dry leaves and twigs of Murraya paniculata and M. exotica are used to treat stomach aches, rheumatism, toothaches, swelling, and insect and snake bites. They are also used to prepare spicy chicken dishes.Aim of the review: This review comprehensively summarizes the available information on the botanical characterization, phytochemistry, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC.Methods: Relevant scientific literature up to August 2023 was included in the study. Chinese and English studies on MFC were collected from databases, including PubMed, Elsevier, Web of Science, Springer, Science Direct, Wiley, ACS, and CNKI (Chinese). Doctoral and Master’s dissertations were also included.Results: In total, 720 compounds have been identified and reported in the literature, including flavonoids, coumarins, alkaloids, sterols, phenylpropenols, organic acids, spirocyclopentenones, and volatile oils. Flavonoids and coumarins are the two most important bioactive compounds responsible for these pharmacological activities. MFC has anti-inflammatory, anti-bacterial, anti-microbial, anti-diabetic, anti-tumor, anti-oxidant, anti-depressant, potential anti-Alzheimer’s disease, chondroprotective, and analgesic properties. The pharmacological effects include interrupting the STAT3/NF-κB/COX-2 and EGFR signaling pathways, downregulating EpCAM expression, inhibiting NF-κB and ERK signals, inhibiting the EP/cAMP/PKA signaling pathway and miR-29a/Wnt/β-catenin signaling activity, and upregulating Foxo3a expression.Conclusion: This review demonstrates that the chemical constituents, pharmacological activities, pharmacodynamics, pharmacokinetics, and toxicity of MFC support its use in traditional Chinese botanical medicines. MFC contains a wide range of chemical compounds. Flavonoids and coumarins promote strong pharmacological activity and, are low-toxicity natural phytomedicines that are widely used in medicine, food, ornamentation, and cosmetics, making MFC a promising compound for development and use in the treatment of several medical conditions.

Ultrasonic electrodeposition was employed to manufacture ZnCo2O4 anode nanomaterials (ZCOAN), with the objective of utilization as high-performance anode materials for lithium-ion batteries. The influence of ultrasonic power on various characteristics of ZCOAN, including surface morphology, phase composition, crystal structure, and electrochemical properties was also investigated. The results indicated that ZnCo2O4 anode nanomaterials prepared at 600 W demonstrated a spinel surface structure with polyporous dendrite spores and a subcrystalline size of 11.68 nm. Moreover, the prepared ZCOAN material demonstrated polyporous morphological characteristics and well-organized particles. Diffraction peaks were identified at specified angles in all ZCOAN samples: 31.26°, 36.93°, 46.38°, 54.13°, 59.87°, and 66.17° corresponding to the crystallographic planes (200), (311), (400), (422), (511), and (440), respectively. The appearance of these peaks confirms the presence of a spinel structure in the ZCOAN samples. A smaller grain size results in increased gaps and a larger surface area, thereby promoting ion exchange. Therefore, ZnCo2O4 anode nanomaterials synthesized at 600 W showed superior electrochemical performance compared to other samples. They demonstrated the highest charge capacity (∼1176 mAh·g−1), discharge capacity (∼1160 mAh·g−1), and stability, along with a minimal electrical impedance (35.65 Ω) at a constant current density of 150 mA·g−1. Furthermore, the coulomb efficiency of this nanomaterial remained high at 98.6 % after 1200 cycles, indicating its excellent cycling performance.

Abstract Background Different posterior inclinations of tibial component after unicompartmental knee arthroplasty (UKA) may lead to different biomechanical characteristics of the knee joint. This finite element study was designed to investigate the tibiofemoral contact pressures after UKA with different posterior inclinations of tibial component. Methods Finite element model of a healthy knee joint was constructed, and mobile-bearing (MB) UKA models with 5 different posterior inclinations (3°, 5°, 7°, 9° and 11°) of tibial components were simulated. The maximum contact pressures of tibial plateau cartilage in the lateral compartment and polyethylene insert in the medial compartment were calculated based on the ground reaction force and the angle of the knee flexion obtained by 3D motion capture system. Results The loading ratio of medial and lateral compartments during standing stance (medial 54.49%, lateral 45.51%) and tibial anterior displacement (134 N, 3.89 mm) of healthy knee was basically consistent with previous experimental data. The maximum contact pressures of the medial meniscus and lateral tibial plateau cartilage of the healthy knee during standing stance were 2.14 MPa and 1.57 MPa, respectively. At the static standing phase, the maximum contact pressures of the polyethylene insert decreased from 17.90 to 17.29 Mpa, and the maximum contact pressures of the tibial plateau cartilage in the lateral compartment increased from 0.81 to 0.92 Mpa following an increase in the posterior inclination of the tibial component. At the first peak of ground reaction force, the maximum contact pressures of polyethylene insert increased from 22.37 to 25.16 MPa, and the maximum contact pressures of tibial plateau cartilage in the lateral compartment increased from 3.03 to 3.33 MPa, with the increase in the posterior inclination of the tibial component. At the second peak of ground reaction force, the maximum contact pressures of polyethylene insert decreased from 2.34 to 2.22 MPa with the increase in posterior inclination of tibial component. Conclusion The preoperative and postoperative finite element models of MB UKA were well established. The results showed that the maximum contact pressures of the polyethylene insert did not change significantly with the increase in the posterior inclination of the tibial prosthesis, while the maximum contact pressures of the tibial plateau cartilage of the lateral compartment increased when the posterior inclination of the tibial prosthesis was > 7°. Our results also show that the maximum contact pressures were greater with an excessive inclination angle (11°) of the tibial component, and the pressures of the tibial plateau cartilage in the lateral compartment were more concentrated on the posterior area. This study, therefore, proposes that excessive osteotomy should be avoided.

Abstract Background Metagenomic sequencing is an unbiased approach that can potentially detect all the known and unidentified strains in pathogen detection. Recently, nanopore sequencing has been emerging as a highly potential tool for rapid pathogen detection due to its fast turnaround time. However, identifying pathogen within species is nontrivial for nanopore sequencing data due to the high sequencing error rate. Results We developed the core gene alleles metagenome strain identification (cgMSI) tool, which uses a two-stage maximum a posteriori probability estimation method to detect pathogens at strain level from nanopore metagenomic sequencing data at low computational cost. The cgMSI tool can accurately identify strains and estimate relative abundance at 1× coverage. Conclusions We developed cgMSI for nanopore metagenomic pathogen detection within species. cgMSI is available at https://github.com/ZHU-XU-xmu/cgMSI .

Abstract Background The influence of sarcopenic obesity (SO) on overall survival in older adults with hypertension has not been addressed. The aim of this study was to investigate the prevalence and mortality predictive value of various body composition phenotypes, focusing mainly on SO, in older adults with hypertension. Methods We included 1105 hypertensive patients aged ≥ 60 years from the National Health and Nutrition Examination Survey 1999–2004. Sarcopenia was broadly defined based on low lean mass (LLM; as measured by dual-energy X-ray absorptiometry), and was defined using appendicular lean mass (ALM) divided by height squared (ALM/height2), weight (ALM/weight), and body mass index (BMI; ALM/BMI), respectively. Obesity was defined as BMI ≥ 30 kg/m2, body fat percentage ≥ 30/42%, or waist circumference ≥ 102/88 cm. The prevalence of LLM with obesity was estimated according to each ALM index (ALMI). Multivariable Cox regression analysis and sensitivity analysis were used to examine the association between various body composition phenotypes and all-cause mortality. Results In older adults with hypertension, the prevalence of LLM with obesity by the ALM/height2 index (9.8%) was lower relative to the ALM/weight (11.7%) and ALM/BMI indexes (19.6%). After a median follow-up of 15.4 years, 642 deaths occurred. In the fully adjusted models, LLM with obesity was significantly associated with a higher risk of all-cause mortality (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.14–2.49, P = 0.008; HR 1.48, 95% CI 1.04–2.10, P = 0.028; HR 1.30, 95% CI 1.02–1.66, P = 0.037; respectively) compared with the normal body phenotype, with no statistical differences found in individuals with LLM or obesity alone. Sensitivity analysis confirmed the robustness of the results. Conclusions The prevalence of LLM with obesity markedly differed in older adults with hypertension according to the 3 different ALMIs, varying from 9.8%, 11.7%, to 19.6%. Patients with both LLM and obesity had a higher risk of all-cause mortality. Further large, prospective, cohort studies are warranted to validate these findings and uncover underlying mechanisms.

Abstract Genome-wide association studies have identified numerous variants associated with human complex traits, most of which reside in the non-coding regions, but biological mechanisms remain unclear. However, assigning function to the non-coding elements is still challenging. Here we apply Activity-by-Contact (ABC) model to evaluate enhancer-gene regulation effect by integrating multi-omics data and identified 544,849 connections across 20 cancer types. ABC model outperforms previous approaches in linking regulatory variants to target genes. Furthermore, we identify over 30,000 enhancer-gene connections in colorectal cancer (CRC) tissues. By integrating large-scale population cohorts (23,813 cases and 29,973 controls) and multipronged functional assays, we demonstrate an ABC regulatory variant rs4810856 associated with CRC risk (Odds Ratio = 1.11, 95%CI = 1.05–1.16, P = 4.02 × 10−5) by acting as an allele-specific enhancer to distally facilitate PREX1, CSE1L and STAU1 expression, which synergistically activate p-AKT signaling. Our study provides comprehensive regulation maps and illuminates a single variant regulating multiple genes, providing insights into cancer etiology.

Abstract Background IFN-λ has been shown to have a dual function in cancer, with its tumor-suppressive roles being well-established. However, the potential existence of a negative ‘‘tumor-promoting’’ effect of endogenous IFN-λ is still not fully understood. Methods We conducted a comprehensive review and analysis of the perturbation of IFN-λ genes across various cancer types. Correlation coefficients were utilized to examine the relationship between endogenous IFN-λ expression and clinical factors, immune cell infiltration, tumor microenvironment, and response to immunotherapy. Genes working together with IFN-λ were obtained by constructing the correlation-based network related to IFN-λ and the gene interaction network in the KEGG pathway and IFN-λ-related genes obtained from the networks were integrated as candidate markers for the prognosis model. We then applied univariate and multivariate COX regression models to select cancer-specific independent prognostic markers associated with IFN-λ and to investigate risk factors for these genes by survival analysis. Additionally, computational methods were used to analyze the transcriptome, copy number variations, genetic mutations, and methylation of IFN-λ-related patient groups. Result Endogenous expression of IFN-λ has been linked to poor prognosis in cancer patients, with the genes IFN-λ2 and IFN-λ3 serving as independent prognostic markers. IFN-λ acts in conjunction with related genes such as STAT1, STAT2, and STAT3 to affect the JAK-STAT signaling pathway, which promotes tumor progression. Abnormalities in IFN-λ genes are associated with changes in immune checkpoints and immune cell infiltration, which in turn affects cancer- and immune-related pathways. While there is increased immune cell infiltration in patients with IFN-λ expression, this does not improve survival prognosis, as T-cell dysfunction and an inflammatory environment are also present. The amplification of IFNL2 and IFNL3 copy number variants drives specific endogenous expression of IFN-λ in patients, and those with this specific expression have been found to have more mutations in the TP53 gene and lower levels of DNA methylation. Conclusion Our study integrated multi-omics data to provide a comprehensive insight into the dark side of endogenous IFN-λ, providing a fundamental resource for further discovery and therapeutic exploration in cancer.

Owing to the convenience of online loans, an increasing number of people are borrowing money on online platforms. With the emergence of machine learning technology, predicting loan defaults has become a popular topic. However, machine learning models have a black-box problem that cannot be disregarded. To make the prediction model rules more understandable and thereby increase the user’s faith in the model, an explanatory model must be used. Logistic regression, decision tree, XGBoost, and LightGBM models are employed to predict a loan default. The prediction results show that LightGBM and XGBoost outperform logistic regression and decision tree models in terms of the predictive ability. The area under curve for LightGBM is 0.7213. The accuracies of LightGBM and XGBoost exceed 0.8. The precisions of LightGBM and XGBoost exceed 0.55. Simultaneously, we employed the local interpretable model-agnostic explanations approach to undertake an explainable analysis of the prediction findings. The results show that factors such as the loan term, loan grade, credit rating, and loan amount affect the predicted outcomes.

In the field of unmanned aerial vehicle (UAV) control, high-precision navigation algorithms are a research hotspot. To address the problem of poor localization caused by non-line-of-sight (NLOS) errors in ultra-wideband (UWB) systems, an UWB/MIMU integrated navigation method was developed, and a particle filter (PF) algorithm for data fusion was improved upon. The extended Kalman filter (EKF) was used to improve the method of constructing the importance density function (IDF) in the traditional PF, so that the particle sampling process fully considers the real-time measurement information, increases the sampling efficiency, weakens the particle degradation phenomenon, and reduces the UAV positioning error. We compared the positioning accuracy of the proposed extended Kalman particle filter (EKPF) algorithm with that of the EKF and unscented Kalman filter (UKF) algorithm used in traditional UWB/MIMU data fusion through simulation, and the results proved the effectiveness of the proposed algorithm through outdoor experiments. We found that, in NLOS environments, compared with pure UWB positioning, the accuracy of the EKPF algorithm in the X- and Y-directions was increased by 35% and 39%, respectively, and the positioning error in the Z-direction was considerably reduced, which proved the practicability of the proposed algorithm.

In-depth insights into the oligomers of carbon dots (CDs) prepared from small-molecule precursors are important in the study of the carbonization mechanism of CDs and for our knowledge of their complex structure. Herein, citric acid (CA) and ethylenediamine (EDA) were used as small-molecule precursors to prepare CDs in an aqueous solution. The structure of oligomers acquired from CA and EDA in different molar ratios and their formation process were first studied using density functional theory, including the dispersion correction (DFT-D3) method. The results showed that the energy barrier of dimer cyclization was higher than that of its linear polymerization, but the free energy of the cyclized product was much lower than that of its reactant, and IPCA (5-oxo-1,-2,3,5-tetrahydroimidazo [1,2-a]pyridine-7-carboxylic acid) could therefore be obtained under certain conditions. The oligomers obtained from different molar ratios of EDA and CA were molecular clusters formed by short polyamide chains through intermolecular forces; with the exception of when the molar ratio of EDA to CA was 0.5, excessive CA did not undergo an amidation reaction but rather attained molecular clusters directly through intermolecular forces. These oligomers exhibited significant differences in their surface functional groups, which would affect the carbonization process and the surface structure of CDs.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by pruritus. The efficacy of traditional treatment for moderate and severe AD is not satisfactory. AD has complex and multi-factor pathophysiological mechanisms.JAK-STAT pathway plays an important role in the pathogenesis of AD. Abrocitinib is a highly selective oral inhibitor of janus kinase 1 (JAK1), which can inhibit JAK-STAT signal transduction and activation pathways, resulting in down-regulation of the expression of IL-4, IL-13 and IL-31, which all are involved in the pathogenesis of AD, and ultimately blocks the occurrence and the development of AD. Abrocitinib has shown a good efficacy, tolerability and safety in the treatment of refractory moderate to severe AD. This article reviews the pharmacological mechanisms, clinical efficacy, safety and clinical applications of abrocitinib.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder that usually manifests in childhood and is thought to be caused by a complex interaction of genetic, environmental, and immune factors. The majority of current ASD diagnostic methods rely on subjective behavioral observation and scale assessment, making early detection difficult. In this study, we confirmed that lysosomal-associated membrane protein 1 (LAMP1), a functional marker of immune cell activation and cytotoxic degranulation, was upregulated in ASD blood, brain cortex, and various genetic animal models or cells using bioinformatics approaches. The prognostic value of LAMP1 was investigated by correlating its expression with clinical ASD rating scales, and the receiver operating characteristic (ROC) curve analysis in ASD also revealed that it has a favorable diagnostic ability in distinguishing ASD from control cohort. According to gene set enrichment analysis (GSEA) results, LAMP1 correlated with genes that were enriched in natural kill and T cell immune function. Taking all of the evidence into account, we discovered that abnormal elevations of LAMP1 mRNA and protein in the blood of ASD children, may influence the development of ASD through its involvement in immune cell activity regulation. This report highlights a novel marker for ASD early detection as well as potential therapeutic targets.

Abstract Chimeric antigen receptor (CAR)-T cell therapy is rapidly advancing as cancer treatment, however, designing an optimal CAR remains challenging. A single-chain variable fragment (scFv) is generally used as CAR targeting moiety, wherein the complementarity-determining regions (CDRs) define its specificity. We report here that the CDR loops can cause CAR clustering, leading to antigen-independent tonic signalling and subsequent CAR-T cell dysfunction. We show via CARs incorporating scFvs with identical framework and varying CDR sequences that CARs may cluster on the T cell surface, which leads to antigen-independent CAR-T cell activation, characterized by increased cell size and interferon (IFN)-γ secretion. This results in CAR-T cell exhaustion, activation-induced cell death and reduced responsiveness to target-antigen-expressing tumour cells. CDR mutagenesis confirms that the CAR-clustering is mediated by CDR-loops. In summary, antigen-independent tonic signalling can be induced by CDR-mediated CAR clustering, which could not be predicted from the scFv sequences, but could be tested for by evaluating the activity of unstimulated CAR-T cells.

Abstract Aims The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all‐cause mortality in AHF patients. Methods and results Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all‐cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan–Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93–0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36–6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17–0.82; P = 0.014), N‐terminal pro‐B‐type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01–1.03; P

Abstract Background & objective Little research was available to explore which surgical fixation was better between fixation of both clavicle and scapula and clavicle alone in management of floating shoulder injury. Methods Total 69 patients with floating shoulder injury receiving surgery from February 2005 to July 2020 participated in the study. 49 patients underwent fixation of the clavicle alone (Group C) while 20 patients underwent fixation of both clavicle and scapula (Group C + S). They were further divided into subgroups according to age: Group C1, Group C + S1 (age ≤ 55 years old) and Group C2, Group C + S2 (age>55 years old). The radiological parameter (glenopolar angle (GPA)) and clinical outcomes (Herscovici score, Constant-Murley shoulder outcome score (CSS score), and Visual Analogue Scale score (VAS score)) were collected and compared between these groups. The correlation between age and radiological parameter and clinical outcomes was calculated by the Spearman correlation analysis. Results All people were followed up for at least 1 year. The degree of change in GPA before and after surgery in Group C + S is significantly better than that in Group C. The Herscovici and CSS score in Group C + S2 were significantly higher than those in Group C2 at 1 month, 3 months and 1 year after surgery. However, no significant difference in Herscovici and CSS score was found at final follow-up (1 year after surgery) between Group C + S1 and Group C1. The VAS score in Group C + S2 at final follow-up was significantly lower than that in Group C2. No significant difference in VAS score at final follow-up was found between Group C + S1 and Group C1. In addition, the VAS score was negatively correlated with Herscovici and CSS score. No correlation was found between VAS score and GPA. Conclusions Both types of surgical fixation are effective in management of floating shoulder injury. For young people with floating shoulder injury, both types of surgical fixation are equally effective. However, for older people with floating shoulder injury, fixation of both clavicle and scapula is better in prognosis than fixation of clavicle alone.

Abstract Background The triglyceride glucose (TyG) index, an indicator of insulin resistance, is often associated with adverse outcomes in various cardiovascular diseases, while hypertension is associated with an increased risk of cardiovascular diseases. As the loss of muscle mass in people with hypertension is poorly understood, the current study aimed to explore the relationship between TyG index and muscle mass in hypertensive population. Methods We analyzed data from hypertensive adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. The TyG index and body mass index (BMI)-adjusted skeletal muscle mass index (SMI) were calculated and the relationship between the two was evaluated using multivariable linear regression and restricted cubic spline (RCS) regression models. Results A total of 1633 participants in the dataset were included for the final analysis. In the multivariable regression analysis, the adjusted β of SMI with a 95% confidence interval (CI) for the highest TyG index quartile was − 5.27 (− 9.79 to − 0.75), compared with the lowest quartile. A negative linear relationship between TyG index and SMI was plotted by RCS regression (nonlinear P = 0.128). Stratified models of non-smoking women of different ages also demonstrated that SMI decreased as TyG index increased (all P for trend

Abstract Background Anterior cervical discectomy and fusion (ACDF) is the gold standard for treating cervical spondylotic myelopathy (CSM). While implanting plates in ACDF may increase the risk of complications. Zero-P and ROI-C implants have been gradually applied for CSM. Methods 150 patients with CSM were retrospectively analyzed from January 2013 to July 2016. Group A consisted of 56 patients who received traditional titanium plates with cage. 94 patients underwent ACDF using zero-profile implants and were divided into 50 patients with the Zero-P device (Group B) and 44 with the ROI-C device (Group C). Related indicators were measured and compared. The clinical outcomes were evaluated by JOA, VAS, and NDI scores. Results Compared with group A, group B and C had a less blood loss and shorter operation time. The JOA and VAS scores improved significantly from pre-operative to 3 months postoperative and last follow-up in three groups. The cervical physiological curvature and segmental lordosis at final follow-up were higher than that of pre-operation (p

As an effective tool for refining local gravity data with mGal accuracy, vehicle gravimetry system usually consists of Strapdown Inertial Navigation System (SINS) and Global Navigation Satellite System (GNSS). However, the traditional system is unable to achieve gravimetry in an environment without GNSS signal dues to heavy dependence on GNSS signal. To solve this problem, this study proposed a gravimetry method specifically for the environment without GNSS signal, which consists of the high-precision Strapdown Inertial Navigation System (SINS) and Laser Doppler Velocimeter (LDV) developed by our unit. Based on the error analysis, the system index requirements were proposed, and the relevant indexes of the LDV are verified through simulation and vehicle experiment. The simulation results for different velocimeter accuracies show that the internal accord accuracy of the system is within 1mGal when the velocimeter accuracy is 1 ‰, and the internal accord accuracies of the system are more than 1mGal when the velocimeter accuracies are 5 ‰ and 10‰. The results of the vehicle experiment for different dimensional velocimeters show that when the spatial resolution is 1.7 km, the SINS/LDV (2D) and SINS/GNSS integrated systems have an internal accord accuracy of 0.68 mGal and 0.54 mGal, respectively, while the SINS/LDV (1D) integrated system has an internal accord accuracy of 1.50 mGal. The feasibility of the SINS/LDV system and the necessity of the SINS/LDV system for the dimension and accuracy of the velocimeter are illustrated.

Abstract Left ventricle ejection fraction (LVEF) is still not well acknowledged in classification of pediatric heart failure (PHF). We categorized PHF according to LVEF and aimed to determine the role of LVEF in PHF classification. Patients who were diagnosed with HF were divided into three groups according to their LVEF values: HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF), and HF with preserved ejection fraction (HFpEF). The clinical information of PHF patients was compared among those three groups. Factors associated with HF with improved EF (HFimpEF) and risk factors for in‐hospital death in PHF patients were analyzed. A total number of 1228 cases were collected. The proportion of HF patients with preserved LVEF (66.3%) was significantly higher than those with mildly reduced LVEF (21.7%) and reduced LVEF (12%). Clinical features such as age, B‐type natriuretic peptide (BNP) level, Ross classification, and E/A abnormal proportion in HF children with different LVEF value were statistically different. HF patients with younger age, lower BNP levels, minor cardiac dysfunction and less E/A abnormality could be found with higher LVEF value. The proportion of primary disease in PHF was largely different in HFpEF, HFmrEF and HFrEF groups. Medication treatment was more aggressive in patients with lower LVEF, except for vasoactive drugs. Children with congenital heart disease in HFrEF group were more prone to develop into HFimpEF. Sepsis, renal insufficiency, and an abnormal E/A ratio are risk factors for in‐hospital death of HF children. Clinical features of PHF could be well classified by LVEF, which is an essential and helpful indicator for PHF classification and management.

Introduction: Image recognition technology has immense potential to be applied in industrial energy systems for energy conservation. However, the low recognition accuracy and generalization ability under actual operation conditions limit its commercial application. Objectives: To improve the recognition accuracy and generalization ability, a novel image recognition method integrating deep learning and domain knowledge was applied to assist energy saving and emission reduction for industrial energy systems. Methods: As a typical industrial scenario, the defrosting control in the refrigeration system was selected as the specific optimization object. By combining deep learning algorithm with domain knowledge, a residual-based convolutional neural network model (RCNN) was proposed specifically for frosty state recognition, which features the residual input and average pooling output. Based on the real-time recognition of frosty levels, a defrosting control optimization method was proposed to initiate and terminate the defrosting operation on demand. Results: By combining the advanced image recognition technique with specific energy domain knowledge, the proposed RCNN enables both high recognition accuracy and strong generalization ability. The recognition accuracy of RCNN reached 95.06% for the trained objects and 93.67% for non-trained objects while that of only 75.86% for the conventional CNN. By adopting the presented system optimization method assisted by RCNN, the defrosting frequency, accumulated time and energy consumption were 53.8%, 57.02% and 34.5% less than the original control method. Furthermore, the environmental and cost analysis illustrated that the annual reduction in CO2 emissions is 2145.21 to 3412.84 kg and the payback time was less than 2.5 years which was far below the service life. Conclusion: The technical feasibility and significant energy-saving benefits of deep learning-based image recognition method were demonstrated through the field experiment. Our study shows the great application potential of image recognition technology and promotes carbon neutrality in industrial energy systems.

Abstract Background Recent studies have reported that the circadian transcription factor aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) promotes the metastatic progression of lung adenocarcinoma. However, the molecular mechanisms of ARNTL2 in non-small cell lung cancer (NSCLC) cell growth and proliferation remain to be explored. Methods The expression of ARNTL2 and acyl-CoA thioesterase 7 (ACOT7) in lung cancer patients was analyzed based on TCGA database. Gain-of-function of ARNTL2 and ACOT7 was conducted by transfecting the cells with plasmids or lentivirus. Knockdown assay was carried out by siRNAs. Western blot and qRT-PCR were performed to check the protein and mRNA expression. Dual luciferase and ChIP-qPCR assay was applied to check the interaction of ARNTL2 on ACOT7’s promoter sequence. Triglyceride level, MDA production, the activity of casapase 3 to caspase 7, and lipid ROS were measured by indicated assay kit. Cellular function was detected by CCK8, colony formation and flow cytometry analysis of cell death and cell cycle. Results We demonstrated that ARNTL2 upregulation of ACOT7 was critical for NSCLC cell growth and proliferation. Firstly, overexpression of ARNTL2 conferred the poor prognosis of LUAD patients and supported the proliferation of NSCLC cells. Based on molecular experiments, we showed that ARNTL2 potentiated the transcription activity of ACOT7 gene via direct binding to ACOT7’s promoter sequence. ACOT7 high expression was correlated with the worse prognosis of LUAD patients. Gain-of-function and loss-of-function experiments revealed that AOCT7 contributed to NSCLC cell growth and proliferation. ACOT7 regulated the apoptosis and ferroptosis of NSCLC cells, while exhibited no effect on cell cycle progression. ACOT7 overexpression also potentiated fatty acid synthesis and suppressed lipid peroxidation. Lastly, we showed that ARNTL2 knockdown and overexpression inhibited and promoted the cellular triglyceride production and subsequent cell proliferation, which could be reversed by ACOT7 overexpression and knockdown. Conclusion Our study illustrated the oncogenic function of ARNTL2/ACOT7 axis in the development of NSCLC. Targeting ARNTL2 or ACOT7 might be promising therapeutic strategies for NSCLC patients with highly expressed ARNTL2.

Abstract Background Given their potent antioxidation properties, carotenoids play a role in delaying and preventing dementia and mild cognitive impairment (MCI). However, observational studies have found inconsistent results regarding the associations between blood carotenoid levels and the risk of dementia and MCI. We conducted this systematic review and meta-analysis to investigate the relationship between blood carotenoid levels and the risk of dementia and MCI. Methods A systematic search was performed in the Web of Science, PubMed, Embase, and Cochrane Library electronic databases to retrieve relevant English articles published from their inception until February 23, 2023. Study quality was assessed by the Newcastle-Ottawa scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were pooled using random-effect meta-analyses. Ultimately, 23 studies (n = 6610) involving 1422 patients with dementia, 435 patients with MCI, and 4753 controls were included. Results Our meta-analysis showed that patients with dementia had lower blood lycopene (SMD: -0.521; 95%CI: -0.741, -0.301), α-carotene (SMD: -0.489; 95%CI: -0.697, -0.281), β-carotene (SMD: -0.476; 95%CI: -0.784, -0.168), lutein (SMD: -0.516; 95%CI: -0.753, -0.279), zeaxanthin (SMD: -0.571; 95%CI: -0.910, -0.232) and β-cryptoxanthin (SMD: -0.617; 95%CI: -0.953, -0.281) than the controls. Our results indicated that blood carotenoid levels were significantly lower in patients with dementia than in controls, despite high heterogeneity across the studies. Owing to insufficient data, we did not observe a similar and stable relationship between blood carotenoid levels and MCI. Conclusions Our meta-analysis indicated that lower blood carotenoid levels may be a risk factor for dementia and MCI.

Physalis philadelphica, a member of the Solanaceae family, commonly known as Physalis, is a one-year-old herbaceous plant with both medicinal and edible properties, as well as ornamental value. At present, only limited research is available on the flower color of P. philadelphica. This study aimed to elucidate the metabolic characteristics underlying the flower color of P. philadelphica and to identify key genes associated with flower color metabolism. We selected two representative varieties of P. philadelphica with significant differences in flower color, namely, “Tieba” (yellow flower) and “Qingjin” (yellow-purple flower), as the experimental materials. The analysis of related pigment components and the determination of relative content by high-performance liquid chromatography were conducted to investigate the flower color-related metabolic pathways of P. philadelphica. Through next-generation sequencing, these pathways were further investigated for the characteristics and differentially expressed genes (DEGs) associated with flower color formation. The results of the research show that: Anthocyanin is the main component of petal coloring of P. philadelphica var. Qingjin, while malvidin pigment, pelargonidin, delphinidin, and cyanidin are the main components of flower color intensity. Carotenoids are the main components of the petal coloring of P. philadelphica var. Tieba and β-carotene is the main component of flower color intensity. Comparing different developmental stages of these two kinds of Physalis pubescens, we identified two key transcription factors (TFs) (eBP and STAT) that were involved in the inhibition of anthocyanin synthesis and regulate the inhibition of pf05G124640 (dihydroflavonol 4-reductase) and pf09G224140 (anthocyanin synthase) in anthocyanin synthesis. One heat shock transcription factor was found to regulate the flavonoid and flavonol synthesis pathway of pf01G020090 (anthocyanin 3-O-glucosyltransferase); two key TFs (NAC and G2-Like), pf10G255070 (isoricin dehydrogenase) and pf09G237080 (abscisic acid 8′-hydroxylase), played important roles in carotene biosynthesis. This study provides new insights for further exploration of the genetic diversity of petal coloring in P. philadelphica and establishes a foundation for subsequent molecular breeding efforts.

In this paper, the solid-state shear milling (S3M) strategy featuring a very strong three-dimensional shear stress field was adopted to prepare the high-performance polyoxymethylene (POM)/molybdenum disulfide (MoS2) functional nanocomposite. The transmission electron microscope and Raman measurement results confirmed that the bulk MoS2 particle was successfully exfoliated into few-layer MoS2 nanoplatelets by the above simple S3M physical method. The polarized optical microscope (PLM) observation indicated the pan-milled nanoscale MoS2 particles presented a better dispersion performance in the POM matrix. The results of the tribological test indicated that the incorporation of MoS2 could substantially improve the wear resistance performance of POM. Moreover, the pan-milled exfoliated MoS2 nanosheets could further substantially decrease the friction coefficient of POM. Scanning electron microscope observations on the worn scar revealed the tribological mechanism of the POM/MoS2 nanocomposite prepared by solid-state shear milling. The tensile test results showed that the pan-milled POM/MoS2 nanocomposite has much higher elongation at break than the conventionally melt-compounded material. The solid-state shear milling strategy shows a promising prospect in the preparation of functional nanocomposite with excellent comprehensive performance at a large scale.

Using the rotating vector model (RVM) and aiming to constrain the value of the magnetic inclination angle (α), we perform a least-squares fit on the linearly polarized position angles of 125 pulsars from Parkes 64 m archive data at 1400 MHz. Subsequently, a statistical analysis of the normalized Q parameters is carried out. Furthermore, based on the Q-parameter, we provide a further understanding of the geometry of the radio emission region of the pulsar. In this statistical sample, about 1/5 of the sample is clustered at 0, suggesting that this part of the pulsar is viewed from the center of the radiation cone. For the rest of the pulsars, the Q parameters follow a uniform distribution, supporting the conclusion that the interface of the radiation cone is non-elliptical.

Brusatol (Bru), a bioactive compound found in Brucea sumatrana, exerts antitumour effects on several malignancies. However, the role and molecular mechanism of Bru in squamous cell carcinoma of the oesophagus (ESCC) remain unclear. Here, we found that Bru decreased the survival of ESCC cells. Subsequently, the ferroptosis inhibitors, deferoxamine and liproxstatin-1, rescued Bru-induced cell death, indicating that ferroptosis plays a major role in Bru-induced cell death. Furthermore, Bru promoted lipid peroxidation, glutathione (GSH) depletion, and ferrous iron overload in vitro. Consistent with these in vitro results, Bru significantly inhibited tumour growth in KYSE150 xenograft nude mice by triggering ferroptosis. Mechanistically, nuclear factor E2-related factor 2 (NRF2) inactivation via increased ubiquitin-proteasome degradation was found to be a vital determinant of ferroptosis induced by Bru. Notably, Bru significantly decreases GSH synthesis, iron storage, and efflux by downregulating the expression of NRF2 target genes (glutamate-cysteine ligase catalytic subunit (GCLC), solute carrier family 7 member 11 (SLC7A11), ferritin heavy chain 1 (FTH1), and solute carrier family 40 member 1 (SLC40A1)), resulting in the accumulation of lethal lipid-based reactive oxygen species (ROS) and intracellular enrichment of chelated iron. Taken together, our findings indicate that ferroptosis is a novel mechanism underlying Bru-induced antitumour activity and will hopefully provide a valuable compound for ESCC treatment.