FTY720 ameliorates experimental MPO-ANCA-associated vasculitis by regulating fatty acid oxidation via the neutrophil PPARα-CPT1a pathway.

OBJECTIVES: Increasing studies demonstrated the importance of C5a and anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation in the pathogenesis of ANCA-associated vasculitis (AAV). Sphingosine-1-phosphate (S1P) acts as a downstream effector molecule of C5a and enhances neutrophil activation induced by C5a and ANCA. The current study investigated the role of a S1P receptor modulator FTY720 in experimental autoimmune vasculitis (EAV) and explored the immunometabolism-related mechanisms of FTY720 in modulating ANCA-induced neutrophil activation. METHODS: The effects of FTY720 in EAV were evaluated by quantifying hematuria, proteinuria, crescent formation, tubulointerstitial injury and pulmonary hemorrhage. RNA sequencing of renal cortex and gene enrichment analysis were performed. The proteins of key identified pathways were analyzed in neutrophils isolated from peripheral blood of patients with active AAV and normal controls. We assessed the effects of FTY720 on ANCA-induced neutrophil respiratory burst and neutrophil extracellular traps formation (NETosis). RESULTS: FTY720 treatment significantly attenuated renal injury and pulmonary hemorrhage in EAV. RNA sequencing analyses of renal cortex demonstrated enhanced fatty acid oxidation (FAO) and peroxisome proliferators-activated receptors (PPAR) signalling in FTY720-treated rats. Compared with normal controls, patients with active AAV showed decreased FAO in neutrophils. FTY720-treated differentiated HL-60 cells showed increased expression of carnitine palmitoyltransferase 1A (CPT1a) and PPARα. Blocking or knockdown of CPT1a or PPARα in isolated human neutrophils and HL-60 cells reversed the inhibitory effects of FTY720 on ANCA-induced neutrophil respiratory burst and NETosis. CONCLUSION: FTY720 attenuated renal injury in EAV through upregulating FAO via the PPARα-CPT1a pathway in neutrophils, offering potential immunometabolic targets in AAV treatment.

Malignancy is increased in patients with antineutrophil cytoplasmic antibody-associated vasculitis in China.

OBJECTIVE: It has been reported that in western countries malignancy risk was higher in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) compared with that in the general population. In the current study, we investigated the incidence, spectrum and risk factors of malignancy in Chinese AAV patients. METHODS: AAV patients diagnosed from 1995 to 2021 in Peking University First Hospital with a follow-up more than 12 months were recruited. Standardized incidence ratios (SIR) were calculated to describe the risk of malignancy, adjusted for sex, age and follow-up time. RESULTS: A total of 552 AAV patients were recruited, among which 23 patients had malignancies either preceding or concurrent with AAV diagnosis, and 43 of the remaining 529 patients developed malignancies within 4.3 ± 4.2 years post AAV diagnosis (SIR: 2.24; 95% CI: 1.68-2.99; p < 0.001). Among these 66 patients, twenty different sites of malignancy were observed, lung cancer being most frequent. To get exactly expected malignancies for the calculation of SIR, 529 patients without preceding or concurrent malignancies were included in the following analysis. Lung cancer was still the leading malignancy diagnosis (SIR: 5.01; 95% CI: 3.29-7.62), followed by malignancies in the kidney, bladder, ureter and prostate. Male gender (HR:2.84; 95%CI:1.36-5.96; p = 0.006) and older age (per year, HR:1.04; 95%CI:1.00-1.07; p = 0.038) were significantly associated with increased risk of malignancy. For patients with malignancy developed beyond 5 years after the diagnosis of AAV, a significantly higher malignancy risk was observed in those with a cumulative cyclophosphamide dose over 20.0 g (SIR: 11.54; 95% CI: 4.77-27.93; p < 0.001). Within the first 2 years after the diagnosis of AAV, the risk of malignancy was still significantly higher than that in the general population, but the cumulative cyclophosphamide dose was not significantly associated with malignancy occurrence in this subgroup of patients. CONCLUSIONS: Malignancy risk is higher in Chinese AAV patients than that in the general population, with a different malignancy spectrum from western countries. Both the use of cyclophosphamide and AAV per se might be associated with higher incidence of malignancy occurrence.

The WRKY gene family in the halophyte Limonium bicolor: identification, expression analysis, and regulation of salt stress tolerance.

KEY MESSAGE: 63 L. bicolor WRKY genes were identified and their informatics was analyzed. The results suggested that the LbWRKY genes involved in the development and salt secretion of salt glands in L. bicolor. Salt stress, as a universal abiotic stress, severely inhibits the growth and development of plants. WRKY transcription factors play a vital role in plant growth and development, as well as in response to various stresses. Nevertheless, little is known of systematic genome-wide analysis of the WRKY genes in Limonium bicolor, a model recretohalophyte. In this study, 63 L. bicolor WRKY genes were identified (LbWRKY1-63), which were unevenly distributed across seven chromosomes and one scaffold. Based on the structural and phylogenetic characteristics, 63 LbWRKYs are divided into three main groups. Cis-elements in the LbWRKY promoters were related to growth and development, phytohormone responses, and stress responses. Colinearity analysis showed strong colinearity between LbWRKYs and GmWRKYs from soybean (Glycine max). Therefore, LbWRKY genes maybe have similar functions to GmWRKY genes. Expression analysis showed that 28 LbWRKY genes are highly expressed in roots, 9 in stems, 26 in leaves, and 12 in flowers and most LbWRKY genes responded to NaCl, ABA, and PEG6000. Silencing LbWRKY10 reduced salt gland density and salt secretion ability of leaves, and the salt tolerance of the species. Consistent with this, genes associated with salt gland development were markedly down-regulated in the LbWRKY10-silenced lines. Our findings suggested that the LbWRKY genes involved in the development and salt secretion of salt glands in L. bicolor. Our research provides new insights into the functions of the WRKY family in halophytes.

Loss of sigma-2 receptor/TMEM97 is associated with neuropathic injury-induced depression-like behaviors in female mice.

Previous studies have shown that ligands that bind to sigma-2 receptor/TMEM97 (σ2R/TMEM97), a transmembrane protein, have anxiolytic/antidepressant-like properties and relieve neuropathic pain-like effects in rodents. Despite medical interest in σ2R/TMEM97, little affective and pain behavioral characterization has been done using transgenic mice, which limits the development of σ2R/TMEM97 as a viable therapeutic target. Using wild-type (WT) and global Tmem97 knockout (KO) mice, we sought to identify the contribution of Tmem97 in modulating affective and pain-like behaviors using a battery of affective and pain assays, including open field, light/dark preference, elevated plus maze, forced swim test, tail suspension test, and the mechanical sensitivity tests. Our results demonstrate that female Tmem97 KO mice show less anxiety-like and depressive-like behaviors in light/dark preference and tail suspension tests but not in an open field, elevated plus maze, and forced swim tests at baseline. We next performed spared nerve injury in WT and Tmem97 KO mice to assess the role of Tmem97 in neuropathic pain-induced anxiety and depression. WT mice, but not Tmem97 KO mice, developed a prolonged neuropathic pain-induced depressive-like phenotype when tested ten weeks after nerve injury in females. Our results show that Tmem97 plays a role in modulating anxiety-like and depressive-like behaviors in naïve animals with a significant change in the presence of nerve injury in female mice. Overall, these data demonstrate that Tmem97 could be a target to alleviate affective comorbidities of pain disorders.Significance Statement Chronic pain comorbidities, including anxiety and depression, present a significant public health challenge. Pharmacological agents developed to target the sigma-2 receptor/TMEM97 (σ2R/TMEM97) have demonstrated promising effects in alleviating anxiety, depression, and pain individually. Our work provides insight on the interaction between σ2R/TMEM97 and neuropathic pain-induced affective behaviors using transgenic mice, suggesting its potential as a novel therapeutic target for addressing both the pain and psychiatric components in complex chronic pain disorders.

Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy.

AIMS: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

In-situ tool wear condition monitoring during the end milling process based on dynamic mode and abnormal evaluation.

Rapid tool wear conditions during the manufacturing process are crucial for the enhancement of product quality. As an extension of our recent works, in this research, a generic in-situ tool wear condition monitoring during the end milling process based on dynamic mode and abnormal evaluation is proposed. With the engagement of dynamic mode decomposition, the real-time response of the sensing physical quantity during the end milling process can be predicted. Besides, by constructing the graph structure of the time series and calculating the difference between the predicted signal and the real-time signal, the anomaly can be acquired. Meanwhile, the tool wear state during the end milling process can be successfully evaluated. The proposed method is validated in milling tool wear experiments and received positive results (the mean relative error is recorded as 0.0507). The research, therefore, paves a new way to realize the in-situ tool wear condition monitoring.

Immersive virtual reality as a surgical training tool: A cohort study.

Background: Few studies have studied the efficacy of using immersive virtual reality (iVR) to teach surgical skills, especially by using real-world iVR recordings rather than simulations. This study aimed to investigate whether viewing 360° iVR instructional recordings produces greater improvements in basic suturing skills of students without prior medical training, beyond traditional methods like reading written manuals or watching 2D instructional videos. Materials and methods: This was a partially blinded randomized cohort study. 44 pre-university students (aged 17) were randomized equally to either the written instruction manual, 2D instructional video, or iVR recordings. All students first watched a silent 2D demonstration video of the suturing task, before attempting to place three simple interrupted sutures on a piece of meat as a baseline. The time taken for the first attempt was recorded. Students were then given an hour to train using their allocated modality. They attempted the suturing task again, and timings were re-recorded. Four blinded surgically-trained judges independently assessed the quality of the stitches placed both pre and post-intervention. One-way analysis of variance tests (ANOVAs) and independent two-sample t-tests were used to determine the effect of training modality on improvements in suturing scores and time taken to complete suturing from pre to post-training. Results: For suturing scores, the iVR group showed significantly larger score improvements than the Written Manual group (p = 0.031, Cohen's D = 0.92), while this iVR advantage was less pronounced when compared with the 2D Video group (p = 0.16, Cohen's D = 0.65). Similarly for time taken to complete suturing, the iVR group had significantly larger time improvements than the Written Manual group (p = 0.045), although this difference was less robust compared to the 2D Instructional Video group (p = 0.34). Conclusion: This study demonstrates that iVR training using real-world 360° instructional recordings produced significantly greater training gains in suturing scores and efficiency compared to reading written text. iVR training also led to larger training gains in both outcome measures than viewing 2D instructional videos, although the differences between them did not reach statistical significance.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Long Non-Coding RNA PCAT19 Suppresses Cell Proliferation and Angiogenesis in Coronary Artery Disease through Interaction with GCNT2.

LncRNAs involvement in heart disease, however, the effect of lncRNA prostate cancer-associated transcript 19 (PCAT19) in coronary artery disease (CAD) remains unclear. In the current study, we aimed to verify the role of PCAT19 in CAD. We first investigated the differentially expressed lncRNAs in different Genes Expression Omnibus (GEO) database. We then detected lncRNAs expression in healthy volunteers and acute myocardial infarction (AMI) patients by qRT­PCR. The correlation of PCAT19 and Glucosaminyl (N-Acetyl) Transferase 2 (GCNT2) was analyzed. Human coronary artery endothelial cells (HCAECs) was used to conduct cell hypoxia-reoxygenation (H/R) injury model to imitate AMI injury. CCK8, BrdU, tube formation assay were used to detect cell viability, proliferation, and angiogenesis. Immunofluorescence, western blotting were used to detect ki67, VEGFA, PCNA, CD31, and GCNT2 expression, respectively. We obtained six different lncRNAs from GEO database and identified PCAT19 high expression in AMI patients. PCAT19 was positive correlation to GCNT2. Further experiments presented that PCAT19 knockdown promoted cell viability, proliferation and angiogenesis, GCNT2 knockdown also promoted cell viability, proliferation, and angiogenesis. These results confirmed by the inhibition of Ki67 and VEGFA. Importantly, PCAT19 overexpression suppressed cell proliferation and angiogenesis, these results also confirmed by the inhibition of PCNA and CD31. However, the inhibitory effect of PCAT19 overexpression was reversed by GCNT2 knockdown. Our study indicated that PCAT19 plays an important role in the CAD disease, its effects was related to GCNT2. Our research provides a novel sight for the effect of PCAT19 on CAD.

An in vivo "turning model" reveals new RanBP9 interactions in lung macrophages.

The biological functions of the scaffold protein Ran Binding Protein 9 (RanBP9) remain elusive in macrophages or any other cell type where this protein is expressed together with its CTLH (C-terminal to LisH) complex partners. We have engineered a new mouse model, named RanBP9-TurnX, where RanBP9 fused to three copies of the HA tag (RanBP9-3xHA) can be turned into RanBP9-V5 tagged upon Cre-mediated recombination. We created this model to enable stringent biochemical studies at cell type specific level throughout the entire organism. Here, we have used this tool crossed with LysM-Cre transgenic mice to identify RanBP9 interactions in lung macrophages. We show that RanBP9-V5 and RanBP9-3xHA can be both co-immunoprecipitated with the known members of the CTLH complex from the same whole lung lysates. However, more than ninety percent of the proteins pulled down by RanBP9-V5 differ from those pulled-down by RanBP9-HA. The lung RanBP9-V5 associated proteome includes previously unknown interactions with macrophage-specific proteins as well as with players of the innate immune response, DNA damage response, metabolism, and mitochondrial function. This work provides the first lung specific RanBP9-associated interactome in physiological conditions and reveals that RanBP9 and the CTLH complex could be key regulators of macrophage bioenergetics and immune functions.

Oridonin represses lung cancer cell proliferation and migration by modulating AFAP1-AS1/IGF2BP1.

Oridonin belongs to a small molecule from the Chinese herb Rabdosia rubescens with potent anticancer activity. In spite of the lncRNA AFAP1-AS1 has been proven to exert promoting function in lung cancer, its relationship with oridonin in lung cancer is obscure. Therefore, our study planned to explore the potential of oridonin in lung cancer as well as unveil the regulatory mechanism of oridonin on AFAP1-AS1 in lung cancer cells. In the present study, oridonin inhibited lung cancer cell proliferation, migration, as well as invasion, as evidenced by MTT, wound healing, as well as transwell assays. Besides, we observed that oridonin could downregulate AFAP1-AS1 expression, and overexpressed AFAP1-AS1 could reverse the repressive effects of oridonin on lung cancer cell proliferation, migration, as well as invasion. More importantly, we found that AFAP1-AS1 could bind to IGF2BP1 through starBase prediction and RIP assay. The expression level of IGF2BP1 was also reduced by oridonin treatment but reversed after AFAP1-AS1 overexpression. Additionally, we proved that overexpressed IGF2BP1 could reverse the repressive impacts of oridonin on lung cancer cell proliferation, migration, as well as invasion. Further, in vivo experiments validated the repressive role of oridonin on tumor growth of lung cancer. Together, oridonin inhibits lung cancer cell proliferation as well as migration by modulating AFAP1-AS1/IGF2BP1, and AFAP1-AS1/IGF2BP1 possesses the potential to be a promising therapy targeting for lung cancer, especially in oridonin treatment.

Bioorthogonal Labeling and Enrichment of Histone Monoaminylation Reveal Its Accumulation and Regulatory Function in Cancer Cell Chromatin.

Histone monoaminylation (i.e., serotonylation and dopaminylation) is an emerging category of epigenetic mark occurring on the fifth glutamine (Q5) residue of H3 N-terminal tail, which plays significant roles in gene transcription. Current analysis of histone monoaminylation is mainly based on site-specific antibodies and mass spectrometry, which either lacks high resolution or is time-consuming. In this study, we report the development of chemical probes for bioorthogonal labeling and enrichment of histone serotonylation and dopaminylation. These probes were successfully applied for the monoaminylation analysis of in vitro biochemical assays, cells, and tissue samples. The enrichment of monoaminylated histones by the probes further confirmed the crosstalk between H3Q5 monoaminylation and H3K4 methylation. Finally, combining the ex vivo and in vitro analyses based on the developed probes, we have shown that both histone serotonylation and dopaminylation are highly enriched in tumor tissues that overexpress transglutaminase 2 (TGM2) and regulate the three-dimensional architecture of cellular chromatin.

Three-pillar expansive craniotomy in children with acute ruptured supratentorial brain arteriovenous malformations.

OBJECTIVE: Acute rupture and hemorrhage of pediatric brain arteriovenous malformations (AVMs) may lead to cerebral herniation or intractable intracranial hypertension, necessitating emerging surgical interventions to alleviate intracranial pressure. However, there is still controversy regarding the timing of treatment for ruptured AVMs. This study aimed to assess the feasibility of utilizing three-pillar expansive craniotomy (3PEC) at different times during the treatment of pediatric ruptured supratentorial AVMs. METHODS: A retrospective analysis was conducted on all consecutive cases of acute rupture in supratentorial AVMs children who underwent 3PEC at a single institution from 2020 to 2022. General information, clinical characteristics, radiological data, and prognosis were reviewed and analyzed. RESULTS: Thirteen children were included in the analysis. The intracranial pressure of all patients decreased to below 15 mmHg within 10 days. The expansion volume of the cranial cavity of the patients increased by 18.3 cm3 (95% CI, 10.2- 26.3; P < .001) compared to the hematoma volume. None of the patients required decompressive craniectomy due to intractable intracranial hypertension caused by cerebral swelling. The median waiting period for patients with delayed AVMs treatment was 8 days, during which no rebleeding occurred. CONCLUSIONS: Emergency intervention with 3PEC in children experiencing acutely ruptured supratentorial AVMs appears to be feasible. For children requiring delayed management of the AVMs, 3PEC may diminish the risk of rebleeding during the waiting period and shorten the waiting period.

Intra-islet α-cell Gs signaling promotes glucagon release.

Glucagon, a hormone released from pancreatic α-cells, is critical for maintaining euglycemia and plays a key role in the pathophysiology of diabetes. To stimulate the development of new classes of therapeutic agents targeting glucagon release, key α-cell signaling pathways that regulate glucagon secretion need to be identified. Here, we focused on the potential importance of α-cell Gs signaling on modulating α-cell function. Studies with α-cell-specific mouse models showed that activation of α-cell Gs signaling causes a marked increase in glucagon secretion. We also found that intra-islet adenosine plays an unexpected autocrine/paracrine role in promoting glucagon release via activation of α-cell Gs-coupled A2A adenosine receptors. Studies with α-cell-specific Gαs knockout mice showed that α-cell Gs also plays an essential role in stimulating the activity of the Gcg gene, thus ensuring proper islet glucagon content. Our data suggest that α-cell enriched Gs-coupled receptors represent potential targets for modulating α-cell function for therapeutic purposes.

Clustering-resistant Cu Single Atoms on Porous Au Nanoparticles Supported by TiO2 for Sustainable Photoconversion of CO2 into CH4.

Photocatalysts based on single atoms (SAs) modification can lead to unprecedented reactivity with recent advances. However, the deactivation of SAs-modified photocatalysts remains a critical challenge in the field of photocatalytic CO2 reduction. In this study, we unveil the detrimental effect of CO intermediates on Cu single atoms (Cu-SAs) during photocatalytic CO2 reduction, leading to clustering and deactivation on TiO2. To address this, we developed a novel Cu-SAs anchored on Au porous nanoparticles (CuAu-SAPNPs-TiO2) via a vectored etching approach. This system not only enhances CH4 production with a rate of 748.8 µmol·g-1·h-1 and 93.1% selectivity but also mitigates Cu-SAs clustering, maintaining stability over 7 days. This sustained high performance, despite the exceptionally high efficiency and selectivity in CH4 production, highlights the CuAu-SAPNPs-TiO2 overarching superior photocatalytic properties. Consequently, this work underscores the potential of tailored SAs-based systems for efficient and durable CO2 reduction by reshaping surface adsorption dynamics and optimizing the thermodynamic behavior of the SAs.

Exploring potential circRNA biomarkers for cancers based on double-line heterogeneous graph representation learning.

BACKGROUND: Compared with the time-consuming and labor-intensive for biological validation in vitro or in vivo, the computational models can provide high-quality and purposeful candidates in an instant. Existing computational models face limitations in effectively utilizing sparse local structural information for accurate predictions in circRNA-disease associations. This study addresses this challenge with a proposed method, CDA-DGRL (Prediction of CircRNA-Disease Association based on Double-line Graph Representation Learning), which employs a deep learning framework leveraging graph networks and a dual-line representation model integrating graph node features. METHOD: CDA-DGRL comprises several key steps: initially, the integration of diverse biological information to compute integrated similarities among circRNAs and diseases, leading to the construction of a heterogeneous network specific to circRNA-disease associations. Subsequently, circRNA and disease node features are derived using sparse autoencoders. Thirdly, a graph convolutional neural network is employed to capture the local graph network structure by inputting the circRNA-disease heterogeneous network alongside node features. Fourthly, the utilization of node2vec facilitates depth-first sampling of the circRNA-disease heterogeneous network to grasp the global graph network structure, addressing issues associated with sparse raw data. Finally, the fusion of local and global graph network structures is inputted into an extra trees classifier to identify potential circRNA-disease associations. RESULTS: The results, obtained through a rigorous five-fold cross-validation on the circR2Disease dataset, demonstrate the superiority of CDA-DGRL with an AUC value of 0.9866 and an AUPR value of 0.9897 compared to existing state-of-the-art models. Notably, the hyper-random tree classifier employed in this model outperforms other machine learning classifiers. CONCLUSION: Thus, CDA-DGRL stands as a promising methodology for reliably identifying circRNA-disease associations, offering potential avenues to alleviate the necessity for extensive traditional biological experiments. The source code and data for this study are available at https://github.com/zywait/CDA-DGRL .

The brain-bone axis: unraveling the complex interplay between the central nervous system and skeletal metabolism.

The brain-bone axis has emerged as a captivating field of research, unveiling the intricate bidirectional communication between the central nervous system (CNS) and skeletal metabolism. This comprehensive review delves into the current state of knowledge surrounding the brain-bone axis, exploring the complex mechanisms, key players, and potential clinical implications of this fascinating area of study. The review discusses the neural regulation of bone metabolism, highlighting the roles of the sympathetic nervous system, hypothalamic neuropeptides, and neurotransmitters in modulating bone remodeling. In addition, it examines the influence of bone-derived factors, such as osteocalcin and fibroblast growth factor 23, on brain function and behavior. The therapeutic potential of targeting the brain-bone axis in the context of skeletal and neurological disorders is also explored. By unraveling the complex interplay between the CNS and skeletal metabolism, this review aims to provide a comprehensive resource for researchers, clinicians, and students interested in the brain-bone axis and its implications for human health and disease.

Risk factors of missed early gastric cancer in endoscopic resected population: a retrospective, case-control study.

BACKGROUND: Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. METHODS: This retrospective, case-control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. RESULTS: A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95% CI 0.27-0.74, P = 0.002) and invasion depth of submucosa (OR 0.26, 95% CI 0.10-0.69, P = 0.007) were negatively associated with MEGC. Use of sedation (OR 0.32, 95% CI 0.20-0.52, P < 0.001) and longer observation time (OR 0.60, 95% CI 0.37-0.96, P = 0.034) exhibited protective effect on MEGC. CONCLUSIONS: Smaller and more superficial EGC lesions are more susceptible to misdiagnosis. The use of sedation and prolonged observation time during EGD could help reduce the occurrence of MEGC.

[Seasonal changes of ammonia-oxidizing bacterial communities during tropical forest restoration]. / 热带森林恢复过程中氨氧化细菌群落的季节变化.

In this study, we used a high-throughput sequencing technology to survey the dry-wet seasonal change characteristics of soil ammonia-oxidizing bacteria (AOB) communities in the three restoration stages [i.e., Mallotus paniculatus community (early stage), Millettia leptobotrya community (middle stage), and Syzygium oblatum community (later stage)] of Xishuangbanna tropical forest ecosystems. We analyzed the effects of soil physicochemical characteristics on AOB community composition and diversity during tropical forest restoration. The results showed that tropical forest restoration significantly affected the relative abundance of dominant AOB phyla and their dry-wet seasonal variation. The maximum relative abundance of Proteobacteria (71.3%) was found in the early recovery stage, while that of Actinobacteria was found in the late recovery stage (1.0%). The abundances of Proteobacteria and Actinobacteria had the maximum ranges of dry-wet seasonal variation in the early and late stages, respectively. The abundance of dominant AOB genera and its dry-wet seasonal variation varied across tropical forest restoration stages. The maximum average relative abundance of Nitrosospira and Nitrosomonas in the late recovery stage was 66.2% and 1.5%, respectively. In contrast, the abundance of Nitrosovibrio reached its maximum (25.6%) in the early recovery stage. The maximum dry-wet seasonal variation in relative abundance of Nitrosospira and Nitrosomonas occurred in the early recovery stage, while that of Nitrosovibrio occurred in the middle recovery stage. The Chao1, Shannon, and Simpson diversity indices of AOB communities increased along the restoration stages, which were significantly higher in the wet season than in the dry season. The results of canonical correspondence analysis showed that soil easily oxidized carbon was the main factor controlling AOB community diversity and Actinobacteria abundance. Soil bulk density and temperature were the main factors affecting Proteobacteria abundance. Soil pH, microbial biomass carbon, water content, ammonium nitrogen, bulk density, and temperature were the main factors controlling the abundances of Nitrosospira, Nitrosomonas, and Nitrosovibrio. Therefore, tropical forest restoration can regulate the change of relative abundance of dominant AOB taxa via mediating the changes of soil temperature, bulk density, and readily oxidized carbon, leading to an increase in soil AOB community diversity.

Comparison of clinical outcomes between family caregivers and professional caregivers in in-hospital patients with acute ischaemic stroke: A prospective cohort study.

AIM: This study explored the impact of different care modes on the outcome of hospitalized patients with acute ischaemic stroke (AIS) during hospitalization and 3 months after discharge. METHODS: This was a prospective cohort study comparing the outcomes at hospitalization, at discharge, and at 3 months post discharge among AIS patients with different caregiving arrangements from 9, December 2022 to 20, August 2023. The general information questionnaire, Modified Barthel Index, Shortened General Comfort Questionnaire, Perceived Social Support scale, Herth Hope Index, modified Rankin scale and EQ-5D-5L were utilized for the investigation. RESULTS: The psychological evaluation scores during hospitalization, including comfort, perceived social support, and hope, did not significantly differ between the two groups of AIS patients (p > .05). Moreover, there were no significant impacts observed in terms of length of stay (LOS) at the hospital or hospitalization expense (p > .05). The proportion of patients with intact functionality was greater in the family caregiver group 3 months after discharge (16.5%). However, when stratified based on prognosis, the difference in outcomes between the two groups of patients did not reach statistical significance (p > .05). The analysis of ADL, quality of life and stroke recurrence in 276 surviving ischaemic stroke patients 3 months post discharge indicated no differences between the two groups across all three aspects (p > .05). CONCLUSION: Older and divorced or widowed AIS patients tend to prefer professional caregivers. The psychological state during hospitalization, length of hospital stay and hospitalization expenses are not influenced by the caregiving model. Three months post discharge, a greater proportion of patients in the family caregiving group had intact mRS functionality, but this choice did not impact patient prognosis, stroke recurrence, quality of life or independence in ADL.