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Abstract Endo-periodontal lesions (EPLs) involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms, including unique anatomical and microbiological characteristics and multiple contributing factors. This etiological complexity leads to difficulties in determining patient prognosis, posing great challenges in clinical practice. Furthermore, EPL-affected teeth require multidisciplinary therapy, including periodontal therapy, endodontic therapy and others, but there is still much debate about the appropriate timing of periodontal therapy and root canal therapy. By compiling the most recent findings on the etiology, pathogenesis, clinical characteristics, diagnosis, therapy, and prognosis of EPL-affected teeth, this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

ObjectivesThere is already substantial evidence indicating that neutrophil extracellular trap (NET) formation contributes to the inflammatory cascade in ulcerative colitis (UC). However, the precise regulatory mechanisms governing this process remain elusive. This study aimed to determine the role of NET-related genes in UC and reveal possible mechanisms.MethodsEmploying a two-sample MR methodology, we investigated the correlations between NET-associated genes (NRGs) and UC with summary data derived from a genome-wide association study (12,366 cases vs. 33,609 controls) and FinnGen (8,279 cases vs. 261,098 controls). The main analysis employed the inverse variance weighted method, supplemented by the MR-Egger method and weighted median method. Sensitivity analysis was conducted to rule out the interference of heterogeneity and pleiotropy among utilized instrument variables. The colocalization analysis was used to determine whether the identified NRGs and UC shared casual variants. Cross-tissue expression analysis was performed to characterize the expression patterns of target NRGs, while multi-gene correlation analysis and GSEA analysis were conducted to explore the mechanisms by which target NRGs promote UC and NET formation. Immunohistochemistry was used to validate the protein expression of target NRGs in the colon tissue of UC patients.ResultsAfter the validation of two datasets, seven NRGs were associated with the risk of UC. The higher expression of ITGB2 was associated with increased UC risk, while the expression of CXCR1, CXCR2, IRAK4, MAPK3, SIGLEC14, and SLC22A4 were inversely associated with UC risk. Colocalization analysis supported the correlation between CXCR1/2 and UC risk. Expression analysis indicated that CXCR1/2 were down-regulated in peripheral blood, but up-regulated in colon tissue. GSEA analysis and correlation analysis indicated that CXCR1/2 promoted UC and NET formation through neutrophil chemotaxis and PAD4-mediated pathways, separately. Immunohistochemical results confirmed the high expression of CXCR1/2 in colon tissues of UC patients.ConclusionsOur study identified CXCR1/2 as candidate targets in UC among all NRGs through multi-method argumentation, providing new insights of the regulation mechanisms of NET formation in the pathogenesis of UC.

Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation of membrane pores mediated by the gasdermin protein family. Two main activation pathways have been documented: the caspase-1-dependent canonical pathway and the caspase-4/5/11-dependent noncanonical pathway. Pyroptosis leads to cell swelling, lysis, and the subsequent release of inflammatory mediators, including interleukin-1β (IL-1β) and interleukin-18 (IL-18). Chronic inflammation is a well-established foundation and driver for the development of metabolic diseases. Conversely, metabolic pathway dysregulation can also induce cellular pyroptosis. Recent studies have highlighted the significant role of pyroptosis modulation in various metabolic diseases, including type 2 diabetes mellitus, obesity, and metabolic (dysfunction) associated fatty liver disease. These findings suggest that pyroptosis may serve as a promising novel therapeutic target for metabolic diseases. This paper reviews an in-depth study of the current advancements in understanding the role of pyroptosis in the progression of metabolic diseases.

Abstract Background Multi-b-value diffusion-weighted imaging (DWI) with different postprocessing models allows for evaluating hepatocellular carcinoma (HCC) proliferation, spatial heterogeneity, and feasibility of treatment strategies. We assessed synergistic effects of bufalin+sorafenib in orthotopic HCC-LM3 xenograft nude mice by using intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), a stretched exponential model (SEM), and a fractional-order calculus (FROC) model. Methods Twenty-four orthotopic HCC-LM3 xenograft mice were divided into bufalin+sorafenib, bufalin, sorafenib treatment groups, and a control group. Multi-b-value DWI was performed using a 3-T scanner after 3 weeks’ treatment to obtain true diffusion coefficient Dt, pseudo-diffusion coefficient Dp, perfusion fraction f, mean diffusivity (MD), mean kurtosis (MK), distributed diffusion coefficient (DDC), heterogeneity index α, diffusion coefficient D, fractional order parameter β, and microstructural quantity μ. Necrotic fraction (NF), standard deviation (SD) of hematoxylin-eosin staining, and microvessel density (MVD) of anti-CD31 staining were evaluated. Correlations of DWI parameters with histopathological results were analyzed, and measurements were compared among four groups. Results In the final 22 mice, f positively correlated with MVD (r = 0.679, p = 0.001). Significantly good correlations of MK (r = 0.677), α (r = -0.696), and β (r= -0.639) with SD were observed (all p < 0.010). f, MK, MVD, and SD were much lower, while MD, α, β, and NF were higher in bufalin plus sorafenib group than control group (all p < 0.050). Conclusion Evaluated by IVIM, DKI, SEM, and FROC, bufalin+sorafenib was found to inhibit tumor proliferation and angiogenesis and reduce spatial heterogeneity in HCC-LM3 models. Relevance statement Multi-b-value DWI provides potential metrics for evaluating the efficacy of treatment in HCC. Key points • Bufalin plus sorafenib combination may increase the effectiveness of HCC therapy. • Multi-b-value DWI depicted HCC proliferation, angiogenesis, and spatial heterogeneity. • Multi-b-value DWI may be a noninvasive method to assess HCC therapeutic efficacy. Graphical Abstract

Abstarct Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.

Objective To investigate the effects of adenovirus-associated virus (AAV)-mediated overexpression of LINGO-1 in the hippocampus on spatial learning and memory abilities, as well as the volume and Spinophilin+ dendritic spines of different subregions within the hippocampus in mice. Methods Male C57 mice at 7 months of age were randomly divided into a control group and a LINGO-1 overexpression group. The control group received hippocampal stereotaxic injection of AAV carrying green fluorescent protein (GFP), while the LINGO-1 overexpression group received hippocampal stereotaxic injection of AAV carrying both GFP and LINGO-1 overexpression vector. Morris water maze was used to evaluate spatial learning and memory abilities of the mice. Quantitative PCR and immunofluorescence staining were used to detect LINGO-1 mRNA expression and fluorescence intensity in the hippocampus, and 3-dimensional stereology was used to quantify the volume and the total number of Spinophilin+ dendritic spines. Results There was no significant difference in body weight between the control group and the LINGO-1 overexpression group before and after virus injection. LINGO-1 overexpression induced an increase in hippocampal LINGO-1 at mRNA level and in fluorescent intensity(P < 0.01). The LINGO-1 overexpression group performed significantly worse in the Morris water maze test compared to the control group(P < 0.05). Moreover, LINGO-1 overexpression led to a significant reduction in the volumes of different hippocampal subregions(P < 0.05, P < 0.01), accompanied by marked decreases in the density(P < 0.01, P < 0.05) and total number of Spinophilin+ dendritic spines(P < 0.05). Conclusion Stereotaxic injection of AAV-mediated LINGO-1 overexpression specifically upregulates LINGO-1 in the hippocampus of mice. Abnormally high expression of LINGO-1 in the hippocampus leads to decreased hippocampal volume and loss of Spinophilin+ dendritic spines, as well as impaires spatial learning and memory abilities of mice to a certain extent.

BackgroundNumerous studies have established that alterations in the gut microbiota (GM) constitute an embedded mechanism in functional dyspepsia (FD). However, the specific GM taxa implicated in the pathological process of FD have remained unclear.MethodsA two-sample Mendelian randomization analysis was initially conducted to examine the causal relationships between GM and FD, utilizing GWAS data from the MiBioGen Consortium (18,340 cases) and FinnGenn (8,875 cases vs. 320,387 controls). The MR study primarily employed the inverse-variance weighted (IVW) method. Sensitivity analyses were performed to test for heterogeneity and pleiotropy. Single-nucleotide polymorphisms of causal GM taxa were mapped to genes, which were subsequently assessed for causal relationships with FD employing the same methodology.ResultsIVW results revealed that the genus Clostridium innocuum group (OR: 1.12, 95% CI: 1.02–1.24, P = 0.020) and genus Ruminiclostridium 9 were positively associated with FD risk (OR: 1.27, 95% CI: 1.03–1.57, P = 0.028), while the genus Lachnospiraceae FCS020 group tended to exert a negative effect on FD risk (OR = 0.84, 95% CI: 0.73–0.98, P = 0.023). Among GM-related genes, a notable association was observed between RSRC1 and increased FD risk (OR = 1.13, 95% CI: 1.07–1.20, P < 0.001). In sensitivity analyses, no significant pleiotropy or heterogeneity of the results was found.ConclusionsThis study furnished evidence for distinct effects of specific GM taxa on FD risk and hinted at a potential biological mechanism, thereby offering theoretical underpinning for future microbiotherapy of FD.

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

Drug-associated long-term memories underlie substance use disorders, including heroin use disorder (HUD), which are difficult to eliminate through existing therapies. Addictive memories may become unstable when reexposed to drug-related cues and need to be stabilized again through protein resynthesis. Studies have shown the involvement of histone acetylation in the formation and reconsolidation of long-term drug-associated memory. However, it remains unknown whether and how histone acetyltransferases (HAT), the essential regulators of histone acetylation, contribute to the reconsolidation of heroin-associated memories. Herein, we investigated the function of HAT in the reconsolidation concerning heroin-conditioned memory by using a rat self-administration model. Systemic administration of the HAT inhibitor garcinol inhibited cue and heroin-priming induced reinstatement of heroin seeking, indicating the treatment potential of garcinol for relapse prevention.

Abstract Background The overexpression of ALOX5AP has been observed in many types of cancer and has been identified as an oncogene. However, its role in acute myeloid leukemia (AML) has not been extensively studied. This study aimed to identify the expression and methylation patterns of ALOX5AP in bone marrow (BM) samples of AML patients, and further explore its clinical significance. Methods Eighty-two de novo AML patients and 20 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the alteration of ALOX5AP. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of ALOX5AP expression to discriminate AML. The prognostic value of ALOX5AP was identified by the Kaplan–Meier method and log-rank test. It was further validated in four independent cohorts (n = 1186). Significantly different genes associated with ALOX5AP expression were subsequently compared by LinkedOmics, and Metascape database. Results The level of ALOX5AP expression was significantly increased in bone marrow cells of AML patients compared with healthy donors (P

We report the isolation of a rare Gram-positive coccobacillary bacterium from synovial fluids of a patient with periprosthetic joint infection on three occasions over an 8-month period. As routine microbiological methods were not able to identify the isolate definitely, sequence analyses of the bacterial 16S ribosomal RNA gene and whole genome were performed. Analysis of the bacterial 16S ribosomal RNA gene showed the highest similarity (98.1%) with that of Falsarthrobacter (previously known as Arthrobacter) nasiphocae, which was first isolated from the nasal cavities of common seals (Phoca vitulina). The genome size of the strain (designated as UM1) is 2.4 Mb. With a high G+C content (70.4 mol%), strain UM1 is phylogenetically most closely related to F. nasiphocae based on whole genome analysis. Strain UM1 was susceptible to vancomycin, linezolid, trimethoprim-sulfamethoxazole, doxycycline, and intermediate to penicillin and ciprofloxacin. Ceftriaxone resistance was noted. The patient who was also on hemodialysis for his end stage kidney disease died approximately 3 weeks following implant removal and fusion with an external fixator. This study describes the first isolation of F. nasiphocae from human clinical samples. The use of emerging technologies has supported more definitive etiological diagnosis associated with rarely encountered organisms in periprosthetic joint infection.

Abstract Objectives Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. Methods Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. Results The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812–0.884), 0.759 (95% CI 0.722–0.797), 0.956 (95% CI 0.938–0.974), and 0.876 (95% CI 0.844–0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660–0.786), 0.688 (95% CI 0.643–0.732), 0.870 (95% CI 0.824–0.918), and 0.830 (95% CI 0.780–0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820–0.855) in the TC to 0.758 (95% CI 0.758–0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660–0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595–0.679). Conclusions CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Abstract The interaction between tumor cells and stromal cells within the tumor microenvironment plays a critical role in cancer progression. Mesenchymal stem cells (MSCs) are important tumor stromal cells that exhibit pro-oncogenic activities when reprogrammed by the tumor. However, the precise mechanisms underlying MSC reprogramming in gastric cancer remain not well understood. QRT-PCR, western blot, and immunohistochemistry were used to examine gene and protein expression levels. In vitro and in vivo experiments were conducted to assess the biological functions of gastric cancer cells. RNA-sequencing, RNA immunoprecipitation (RIP), and meRIP assays were performed to investigate underlying molecular mechanisms. We found a significant increase in the expression and N6-methyladenosine (m6A) modification levels of colony-stimulating factor 2 (CSF2) in gastric cancer MSCs. CSF2 gene overexpression induced the reprogramming of normal MSCs into cancer-promoting MSCs, thereby enhancing the proliferation, migration, and drug resistance of gastric cancer cells through the secretion of various pro-inflammatory factors. Additionally, we demonstrated that the m6A reader IGF2BP2 bound to and stabilized CSF2 mRNA in gastric cancer MSCs. Notably, overexpression of IGF2BP2 mimicked the effect of CSF2 on MSCs, promoting gastric cancer progression. Finally, we unveiled that CSF2 induced the ubiquitination of Notch1 to reprogram MSCs. Our study highlights a critical role of IGF2BP2-mediated m6A modification of CSF2 in reprogramming MSCs, which presents a promising therapeutic target for gastric cancer.

Pinctada fucata meat is the main by-product of the pearl harvesting industry. It is rich in nutrition, containing a lot of protein and peptides, and holds significant value for both medicine and food. In this study, a new active protein was discovered and expressed heterogeneously through bioinformatics analysis. It was then identified using Western blot, molecular weight, and mass spectrometry. The antibacterial activity, hemolysis activity, antioxidant activity, and Angiotensin-Converting Enzyme II (ACE2) inhibitory activity were investigated. An unknown functional protein was screened through the Uniprot protein database, and its primary structure did not resemble existing proteins. It was an α-helical cationic polypeptide we named PFAP-1. The codon-optimized full-length PFAP-1 gene was synthesized and inserted into the prokaryotic expression vector pET-30a. The induced expression conditions were determined with a final isopropyl-β-d-thiogalactoside (IPTG) concentration of 0.2 mM, an induction temperature of 15 °C, and an induction time of 16 h. The recombinant PFAP-1 protein, with low endotoxin and sterility, was successfully prepared. The recombinant PFAP-1 protein exhibited strong antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in vitro, and the diameter of the inhibition zone was 15.99 ± 0.02 mm. Its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were 37.5 μg/mL and 150 μg/mL, respectively, and its hemolytic activity was low (11.21%) at the bactericidal concentration. The recombinant PFAP-1 protein significantly inhibited the formation of MRSA biofilm and eradicated MRSA biofilm. It also demonstrated potent 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) scavenging activity with a half-maximal inhibitory concentration (IC50) of 40.83 μg/mL. The IC50 of ACE2 inhibition was 5.66 μg/mL. Molecular docking results revealed that the optimal docking fraction of PFAP-1 protein and ACE2 protein was −267.78 kcal/mol, with a confidence level of 0.913. The stable binding complex was primarily formed through nine groups of hydrogen bonds, three groups of salt bridges, and numerous hydrophobic interactions. In conclusion, recombinant PFAP-1 can serve as a promising active protein in food, cosmetics, or medicine.

Drug-associated pathological memory remains a critical factor contributing to the persistence of substance use disorder. Pharmacological amnestic manipulation to interfere with drug memory reconsolidation has shown promise for the prevention of relapse. In a rat heroin self-administration model, we examined the impact of rimonabant, a selective cannabinoid receptor indirect agonist, on the reconsolidation process of heroin-associated memory. The study showed that immediately administering rimonabant after conditioned stimuli (CS) exposure reduced the cue- and herion + cue-induced heroin-seeking behavior. The inhibitory effects lasted for a minimum of 28 days. The effect of Rimonabant on reduced drug-seeking was not shown when treated without CS exposure or 6 hours after CS exposure. These results demonstrate a disruptive role of rimonabant on the reconsolidation of heroin-associated memory and the therapeutic potential in relapse control concerning substance use disorder.

Summary: Concerns around reliability in China’s electricity sector have rekindled interest in a traditional solution: building more coal-fired generation. However, over the past decade China’s electricity sector has seen significant changes in supply costs, demand patterns, and regulation and markets, with falling costs for renewable and storage generation, “peakier” demand, and the creation of wholesale markets. These changes suggest that traditional approaches to evaluating the economics of different supply options may be outdated. This paper illustrates how a net capacity cost metric – fixed costs minus net market revenues – might be a useful metric for evaluating supply options to meet peak demand growth in China. Using a simplified example with recent resource cost data, the paper illustrates how, with a net capacity cost metric, electricity storage and solar PV may be a more cost-effective option for meeting peak demand growth than coal-fired generation.

Background: There is currently no consensus regarding the optimal perioperative antiplatelet strategy for carotid artery surgery. This multicentre study aimed to analyse the association between preoperative aspirin monotherapy following postoperative dual antiplatelet therapy (DAPT) and the risk for stroke and death after carotid endarterectomy (CEA). Methods: This cohort study included 821 patients with carotid artery stenosis who underwent CEA. Primary outcomes included any stroke or death up to the one-month postoperative follow-up. Multilevel multivariate regression analyses and descriptive statistics were performed. Results: Patients were predominantly male (53 %), with a mean age of 66.2 years. The primary outcome occurred in 1.6 % of patients. Univariate and multivariate analyses revealed that patients with chronic obstructive pulmonary disease (COPD) exhibited a high risk for stroke or death (P = 0.011). The occurrence of any local complications in the neck was accompanied by an increase in diastolic blood pressure (DBP) (P = 0.007). Patients with a high systolic blood pressure (SBP) (P = 0.002) experienced a longer operative duration. The length of hospital stay was longer in the patients with COPD (P = 0.020), minor stroke (P = 0.011), and major stroke (P = 0.001). A positive linear correlation was found between SBP and operative duration in the overall population (β 0.4 [95 % confidence interval (CI) 0.1–0.7]; P = 0.002). The resultant curve for DBP and any local complications in the neck exhibited a two-stage change and one breakpoint in the entire population (k = 68 mmHg,

Background and purpose: Glioma is a common malignant tumor of central nervous system with poor prognosis. Postoperative concurrent chemoradiotherapy with temozolomide (TMZ) is the main treatment for glioma. The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter can predict the sensitivity of glioma patients to TMZ treatment, however its relationship with clinical pathology and how to better predict treatment and prognosis still need further research. The purpose of this study was to analyze the status of MGMT promoter methylation (MGMTmet) in gliomas and its correlation with clinical pathological features and other common molecular abnormalities, and to explore the value of combined analysis of MGMTmet and other molecular abnormalities in predicting the prognosis of glioma and the efficacy of TMZ treatment. Methods: We retrospectively collected clinical and pathological data from 205 glioma patients diagnosed by the Department of Pathology, Fudan University Shanghai Cancer Center from July 2019 to September 2022. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect MGMTmet status. Sanger sequencing was used to detect the mutation of isocitrate dehydrogenase 1 and 2 (IDH1/2) and telomerase reverse transcriptase (TERT) genes. Fluorescence in situ hybridization (FISH) was used to detect the deletion of the short arm of chromosome 1 and the long arm of chromosome 19 (1p19q). Results: Among 205 patients, the incidence of MGMTmet was higher in female patients than in male patients. Compared to glioblastoma (47.3%), astrocytoma (74.1%) and oligodendroglioma (100.0%) were more prone to methylation of the MGMT gene promoter (P

Abstract Background The microbiome plays a crucial role in odontogenic sinusitis (OS); however, the bacterial characteristics of the sinuses and connected dental regions in OS are poorly understood. In this study, nasal secretion samples were collected from 41 OS patients and 20 simple nasal septum deviation patients, and oral mucosa samples from dental regions were collected from 28 OS patients and 22 impacted tooth extraction patients. DNA was extracted, and 16S rRNA sequencing was performed to explore the characteristics and structure of the microbiome in the sinuses and dental regions of OS patients. Results The alpha diversity of the oral and nasal microbiomes in OS patients was higher than that in controls. Principal coordinate analysis (PCoA) showed that oral samples clustered separately from nasal samples, and the beta diversity of oral and nasal samples in OS patients was higher than that in controls. The dominant phylum was Bacteroidetes in OS patients and Firmicutes in controls in both the oral and nasal cavity. The dominant genera in the oral microbiome and nasal microbiome of OS patients were similar, including Fusobacterium, Porphyromonas and Prevotella. Co-occurrence network analysis showed decreased microbial connectivity in the oral mucosa and nasal secretion samples of OS patients. Conclusions Odontogenic infection promotes structural and functional disorders of the nasal microbiome in OS. The interaction of dominant pathogens in the nasal and oral regions may promote the development of OS. Our study provides the microbiological aetiology of the nasal and connected dental regions in OS and is expected to provide novel insights into the diagnosis and therapeutic strategies for OS.

Background and aim: Recent studies show that combination of apoptosis and oxidative stress forms a “vicious circle” in the process of premature ovarian failure (POF). Pearl extract has a good effect for anti-oxidation and anti-aging in vitro and vivo and can be used to treat various aging diseases. However, reports about effect and mechanism of pearl on ovarian function of premature ovarian failure (POF)are limited. Experimental procedure: The effect and mechanism of pearl on ovarian function of rats with POF were evaluated using rats with premature ovarian failure induced by tripterygium glycosides. The estrous cycle, contents of serum reproductive hormones, tissue structure, oxidative stress level, autophagy and apoptotic protein expression, and MAPK signaling pathway of ovary were assessed to characterise pearl. Result and conclusion: Low, medium and high-dose pearl improved the estrous cycle in POF rats, and high-dose pearl was the best in terms of recovery effect; high-dose pearl significantly increased (P

When resource demand increases and decreases rapidly, container clusters in the cloud environment need to respond to the number of containers in a timely manner to ensure service quality. Resource load prediction is a prominent challenge issue with the widespread adoption of cloud computing. A novel cloud computing load prediction method has been proposed, the Double-channel residual Self-attention Temporal convolutional Network with Weight adaptive updating (DSTNW), in order to make the response of the container cluster more rapid and accurate. A Double-channel Temporal Convolution Network model (DTN) has been developed to capture long-term sequence dependencies and enhance feature extraction capabilities when the model handles long load sequences. Double-channel dilated causal convolution has been adopted to replace the single-channel dilated causal convolution in the DTN. A residual temporal self-attention mechanism (SM) has been proposed to improve the performance of the network and focus on features with significant contributions from the DTN. DTN and SM jointly constitute a dual-channel residual self-attention temporal convolutional network (DSTN). In addition, by evaluating the accuracy aspects of single and stacked DSTNs, an adaptive weight strategy has been proposed to assign corresponding weights for the single and stacked DSTNs, respectively. The experimental results highlight that the developed method has outstanding prediction performance for cloud computing in comparison with some state-of-the-art methods. The proposed method achieved an average improvement of 24.16% and 30.48% on the Container dataset and Google dataset, respectively.

The traction motor is a crucial component of high-speed electric multiple units, and its operational reliability is directly impacted by the temperature increase in the bearings. To accurately predict and simulate the temperature change process of traction motor bearings during operation, a fluid–solid–thermal simulation analysis model of grease-lubricated deep groove ball bearings was constructed. This model aimed to simulate the temperature rise of the bearing and the grease flow process, which was validated through experiments. The results from the simulation analysis and tests indicate that the temperature in the contact zone between the bearing rolling element and the raceway, as well as the ring temperature, initially increases to a peak and then gradually decreases, eventually stabilizing once the bearing’s heat generation power and heat transfer power reach equilibrium. Furthermore, the established fluid–solid–thermal coupling simulation analysis model can accurately predict the amount of grease required for effective lubrication in the bearing cavity, which stabilizes along with the bearing temperature. The findings of this research can serve as a theoretical foundation and technical support for monitoring the health status of high-speed EMU traction motor bearings.

AIM: To evaluate the clinical efficacy of wearing base curve aspheric orthokeratology(OK)lens in the control of myopia.METHODS: A prospective study was conducted. A total of 94 cases(94 eyes)of myopia aged 8～13 years old who were fitted with orthokeratology(OK)lens in our hospital from January 2020 to July 2021 were selected(for patients who received OK lens in one eye, the eye is selected as the observation eye, and for patients who receive OK lens in both eyes, the right eye is used as the observation eye). Patients were divided into two groups according to the design of the OK lens, with 46 cases wearing base curve aspheric OK lens in study group and 48 cases wearing base curve spheric OK lens in control group. The study group and the control group were further divided into low myopia group(-3.00D< SE ≤-0.75D)and moderate myopia group(-6.00D< SE ≤-3.00D)according to the baseline spherical equivalent(SE), with 52 cases(52 eyes)in the low myopia group and 42 cases(42 eyes)in the moderate myopia group. Uncorrected visual acuity(UCVA)was evaluated at 1d, 1wk, 1, 3, 6 and 9mo after wearing lenses, and axial length were measured at 6mo and 1a after wearing lenses respectively.RESULTS: All patients completed follow-up, and there was no significant differences in UCVA(LogMAR)between the study group(-0.12±0.08)and the control group(-0.17±0.07)after wearing the OK lens for 1mo(P>0.05); the mean axial length elongation between the two groups had no significant differences after wearing lenses for 6mo and 1a(all P>0.05). In the low myopia group, the axial length elongation of the study group was 0.19±0.17mm after wearing OK lens for 1a, which was significantly lower than that of the control group(0.31±0.18mm; P0.05). There was no significant differences in axial length elongation between the low myopia group and the moderate myopia group in study group after wearing lenses for 6mo and 1a(P>0.05), while there was differences in axial length elongation between low myopia group and moderate myopia group in the control group after wearing lenses for 6mo(0.15±0.13 vs. 0.05±0.12mm)and 1a(0.31±0.18 vs. 0.19±0.12mm; all P

Investigation was performed to evaluate the puncture resistance of multi-walled carbon nanotubes (MWCNTs)/glass fibre epoxy laminate composites using different indenters (conical, elliptical, flat, and hemispherical). For the puncture tests, MWCNT weight percentage and indenter type were varied. Furthermore, the impact of MWCNT on tensile, flexural, and interlaminar shear strength was evaluated. Ultrasonic C-scan provided insights into the damage evolution and failure mechanisms of the laminates under puncture. The results indicate that the flat indenter exhibits prolonged indentation time and enhanced energy absorption, resulting in a disc-shaped failure pattern. On the other hand, the conical indenter demonstrates rapid penetration due to its smaller contact surface area. The elliptical indenter generates higher frictional energy, leading to bulging damage. The hemispherical indenter showed an even distribution of force across the impacted surface, minimizing force concentration and reducing the extent of damage. These findings shed light on the puncture mechanisms of MWCNT/Glass fibre epoxy laminate composites, paving the way for more precise glass fibre laminate composite design and optimisation in practical applications such as aerospace, automotive, and sporting goods, where puncture loading is a critical consideration.

Abstract Background CD300s are a group of proteins playing vital roles in immune responses. However, much is yet to be elucidated regarding the expression patterns and clinical significances of CD300s in cancers. Methods In this study, we comprehensively investigated CD300s in a pan‐cancer manner using multi‐omic data from The Cancer Genome Atlas. We also studied the relationship between CD300s and the immune landscape of AML. Results We found that CD300A‐CD300LF were generally overexpressed in tumors (especially AML), whereas CD300LG was more often downregulated. In AML, transactivation of CD300A was not mediated by genetic alterations but by histone modification. Survival analyses revealed that high CD300A‐CD300LF expression predicted poor outcome in AML patients; the prognostic value of CD300A was validated in seven independent datasets and a meta dataset including 1115 AML patients. Furthermore, we demonstrated that CD300A expression could add prognostic value in refining existing risk models in AML. Importantly, CD300A‐CD300LF expression was closely associated with T‐cell dysfunction score and could predict response to AML immunotherapy. Also, CD300A was found to be positively associated with HLA genes and critical immune checkpoints in AML, such as VISTA, CD86, CD200R1, Tim‐3, and the LILRB family genes. Conclusions Our study demonstrated CD300s as potential prognostic biomarker and an ideal immunotherapy target in AML, which warrants future functional and clinical studies.

Understanding the costs and the spatial distribution of health and employment outcomes of low-carbon electricity pathways is critical to enable an equitable transition. We integrate an electricity system planning model (GridPath), a health impact model (InMAP), and a multiregional input–output model to quantify China’s provincial-level impacts of electricity system decarbonization on costs, health outcomes, employment, and labor compensation. We find that even without specific CO _2 constraints, declining renewable energy and storage costs enable a 26% decline in CO _2 emissions in 2040 compared to 2020 under the Reference scenario. Compared to the Reference scenario, pursuing 2 °C and 1.5 °C compatible carbon emission targets (85% and 99% decrease in 2040 CO _2 emissions relative to 2020 levels, respectively) reduces air pollution-related premature deaths from electricity generation over 2020–2040 by 51% and 63%, but substantially increases annual average costs per unit of electricity demand in 2040 (21% and 39%, respectively). While the 2 °C pathway leads to a 3% increase in electricity sector-related net labor compensation, the 1.5 °C pathway results in a 19% increase in labor compensation driven by greater renewable energy deployment. Although disparities in health impacts across provinces narrow as fossil fuels phase out, disparities in labor compensation widen with wealthier East Coast provinces gaining the most in labor compensation because of materials and equipment manufacturing, and offshore wind deployment.

Objective: Wear and surface hardness of resin composites are of relevance from the clinical standpoint. With the incorporation of novel filler system, more studies need to be performed to investigate newly marketed resin composites. The objective of this study was to investigate the abrasive wear and surface hardness of dental restorative with different filler types. Methods: Nanohybrid filled Harmonize (HM) and Tetric N-Ceram (TNC), microhybrid filled Filtek Z250 (Z250), nanofilled Filtek Z350 (Z350) were included in the study. Twelve cylindrical resin composites specimens with 10 mm in diameter and 6 mm in thickness were prepared for abrasive wear test. Eight hundred cycles under 17 kg load were conducted for final wear by CW3-1 wear machine. The specimen was cleaned with an ultrasonic unit for 3 min followed with drying procedure. After measurement of weight loss and the density of specimens, the specimens were kept for measurement of surface hardness. Surface hardness was measured using a micro-hardness tester with a Vickers diamond indenter after polishing. Three specimens of each material were observed by scanning electron microscopy (SEM) after the abrasion to evaluate the morphology of the surface. Data were analyzed using one-way analysis of variance (ANOVA), followed by Tukey HSD test ( α = .05). Results: Z250 performed the least volume wear loss (41.1 ± 2.1 mm 3 ), as well as the hardest value (102.7 ± 2.9 HV). There was no significant difference with the volume wear loss ( p = 1.000) and surface hardness ( p = 0.874) of HM and TNC. SEM images of nanohybrid filled HM and TNC represented smoother surface compared with other types of resin composites. Conclusions: Microhybrid Z250 showed the highest wear resistance and surface hardness, nanofilled and nanohybrid resin composites may still face the insufficient of wear and surface hardness quality.

Ulcerative colitis (UC) is a refractory inflammatory bowel disease, and the outcomes of conventional therapies of UC, including 5-aminosalicylic acid, glucocorticoids, immunosuppressants, and biological agents, are not satisfied with patients and physicians with regard to adverse reactions and financial burden. The abnormality of the intestinal mucosal barrier in the pathogenesis of UC was verified. Qingchang Suppository (QCS) is an herbal preparation and is effective in treating ulcerative proctitis. The mechanism of QCS and its active ingredients have not been concluded especially in mucosal healing. This review elucidated the potential mechanism of QCS from the intestinal mucosal barrier perspective to help exploring future QCS research directions.

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of high mortality and heavy burden in the world. Unfortunately, emphysema, as an important component of COPD, has no curative treatments currently. Recently, human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSC-Ex) constitute a promising alternative approach for tissue regeneration and repair. However, the roles of hUCMSC-Ex in emphysema and its mechanism are largely unknown. Here, we investigated the effect and the action mechanism of hUCMSC-Ex in repairing emphysema induced by papain in rats. Methods: SD rats were used to establish a papain-induced emphysema model and estimate the effect and mechanism of hUCMSC-Ex treatment. H&E staining and mean linear intercept (MLI) were used to evaluate the hUCMSC-Ex effect on emphysema. Western blotting, TUNEL and miRNA-seq were used to investigate the molecular mechanisms of hUCMSC-Ex treatment in models of papain-induced emphysema. Results: Papain treatment led to typical emphysema, while hUCMSC-Ex reversed emphysematous changes effectively. Apoptosis of endothelial cells and other types of cells were observed in models, while hUCMSC-Ex effectively prevented their apoptosis. hUCMSC-Ex repressed active caspase-3, activated VEGF-VEGFR2-mediated AKT pathway and MEK/ERK pathway in emphysematous lungs. Notably, several miRNAs, such as hsa-miR-10a-5p and hsa-miR-146a-5p, were target related to the roles of hUCMSC-Ex in papain-induced emphysema through VEGF-VEGFR2-mediated AKT and MEK/ERK pathways. Conclusions: hUCMSC-Ex effectively rescued the papain-induced emphysema injury through VEGF-VEGFR2-mediated AKT pathway and MEK/ERK pathway.

Abstract Background Aberrant DNA methylation plays a crucial role in the progression of myeloid neoplasms. Previously, our literature reported that slit guidance ligand 2 (SLIT2) promoter methylation was associated with disease progression and indicated a poor prognosis in patients with myelodysplastic syndrome. Herein, we further investigated the clinical implications and role of SLIT2 promoter methylation in patients with chronic myeloid leukemia (CML). Methods The level of SLIT2 promoter methylation was determined in 104 CML patients, and its clinical significance was analyzed. Moreover, demethylation studies were performed in K562 cells to determine the epigenetic mechanism by which SLIT2 promoter methylation is regulated in CML. Results The level of SLIT2 promoter methylation was similar between CML patients and controls. However, deeper analysis revealed that the SLIT2 promoter methylation level in the accelerated phase (AP) and blast crisis (BC) was markedly higher than that in the chronic phase (CP) and controls. Additionally, a marked difference was identified between the SLIT2 promoter hypermethylated and non-hypermethylated groups among CML patients grouped by clinical stage. The frequency of SLIT2 hypermethylation was markedly increased with the progression of clinical stage, that is, it was the lowest in CP samples (12/80, 15%), higher in AP samples (4/8, 50%) and the highest in BC samples (11/16, 69%). Importantly, the level/density of SLIT2 promoter methylation was significantly higher in the advanced stage than in the early stage among the 6 tested paired CML patients. Epigenetically, the expression of the SLIT2-embedded non-coding genes SLIT2-IT1 and miR-218 expression was decreased in patients with CML. SLIT2 promoter hypermethylated cases had a markedly lower SLIT2-IT1 expression level than SLIT2 promoter non-hypermethylated cases. Moreover, SLIT2-IT1 and miR-218 expression was remarkably upregulated in a dose-dependent manner after demethylation treatment of K562 cells. Conclusions Hypermethylation of the SLIT2 promoter is correlated with disease progression in CML. Furthermore, SLIT2 promoter methylation may function by regulating the expression of the SLIT2-embedded non-coding genes SLIT2-IT1 and miR-218 during CML progression.

Acute myeloid leukemia (AML) is the most common type of hematological malignancy. Recently, an increasing number of reports have shown that many circular RNAs can act as effective targets for AML. However, the roles of circ_0059707 in AML remain largely unclear. In this study, we found that the expression levels of circ_0059707 were significantly decreased in AML patients with respect to normal controls (p < 0.001). Low expression levels of circ_0059707 were also associated with a poor prognosis. Furthermore, circ_0059707 overexpression inhibited cell growth and promoted apoptosis in leukemia cells, compared with control cells. Circ_0059707- and empty plasmid-transfected cells were injected subcutaneously into BALB/c nude mice. We found that the tumor volume was significantly lower in mice in the circ_0059707 group than in control mice (p < 0.01). Nuclear pyknosis, nuclear fragmentation, nuclear dissolution, and cell necrosis were observed in the circ_0059707 group by HE staining. CircInteractome analysis showed that 25 microRNAs (miRNAs), including miR-1287-5p, ©-miR-1825, a©hsa-miR-326, may be potential targets for circ_0059707. The expression of these miRNAs was analyzed in both the GEO GSE51908 and the GSE142700 databases. miR-1287-5p expression was lower in AML patients compared with controls in both the GSE51908 and the GSE142700 datasets. Moreover, we demonstrated that miR-1287-5p expression was down-regulated in AML patients and up-regulated in circ_0059707-overexpressing cells. Collectively, our research demonstrated that the down-regulation of circ_0059707 was highly evident in de novo AML patients. Our analysis also demonstrated that circ_0059707 inhibited cell growth and promoted apoptosis by up-regulating miR-1287-5p.

Leukocyte immunoglobulin (Ig)-like receptor Bs (LILRBs), a family of type I transmembrane glycoproteins, are known to inhibit immune activation. Here, we comprehensively evaluated the molecular, prognostic, and immunological characteristics of LILRB members in a broad spectrum of cancer types, focusing on their roles in acute myeloid leukemia (AML). We showed that LILRBs were significantly dysregulated in a number of cancers and were associated with immune-inhibitory phenotypes. Clinically, high expression of LILRB1-LILRB4 predicted poor survival in six independent AML cohorts. Genetically, LILRB1 was associated with more mutational events than other LILRB members, and multiple genes involved in immune activation were deleted in LILRB1high patients. Epigenetically, LILRB4 was significantly hypomethylated and marked by MLL-associated histone modifications in AML. Immunologically, LILRBs were positively associated with monocytic cells, including M2 macrophages, but were negatively associated with tumor-suppressive CD8 T cells. Importantly, patients with higher LILRB expression generally showed a better response to immune checkpoint blockade (ICB) in five independent immunotherapy cohorts. Our findings reveal critical immunological and clinical implications of LILRBs in AML and indicate that LILRBs may represent promising targets for immunotherapy of AML.

Abstract Background Previously, we reported the expression of DLX4 isoforms (BP1 and DLX7) in myeloid leukemia, but the functional role of DLX4 isoforms remains poorly understood. In the work described herein, we further determined the underlying role of DLX4 isoforms in chronic myeloid leukemia (CML) leukemogenesis. Methods The expression and methylation of DLX4 isoforms were detected by real-time quantitative PCR (RT-qPCR) and real-time quantitative methylation-specific PCR (RT-qMSP) in patients with CML. The functional role of DLX4 isoforms was determined in vitro and in vivo. The molecular mechanism of DLX4 isoforms in leukemogenesis was identified based on chromatin immunoprecipitation with high-throughput sequencing (ChIP-Seq)/assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-Seq) and RNA sequencing (RNA-Seq). Results BP1 expression was increased in patients with CML with unmethylated promoter, but DLX7 expression was decreased with hypermethylated promoter. Functionally, overexpression of BP1 increased the proliferation rate of K562 cells with S/G2 promotion, whereas DLX7 overexpression reduced the proliferation rate of K562 cells with G1 arrest. Moreover, K562 cells with BP1 overexpression increased the tumorigenicity in NCG mice, whereas K562 cells with DLX7 overexpression decreased the tumorigenicity. Mechanistically, a total of 91 genes including 79 messenger RNAs (mRNAs) and 12 long noncoding RNAs (lncRNAs) were discovered by ChIP-Seq and RNA-Seq as direct downstream targets of BP1. Among the downstream genes, knockdown of RREB1 and SGMS1-AS1 partially revived the proliferation caused by BP1 overexpression in K562 cells. Similarly, using ATAC-Seq and RNA-Seq, a total of 282 genes including 151 mRNA and 131 lncRNAs were identified as direct downstream targets of DLX7. Knockdown of downstream genes PTPRB and NEAT1 partially revived the proliferation caused by DLX7 overexpression in K562 cells. Finally, we also identified and validated a SGMS1-AS1/miR-181d-5p/SRPK2 competing endogenous RNA (ceRNA) network caused by BP1 overexpression in K562 cells. Conclusions The current findings reveal that DNA methylation-mediated differential expression of DLX4 isoforms BP1 and DLX7 plays opposite functions in leukemogenesis. BP1 plays an oncogenic role in leukemia development, whereas DLX7 acts as a tumor suppressor gene. These results suggest DLX4 as a therapeutic target for antileukemia therapy.

Cocaine, methamphetamine and opioids are leading causes of drug abuse-related deaths worldwide. In recent decades, several studies revealed the connection between and epigenetics. Neural cells acquire epigenetic alterations that drive the onset and progress of the SUD by modifying the histone residues in brain reward circuitry. Histone modifications, especially acetylation and methylation, participate in the regulation of gene expression. These alterations, as well as other host and microenvironment factors, are associated with a serious of negative neurocognitive disfunctions in various patient populations. In this review, we highlight the evidence that substantially increase the field's ability to understand the molecular actions underlying SUD and summarize the potential approaches for SUD pharmacotherapy.

Diabetic retinopathy (DR) is one of the leading causes of blindness. Periodontitis is one of the highest oral incidences and has been closely related to various systemic conditions through Porphyromonas gingivalis (P. gingivalis). P. gingivalis OMVs, derived from P. gingivalis, can cause endothelial dysfunction and potentially affect microvascular diseases. Current epidemiological studies provide limited evidence suggesting that periodontitis is associated with DR. However, there is a lack of basic research elucidating how periodontitis affects the severity of DR. This study aimed to explore the potential of P. gingivalis OMVs to contribute to the pathogenesis of DR and explore how it affect the retinal microvascular endothelium. The results demonstrated that P. gingivalis OMVs accelerated the blood-retinal barrier damage in DR mice. In vitro studies showed that the expression of inflammatory factors in human retinal microvascular endothelial cells (HRMECs) was increased after P. gingivalis OMVs stimulation, and the increased reactive oxygen species production, mitochondrial dysfunction, apoptosis, and altered endothelial permeability were observed in HRMECs under P. gingivalis OMVs stimulation. In addition, we found that protease-activated receptor-2 (PAR-2) regulated OMVs-induced TNF-α, MMP-9 mRNA expression, cell death, and endothelial permeability. Overall, we suggested that P. gingivalis OMVs induced mitochondria-related cell death of HRMECs and accelerated endothelial dysfunction, thus aggravating DR, in which PAR-2 plays a potential role. This study is the first research report to delineate the potential molecular mechanism of P. gingivalis OMVs on DR pathogenesis, which uniquely focused on elucidating the possible impact of periodontal pathogen derivatives on DR progression.

Objective To investigate the effects of running on the volume change of medial prefrontal cortex (mPFC), as well as amyloid beta protein (Aβ) and microglia in mPFC in mouse model of Alzheimer′s disease (AD). Methods Male APP/PS1 transgenic AD mice aged 10 months were randomly divided into AD running group (AD Run, given active running intervention for 4 months) and AD control group (AD Ctrl), while non-transgenic mice at the same age were set as normal control group (Ctrl). The mice from the AD Ctrl and Ctrl groups received no treatment. Morris water maze test was used to evaluate the abilities of spatial learning and memory of mice, and Y maze test was adopted to assess the working memory and reference memory in the mice. The volume of mPFC and the total number of microglia (IBA1+cells) in the mPFC were quantified with stereological methods. The number of activated microglia (CD68+/IBA1+ cells) in the mPFC, cell body area, and process number of microglia, number and area of Aβ plaques, and area of Aβ plaques in IBA1+ microglia were quantitatively measured by immunofluorescence multiple labeling and laser confocal microscopy, and the ratio of area of Aβ plaques in IBA1+ microglia to the total area of Aβ plaques was calculated. Results The AD Run group and Ctrl group performed better than the AD Ctrl group in Morris water maze and Y maze tests. The volume of mPFC was significantly less in the AD Ctrl group than the Ctrl group (P < 0.05), while that of the AD Run group was obviously larger than that of the AD Ctrl (P < 0.01). The AD Ctrl group had greatly larger numbers of IBA1+ cells and CD68+/IBA1+ cells in the mPFC than the Ctrl group (P < 0.05), whereas the AD Run group had much larger numbers of those cells than the AD Ctrl group (P < 0.05). The total and average area of Aβ plaques in the mPFC was greatly diminished in the AD Run group than the AD Ctrl group (P < 0.05). In addition, the AD Run group also presented larger numbers of IBA1+ cells and CD68+/IBA1+ cells around Aβ, larger average body area of single microglia and CD68+/IBA1+ cells, and elevated area of Aβ plaques in IBA1+ cells, along with its ratio to the total area of Aβ plaques in mPFC improved (P < 0.05). Conclusion Running exercise increases the number of CD68+ microglia in the mPFC, reduces the Aβ plaques, delays the atrophy of mPFC, and thus improves the spatial learning and memory abilities as well as working memory and reference memory in APP/PS1 transgenic AD mice.

Objective To investigate the effects of targeted silence/overexpression of PGC-1α in the hippocampus on depression-like behaviors in mice and on the number of glial fibrillary acidic protein positive (GFAP+) astrocytes in the subregions of the hippocampus. Methods After adaptive feeding and sucrose preference baseline adjustment, 32 male C57BL/6 mice aged 6~8 weeks were randomly divided into empty virus group (n=14), PGC-1α silencing group (n=11) and PGC-1α overexpression group (n=7). The latter 2 groups were injected with adeno-associated virus (AAV)-mediated genes silencing or overexpressing PGC-1α in the hippocampus, respectively, with aid of stereotactic injection technique. Sucrose preference test (SPT) and forced swimming test (FST) were performed to assess the depression-like behaviors, and the number of GFAP+ astrocytes in each hippocampal subregion was accurately quantified in 3 dimensions by immunohistochemistry and stereology. Results As compared with the empty virus group, the PGC-1α silencing group had significantly decreased percentage of sucrose preference (P < 0.01), prolonged immobility time in FST (P < 0.05), and larger number of GFAP+ astrocytes in both CA1 and DG subregions(P < 0.05). However, the immobility time in FST was remarkably shortened in the PGC-1α overexpression group (P < 0.01), with the number of GFAP+ astrocytes in CA1 and DG subregions diminished (P < 0.05). There was no significant difference in the percentage of sucrose preference between the empty virus group and PGC-1α overexpression group, and silencing or overexpressing PGC-1α showed no obvious impact on the number of astrocytes in CA3 subregion. Conclusion PGC-1α is closely associated with the depression-like behaviors and participates in regulating the number of GFAP+ astrocytes in CA1 and DG subregions in mice.

Carotid atherosclerotic stenosis of the carotid artery is an important cause of ischemic cerebrovascular disease. The aim of this study was to predict the presence or absence of clinical symptoms in unknown patients by studying the existence or lack of symptoms of patients with carotid atherosclerotic stenosis. First, a deep neural network prediction model based on brain MRI imaging data of patients with multiple modalities is constructed; it uses the multi-modality features extracted from the neural network as inputs and the incidence of diagnosis as output to train the model. Then, a machine learning-based classification algorithm is developed to utilize the clinical features for comparison and evaluation. The experimental results showed that the deep learning model using imaging data could better predict the clinical symptom classification of patients. As part of preventive medicine, this study could help patients with carotid atherosclerosis narrowing to prepare for stroke prevention based on the prediction results.

Abstract Background Recently, an increasing number of studies have reported that sperm-associated antigen (SPAG) proteins play crucial roles in solid tumorigenesis, and may serve as potentially helpful biomarkers for cancer diagnosis and prognosis. However, very few studies systematically investigated the expression of SPAG family members and their clinical significance in acute myeloid leukemia (AML). Methods The expression of SPAGs and their prognostic significance in AML were determined by a systematic analysis on data gathered from public databases, and the results were validated in clinical samples. Results Using public data, we identified only increased SPAG1 expression negatively associated with survival in AML by Cox regression (P

Abstract The role of B7‐H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7‐H3 expression using multi‐omics data in the public domain. We found significantly increased B7‐H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7‐H3 expression was associated with old age, TP53 mutations, wild‐type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7‐H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the “EMT” oncogenic gene signatures in high B7‐H3 expressers. Further investigation suggested that B7‐H3 was more likely to be associated with immune‐suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7‐H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7‐H5), CD80 (B7‐1), CD86 (B7‐2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7‐H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7‐H3 dysregulation in AML and to the development of novel therapeutic strategies.

BackgroundMyopic shift had been observed during the COVID-19 lockdown in young school children. It remains unknown whether myopic shift is accompanied with increase in axial length. We aimed to evaluate the impact of the COVID-19 lockdown on myopia and axial length of school children in China by comparing them before, during and after the lockdown.MethodsIn this population-based cross-sectional study, school-based myopia screenings were conducted in the Fall of 2019, 2020, and 2021 (representing before, during and after COVID-19 lockdown respectively) in Chengdu, China. Myopia screenings were performed on 83,132 students aged 6 to 12 years. Non-cycloplegic refractive error was examined using NIDEK auto-refractor (ARK-510A; NIDEK Corp., Tokyo, Japan) and axial length was measured using AL-Scan (NIDEK Corp., Tokyo, Japan). Spherical equivalent (SER, calculated as sphere+ 0.5*cylinder), prevalence of myopia (SER ≤ -0.50 D), and axial length were compared across 3 years stratified by age.ResultsMyopia prevalence rate was 45.0% (95% CI: 44.6–45.5%) in 2019, 48.7% (95% CI: 48.3–49.1%) in 2020, and 47.5% (95% CI: 47.1–47.9%) in 2021 (p < 0.001). The mean non-cycloplegic SER (SD) was −0.70 (1.39) D, −0.78 (1.44) D, and −0.78 (1.47) D respectively (p < 0.001). The mean (SD) axial length was 23.41 (1.01) mm, 23.45 (1.03) mm, and 23.46 (1.03) mm across 3 years respectively (p < 0.001). From the multivariable models, the risk ratio (RR) of myopia was 1.07 (95% CI: 1.06–1.08) times, the SER was 0.05 D (95% CI: 0.04 D to 0.06 D) more myopic and the mean axial length increased by 0.01 mm (95% CI: 0.01 mm to 0.02 mm) in 2020 compared to 2019. In 2021, the risk ratio (RR) of myopia was 1.05 (95% CI: 1.04–1.06), the mean SER was 0.06 D (95% CI: 0.05 D to 0.07 D) more myopic, and the mean axial length increased by 0.03 mm (95% CI: 0.02 mm to 0.04 mm) compared to 2019.ConclusionsThe COVID-19 lockdown had significant impact on myopia development and axial length, and these impacts remained 1 year after the lockdown. Further longitudinal studies following-up with these students are needed to help understand the long-term effects of COVID-19 lockdown on myopia.

Background: Various circular RNA (circRNA) molecules are abnormally expressed in acute myeloid leukemia (AML), and associated with disease occurrence and development, as well as patient prognosis. The roles of circ_0059706, a circRNA derived from ID1, in AML remain largely unclear.Results: Here, we reported circ_0059706 expression in de novo AML and its association with prognosis. We found that circ_0059706 expression was significantly lower in AML patients than in controls (p < 0.001). Survival analysis of patients with AML divided into two groups according to high and low circ_0059706 expression showed that overall survival (OS) of patients with high circ_0059706 expression was significantly longer than that of those with low expression (p < 0.05). Further, female patients with AML and those aged >60 years old in the high circ_0059706 expression group had longer OS than male patients and those younger than 60 years. Multiple regression analysis showed that circ_0059706 was an independent factor-affecting prognosis of all patients with AML. To evaluate the prospects for application of circ_0059706 in machine learning predictions, we developed seven types of algorithm. The gradient boosting (GB) model exhibited higher performance in prediction of 1-year prognosis and 3-year prognosis, with AUROC 0.796 and 0.847. We analyzed the importance of variables and found that circ_0059706 expression level was the first important variables among all 26 factors included in the GB algorithm, suggesting the importance of circ_0059706 in prediction model. Further, overexpression of circ_0059706 inhibited cell growth and increased apoptosis of leukemia cells in vitro.Conclusion: These results provide evidence that high expression of circ_0059706 is propitious for patient prognosis and suggest circ_0059706 as a potential new biomarker for diagnosis and prognosis evaluation in AML, with high predictive value and good prospects for application in machine learning algorithms.

Summary: Dramatic reductions in solar, wind, and battery storage costs create new opportunities to reduce emissions and costs in China’s electricity sector, beyond current policy goals. This study examines the cost, reliability, emissions, public health, and employment implications of increasing the share of non-fossil fuel (“carbon free”) electricity generation in China to 80% by 2035. The analysis uses state-of-the-art modeling with high resolution load, wind, and solar inputs. The study finds that achieving an 80% carbon-free electricity system in China by 2035 could reduce wholesale electricity costs, relative to a current policy baseline, while maintaining high levels of reliability, reducing deaths from air pollution, and increasing employment. In our 80% scenario, wind and solar generation capacity reach 3 TW and battery storage capacity reaches 0.4 TW by 2035, implying a rapid scale up in these resources that will require changes in policy targets, markets and regulation, and land use policies.

Abstract It was previously reported that PRR34‐AS1 was overexpressed in some solid tumors. PRR34‐AS1 promoter was shown to have a differential methylation region (DMR), and was hypomethylated in acute myeloid leukemia (AML). Therefore, the present study used real‐time quantitative PCR (RQ‐PCR) to explore the expression characteristics of PRR34‐AS1 in AML. In addition, the correlation between the expression of PRR34‐AS1 and clinical prognosis of AML was determined. The findings of this study indicated that high PRR34‐AS1 expression was bound up with shorter overall survival (OS) in AML patients (p = 0.002). Moreover, patients with high expression of PRR34‐AS1 had significantly lower complete remission (CR) rate compared with those with low expression of PRR34‐AS1 after induction chemotherapy. Furthermore, multivariate analysis confirmed that PRR34‐AS1 expression was an independent factor affecting CR in whole‐AML, non‐APL‐AML, and CN‐AML patients (p = 0.032, 0.039, and 0.036, respectively). Methylation‐specific PCR (MSP) and bisulfite sequencing PCR (BSP) were used to explore the methylation status of PRR34‐AS1. PRR34‐AS1 promoter showed a pattern of hypomethylation in AML patients compared with normal controls (p = 0.122). Notably, of whole‐AML and non‐APL‐AML patients, PRR34‐AS1 hypomethylated patients presented a significantly shorter OS than those with a hypermethylated PRR34‐AS1 (p = 0.010 and 0.037, respectively). Multivariate analysis confirmed that the hypomethylation of PRR34‐AS1 served as an independent prognostic indicator in both whole‐cohort AML and non‐APL‐AML categories (p = 0.057 and 0.018, respectively). In summary, the findings of this study showed that abnormalities in PRR34‐AS1 are associated with poor prognosis in AML. Therefore, monitoring this index may be important in the prognosis of AML and can provide information on effective chemotherapy against the disease.

Combined with the characteristics of open-pit mines in China, the definition of intelligent open-pit mines is given. This paper introduces the overall network architecture, business architecture and collaborative process of the intelligent open-pit mine. The overall network architecture of cloud, edge and end is adopted to realize the collaborative correlation of various production links in the open-pit mine by accessing multi-source heterogeneous data and fully applying advanced technologies such as big data and cloud computing. The business architecture adopts the "5 layers + 3 system" model. The "5 layers" from bottom to top are the basic equipment layer, business data layer, analysis service layer, analysis business layer and analysis presentation layer. And the "3 systems" are data analysis standard system, safety specification standard system, metadata and code specification standard system. The bottom-up collaboration of intelligent open-pit mine should realize "basic + data" support, mine production system collaboration, disaster risk analysis collaboration and business decision-making collaboration. The key technologies such as unmanned technology, digital twin technology, big data collection and analysis technology, risk monitoring and early warning technology of intelligent open-pit mine are discussed. It is pointed out that technologies such as big data and artificial intelligence will become the core driver of open-pit mine intelligence. The platform-based architecture will become the common choice for future intelligent open-pit mine systems.

Periodontitis, an oral inflammatory disease, originates from periodontal microbiota dysbiosis which is associated with the dysregulation of host immunoinflammatory response. This chronic infection is not only harmful to oral health but is also a risk factor for the onset and progress of various vascular diseases, such as hypertension, atherosclerosis, and coronary arterial disease. Vascular endothelial dysfunction is the initial key pathological feature of vascular diseases. Clarifying the association between periodontitis and vascular endothelial dysfunction is undoubtedly a key breakthrough for understanding the potential relationship between periodontitis and vascular diseases. However, there is currently a lack of an updated review of their relationship. Therefore, we aim to focus on the implications of periodontitis in vascular endothelial dysfunction in this review.