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Abstract To address the issue of green transformation in resource-exhausted cities, this study employs the Policy Modeling Consistency (PMC) index model to carry out a comprehensive analysis of the effectiveness of support policies execution at both central and local levels, covering 16 policies at the different administrative levels. Meanwhile, utilizing the fuzzy-set Qualitative Comparative Analysis (fsQCA) method, the study investigates the interaction mechanisms and effects of various internal and external factors in the context of policy coordination, from the perspective of green transformation condition configurations. The findings reveal that the overall effect of supporting policies for resource-exhausted cities in China is generally commendable. Moreover, there is a notable characteristic that “the lower the administrative level, the higher the quality of the support policies”. Notably, organizational, technological, environmental, and policy conditions alone cannot solely facilitate the green transition of resource-exhausted cities. Instead, it is the harmonious configuration of these antecedents that drives successful green transformation. Additionally, the configuration of antecedent conditions for green transformation exhibits the heterogeneity of different types. Specifically, the eastern region primarily relies on technological innovation and production process improvement, while the central region focuses on both production process improvement and support policy combinations. By contrast, the western region primarily emphasizes support policy combinations and the fostering of environmental conditions. Furthermore, the green transformation of resource-exhausted cities with coal and oil types mainly depends on the combination of policy support and technological innovation. Metal, forestry, and other types of resource-exhausted cities rely on the upgrading and advancement of industrial structures. In the grouped analysis of administrative level, innovation capability, and distance to the provincial capital city, cities with higher administrative levels, higher innovation capabilities, and closer proximity to the provincial capital city are more likely to achieve green transformation. Thereby, this study emphasizes the critical role of support policies and the identification of effective pathways in promoting the green transformation of resource-exhausted cities.

Abstract This research investigates the intricate involvement of nuclear Transcription Factor Y Subunit Alpha (NFYA) in the advancement of castration-resistant prostate cancer (CRPC) and its consequential impact on early Growth Response 4 (EGR4) expression. NFYA demonstrates a significant elevation in CRPC tissues and cell lines, displaying robust upregulation in metastatic prostate cancer (mPCa) samples, closely associated with the Gleason score. Immunohistochemistry validates heightened nuclear staining of NFYA in CRPC patients, highlighting its crucial role in the progression of advanced prostate cancer. Silencing NFYA through siRNA in androgen-independent cell lines markedly impedes cell growth and migration, emphasizing NFYA’s pivotal role in promoting CRPC behavior. RNA-seq analysis identifies EGR4 as a downstream target of NFYA, with both genes consistently upregulated in CRPC. Validating this finding, heightened expression of EGR4 is observed in CRPC samples. In vivo studies utilizing a mouse model demonstrate that NFYA silencing substantially inhibits LNCaP-AI/22RV1shNFYA xenograft tumor growth, accompanied by reduced expression of EGR4 and Ki67. This comprehensive study reveals the multifaceted role of NFYA in CRPC progression, elucidates its downstream impact on EGR4, and underscores the therapeutic potential of targeting NFYA to inhibit CRPC growth in vivo. These findings contribute valuable insights into potential therapeutic strategies for managing CRPC.

Abstract Cotton thrip, Thrips tabaci is a major polyphagous pest widely distributed on a variety of crops around the world, causing huge economic losses to agricultural production. Due to its biological and genomic characteristics, this pest can reproduce quickly and develop resistance to various pesticides in a very short time. However, the lack of high-quality reference genomes has hindered deeper gene function exploration and slows down the development of new management strategies. Here, we assembled a high-quality genome of T. tabaci at the chromosome level for the first time by using Illumina, PacBio long reads, and Hi-C technologies. The 329.59 Mb genome was obtained from 320 contigs, with a contig N50 of 1.53 Mb, and 94.21% of the assembly was anchored to 18 chromosomes. In total, 17,816 protein-coding genes were annotated, and 96.78% of BUSCO genes were fully represented. In conclusion, this high-quality genome provides a valuable genetic basis for our understanding of the biology of T. tabaci and contributes to the development of management strategies for cotton thrip.

Abstract Background Radiation-induced skin injury is a significant adverse reaction to radiotherapy. However, there is a lack of effective prevention and treatment methods for this complication. Ferulic acid (FA) has been identified as an effective anti-radiation agent. Conventional administrations of FA limit the reaching of it on skin. We aimed to develop a novel FA hydrogel to facilitate the use of FA in radiation-induced skin injury. Methods We cross-linked carbomer 940, a commonly used adjuvant, with FA at concentrations of 5%, 10%, and 15%. Sweep source optical coherence tomography system, a novel skin structure evaluation method, was applied to investigate the influence of FA on radiation-induced skin injury. Calcein-AM/PI staining, CCK8 assay, hemolysis test and scratch test were performed to investigate the biocompatibility of FA hydrogel. The reducibility of DPPH and ABTS radicals by FA hydrogel was also performed. HE staining, Masson staining, laser Doppler blood flow monitor, and OCT imaging system are used to evaluate the degree of skin tissue damage. Potential differentially expressed genes were screened via transcriptome analysis. Results Good biocompatibility and in vitro antioxidant ability of the FA hydrogels were observed. 10% FA hydrogel presented a better mechanical stability than 5% and 15% FA hydrogel. All three concentrations of FA remarkably promoted the recovery of radiation-induced skin injury by reducing inflammation, oxidative conidiation, skin blood flow, and accelerating skin tissue reconstruction, collagen deposition. FA hydrogel greatly inhibiting the levels of NLRP3, caspase-1, IL-18, pro-IL-1β and IL-1β in vivo and vitro levels through restraining the activation of NLRP3 inflammasome. Transcriptome analysis indicated that FA might regulate wound healing via targeting immune response, inflammatory response, cell migration, angiogenesis, hypoxia response, and cell matrix adhesion. Conclusions These findings suggest that the novel FA hydrogel is a promising therapeutic method for the prevention and treatment of radiation-induced skin injury patients. Graphical Abstract

Objective To explore the effect of extended care on improving the compliance, efficacy and quality of life of antiviral therapy in elderly patients with acquired immunodeficiency syndrome (AIDS) . Methods A total of 200 elderly patients with acquired immunodeficiency syndrome who received initial antiviral therapy in Beijing You'an Hospital from January 2015 to December 2021 were selected as the study subjects and randomly divided into the control group and the test group according to the lottery method, with 100 cases in each group. The control group received routine care and health education, and the experimental group was given extended care on the basis of the control group. After 1 year of follow-up, medication compliance, efficacy, and quality of life were compared between the two groups. Results During 1-year follow-up, the medication compliance of the test group was higher than that in the control group, and the difference was statistically significant (P < 0.05); the increase of CD4+ T lymphocyte count in the test group was higher than that in the control group (P < 0.05); the viral load was undetectable after treatment in both groups. The scores of physical domain, psychological domain, social relationship domain and environmental domain of quality of life in the test group were higher than those in the control group, and the differences were statistically significant (P < 0.05) . Conclusion Extended care is beneficial to improve the medication compliance and antiviral effect of elderly patients with acquired immunodeficiency syndrome, and improve the quality of life of patients. It is worthy of clinical promotion and application.

Practical real-world scenarios such as the Internet, social networks, and biological networks present the challenges of data scarcity and complex correlations, which limit the applications of artificial intelligence. The graph structure is a typical tool used to formulate such correlations, it is incapable of modeling high-order correlations among different objects in systems; thus, the graph structure cannot fully convey the intricate correlations among objects. Confronted with the aforementioned two challenges, hypergraph computation models high-order correlations among data, knowledge, and rules through hyperedges and leverages these high-order correlations to enhance the data. Additionally, hypergraph computation achieves collaborative computation using data and high-order correlations, thereby offering greater modeling flexibility. In particular, we introduce three types of hypergraph computation methods: ① hypergraph structure modeling, ② hypergraph semantic computing, and ③ efficient hypergraph computing. We then specify how to adopt hypergraph computation in practice by focusing on specific tasks such as three-dimensional (3D) object recognition, revealing that hypergraph computation can reduce the data requirement by 80% while achieving comparable performance or improve the performance by 52% given the same data, compared with a traditional data-based method. A comprehensive overview of the applications of hypergraph computation in diverse domains, such as intelligent medicine and computer vision, is also provided. Finally, we introduce an open-source deep learning library, DeepHypergraph (DHG), which can serve as a tool for the practical usage of hypergraph computation.

Introduction:: Accurate identification of pulmonary arterial hypertension (PAH) in primary care and rural areas can be a challenging task. However, recent advancements in computer vision offer the potential for automated systems to detect PAH from echocardiography. Objectives:: Our aim was to develop a precise and efficient diagnostic model for PAH tailored to the unique requirements of intelligent diagnosis, especially in challenging locales like high-altitude regions. Methods:: We proposed the Chamber Attention Network (CAN) for PAH identification from echocardiographic images, trained on a dataset comprising 13,912 individual subjects. A convolutional neural network (CNN) for view classification was used to select the clinically relevant apical four chamber (A4C) and parasternal long axis (PLAX) views for PAH diagnosis. To assess the importance of different heart chambers in PAH diagnosis, we developed a novel Chamber Attention Module. Results:: The experimental results demonstrated that: 1) The substantial correspondence between our obtained chamber attention vector and clinical expertise suggested that our model was highly interpretable, potentially uncovering diagnostic insights overlooked by the clinical community. 2) The proposed CAN model exhibited superior image-level accuracy and faster convergence on the internal validation dataset compared to the other four models. Furthermore, our CAN model outperformed the others on the external test dataset, with image-level accuracies of 82.53% and 83.32% for A4C and PLAX, respectively. 3) Implementation of the voting strategy notably enhanced the positive predictive value (PPV) and negative predictive value (NPV) of individual-level classification results, enhancing the reliability of our classification outcomes. Conclusions:: These findings indicate that CAN is a feasible technique for AI-assisted PAH diagnosis, providing new insights into cardiac structural changes observed in echocardiography.

Clavulina possesses important ecological and economic value and has attracted extensive attention from mycologists. Macrofungal diversity is high in China, but Clavulina species have not been thoroughly studied. In this study, based on morphological evidence and phylogenetic analyses of the nucleotide sequences of three loci (nrITS, nrLSU, and rpb2), three new species of Clavulina from North China were identified. Morphologically, Clavulina chengdeensis is characterized by its white to dirty white basidiomata with somewhat pale orange tips and somewhat wrinkled hymenium. Clavulina griseoviolacea is characterized by its gray to dark grayish violet basidiomata, with a sometimes-white stipe base, monopodial or irregularly polychotomous toward branch apices. Clavulina pallida is characterized by its white to pale cream white basidiomata with somewhat orange tips. Phylogenetically, the three new species form three independent branches with high support values in the phylogenetic tree.

Abstract Background The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). Methods A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. Results Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P

Abstract Episyrphus balteatus can provide dual ecosystem services including pest control and pollination, which the larvae are excellent predators of aphid pest whereas adults are efficient pollinator. In this study, we assembled a high-quality genome of E. balteatus from northern China geographical population at the chromosome level by using Illumina, PacBio long reads, and Hi-C technologies. The 467.42 Mb genome was obtained from 723 contigs, with a contig N50 of 9.16 Mb and Scaffold N50 of 118.85 Mb, and 90.25% (431.75 Mb) of the assembly was anchored to 4 pseudo-autosomes and one pseudo-heterosome. In total, 14,848 protein-coding genes were annotated, and 95.14% of genes were fully represented in NR, GO, KEGG databases. Besides, we also obtained the mitochondrial genome of E. balteatus of 16, 837 bp in length with 37 typical mitochondrial genes. Overall, this high-quality genome is valuable for evolutionary and genetic studies of E. balteatus and other Syrphidae hoverfly species.

Effective treatment of Parkinson's disease (PD), a prevalent central neurodegenerative disorder particularly affecting the elderly population, still remains a huge challenge. We present here a novel nanomedicine formulation based on bioactive hydroxyl-terminated phosphorous dendrimers (termed as AK123) complexed with fibronectin (FN) with anti-inflammatory and antioxidative activities. The created optimized AK123/FN nanocomplexes (NCs) with a size of 223 nm display good colloidal stability in aqueous solution and can be specifically taken up by microglia through FN-mediated targeting. We show that the AK123/FN NCs are able to consume excessive reactive oxygen species, promote microglia M2 polarization and inhibit the nuclear factor-kappa B signaling pathway to downregulate inflammatory factors. With the abundant dendrimer surface hydroxyl terminal groups, the developed NCs are able to cross blood-brain barrier (BBB) to exert targeted therapy of a PD mouse model through the AK123-mediated anti-inflammation for M2 polarization of microglia and FN-mediated antioxidant and anti-inflammatory effects, thus reducing the aggregation of α-synuclein and restoring the contents of dopamine and tyrosine hydroxylase to normal levels in vivo. The developed dendrimer/FN NCs combine the advantages of BBB-crossing hydroxyl-terminated bioactive per se phosphorus dendrimers and FN, which is expected to be extended for the treatment of different neurodegenerative diseases.

Abstract Background Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. Results Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. Conclusions Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.

Abstract Background Heart failure with reduced ejection fraction (HFrEF) is associated with a high rate of mortality and morbidity. Evidence has shown that sex differences may be an important contributor to phenotypic heterogeneity in patients with HFrEF. Although diabetes mellitus (DM) frequently coexists with HFrEF and results in a worse prognosis, there remains a need to identify sex-related differences in the characteristics and outcomes of this population. In this study, we aimed to investigate the between-sex differences in clinical profile, left ventricular (LV) remodeling, and cardiovascular risk factors and outcomes in patients with HFrEF concomitant with DM. Methods A total of 273 patients with HFrEF concomitant with DM who underwent cardiac MRI were included in this study. Clinical characteristics, LV remodeling as assessed by cardiac MRI, and cardiovascular risk factors and outcomes were compared between sexes. Results Women were older, leaner and prone to have anemia and hypoproteinemia but less likely to have ischemic etiology. Cardiac MRI revealed that despite similar LVEFs between the sexes, there was more LV concentric remodeling, less impaired global systolic peak strain in longitudinal and circumferential components and a decreased likelihood of late gadolinium enhancement presence in women than in men. During a median follow-up time of 34.6 months, women exhibited better overall survival than men did (log-rank P = 0.042). Multivariable Cox proportional hazards analysis indicated different risk factors for predicting outcomes between sexes, with hypertension [hazard ratio (HR) = 2.05, 95% confidence interval (CI) 1.05 to 4.85, P = 0.041] and hypoproteinemia (HR = 2.27, 95% CI 1.06 to 4.37, P = 0.039) serving as independent determinants of outcomes in women, whereas ischemic etiology (HR = 1.96, 95% CI 1.11 to 3.48, P = 0.021) and atrial fibrillation (HR = 1.86, 95% CI 1.02 to 3.41, P = 0.044) served as independent determinants of outcomes in men. Conclusions Among patients with HFrEF concomitant with DM, women displayed different LV remodeling and risk factors and had better survival than men did. Sex-based phenotypic heterogeneity in patients with HFrEF in the context of DM should be addressed in clinical practice.

Abstract Backgroud Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. Methods RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. Results A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. Conclusions In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

Abstract When conducting spine-related diagnosis and surgery, the three-dimensional (3D) upright posture of the spine under natural weight bearing is of significant clinical value for physicians to analyze the force on the spine. However, existing medical imaging technologies cannot meet current requirements of medical service. On the one hand, the mainstream 3D volumetric imaging modalities (e.g. CT and MRI) require patients to lie down during the imaging process. On the other hand, the imaging modalities conducted in an upright posture (e.g. radiograph) can only realize 2D projections, which lose the valid information of spinal anatomy and curvature. Developments of deep learning-based 3D reconstruction methods bring potential to overcome the limitations of the existing medical imaging technologies. To deal with the limitations of current medical imaging technologies as is described above, in this paper, we propose a novel deep learning framework, ReVerteR, which can realize automatic 3D Reconstruction of Vertebrae from orthogonal bi-planar Radiographs. With the utilization of self-attention mechanism and specially designed loss function combining Dice, Hausdorff, Focal, and MSE, ReVerteR can alleviate the sample-imbalance problem during the reconstruction process and realize the fusion of the centroid annotation and the focused vertebra. Furthermore, aiming at automatic and customized 3D spinal reconstruction in real-world scenarios, we extend ReVerteR to a clinical deployment-oriented framework, and develop an interactive interface with all functions in the framework integrated so as to enhance human–computer interaction during clinical decision-making. Extensive experiments and visualization conducted on our constructed datasets based on two benchmark datasets of spinal CT, VerSe 2019 and VerSe 2020, demonstrate the effectiveness of our proposed ReVerteR. In this paper, we propose an automatic 3D reconstruction method of vertebrae based on orthogonal bi-planar radiographs. With the 3D upright posture of the spine under natural weight bearing effectively constructed, our proposed method is expected to better support doctors make clinical decision during spine-related diagnosis and surgery.

Abstract Background The abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM. Materials and methods This study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P

Fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, is widely prescribed for hyperlipidemia management. Recent studies also showed that it has therapeutic potential in various liver diseases. However, its effects on hepatomegaly and liver regeneration and the involved mechanisms remain unclear. Here, the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice, which was dependent on hepatocyte-expressed PPARα. Yes-associated protein (YAP) is pivotal in manipulating liver growth and regeneration. We further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination, promoting its K63-linked ubiquitination, and enhancing the interaction and transcriptional activity of the YAP–TEAD complex. Pharmacological inhibition of YAP–TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced hepatomegaly. Other factors, such as MYC, KRT23, RAS, and RHOA, might also participate in fenofibrate-promoted hepatomegaly and liver regeneration. These studies demonstrate that fenofibrate-promoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling, with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

Abstract Background Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. Methods One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. Results The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: − 15.03 ± 2.52% vs. − 13.39 ± 2.48% vs. − 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (β = − 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (β = 0.283 and − 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (β = − 0.266, p = 0.007). Conclusions There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.

Abstract Background Stress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI. Methods A total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8–11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients. Results LV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P

Abstract Keratinocyte proliferation and differentiation in epidermis are well-controlled and essential for reacting to stimuli such as ultraviolet light. Imbalance between proliferation and differentiation is a characteristic feature of major human skin diseases such as psoriasis and squamous cell carcinoma. However, the effect of keratinocyte metabolism on proliferation and differentiation remains largely elusive. We show here that the gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) promotes differentiation while inhibits proliferation of keratinocyte and suppresses psoriasis development. FBP1 is identified among the most upregulated genes induced by UVB using transcriptome sequencing and is elevated especially in upper epidermis. Fbp1 heterozygous mice exhibit aberrant epidermis phenotypes with local hyperplasia and dedifferentiation. Loss of FBP1 promotes proliferation and inhibits differentiation of keratinocytes in vitro. Mechanistically, FBP1 loss facilitates glycolysis-mediated acetyl-CoA production, which increases histone H3 acetylation at lysine 9, resulting in enhanced transcription of proliferation genes. We further find that the expression of FBP1 is dramatically reduced in human psoriatic lesions and in skin of mouse imiquimod psoriasis model. Fbp1 deficiency in mice facilitates psoriasis-like skin lesions development through glycolysis and acetyl-CoA production. Collectively, our findings reveal a previously unrecognized role of FBP1 in epidermal homeostasis and provide evidence for FBP1 as a metabolic psoriasis suppressor.

In the soil environment, microplastics (MPs) commonly coexist with organic pollutants such as nonylphenol (NP), affecting the migration of NP through adsorption/desorption. However, few studies have focused on the interaction between NP and MPs in soil, especially for MPs of different types and ageing characteristics. In this study, non-polar polypropylene (PP) and polar polyamide (PA) MPs were aged either photochemically (144 h) or within soil (60 days), then used to determine the effect of 5 % MPs on the adsorption behaviour of NP (0.1–4.0 mg/L) in soil. Results showed that both ageing processes significantly promoted the conversion of -CH3 groups to C-O and CO on the surface of PPMPs, while PAMPs exhibited amide groups changes and a reduction in average particle size due to ageing. Additionally, both ageing processes promoted the adsorption of NP by soil containing PPMPs, due to an increase in oxygen-containing functional groups and specific surface area. In contrast, the NP adsorption capacity of soil containing PAMPs decreased by 15.4 % following photochemical ageing due to hydrolysis of amide groups, but increased by 21.15 % after soil ageing due to reorganization of amide groups, respectively. The soil-PAMPs systems exhibited a stronger affinity for NP compared to the soil-PPMPs systems, which was primarily attributed to the dominant role of hydrogen bonding. NP was found to be distributed mainly on soil particles in the soil-PPMPs systems, while it tended to be adsorbed by MPs in the soil-PAMPs systems, especially in the soil aged MPs system. This study provides a comprehensive analysis of the complex effects of MPs on coexisting pollutants in soil environments, highlighting the effect of MP characteristics on the adsorption of organic pollutants, which is essential for understanding the transport behaviour of organic pollutants.

IntroductionVigorous physical activity (VPA) has been demonstrated to enhance cardiorespiratory fitness (CRF) in sedentary college students more effectively than other PA. However, differences in training volume may affect this outcome. This study examines the physiological, psychological, and internal training load (ITL) characteristics of VPA with varying volumes in a single session.MethodsThirty sedentary college students were divided into three groups: high-intensity interval training (HIIT), sprint interval training (SIT), and threshold training (THR). PA process was monitored. The study measured various cardiorespiratory parameters, including heart rate (HR), respiratory waveform and amplitude, respiratory rate (RR), tidal volume (TV), minute ventilation volume (VE), fractional concentration of oxygen in end-tidal gas (O2%), fractional concentration of end-tidal carbon dioxide (CO2%), global oxygen consumption (VO2), carbon dioxide discharge (VCO2), and the amount of carbon dioxide in the air. The following physiological indicators were measured: carbon dioxide discharge (VCO2), Oxygen pulse (OP), and respiratory exchange ratio (RER). Additionally, subjective perception indicators were recorded, including the feeling scale (FS), rating of perceived exertion (RPE), and dual-mode model (DMM). The session-RPE (s-RPE) and Edward's TRIMP were used to measure ITL.ResultsThere were no significant differences in HR across the three conditions. THR had the highest level of TV (p = 0.043), but RR was significantly lower than that of HIIT and SIT (p < 0.01). HIIT had the highest levels of VO2, VCO2, O2%, and OP (p < 0.05). RPE was higher in HIIT and SIT compared to THR (p < 0.01), but the difference in FS was not significant. The DMM time-domain trajectories were similar in HIIT and THR. The correlation between exercise intensity, RPE, and FS was highest in THR group (r = 0.453, r = −0.58, r = −0.885). ITL did not show a significant difference between three conditions, but TRIMP and s-RPE readings were opposite in magnitude.ConclusionThis study proposes that using an appropriate amount of THR to foster interest and adaptive strength during the PA habit establishment period, incorporating HIIT to enhance exercise efficiency during the adaptation period, and implementing SIT to reduce the monotony may effectively enhance the cardiorespiratory fitness of sedentary college students and establish PA habit.

Abstract Understanding the endogenous mechanism of adaptive response to drug‐induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin‐induced liver injury (TILI) of mice. Exosomal miR‐106b‐5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR‐106b‐5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR‐106b‐5p protects mice from liver injury. Injured hepatocytes released miR‐106b‐5p‐enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR‐106b‐5p by dual luciferase reporter and siRNA assays. Furthermore, single‐cell RNA‐sequencing analysis of toosendanin‐injured mouse liver revealed a cluster of Vim+ hepatocytes; nonetheless declined following miR‐106b‐5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR‐106b‐5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR‐106b‐5p safeguards restorative tissue repair by targeting vimentin.

Epimedium Folium has been extensively utilized for medicinal purposes in China for a significant period. This review undertakes a comprehensive examination of literature pertaining to Epimedium and its metabolites over the past decade, drawing from databases such as PubMed. Through meticulous organization and synthesis of pertinent research findings, including disease models, pharmacological effects, and related aspects, this narrative review sheds light on the principal pharmacological activities and associated mechanisms of Epimedium in safeguarding the reproductive system, promoting bone health, mitigating inflammation, and combating tumors and viral infections. Consequently, this review contributes to a more profound comprehension of the recent advances in Epimedium research.

The peel stripe margin pattern is one of the most important quality traits of watermelon. In this study, two contrasted watermelon lines [slb line (P1) with a clear peel stripe margin pattern and GWAS-38 line (P2) with a blurred peel stripe margin pattern] were crossed, and biparental F2 mapping populations were developed. Genetic segregation analysis revealed that a single recessive gene is modulating the main-effect genetic locus (Clcsm) of the clear stripe margin pattern of peel. Bulked segregant analysis-based sequencing (BSA-Seq) and fine genetic mapping exposed the delimited Clcsm locus to a 19.686-kb interval on chromosome 6, and the Cla97C06G126680 gene encoding the MYB transcription factor family was identified. The gene mutation analysis showed that two non-synonymous single-nucleotide polymorphism (nsSNP) sites [Chr6:28438793 (A-T) and Chr6:28438845 (A-C)] contribute to the clear peel stripe margin pattern, and quantitative real-time polymerase chain reaction (qRT-PCR) also showed a higher expression trend in the slb line than in the GWAS-38 line. Further, comparative transcriptomic analysis identified major differentially expressed genes (DEGs) in three developmental periods [4, 12, and 20 days after pollination (DAP)] of both parental lines. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses indicated highly enriched DEGs involved in metabolic processes and catalytic activity. A total of 44 transcription factor families and candidate genes belonging to the ARR-B transcription factor family are believed to regulate the clear stripe margin trait of watermelon peel. The gene structure, sequence polymorphism, and expression trends depicted significant differences in the peel stripe margin pattern of both parental lines. The ClMYB36 gene showed a higher expression trend for regulating the clear peel stripe margin of the slb line, and the ClAPRR5 gene depicted a higher expression for modulating the blurred peel stripe margin in the GWAS-38 line. Overall, our fine genetic mapping and transcriptomic analysis revealed candidate genes differentiating the clear and blurred peel stripe patterns of watermelon fruit.

Various biological effects of ionizing radiation, especially continuous exposure to low-dose radiation (LDR), have attracted considerable attention. Impaired bone structure caused by LDR has been reported, but little is known about the mechanism involved in the disruption of bone metabolism. In this study, given that LDR was found to (at a cumulative dose of 0.10 Gy) disturb the serum Mg2+ level and Notch1 signal in the mouse femur tissues, the effects of LDR on osteogenesis and the underlying molecular mechanisms were investigated based on an in vitro culture system for bone marrow stromal cells (BMSCs). Our data showed that cumulative LDR suppressed the osteogenic potential in BMSCs as a result of upregulation of Notch1 signaling. Further analyses indicated that the upregulation of NICD1 (Notch1 intracellular domain), the key intracellular domain for Notch1 signaling, under LDR was a consequence of enhanced protein stabilization caused by SUMOylation (small ubiquitin-like modification). Specifically, the downregulation of SENP1 (sentrin/SUMO-specific protease 1) expression induced by LDR enhanced the SUMOylation of NICD1, causing the accumulation of Notch1 signaling, which eventually inhibited the osteogenic potential of BMSCs. In conclusion, this work expounded on the mechanisms underlying the impacts of LDR on bone metabolism and shed light on the research on bone regeneration under radiation.

BACKGROUND: Acute respiratory distress syndrome (ARDS), which results in lung injury as a consequence of sepsis and septic shock, is associated with severe systemic inflammation and is responsible for a high worldwide mortality rate. OBJECTIVE: Investigate whether corticosteroids could benefit clinical outcomes in adult with ARDS. METHODS: A comprehensive search of electronic databases Ovid MEDLINE, Ovid EMbase, and Cochrane Library from their inception to 7 May 2023 was conducted to identify studies that met the eligibility criteria, including only randomized controlled trials. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the methods of trial sequential analysis. MAIN OUTCOME MEASURES: Mortality rates, including including the 14-, 28-, 45-, and 60-day mortality, hospital mortality, and intensive care unit (ICU) mortality. SAMPLE SIZE: 17 studies with 2508 patients. RESULTS: Data relating to mortality at 14, 28, 45, and 60 days were not significantly different when treatments with corticosteroids and placebo were compared. In terms of hospital and ICU mortality, the mortality of those who had received corticosteroids was significantly lower than that of those who had not. ARDS patients who received assisted ventilation benefited from corticosteroid therapy, as revealed by the significant difference in outcome days between those who received assisted ventilation and those who did not. Corticosteroid had significantly more days free from mechanical ventilation, ICU-free days, and MODS-free days during the first 28 days, but not more organ support-free days up to day 28. CONCLUSION: Although corticosteroid therapy did not reduce mortality rates at different observation periods, it significantly reduced hospital and ICU mortality. Administering corticosteroids to ARDS patients significantly decreased the days of assisted ventilation and time cost consumption. This study confirmed that long-term use of low-dose glucocorticoids may have a positive effect on early ARDS. LIMITATION: Risk of bias due to the differences in patient characteristics.

Abstract The recent outbreak of mpox epidemic, caused by monkeypox virus (MPXV), poses a new threat to global public health. Here, we initially assessed the preexisting antibody level to the MPXV B6 protein in vaccinia vaccinees born before the end of the immunization program and then identified two monoclonal antibodies (MAbs), hMB621 and hMB668, targeting distinct epitopes on B6, from one vaccinee. Binding assays demonstrate that both MAbs exhibit broad binding abilities to B6 and its orthologs in vaccinia (VACV), variola (VARV) and cowpox viruses (CPXV). Neutralizing assays reveal that the two MAbs showed potent neutralization against VACV. Animal experiments using a BALB/c female mouse model indicate that the two MAbs showed effective protection against VACV via intraperitoneal injection. Additionally, we determined the complex structure of B6 and hMB668, revealing the structural feature of B6 and the epitope of hMB668. Collectively, our study provides two promising antibody candidates for the treatment of orthopoxvirus infections, including mpox.

When a curling rock slides on an ice sheet with an initial rotation, a lateral movement occurs, which is known as the curling phenomenon. The force of friction between the curling rock and the ice sheet changes continually with changes in the environment; thus, the sport of curling requires great skill and experience. The throwing of the curling rock is a great challenge in robot design and control, and existing curling robots usually adopt a combination scheme of a wheel chassis and gripper that differs significantly from human throwing movements. A hexapod curling robot that imitates human kicking, sliding, pushing, and curling rock rotating was designed and manufactured by our group, and completed a perfect show during the Beijing 2022 Winter Olympics Games. Smooth switching between the walking and throwing tasks is realized by the robot’s morphology transformation based on leg configuration switching. The robot’s controlling parameters, which include the kicking velocity vk, pushing velocity vp, orientation angle θc, and rotation velocity ω, are determined by aiming and sliding models according to the estimated equivalent friction coefficient μequ and ratio e of the front and back frictions. The stable errors between the target and actual stopping points converge to 0.2 and 1.105 m in the simulations and experiments, respectively, and the error shown in the experiments is close to that of a well-trained wheelchair curling athlete. This robot holds promise for helping ice-makers rectify ice sheet friction or assisting in athlete training.

Abstract Background Glycemic control, as measured by glycosylated hemoglobin (HbA1c), is an important biomarker to evaluate diabetes severity and is believed to be associated with heart failure development. Type 2 diabetes mellitus (T2DM) and heart failure with reduced ejection fraction (HFrEF) commonly coexist, and the combination of these two diseases indicates a considerably poorer outcome than either disease alone. Therefore, glycemic control should be carefully managed. The present study aimed to explore the association between glycemic control and clinical outcomes, and to determine the optimal glycemic target in this specific population. Methods A total of 262 patients who underwent cardiac MRI were included and were split by HbA1c levels [HbA1c 7.5% (poor control)]. The biventricular volume and function, as well as left ventricular (LV) systolic strains in patients in different HbA1c categories, were measured and compared. The primary and secondary outcomes were recorded. The association of different HbA1c levels with adverse outcomes was assessed. Results Despite similar biventricular ejection fractions, both patients with intensive and poor glycemic control exhibited prominent deterioration of LV systolic strain in the longitudinal component (P = 0.004). After a median follow-up of 35.0 months, 55 patients (21.0%) experienced at least one confirmed endpoint event. Cox multivariable analysis indicated that both patients in the lowest and highest HbA1c categories exhibited a more than 2-fold increase in the risk for primary outcomes [HbA1c 7.5%: HR = 2.24, 95% CI = 1.01–4.99; P = 0.038] and secondary outcomes (HbA1c 7.5%: HR = 2.65, 95% CI = 1.08–6.50; P = 0.038) compared with those in the middle HbA1c category. Conclusions We showed a U-shaped association of glycemic control with clinical outcomes in patients with T2DM and HFrEF, with the lowest risk of adverse outcomes among patients with modest glycemic control. HbA1c between 6.5% and 7.5% may be served as the optimal hypoglycemic target in this specific population.

Abstract Background Metabolic syndrome (MetS) can increase the risk of morbidity and mortality of cardiovascular disease and obstructive coronary artery disease (OCAD), which usually have a poor prognosis. This study aimed to explore the impact of MetS on left ventricular (LV) deformation and function in OCAD patients and investigate the independent factors of impaired LV function and deformation. Materials and methods A total of 121 patients with OCAD and 52 sex- and age-matched controls who underwent cardiac magnetic resonance scanning were enrolled in the study. All OCAD patients were divided into two groups: OCAD with MetS [OCAD(MetS+), n = 83] and OCAD without MetS [OCAD(MetS−), n = 38]. LV functional and global strain parameters were measured and compared among the three groups. Multivariable linear regression analyses were constructed to investigate the independent factors of LV impairment in OCAD patients. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were performed to test the prediction efficiency of MetS for LV impairment. Results From controls to the OCAD(MetS−) group to the OCAD(MetS+) group, LV mass (LVM) increased, and LV global function index (LVGFI) and LV global longitudinal peak strain (GLPS) decreased (all p

Abstract Transcription is crucial for the expression of genetic information and its efficient and accurate termination is required for all living organisms. Rho-dependent termination could rapidly terminate unwanted premature RNAs and play important roles in bacterial adaptation to changing environments. Although Rho has been discovered for about five decades, the regulation mechanisms of Rho-dependent termination are still not fully elucidated. Here we report that Rof is a conserved antiterminator and determine the cryogenic electron microscopy structure of Rho-Rof antitermination complex. Rof binds to the open-ring Rho hexamer and inhibits the initiation of Rho-dependent termination. Rof’s N-terminal α-helix undergoes conformational changes upon binding with Rho, and is key in facilitating Rof-Rho interactions. Rof binds to Rho’s primary binding site (PBS) and excludes Rho from binding with PBS ligand RNA at the initiation step. Further in vivo analyses in Salmonella Typhimurium show that Rof is required for virulence gene expression and host cell invasion, unveiling a physiological function of Rof and transcription termination in bacterial pathogenesis.

Abstract Long non-coding RNAs (lncRNAs) could modulate expression of immune checkpoints (ICPs) by cooperating with immunity genes in tumor immunization. However, precise functions in immunity and potential for predicting ICP inhibitors (ICI) response have been described for only a few lncRNAs. Here we present an integrated framework that leverages network-based analyses and Bayesian network inference to identify the regulated relationships including lncRNA, ICP and immunity genes as ICP-related LncRNAs mediated Core Regulatory Circuitry Triplets (ICP-LncCRCTs) that can make robust predictions. Hub ICP-related lncRNAs such as MIR155HG and ADAMTS9-AS2 were highlighted to play central roles in immune regulation. Specific ICP-related lncRNAs could distinguish cancer subtypes. Moreover, the ICP-related lncRNAs are likely to significantly correlated with immune cell infiltration, MHC, CYT. Some ICP-LncCRCTs such as CXCL10-MIR155HG-ICOS could better predict one-, three- and five-year prognosis compared to single molecule in melanoma. We also validated that some ICP-LncCRCTs could effectively predict ICI-response using three kinds of machine learning algorithms follow five independent datasets. Specially, combining ICP-LncCRCTs with the tumor mutation burden (TMB) improves the prediction of ICI-treated melanoma patients. Altogether, this study will improve our grasp of lncRNA functions and accelerating discovery of lncRNA-based biomarkers in ICI treatment.

Abstract Background Atrial fibrillation (AF) has been linked to an increased risk of cardiovascular death, overall mortality and heart failure in patients with type 2 diabetes mellitus (T2DM). The present study investigated the additive effects of paroxysmal AF on left ventricular (LV) function and deformation in T2DM patients with or without AF using the cardiovascular magnetic resonance feature tracking (CMR-FT) technique. Methods The present study encompassed 225 T2DM patients differentiated by the presence or absence of paroxysmal AF [T2DM(AF+) and T2DM(AF−), respectively], along with 75 age and sex matched controls, all of whom underwent CMR examination. LV function and global strains, including radial, circumferential and longitudinal peak strain (PS), as well as peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were measured and compared among the groups. Multivariable linear regression analysis was used to examine the factors associated with LV global strains in patients with T2DM. Results The T2DM(AF+) group was the oldest, had the highest LV end‑systolic volume index, lowest LV ejection fraction and estimated glomerular filtration rate compared to the control and T2DM(AF−) groups, and presented a shorter diabetes duration and lower HbA1c than the T2DM(AF−) group. LV PS-radial, PS-longitudinal and PDSR-radial declined successively from controls through the T2DM(AF−) group to the T2DM(AF+) group (all p

Actin depolymerizing factors (ADFs), as the important actin-binding proteins (ABPs) with depolymerizing/severing actin filaments, play a critical role in plant growth and development, and in response to biotic and abiotic stresses. However, the information and function of the ADF family in melon remains unclear. In this study, 9 melon ADF genes (CmADFs) were identified, distributed in 4 subfamilies, and located on 6 chromosomes respectively. Promoter analysis revealed that the CmADFs contained a large number of cis-acting elements related to hormones and stresses. The similarity of CmADFs with their Arabidopsis homologue AtADFs in sequence, structure, important sites and tissue expression confirmed that ADFs were conserved. Gene expression analysis showed that CmADFs responded to low and high temperature stresses, as well as ABA and SA signals. In particular, CmADF1 was significantly up-regulated under above all stress and hormone treatments, indicating that CmADF1 plays a key role in stress and hormone signaling responses, so CmADF1 was selected to further study the mechanism in plant tolerance low temperature. Under low temperature, virus-induced gene silencing (VIGS) of CmADF1 in oriental melon plants showed increased sensitivity to low temperature stress. Consistently, the stable genetic overexpression of CmADF1 in Arabidopsis improved their low temperature tolerance, possibly due to the role of CmADF1 in the depolymerization of actin filaments. Overall, our findings indicated that CmADF genes, especially CmADF1, function in response to abiotic stresses in melon.

Objective This study was performed to evaluate the efficacy of robot-assisted thoracoscopic surgery (RATS) in the treatment of pulmonary sequestration (PS) in children.Methods All video-assisted thoracoscopic surgery (VATS) and RAST performed on patients with PS at a single center from May 2019 to July 2023 were identified. The χ2 and Wilcoxon tests were used to compare the perioperative outcomes between VATS and RATS groups.Results Ninety-three patients underwent RATS while 77 patients underwent VATS. In both two groups, one patient converted to thoracotomy and no surgical mortality case. The median operation time was longer for the RATS group compared with the VATS group (75 min vs. 60 min, p

Background: Sepsis-associated encephalopathy (SAE) is a disease characterized by neuroinflammation and cognitive dysfunction caused by systemic infection. Inflammation-induced microglial activation is closely associated with neuroinflammation in SAE. It is widely understood that melatonin has strong anti-inflammatory and immunomodulatory properties beneficial for sepsis-related brain damage. However, the mechanism of melatonin action in SAE has not been fully elucidated. Methods: The SAE cell model and SAE mouse model were induced by lipopolysaccharide (LPS). Behavioral tests were performed to analyze cognitive function. Microglial markers and M1/M2 markers were measured by immunofluorescence. Mitophagy was assessed by western blot, mt-Keima and transmission electron microscopy experiments. Immunoprecipitation and co-immunoprecipitation assays investigated the interactions between AMP-activated protein kinase α2 (AMPKα2) and PTEN-induced putative kinase 1 (PINK1). Results: Melatonin suppresses LPS-induced microglia M1 polarization by enhancing mitophagy, thereby attenuating LPS-induced neuroinflammation and behavioral deficits. However, inhibition or knockdown of AMPKα2 can inhibit the enhancement of melatonin on mitophagy, then weaken its promotion of microglia polarization towards M2 phenotype, and eliminate its protective effect on brain function. Furthermore, melatonin enhances mitophagy through activating AMPKα2, promotes PINK1 Ser495 site phosphorylation, and ultimately regulates microglial polarization from M1 to M2. Conclusions: Our findings demonstrate that melatonin facilitates microglia polarization towards M2 phenotype to alleviate LPS-induced neuroinflammation, primarily through AMPKα2-mediated enhancement of mitophagy.

M420 stainless steel has good mechanical properties, but its corrosion resistance is poor, which limits its application in marine conditions. Single-technology processing has been unable to meet the development needs of modern industry. In this work, plasma nitrocarburizing (PNC) and CrN/CrTiAlSiN/WCrTiAlN multi-layer coating were carried out on M420 martensitic stainless steel by hollow cathode-assisted plasma treatment and multi-arc ion plating, respectively. The modified layers were characterized by X-ray diffraction, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy. The results show that the nitrocarburized layer effectively improves the hardness gradient between the coating and the substrate. The presence of the composite strengthening layer enables the sample to obtain a thick and dense corrosion-resistant surface, effectively blocking the invasion of the corrosive medium. The corrosion rate of the PNC + C sample decreased by an order of magnitude. Combining hollow cathode-assisted rapid nitrocarburizing technology and multi-arc ion plating technology can significantly improve the mechanical properties and corrosion resistance of M420 stainless steel in a shorter time. The duplex surface-treated M420 stainless steel by plasma nitrocarburizing and WCrAlTiSiN multilayer coating exhibited excellent corrosion resistance compared to the nitrided and coated M420 stainless steel.

Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs.

Fatigue exerts a profound impact on human health. Jiuzhuan Huangjing Pills (JHP), comprising two functional foods, exhibits homology of medicine and food. In this study, we found that JHP improved fatigue in both in vivo and in vitro models by protecting against structural damage and functional disorders of mitochondria through the reduction of oxidative stress, thereby preventing cell death and enhancing energy metabolism. By investigating metabolomes in serum, skeletal muscle (SM), and SM mitochondria, JHP primarily mitigated oxidative stress by modulating the abundances of organic acids and lipids at multiple levels. Furthermore, we identified the anti-fatigue ingredients derived from JHP and conducted experimental verification to confirm that their pharmacodynamic effects were similar to those of JHP. Our findings suggested that JHP can serve as a candidate dietary supplement to improve fatigue by maintaining mitochondrial homeostasis through its antioxidant properties to enhance overall energy production in the body.

Ferroptosis is a nonapoptotic form of cell death and differs considerably from the well-known forms of cell death in terms of cell morphology, genetics, and biochemistry. The three primary pathways for cell ferroptosis are system Xc−/glutathione peroxidase 4 (GPX4), lipid metabolism, and ferric metabolism. Since the discovery of ferroptosis, mounting evidence has revealed its critical regulatory role in several diseases, especially as a novel potential target for cancer therapy, thereby attracting increasing attention in the fields of tumor biology and anti-tumor therapy. Accordingly, broad prospects exist for identifying ferroptosis as a potential therapeutic target. In this review, we aimed to systematically summarize the activation and defense mechanisms of ferroptosis, highlight the therapeutic targets, and discuss the design of nanomedicines for ferroptosis regulation. In addition, we opted to present the advantages and disadvantages of current ferroptosis research and provide an optimistic vision of future directions in related fields. Overall, we aim to provide new ideas for further ferroptosis research and inspire new strategies for disease diagnosis and treatment.

Syringin, a phenylpropanoid glycoside, is widely distributed in various plants, such as Acanthopanax senticosus (Rupr. et Maxim.) Harms, Syringa reticulata (BL) Hara var. mandshurica (Maxim.) Hara, and Ilex rotunda Thumb. It serves as the main ingredient in numerous listed medicines, health products, and foods with immunomodulatory, anti-tumor, antihyperglycemic, and antihyperlipidemic effects. This review aims to systematically summarize syringin, including its physicochemical properties, plant sources, extraction and separation methods, total synthesis approaches, pharmacological activities, drug safety profiles, and preparations and applications. It will also cover the pharmacokinetics of syringin, followed by suggestions for future application prospects. The information on syringin was obtained from internationally recognized scientific databases through the Internet (PubMed, CNKI, Google Scholar, Baidu Scholar, Web of Science, Medline Plus, ACS Elsevier, and Flora of China) and libraries. Syringin, extraction and separation, pharmacological activities, preparations and applications, and pharmacokinetics were chosen as the keywords. According to statistics, syringin can be found in 23 families more than 60 genera, and over 100 species of plants. As a key component in many Chinese herbal medicines, syringin holds significant research value due to its unique sinapyl alcohol structure. Its diverse pharmacological effects include immunomodulatory activity, tumor suppression, hypoglycemic action, and hypolipidemic effects. Additionally, it has been shown to provide neuroprotection, liver protection, radiation protection, cardioprotection, and bone protection. Related preparations such as Aidi injection, compound cantharidin capsule, and Tanreqing injection have been widely used in clinical settings. Other studies on syringin such as extraction and isolation, total synthesis, safety profile assessment, and pharmacokinetics have also made progress. It is crucial for medical research to deeply explore its mechanism of action, especially regarding immunity and tumor therapy. Meanwhile, more robust support is needed to improve the utilization of plant resources and to develop extraction means adapted to the needs of industrial biochemistry to further promote economic development while protecting people’s health.

Ferroptosis is linked to various tumor biological traits, and alternative splicing (AS), a crucial step in mRNA processing, plays a role in the post-transcriptional regulation of ferroptosis-related genes (FRGs). A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was utilized to build a prognostic signature based on 12 AS events (p 0.4, FDR

Di-(2-ethylhexyl)-phthalate (DEHP), as distinctive endocrine disrupting chemicals, has become a global environmental pollutant harmful to human and animal health. However, the impacts on offspring and mothers with maternal DEHP exposure are largely unknown and the mechanism remains elusive. We established DEHP-exposed maternal mice to investigate the impacts on mother and offspring and illustrate the mechanism from multiple perspectives. Pregnant mice were administered with different doses of DEHP, respectively. Metagenomic sequencing used fecal and transcriptome sequencing using placentas and livers from offspring have been performed, respectively. The results of the histopathology perspective demonstrated that DEHP exposure could disrupt the function of islets impact placentas and fetus development for maternal mice, and cause the disorder of glucose and lipid metabolism for immature offspring mice, resulting in hyperglycemia. The results of the metagenome of gut microbial communities indicated that the dysbiosis of gut microbiota in mother and offspring mice and the dominant phyla transformed through vertical transmission. Transcriptome analysis found DEHP exposure induced mutations of Ahcy and Gstp3, which can damage liver cells and affect the metabolism of the host. DEHP exposure harms pregnant mice and offspring by affecting gene expression and altering metabolism. Our results suggested that exposure of pregnant mice to DEHP during pregnancy and lactation increased the risk of metabolic disorders by altering key genes in liver and gut microbiota, and these results provided new insights into the potential long-term harms of DEHP.

ObjectivesTo assess the comparative efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S) versus concurrent chemoradiotherapy (CCRT) for patients with cervical cancer stages IB2 to IIB.MethodAn exhaustive literature search was conducted up to November 2023 in databases including PubMed, Embase, Web of Science, and the Cochrane Library, focusing on disease-free survival (DFS) and overall survival (OS). Data were analyzed using STATA version 15.ResultsThe meta-analysis included data from two randomized controlled trials and eight retrospective cohort studies, totaling 2,879 patients with stages IB2 to IIB cervical cancer. Pooled data showed no significant difference in OS [hazard ratio (HR) 0.71, 95% confidence interval (CI): 0.51 to 1.00, p = 0.052] and DFS (HR 0.65, 95% CI: 0.38 to 1.14, p = 0.132) between NACT+S and CCRT. Subgroup analysis revealed that NACT+S provided a better OS in Asian populations, retrospective cohort studies, TP regimen chemotherapy, and multivariate analysis.ConclusionThe findings indicate that CCRT and NACT+S are comparably effective for treating cervical cancer stages IB2 to IIB. Notably, in specific subgroups such as Asian patients and those receiving the TP regimen, NACT+S appears to enhance OS.

BackgroundHigh altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA.MethodsWe established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites.ResultAlthough significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5).ConclusionWe observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

The MIND diet is a healthy dietary pattern that has some benefits for many health outcomes. Our study aims to conduct a bibliometric analysis of the MIND diet, identifying leading edges and hotspots to provide a reference for future research. The research on the MIND diet was gathered from the Web of Science Core Collection (WOSCC) database. For bibliometric analysis, VOSviewer 1.6.16 and the WOSCC Online Analysis Platform were utilized. In total, this comprehensive investigation encompassed 171 documents in the field of the MIND diet. The publications are globally distributed, with contributions from 953 authors across 362 institutions in 37 countries/regions, and published in 94 journals. The United States leads with 72 publications, and Iran and the People’s Republic of China also show notable engagement with 28 and 19 publications, respectively. Rush University stands out with 21 publications, followed by Harvard University and Tehran University of Medical Sciences, demonstrating their substantial contributions to this field. Martha Clare Morris is a key figure with 10 publications, alongside Klodian Dhana and Puja Agarwal, each contributing 9 publications, highlighting their influence in the MIND diet research. The journal “Nutrients” is a major publication venue with 20 related articles, followed by “Frontiers in Nutrition” and “Journal of Nutrition Health Aging,” reflecting their crucial roles in advancing knowledge about the MIND diet. The first high-cited publication was published in Alzheimers & Dementia and conducted by Martha Clare Morris, which focuses on the MIND diet’s relationship with Alzheimer’s disease prevention and cognitive decline and emphasizes the diet’s neuroprotective potential, highlighting how even moderate adherence can substantially reduce Alzheimer’s risk and slow cognitive decline. In conclusion, this is the first comprehensive bibliometric study that quantitatively and qualitatively analyzed the publications in the field of the MIND diet. The MIND diet may be a promising dietary pattern for dementia. However, the current evidence is restricted and highlights the urgency and necessity of further research to investigate the efficacy of this diet for cognitive function. In addition, the MIND diet may have some benefits for other health outcomes, including CVDs, cancer, and diabetes. The number of studies in the field of the MIND diet is limited. More studies are needed, and will give us more knowledge about the MIND diet to improve human health, especially for dementia.