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Abstract Three-dimensional (3D) fetal ultrasound has been widely used in prenatal examinations. Realistic and real-time volumetric ultrasound volume rendering can enhance the effectiveness of diagnoses and assist obstetricians and pregnant mothers in communicating. However, this remains a challenging task because (1) there is a large amount of speckle noise in ultrasound images and (2) ultrasound images usually have low contrasts, making it difficult to distinguish different tissues and organs. However, traditional local-illumination-based methods do not achieve satisfactory results. This real-time requirement makes the task increasingly challenging. This study presents a novel real-time volume-rendering method equipped with a global illumination model for 3D fetal ultrasound visualization. This method can render direct illumination and indirect illumination separately by calculating single scattering and multiple scattering radiances, respectively. The indirect illumination effect was simulated using volumetric photon mapping. Calculating each photon’s brightness is proposed using a novel screen-space destiny estimation to avoid complicated storage structures and accelerate computation. This study proposes a high dynamic range approach to address the issue of fetal skin with a dynamic range exceeding that of the display device. Experiments show that our technology, compared to conventional methodologies, can generate realistic rendering results with far more depth information.

Background: The aim was to explore and characterize dizziness and vertigo (constant vs episodic) and associated problems in patients with Ménière’s disease (MD) to allow characterization of the impact of the disease. Methods: The study used a retrospective survey design. A total of 539 people with MD participated in this study. The online questionnaire included 36 items which had mixture of structured and open-ended questions that were focusing on MD symptoms, impact of their symptoms, vestibular rehabilitation, as well as health-related quality of life (HRQoL). Results: Forty-six percent of the patients had episodic vertigo, 6% had constant dizziness, 15% had both episodic vertigo and constant dizziness, and 31% did not have vertigo or dizziness within the last 2 years. Patients with MD without any vertigo rated their HRQoL as 73.9%, those with episodic vertigo as 71.1%, those with constant dizziness as 56.9%, and those with constant dizziness and episodic vertigo as 57.9% indicating significant reduction in HRQoL in constant dizziness patients. Constant dizziness was associated with cognitive visual problems, fatigue, balance problems, vestibular drop attacks and syncope. The impact of balance problem was more severe among those with constant dizziness. The most common balance problem was tripping-off (34%), followed by swaying (25%) or rocking (8%) sensations. In the self-administered rehabilitative training, there were no differences between any of the vertigo or dizziness groups although disease profile of MD differed significantly. Conclusion: We emphasize that constant dizziness in MD constitutes a long-term maladaptation to a vestibular and visual cognitive function causing cognitive dissonance. Different types of vertigo and their associated complaints require different treatment strategies to the manage balance problems and to cope with the disease, but best practices is still under research.

Abstract Traumatic dental injuries (TDIs) of teeth occur frequently in children and adolescents. TDIs that impact the periodontal tissues and alveolar tissue can be classified into concussion, subluxation, extrusive luxation, intrusive luxation, lateral luxation, and avulsion. In these TDIs, management of injured soft tissue, mainly periodontal ligament, and dental pulp, is crucial in maintaining the function and longevity of the injured teeth. Factors that need to be considered for management in laxation injuries include the maturation stage of the traumatic teeth, mobility, direction of displacement, distance of displacement, and whether there are alveolar fractures. In avulsion, the maturation stage of the permanent tooth, the out-socket time, storage media/condition of the avulsed tooth, and management of the PDL should also be considered. Especially, in this review, we have subdivided the immature tooth into the adolescent tooth (Nolla stage 9) and the very young tooth (Nolla stage 8 and below). This consensus paper aimed to discuss the impacts of those factors on the trauma management and prognosis of TDI to provide a streamlined guide for clinicians from clinical evaluation, diagnostic process, management plan decision, follow-up, and orthodontic treatment for tooth luxation and avulsion injuries.

Background Pulpotomy is a widely recommended treatment for deep caries and reversible pulpitis in primary teeth. However, there is a significant lack of large-scale clinical studies evaluating the long-term efficacy of pulpotomy in primary molars, especially in studies with follow-up periods extending beyond a two years. Aim This study aimed to evaluate the long-term efficacy of mineral trioxide aggregate (MTA) and iRoot BP Plus for pulpotomy in primary molars performed under general anesthesia and to investigate factors influencing the success rate. Methods In this retrospective study, a total of 942 primary molars from 422 children who met the inclusion criteria underwent pulpotomy. Propensity score matching method (PSM) was used to match the MTA and iRoot BP Plus groups in a 1:1 ratio based on covariates. Efficacy was assessed using the Zurn & Seale criteria. Kaplan-Meier survival analysis and Cox proportional hazards model were performed to analyze the outcomes. Results PSM resulted in 266 pairs of matched teeth from 532 teeth of 291 children (mean age: 4.64 ± 1.07 years, ranging from 2 to 8 years). Long-term clinical and radiographic evaluations revealed higher success rates for iRoot BP Plus (24-month: 99.54%/97.25%; 36-month: 97.22%/95.83%) compared to MTA (24-month: 94.76%/95.29%; 36-month: 92.50%/91.25%). Survival analysis indicated a statistically significant difference between two groups (P = 0.0042). Age, gender, tooth position, and decayed tooth surface showed no significant impact on pulpotomy success, whereas the choice of pulp capping materials significantly influenced the outcome (HR [95% CI]=0.3745[0.1857-0.7552], P = 0.006). Conclusion Clinical and radiographic evaluations support the use of iRoot BP Plus for pulpotomy in primary molars.

PurposeThis retrospective study aimed to analyze the symptom profile of Meniere's disease (MD) patients, particularly focusing on the cessation of episodic vertigo and the disease's longitudinal course and the impact of major symptoms on quality of life (QoL).MethodsThe study employed a cross-sectional design and was conducted on 365 out of 560 individuals with definite MD from the Finnish Vestibular and Meniere Federation, utilizing an internet-based questionnaire. Participants were surveyed on vertigo attacks, vestibular drop attacks (VDA), balance issues, selective cognitive complaints, hearing loss, and their effects on overall quality of life (QoL). The study population comprised 79.5% females and 20.5% males, with a mean age of 63 years and an average disease duration of 15.2 years.ResultsThe onset of MD was characterized by simultaneous hearing loss, vertigo, and tinnitus in 38% of participants. There was a significant delay in diagnosis for many, with 20% experiencing a delay of over 5 years. The frequency and duration of vertigo attacks generally decreased over time, with attacks becoming shorter and less severe as the disease progressed. Spontaneous remission from episodic vertigo occurred in 34% of participants variably throughout the course of MD. Of the participants 65.5% reported balance issues, and 34% experienced mild VDAs, with severe falls occurring in 10%. VDAs were more common with longer disease duration. Bilateral hearing loss developed in 34.5% of participants over the long term, with a higher risk associated with younger onset age, migraines, and family history of MD. Fatigue, anxiety, and depression were prevalent, particularly among younger participants. Cognitive impairments were linked to the severity of these symptoms and the presence of constant dizziness. QoL was significantly lower among participants with constant dizziness, with factors like fatigue, depression, VDA, and hearing loss contributing to this reduction.ConclusionsThe study highlights the complexity of MD. While vertigo may spontaneously remit, other symptoms such as VDAs, balance issues, cognitive complaints, and hearing loss often persist and worsen over time. Assessing MD solely on primary symptoms like vertigo and hearing loss is insufficient; a comprehensive evaluation is necessary for effective management.

Abstract Single‐atom catalysts (SACs) have rapidly become a hot topic in photocatalytic research due to their unique physical and chemical properties, high activity, and high selectivity. Among many semiconductor carriers, the special structure of carbon nitride (C3N4) perfectly meets the substrate requirements for stabilizing SACs; they can also compensate for the photocatalytic defects of C3N4 materials by modifying energy bands and electronic structures. Therefore, developing advanced C3N4‐based SACs is of great significance. In this review, we focus on elucidating efficient preparation strategies and the burgeoning photocatalytic applications of C3N4‐based SACs. We also outline prospective strategies for enhancing the performance of SACs and C3N4‐based SACs in the future. A comprehensive array of methodologies is presented for identifying and characterizing C3N4‐based SACs. This includes an exploration of potential atomic catalytic mechanisms through the simulation and regulation of atomic catalytic behaviors and the synergistic effects of single or multiple sites. Subsequently, a forward‐looking perspective is adopted to contemplate the future prospects and challenges associated with C3N4‐based SACs. This encompasses considerations, such as atomic loading, regulatory design, and the integration of machine learning techniques. It is anticipated that this review will stimulate novel insights into the synthesis of high‐load and durable SACs, thereby providing theoretical groundwork for scalable and controllable applications in the field.

ABSTRACT Dental caries is associated with microbial dysbiosis caused by the excessive proliferation of Streptococcus mutans in dental biofilms, where oxidative stress serves as the major stressor to microbial communities. The adaptability of S. mutans to oxidative stress is a prerequisite for its proliferation and even for exerting its virulence. Protein acetylation is a reversible and conserved regulatory mechanism enabling bacteria to rapidly respond to external environmental stressors. However, the functions of protein acetylation in regulating oxidative stress adaptability of S. mutans are still unknown. Here, we unveil the impact of acetyltransferase ActA-mediated acetylation on regulating the oxidative stress response of S. mutans. actA overexpression increased the sensitivity of S. mutans to hydrogen peroxide and diminished its competitive ability against Streptococcus sanguinis. In contrast, actA deletion enhanced oxidative stress tolerance and competitiveness of S. mutans. The mass spectrometric analysis identified pyruvate kinase (PykF) as a substrate of ActA, with its acetylation impairing its enzymatic activity and reducing pyruvate production. Supplementation with exogenous pyruvate mitigated oxidative stress sensitivity and restored competitiveness in multi-species biofilms. In vitro acetylation analysis further confirmed that ActA directly acetylates PykF, negatively affecting its enzymatic activity. Moreover, 18 potential lysine-acetylated sites on PykF were identified in vitro, which account for 75% of lysine-acetylated sites detected in vivo. Taken together, our study elucidates a novel regulatory mechanism of ActA-mediated acetylation of PykF in modulating oxidative stress adaptability of S. mutans by influencing pyruvate production, providing insights into the importance of protein acetylation in microbial environmental adaptability and interspecies interactions within dental biofilms.IMPORTANCEDental caries poses a significant challenge to global oral health, driven by microbial dysbiosis within dental biofilms. The pathogenicity of Streptococcus mutans, a major cariogenic bacterium, is closely linked to its ability to adapt to changing environments and cellular stresses. Our investigation into the protein acetylation mechanisms, particularly through the acetyltransferase ActA, reveals a critical pathway by which S. mutans modulates its adaptability to oxidative stress, the dominant stressor within dental biofilms. By elucidating how ActA affects the oxidative stress adaptability and competitiveness of S. mutans through the regulatory axis of ActA-PykF-pyruvate, our findings provide insights into the dynamic interplay between cariogenic and commensal bacteria within dental biofilms. This work emphasizes the significance of protein acetylation in bacterial stress response and competitiveness, opening avenues for the development of novel strategies to maintain oral microbial balance within dental biofilms.

Abstract Background Coronavirus disease 2019 (COVID-19) has had a global social and economic impact. An easy assessment procedure to handily identify the mortality risk of inpatients is urgently needed in clinical practice. Therefore, the aim of this study was to develop a simple nomogram model to categorize patients who might have a poor short-term outcome. Methods A retrospective cohort study of 189 COVID-19 patients was performed at Shanghai Ren Ji Hospital from December 12, 2022 to February 28, 2023. Chest radiography and biomarkers, including KL-6 were assessed. Risk factors of 28-day mortality were selected by a Cox regression model. A nomogram was developed based on selected variables by SMOTE strategy. The predictive performance of the derived nomogram was evaluated by calibration curve. Results In total, 173 patients were enrolled in this study. The 28-day mortality event occurred in 41 inpatients (23.7%). Serum KL-6 and radiological severity grade (RSG) were selected as the final risk factors. A nomogram model was developed based on KL-6 and RSG. The calibration curve suggested that the nomogram model might have potential clinical value. The AUCs for serum KL-6, RSG, and the combined score in the development group and validation group were 0.885 (95% CI: 0.804–0.952), 0.818 (95% CI: 0.711–0.899), 0.868 (95% CI: 0.776–0.942) and 0.932 (95% CI: 0.862–0.997), respectively. Conclusions Our results suggested that the nomogram based on KL-6 and RSG might be a potential method for evaluating 28-day mortality in COVID-19 patients. A high combined score might indicate a poor outcome in COVID-19 patients with pneumonia.

Abstract Background In diabetic retinopathy (DR), hypoxia-inducible factor (HIF-1α) induces oxidative stress by upregulating glycolysis. This process leads to neurodegeneration, particularly photoreceptor cell damage, which further contributes to retinal microvascular deterioration. Further, the regulation of Wnt-inhibitory factor 1 (WIF1), a secreted Wnt signaling antagonist, has not been fully characterized in neurodegenerative eye diseases. We aimed to explore the impact of WIF1 on photoreceptor function within the context of DR. Method Twelve-week-old C57BL/KsJ-db/db mice were intravitreally injected with WIF1 overexpression lentivirus. After 4 weeks, optical coherence tomography (OCT), transmission electron microscopy (TEM), H&E staining, and electroretinography (ERG) were used to assess the retinal tissue and function. The potential mechanism of action of WIF1 in photoreceptor cells was explored using single-cell RNA sequencing. Under high-glucose conditions, 661 W cells were used as an in vitro DR model. WIF1-mediated signaling pathway components were assessed using quantitative real-time PCR, immunostaining, and western blotting. Result Typical diabetic manifestations were observed in db/db mice. Notably, the expression of WIF1 was decreased at the mRNA and protein levels. These pathological manifestations and visual function improved after WIF1 overexpression in db/db mice. TEM demonstrated that WIF1 restored damaged mitochondria, the Golgi apparatus, and photoreceptor outer segments. Moreover, ERG indicated the recovery of a-wave potential amplitude. Single-cell RNA sequencing and in vitro experiments suggested that WIF1 overexpression prevented the expression of glycolytic enzymes and lactate production by inhibiting the canonical Wnt signaling pathway, HIF-1α, and Glut1, thereby reducing retinal and cellular reactive oxygen species levels and maintaining 661 W cell viability. Conclusions WIF1 exerts an inhibitory effect on the Wnt/β-catenin-HIF-1α-Glut1 glycolytic pathway, thereby alleviating oxidative stress levels and mitigating pathological structural characteristics in retinal photoreceptor cells. This mechanism helps preserve the function of photoreceptor cells in DR and indicates that WIF1 holds promise as a potential therapeutic candidate for DR and other neurodegenerative ocular disorders. Graphical Abstract

AIM: To investigate a pioneering framework for the segmentation of meibomian glands (MGs), using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis. METHODS: Totally 203 infrared meibomian images from 138 patients with dry eye disease, accompanied by corresponding annotations, were gathered for the study. A rectified scribble-supervised gland segmentation (RSSGS) model, incorporating temporal ensemble prediction, uncertainty estimation, and a transformation equivariance constraint, was introduced to address constraints imposed by limited supervision information inherent in scribble annotations. The viability and efficacy of the proposed model were assessed based on accuracy, intersection over union (IoU), and dice coefficient. RESULTS: Using manual labels as the gold standard, RSSGS demonstrated outcomes with an accuracy of 93.54%, a dice coefficient of 78.02%, and an IoU of 64.18%. Notably, these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%, 2.06%, and 2.69%, respectively. Furthermore, despite achieving a substantial 80% reduction in annotation costs, it only lags behind fully annotated methods by 0.72%, 1.51%, and 2.04%. CONCLUSION: An innovative automatic segmentation model is developed for MGs in infrared eyelid images, using scribble annotation for training. This model maintains an exceptionally high level of segmentation accuracy while substantially reducing training costs. It holds substantial utility for calculating clinical parameters, thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

In the dual-energy micro-CT system, the ideal posture relation is a necessary condition for high-quality imaging. However, existing posture calibration methods are not able to correct all the posture parameters of the dual-energy micro-CT system utilizing the optical coupler detector. To address this issue, we propose a posture correction method based on a single-sided nine-grids phantom. Scanning experiments and projection data reconstruction are conducted to validate the effectiveness of the proposed method. After posture correction, the absolute values of the coordinate offsets of dual-energy projection points in two directions are less than the unit pixel size of the detector. Besides, artifacts in the reconstruction images of both optical paths are reduced, leading to improved accuracy in material discrimination results from reconstruction images. The proposed method can correct all the posture parameters of the optical coupler detector, making it certainly practical for the micro-CT system utilizing the optical coupler detector.

Background: Emerging evidence has shown the potential involvement of phthalates (PAEs) exposure in the development of dementia with Lewy bodies (DLB). Metabolomics can reflect endogenous metabolites variation in the progress of disease after chemicals exposure. However, little is known about the association between PAEs, gut microbiota and metabolome in DLB. Objective: We aim to explore the intricate relationship among urinary PAEs metabolites (mPAEs), dysbiosis of gut bacteria, and metabolite profiles in DLB. Methods: A total of 43 DLB patients and 45 normal subjects were included in this study. Liquid chromatography was used to analyze the levels of mPAEs in the urine of the two populations. High-throughput sequencing and liquid chromatography-mass spectrometry were used to analyze gut microbiota and the profile of gut metabolome, respectively. The fecal microbiota transplantation (FMT) experiment was performed to verify the potential role of mPAEs on gut dysbiosis contribute to aggravating cognitive dysfunction in α-synuclein tg DLB/PD mice. Results: The DLB patients had higher DEHP metabolites (MEOHP, MEHHP and MEHP), MMP and MnBP, lower MBP and MBzP than the control group and different microbiota. A significantly higher abundance of Ruminococcus gnavus and lower Prevotella copri, Prevotella stercorea and Bifidobacterium were observed in DLB. Higher 3 DEHP metabolites, MMP, MnBP and lower MBP and MBzP were significantly negatively associated with Prevotella copri, Prevotella stercorea and Bifidobacterium. Additionally, using metabolomics, we found that altered bile acids, short-chain fatty acids and amino acids metabolism are linked to these mPAEs. We further found that FMT of fecal microbiota from highest DEHP metabolites donors significantly impaired cognitive function in the germ-free DLB/PD mice. Conclusion: Our study suggested that PAEs exposure may alter the microbiota-gut-brain axis and providing novel insights into the interactions among environmental perturbations and microbiome-host in pathogenesis of DLB.

IntroductionWe previously reported that ATP1A3 c.823G>C (p.Ala275Pro) mutant causes varying phenotypes of alternative hemiplegia of childhood and rapid-onset dystonia-parkinsonism in the same family. This study aims to investigate the function of ATP1A3 c.823G>C (p.Ala275Pro) mutant at the cellular and zebrafish models.MethodsATP1A3 wild-type and mutant Hela cell lines were constructed, and ATP1A3 mRNA expression, ATP1A3 protein expression and localization, and Na+-K+-ATPase activity in each group of cells were detected. Additionally, we also constructed zebrafish models with ATP1A3 wild-type overexpression (WT) and p.Ala275Pro mutant overexpression (MUT). Subsequently, we detected the mRNA expression of dopamine signaling pathway-associated genes, Parkinson’s disease-associated genes, and apoptosisassociated genes in each group of zebrafish, and observed the growth, development, and movement behavior of zebrafish.ResultsCells carrying the p.Ala275Pro mutation exhibited lower levels of ATP1A3 mRNA, reduced ATP1A3 protein expression, and decreased Na+-K+-ATPase activity compared to wild-type cells. Immunofluorescence analysis revealed that ATP1A3 was primarily localized in the cytoplasm, but there was no significant difference in ATP1A3 protein localization before and after the mutation. In the zebrafish model, both WT and MUT groups showed lower brain and body length, dopamine neuron fluorescence intensity, escape ability, swimming distance, and average swimming speed compared to the control group. Moreover, overexpression of both wild-type and mutant ATP1A3 led to abnormal mRNA expression of genes associated with the dopamine signaling pathway and Parkinson’s disease in zebrafish, and significantly upregulated transcription levels of bad and caspase-3 in the apoptosis signaling pathway, while reducing the transcriptional level of bcl-2 and the bcl-2/bax ratio.ConclusionThis study reveals that the p.Ala275Pro mutant decreases ATP1A3 protein expression and Na+/K+-ATPase activity. Abnormal expression of either wild-type or mutant ATP1A3 genes impairs growth, development, and movement behavior in zebrafish.

Wasp venom injections from wasp stings can damage several organs, most commonly the kidneys. Despite literature evidence, wasp sting-induced acute kidney injury (AKI) is rare and involves complex pathophysiological processes. While acute tubular necrosis (ATN) is the most prevalent histological result of wasp sting-induced AKI, uncommon combinations of chronic renal lesions have been described, alerting us to the patient's underlying illness. We report a 55-year-old hypertensive patient with unknown renal function who got AKI following multiple wasp stings. His renal function had not improved after continuous hemodialysis and plasma exchange; therefore, a kidney biopsy was performed. The pathology revealed that in addition to ATN, his kidney's distinguishing feature was a mix of chronic interstitial renal disease and chronic glomerulosclerosis. We think that his current renal pathological results were caused by hypertension in addition to wasp venom.

The aim of the present study was to investigate adverse effects of head injury, neck trauma, and chronic noise exposure on the complaint profile in people with Ménière’s disease (MD). The study used a retrospective design. Register data of 912 patients with MD from the Finnish Ménière Federation database were studied. The data comprised case histories of traumatic brain injury (TBI), neck trauma and occupational noise exposure, MD specific complaints, impact related questions, and the E-Qol health-related quality of life instrument. TBI was classified based on mild, moderate, and severe categories of transient loss of consciousness (TLoC). The mean age of the participants was 60.2 years, the mean duration of the disease was 12.6 years, and 78.7% were females. Logistic regression analysis, linear correlation, and pairwise comparisons were used in evaluating the associations. 19.2% of the participants with MD had a history of TBI. The phenotype of participants with TBI was associated with frequent vestibular drop attacks (VDA), presyncope, headache-associated vertigo, and a reduction in the E-QoL. Logistic regression analysis explained the variability of mild TBI in 6.8%. A history of neck trauma was present in 10.8% of the participants. Neck trauma associated with vertigo (NTwV) was seen in 47 and not associated with vertigo in 52 participants. The phenotype of NTwV was associated with balance problems, VDA, physical strain-induced vertigo, and hyperacusia. Logistic regression analysis explained 8.7% of the variability of the complaint profile. Occupational noise exposure was recorded in 25.4% of the participants and correlated with the greater impact of tinnitus, hyperacusis, and hearing loss. Neither the frequency, duration, or severity of vertigo or nausea were significantly different between the baseline group and the TBI, NTwV, or noise-exposure groups. The results indicate that TBI and NTwV are common among MD patients and may cause a confounder effect.

Abstract Host anti-viral factors are essential for controlling SARS-CoV-2 infection but remain largely unknown due to the biases of previous large-scale studies toward pro-viral host factors. To fill in this knowledge gap, we perform a genome-wide CRISPR dropout screen and integrate analyses of the multi-omics data of the CRISPR screen, genome-wide association studies, single-cell RNA-Seq, and host-virus proteins or protein/RNA interactome. This study uncovers many host factors that are currently underappreciated, including the components of V-ATPases, ESCRT, and N-glycosylation pathways that modulate viral entry and/or replication. The cohesin complex is also identified as an anti-viral pathway, suggesting an important role of three-dimensional chromatin organization in mediating host-viral interaction. Furthermore, we discover another anti-viral regulator KLF5, a transcriptional factor involved in sphingolipid metabolism, which is up-regulated, and harbors genetic variations linked to COVID-19 patients with severe symptoms. Anti-viral effects of three identified candidates (DAZAP2/VTA1/KLF5) are confirmed individually. Molecular characterization of DAZAP2/VTA1/KLF5-knockout cells highlights the involvement of genes related to the coagulation system in determining the severity of COVID-19. Together, our results provide further resources for understanding the host anti-viral network during SARS-CoV-2 infection and may help develop new countermeasure strategies.

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere's disease (MD) and sudden sensorineural hearing loss (SSHL). Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin. Dexamethasone was constantly released for at least 16 d at a stable level after 7 d in protocol 1 (low-dose), while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2 (high-dose). There were significant differences among the time points in Protocol 2 (p

Abstract Background Identifying host factors is key to understanding RNA virus pathogenicity. Besides proteins, RNAs can interact with virus genomes to impact replication. Results Here, we use proximity ligation sequencing to identify virus-host RNA interactions for four strains of Zika virus (ZIKV) and one strain of dengue virus (DENV-1) in human cells. We find hundreds of coding and non-coding RNAs that bind to DENV and ZIKV viruses. Host RNAs tend to bind to single-stranded regions along the virus genomes according to hybridization energetics. Compared to SARS-CoV-2 interactors, ZIKV-interacting host RNAs tend to be downregulated upon virus infection. Knockdown of several short non-coding RNAs, including miR19a-3p, and 7SK RNA results in a decrease in viral replication, suggesting that they act as virus-permissive factors. In addition, the 3′UTR of DYNLT1 mRNA acts as a virus-restrictive factor by binding to the conserved dumbbell region on DENV and ZIKV 3′UTR to decrease virus replication. We also identify a conserved set of host RNAs that interacts with DENV, ZIKV, and SARS-CoV-2, suggesting that these RNAs are broadly important for RNA virus infection. Conclusions This study demonstrates that host RNAs can impact virus replication in permissive and restrictive ways, expanding our understanding of host factors and RNA-based gene regulation during viral pathogenesis.

IntroductionPhysical weakness is associated with cortical structures, but the exact causes remain to be investigated. Therefore, we utilized Mendelian randomization (MR) analysis to uncover the underlying connection between frailty and cortical structures.MethodsThe Genome-Wide Association Study (GWAS) on frailty pooled data from publicly available sources such as the UK Biobank and included five indicators of frailty: weakness, walking speed, weight loss, physical activity, and exhaustion. GWAS data on cerebral cortical structure were obtained from the ENIGMA consortium, and we assessed the causal relationship between hereditary frailty and cortical surface area (SA) or cortical thickness (TH). Inverse variance weighting (IVW) was used as the primary estimate, and heterogeneity and multidimensionality were monitored by MR-PRESSO to detect outliers. Additionally, MR-Egger, Cochran’s Q test, and weighted median were employed.ResultsAt the aggregate level, there was no causal relationship between frailty and cortical thickness or surface area. At the regional level, frailty was associated with the thickness of the middle temporal lobe, parahippocampus, rostral middle frontal lobe, lower parietal lobe, anterior cingulate gyrus, upper temporal lobe, lateral orbital frontal cortex, pericardial surface area, rostral middle frontal lobe, upper temporal lobe, rostral anterior cingulate gyrus, lower parietal lobe, and upper parietal lobe. These results were nominally significant, and sensitivity analyses did not detect any multidirectionality or heterogeneity, suggesting that the results of our analyses are reliable.DiscussionThe results of our analyses suggest a potential causal relationship between somatic weakness and multiple regions of cortical structure. However, the specific mechanisms of influence remain to be investigated. Preliminary results from our analysis suggest that the effects of physical frailty on cortical structures are influenced by various factors related to frailty exposure. This relationship has been documented, and it is therefore both feasible and meaningful to build on existing research to explore the clinical significance of the relationship.

Viral variant is one known risk factor associated with post-acute sequelae of COVID-19 (PASC), yet the pathogenesis is largely unknown. Here, we studied SARS-CoV-2 Delta variant-induced PASC in K18-hACE2 mice. The virus replicated productively, induced robust inflammatory responses in lung and brain tissues, and caused weight loss and mortality during the acute infection. Longitudinal behavior studies in surviving mice up to 4 months post-acute infection revealed persistent abnormalities in neuropsychiatric state and motor behaviors, while reflex and sensory functions recovered over time. In the brain, no detectable viral RNA and minimal residential immune cell activation was observed in the surviving mice post-acute infection. Transcriptome analysis revealed persistent activation of immune pathways, including humoral responses, complement, and phagocytosis, and gene expression levels associated with ataxia telangiectasia, impaired cognitive function and memory recall, and neuronal dysfunction and degeneration. Furthermore, surviving mice maintained potent systemic T helper 1 prone cellular immune responses and strong sera neutralizing antibodies against Delta and Omicron variants months post-acute infection. Overall, our findings suggest that infection in K18-hACE2 mice recapitulates the persistent clinical symptoms reported in long-COVID patients and provides new insights into the role of systemic and brain residential immune factors in PASC pathogenesis.

Post-transcriptional regulation by small RNAs and post-translational modifications (PTM) such as lysine acetylation play fundamental roles in physiological circuits, offering rapid responses to environmental signals with low energy consumption. Yet, the interplay between these regulatory systems remains underexplored. Here, we unveil the cross-talk between sRNAs and lysine acetylation in Streptococcus mutans, a primary cariogenic pathogen known for its potent acidogenic virulence. Through systematic overexpression of sRNAs in S. mutans, we identified sRNA SmsR1 as a critical player in modulating acidogenicity, a key cariogenic virulence feature in S. mutans. Furthermore, combined with the analysis of predicted target mRNA and transcriptome results, potential target genes were identified and experimentally verified. A direct interaction between SmsR1 and 5'-UTR region of pdhC gene was determined by in vitro binding assays. Importantly, we found that overexpression of SmsR1 reduced the expression of pdhC mRNA and increased the intracellular concentration of acetyl-CoA, resulting in global changes in protein acetylation levels. This was verified by acetyl-proteomics in S. mutans, along with an increase in acetylation level and decreased activity of LDH. Our study unravels a novel regulatory paradigm where sRNA bridges post-transcriptional regulation with post-translational modification, underscoring bacterial adeptness in fine-tuning responses to environmental stress.

To realize the industrial production of pure sour porridge, the traditional sour porridge from Hequ of Shanxi was used as the donor of lactic acid bacteria, which could be used to produce sour porridge under pure culture condition. Lactic acid bacteria were isolated from the sour porridge with CaCO3-MRS medium, and lactic acid bacteria with strong tolerance were screened through acid tolerance, bile salt tolerance and simulated gastrointestinal tolerance tests. The strains were identified by physiological and biochemical tests, 16S rDNA and pheS gene sequence. The results showed that strains L10, W10 and Y3 with strong tolerance were selected from 68 strains of lactic acid bacteria, the three strains of lactic acid bacteria were identified as Lactiplantibacillus plantarum. At aggregation assay, the self-agglutination rate of L10, W10 and Y3 were 48.86%, 30.14% and 27.63% respectively. Strains L10, W10 and Y3 were able to survive at MRS medium containing 1.0 mmol/L hydrogen peroxide. In free radical scavenging assays, the fermentation supernatant of L10 possessed the highest ability to scavenge the DPPH radical (95.27%), and the hydroxyl radical and superoxide anion scavenging ability of Y3 were the highest, which were 51.26% and 20.16% respectively. However, the DPPH radical scavenging ability of the intact cell suspension of W10 was the highest (27.53%), and the hydroxyl radical scavenging ability of Y3 was 24.83%, which was the highest among them. Therefore, the three strains of lactic acid bacteria screened from traditional sour porridge possessed the potential applications in the industrial production of pure sour porridge.

The Mengshan granitoid complex is located in the central part of Jiangnan Orogen and belongs to the western part of Jiangxi Province, where several phases of granitic magmatism record the crustal evolution of the late-Indosinian. However, its petrogenesis remains uncertain, largely due to controversies over its origin, evolutionary process and tectonic setting during intrusion. In this study, the lithological features and contact relationships observed in the systematic field geological investigations indicate that the late magmatic phases of the Mengshan granitoid complex are mainly composed of medium–fine-grained biotite monzogranite and fine-grained monzogranite, both of which developed primary fine-grained muscovite. Petrological, petrographic, geochemical and zircon U-Pb-Hf isotopic studies were further carried out on these rocks. Zircon U-Pb isotopic analyses suggest that the medium–fine-grained biotite monzogranite mainly formed at 220.7 ± 1.0 Ma to 218.0 ± 0.8 Ma, and that the fine-grained monzogranite formed at 211.5 ± 2.9 Ma to 212.9 ± 1.0 Ma. Whole-rock geochemical analysis results suggest that these rocks are rich in Cs, Rb, and U, and deficient in Ba, Sr, and Ti, and that they have properties characteristic of rocks with high silica, low P content and high K calc-alkali. Mineralogical and geochemical analysis results suggest that they are S-type granites. The εHf(t) values of the early-stage medium–fine-grained biotite monzogranite and late-stage fine-grained monzogranite range from –4.7 to 0.3 and from –3.2 to 0.7, respectively. Geochemical and isotopic data suggest that these granitoids were derived from the partial melting of Proterozoic continent basement rocks, and that minor mantle materials were involved during their generation. The presence of the early Mesozoic Mengshan granitoid complex reflects a reduplicated far-field converge effect of the collision of the North China and South China blocks and the subduction of the Palaeo-Pacific plate into the South China block. The thickening of the Earth’s crust facilitated crustal delamination, underplating of mantle-derived magma, and crustal heating, triggering intense partial melting of the lithosphere and magma enrichment.

Massive computational resources are required by a booming number of artificial intelligence (AI) services in the communication network of the smart grid. To alleviate the computational pressure on data centers, edge computing first network (ECFN) can serve as an effective solution to realize distributed model training based on data parallelism for AI services in smart grid. Due to AI services with diversified types, an edge data center has a changing workload in different time periods. Selfish edge data centers from different edge suppliers are reluctant to share their computing resources without a rule for fair competition. AI services-oriented dynamic computational resource scheduling of edge data centers affects both the economic profit of AI service providers and computational resource utilization. This letter mainly discusses the partition and distribution of AI data based on distributed model training and dynamic computational resource scheduling problems among multiple edge data centers for AI services. To this end, a mixed integer linear programming (MILP) model and a Deep Reinforcement Learning (DRL)-based algorithm are proposed. Simulation results show that the proposed DRL-based algorithm outperforms the benchmark in terms of profit of AI service provider, backlog of distributed model training tasks, running time and multi-objective optimization.

In this study, a diagnostic model for evaporation ducts was established based on the Coupled Ocean–Atmosphere–Wave–Sediment Transport (COAWST) and the Naval Postgraduate School (NPS) models. Utilizing this model, four sensitivity tests were conducted over the South China Sea from 21 September to 5 October 2008, when four tropical cyclones affected the study domain. These tests were designed with different roughness schemes to investigate the impact mechanisms of wave processes on evaporation duct simulation under extreme weather conditions. The results indicated that wave processes primarily influenced the evaporation duct heights by altering sea surface roughness and dynamical factors. The indirect impacts of waves without dynamical factors were rather weak. Generally, a decrease in local roughness led to increased wind speed, decreased humidity, and a reduced air–sea temperature difference, resulting in the formation of evaporation ducts at higher altitudes. However, this affecting mechanism between roughness and evaporation ducts was also greatly influenced by changes in regional circulation. In the eastern open sea areas of the South China Sea, changes in evaporative ducts were more closely aligned with local impact mechanisms, whereas the changes in the central and western areas demonstrated greater complexity and fewer local impacts due to variations in regional circulation.

Abstract Background Treatment‐free remission (TFR) has become the main target for chronic myeloid leukemia (CML). Tyrosine kinase inhibitors (TKI) dose optimization is crucial in managing adverse events, and improving adherence in clinical practice. In persons achieving a deep molecular response (DMR), some data suggest TKI dose reduction before discontinuation does not change success rate of achieving TFR, but this is controversial. However, data on quality‐of‐life (QoL) and mental health in CML patients with full‐dose TKI, low‐dose TKI, and TKI discontinuation are limited. Moreover, recent evidence indicating the feasibility of TKI dose reduction and discontinuation after dose reduction, which may change CML patients' perspectives on TKI discontinuation. Methods We conducted a cross‐sectional study using online questionnaires to explore the QoL, mental health in patients with diverse TKI dose, and perspective on TKI dose reduction as a prelude to discontinuation. Results 1450 responses were included in the analysis. 44.3% of respondents reported a moderate‐to‐severe impact of TKI treatment on their QoL. 17% of respondents had moderate‐to‐severe anxiety. 24.4% of respondents had moderate‐to‐severe depression. In 1326 patients who had not discontinued their medication, 1055 (79.6%) patients reported they would try TKI discontinuation because of concerns over side effects of long‐term medication (67.9%), financial burden (68.7%), poor QoL (77.9%), pregnancy needs (11.6%), anxiety and depression while taking TKI (20.8%), inconvenience of TKI treatment (22.2%). 613 of 817 (75.0%) patients on full‐dose TKI therapy indicated they preferred trying a dose reduction before discontinuing TKI therapy after dose reduction compared with 31 (3.8%) preferring no dose reduction before stopping. Conclusions TKI dose reduction showed a significant improvement of patients' QoL and mental health, comparable to the effect of TKI discontinuation. Most patients indicated they preferred dose reduction before stopping TKI therapy. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Our results showed that tyrosine kinase inhibitors (TKI) dose reduction showed a significant improvement of patients' quality‐of‐life and mental health, comparable to the effect of TKI discontinuation. Most patients desire to discontinue TKI in the future. TKI discontinuation after dose reduction is more acceptable compared to discontinuing it directly. In clinical practice, TKI dose reduction can be considered as a bridge from full‐dose treatment to discontinuation. Please do not hesitate to contact me in case further clarification is needed with this submission.

Abstract Background Few studies have investigated how the effectiveness of hand washing in removing hand contaminants is influenced by the performance and duration of each step involved. We conducted an observational study by recruiting participants from a university campus, with the aim to comprehensively evaluate how performance, duration and demographic factors influence hand washing effectiveness. Methods A total of 744 videos were collected from 664 participants in July-October 2022 and independently evaluated by two infection control experts through labelling videos for correct and incorrect performance of each step. The individual hand washing effectiveness was determined by quantifying the percentage of residual fluorescent gel on the dorsum and palm areas of each participant’s hands. A logistic regression analysis was conducted to identify factors that were significantly associated with better hand washing effectiveness. An exposure-response relationship was constructed to identify optimal durations for each step. Approximately 2300 hand images were processed using advanced normalization algorithms and overlaid to visualize the areas with more fluorescence residuals after hand washing. Results Step 3 (rub between fingers) was the most frequently omitted step and step 4 (rub the dorsum of fingers) was the most frequently incorrectly performed step. After adjustment for covariates, sex, performance of step 4 and step 7 (rub wrists), rubbing hands during rinsing, and rinsing time were significantly associated with hand washing effectiveness. The optimal overall hand washing time was 31 s from step 1 to step 7, and 28 s from step 1 to step 6, with each step ideally lasting 4–5 s, except step 3. The palms of both hands had less fluorescence residuals than the dorsums. The areas where residuals most likely appeared were wrists, followed by finger tips, finger webs and thumbs. Conclusions Performance and duration of some hand washing steps, sex and rinsing time were associated with hand washing effectiveness. The optimal duration might be applied to all seven steps to achieve the best decontamination results. Further studies are needed to refine hand hygiene standards and enhance compliance.

Understanding the evolution of Fe–containing intermetallic compounds (Fe–IMCs) in Al–Si–Mg alloys is essential for improving the mechanical performances. This paper aims to systemically evaluate the influences of both the single addition of Mn or Mo, and the combined additions of Mn and Mo on the evolution of Fe–IMCs and mechanical performances of Al–Si–Mg cast alloys. Results reveal that the as–cast microstructures of these alloys are primarily composed of Al3M (M means Ti, Zr, or TiZr), α–Al, eutectic Si, Mg2Si, Q–Al5Cu2Mg8Si6, and some irregular Fe–IMCs. It is clear that the morphology and size of Fe–IMCs are significantly affected by the single or combined addition of Mn and Mo. Moderate Mn content facilitates the formation of Chinese script–like α–Al(FeMn)Si phases that are favorable to the mechanical properties. The combined addition of Mn and Mo refines the α–Al(FeMn)Si phases and promotes the formation of Chinese script–like α–Al(FeMnMo)Si phases. Furthermore, as the Mo level increases, β–AlFeSi, π–Al8FeMg3Si6, and α–Al(FeMn)Si disappear successively, which also helps improve the mechanical performances. In this article, maximum hardness, ultimate tensile strength, yield strength and elongation of 87.04 HV, 275.34 MPa, 139.70 MPa, 7.88% are obtained when Fe, Mn and Mo are added at 0.20wt.%, 0.02wt.%, and 0.27wt.%, respectively. The purpose of this work is to provide an efficient method to minimize or even eliminate the adverse effects of Fe–IMCs and thus improve the mechanical performances of Al–Si–Mg cast alloys.

Abstract Background Dysbiosis of gut microbiota is causally linked to impaired host glucose metabolism. We aimed to study effects of the new method of fecal microbiota transplantation, washed microbiota transplantation (WMT), on reducing glycemic variability (GV) in unstable diabetes. Methods Fourteen eligible patients received three allogenic WMTs and were followed up at 1 week, 1 month, and 3 months. Primary outcomes were daily insulin dose, glucose excursions during meal tests, and GV indices calculated from continuous monitoring or self‐monitoring glucose values. Secondary outcomes were multiomics data, including 16S rRNA gene sequencing, metagenomics, and metabolomics to explore underlying mechanisms. Results Daily insulin dose and glucose excursions markedly dropped, whereas GV indices significantly improved up to 1 month. WMT increased gut microbial alpha diversity, beta diversity, and network complexity. Taxonomic changes featured lower abundance of genera Bacteroides and Escherichia‐Shigella, and higher abundance of genus Prevotella. Metagenomics functional annotations revealed enrichment of distinct microbial metabolic pathways, including methane biosynthesis, citrate cycle, amino acid degradation, and butyrate production. Derived metabolites correlated significantly with improved GV indices. WMT did not change circulating inflammatory cytokines, enteroendocrine hormones, or C‐peptide. Conclusions WMT showed strong ameliorating effect on GV, raising the possibility of targeting gut microbiota as an effective regimen to reduce GV in diabetes.

Abstract Background Previous studies have reported SIRT1 was inversely modulated by miR‐34a, However, mechanism of metformin (MFN)'s renal podocyte protection under high glucose (HG) conditions and the connection between miR‐34a and SIRT1 expression in diabetic nephropathy (DN) remain unclear. Method We aimed to further elucidate the role of miR‐34a in HG‐treated podocytes in DN. A conditionally immortalized human podocyte cell line was cultivated in d‐glucose (30 mM). Results Microarray and RT‐qPCR revealed that miR‐34a was downregulated in HG‐treated podocytes. Additionally, miR‐34a levels increased in MFN‐treated HG‐induced podocytes. CCK‐8 assay, colony formation assay, flow cytometry, and Western blot detection showed that HG treatment reduced cell viability and promoted via HG treatment, and MFN treatment reversed this phenotypic change. MiR‐34a upregulation caused restored cell viability and suppressed cell apoptosis in HG‐treated podocytes, and miR‐34a downregulation led to damaged cell survival and induced apoptosis in MFN‐administered and HG‐treated podocytes. The dual luciferase reporter assay showed that SIRT1 3′‐UTR was a direct miR‐34a target. Further studies demonstrated an elevation in SIRT1 levels in HG‐exposed podocytes, whereas MFN treatment decreased SIRT1 levels. In addition, miR‐34a upregulation led to reduced SIRT1 expression, whereas miR‐34a inhibition increased SIRT1 levels in cells. MFN‐induced miR‐34a suppresses podocyte apoptosis under HG conditions by acting on SIRT1. Conclusion This study proposes a promising approach to interpret the mechanisms of action of the MFN‐miR‐34a axis involved in DN.

The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential to evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live SARS-CoV-2 neutralization assay to compare the neutralization evasion ability of BA.2.86 with other emerged SARS-CoV-2 subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, and XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 and FL.1.5.1. Our results show that BA.2.86 is less neutralization evasive than XBB sublineages. XBB descendants XBB.1.16, EG.5.1, and FL.1.5.1 continue to significantly evade neutralization induced by the parental COVID-19 mRNA vaccine and a BA.5 Bivalent booster. Notably, when compared to XBB.1.5, the more recent XBB descendants, particularly EG.5.1, display increased resistance to neutralization. Among all the tested variants, CH.1.1 exhibits the greatest neutralization evasion. In contrast, XBC.1.6 shows a slight reduction but remains comparably sensitive to neutralization when compared to BA.5. Furthermore, a recent XBB.1.5-breakthrough infection significantly enhances the breadth and potency of cross-neutralization. These findings reinforce the expectation that the upcoming XBB.1.5 mRNA vaccine would likely boost the neutralization of currently circulating variants, while also underscoring the critical importance of ongoing surveillance to monitor the evolution and immune evasion potential of SARS-CoV-2 variants.

ABSTRACTThrombocytopenia is one of the most common hematological adverse reactions in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKI) therapy, causing life-threatening bleeding cases. However, there are fewer therapeutic drugs for TKI-induced thrombocytopenia. Eltrombopag is a non-peptide thrombopoietin receptor agonist used for the treatment of immune thrombocytopenia， aplastic anemia, and hepatitis C-associated thrombocytopenia. Nevertheless, studies of eltrombopag for TKI-induced thrombocytopenia are still lacking. This study retrospectively analyzed the clinical and test data of 21 CML patients with TKI-related thrombocytopenia. The results demonstrated that the median baseline value of thrombocytopenia in the 21 CML patients was 15.57 × 109/L [2–28 × 109/L]. Following treatment with eltrombopag, 16 patients had a significant increase in their platelet levels. The peak median for platelet increase in effective responders was 145.12 × 109/L (51–460 × 109/L). However, 5 patients failed to respond to eltrombopag. Moreover, 4 of the 21 patients enrolled had adverse reactions, including reversible liver function impairment, palpitation, headache, insomnia, and loss of appetite. Nonetheless, no cases of disease progression, thrombotic events, or myelofibrosis were observed. Hence, eltrombopag may be a useful adjunctive therapy for relieving TKI-related thrombocytopenia in patients with CML.

ABSTRACTThe rapid evolution of SARS-CoV-2 Omicron sublineages mandates a better understanding of viral replication and cross-neutralization among these sublineages. Here we used K18-hACE2 mice and primary human airway cultures to examine the viral fitness and antigenic relationship among Omicron sublineages. In both K18-hACE2 mice and human airway cultures, Omicron sublineages exhibited a replication order of BA.5 ≥ BA.2 ≥ BA.2.12.1 > BA.1; no difference in body weight loss was observed among different sublineage-infected mice. The BA.1-, BA.2-, BA.2.12.1-, and BA.5-infected mice developed distinguishable cross-neutralizations against Omicron sublineages, but exhibited little neutralization against the index virus (i.e. USA-WA1/2020) or the Delta variant. Surprisingly, the BA.5-infected mice developed higher neutralization activity against heterologous BA.2 and BA.2.12.1 than that against homologous BA.5; serum neutralizing titres did not always correlate with viral replication levels in infected animals. Our results revealed a distinct antigenic cartography of Omicron sublineages and support the bivalent vaccine approach.

BMP9 mediated osteogenic differentiation mechanisms of MSCs were widely explored, however, mechanisms of BMP9-induced angiogenesis still need to be clarified. We previously characterized that Notch1 promoted BMP9-induced osteogenesis–angiogenesis coupling process in mesenchymal stem cells (MSCs). Here, we explored the underlying mechanisms of lncRNA H19 (H19) mediated regulation of BMP9-induced angiogenesis through activating Notch1 signaling. We demonstrated that basal expression level of H19 was high in MSCs, and silencing H19 attenuates BMP9-induced osteogenesis and angiogenesis of MSCs both in vitro and in vivo. Meanwhile, we identified that BMP9-induced production of CD31+ cells was indispensable for BMP9-induced bone formation, and silencing H19 dramatically blocked BMP9-induced production of CD31+ cells. In addition, we found that down-regulation of H19 inhibited BMP9 mediated blood vessel formation and followed subsequent bone formation in vivo. Mechanistically, we clarified that H19 promoted p53 phosphorylation by direct interacting and phosphorylating binding, and phosphorylated p53 potentiated Notch1 expression and activation of Notch1 targeting genes by binding on the promoter area of Notch1 gene. These findings suggested that H19 regulated BMP9-induced angiogenesis of MSCs by promoting the p53-Notch1 angiogenic signaling axis.

ObjectiveWeight reduction often accompanies muscle loss. Existing studies highlight the involvement of osteocalcin (OC) in energy metabolism and its potential to prevent age-related muscle loss. Nevertheless, these studies predominantly involve individuals with hyperglycemia, yielding conflicting research outcomes. This study investigated the protective role of OC against muscle loss during weight reduction in individuals without metabolic syndrome (MetS).MeasuresWe enrolled 130 overweight or obese individuals without MetS in a 4-month high-protein, energy-restricted dietary weight management program conducted at two clinic centers. Body composition and laboratory tests were assessed both before and after weight loss. Correlation and regression analysis were made between the changes in metabolic indicators and muscle mass during weight loss.ResultsFollowing weight loss, there was a decrease in body mass index (BMI), percentage of body fat (PBF), visceral fat area (VFA), fasting insulin (FINS), homeostasis model assessment insulin resistance (HOMA-IR), glycated haemoglobin (HbA1c), and lipid profile, and increase in the percentage of skeletal muscle (PSM) and vitamin D. There was no change in osteocalcin (OC) during the intervention. Correlation analysis of the relative changes in all metabolic indicators revealed a positive correlation between OC and PSM (r=0.383, p=0.002). Multiple linear regression analysis found that OC has a significant protective effect on muscles during weight loss in males after adjusting for confounding factors (β=0.089, p=0.017).ConclusionHigh-protein, energy-restricted diets demonstrate efficacy in enhancing metabolic indicators within the weight-loss population. Furthermore, OC exhibits a protective effect on muscle mass during weight reduction in individuals without MetS, with this effect being particularly evident in males.

BackgroundThe early adversity is associated with a series of negative outcomes in adulthood, and the impact on the cerebral cortex may be one of the fundamental causes of these adverse consequences in adulthood. In this study, we aim to investigate the causal relationship between early adversity and changes in cerebral cortex structure using Mendelian randomization (MR) analysis.MethodsThe GWAS summary statistics of 6 early adversity traits were obtained from individuals of European ancestry in the UK Biobank. The GWAS summary statistics of 34 known functional cortical regions were obtained from the ENIGMA Consortium. Causal relationships between the adversity factors and brain cortical structure were assessed using the inverse-variance weighted (IVW), MR-Egger, and weighted median methods, with IVW being the primary evaluation method. Cochran’s Q-test, MR-PRESSO, leave-one-out analysis, and funnel plot examination were employed to detect potential heterogeneity and pleiotropy, as well as to identify and exclude outliers.ResultsAt a global level, no causal relationship was found between early adversity and cortical thickness (TH) or surface area (SA) of the brain. However, at the regional level, early adversity was found to potentially influence the TH of the caudal anterior cingulate, superior temporal, entorhinal, paracentral, lateral occipital, banks of the superior temporal sulcus, and supramarginal regions, as well as the SA of the pars triangularis, lateral occipital, parahippocampal, medial orbitofrontal, and isthmus cingulate regions. All findings were nominally significant and passed sensitivity analyses, with no significant heterogeneity or pleiotropy detected.DiscussionOur study provides evidence for the association between early adversity and alterations in brain cortical structure, which may serve as a foundation for certain mental disorders. Furthermore, magnetic resonance imaging (MRI) might be considered as a promising tool to aid healthcare professionals in identifying individuals with a history of adverse experiences, allowing for early interventions.

Abstract Remdesivir (GS-5734; VEKLURY) is a single diastereomer monophosphoramidate prodrug of an adenosine analog (GS-441524). Remdesivir is taken up by target cells and metabolized in multiple steps to form the active nucleoside triphosphate (GS-443902), which acts as a potent inhibitor of viral RNA-dependent RNA polymerases. Remdesivir and GS-441524 have antiviral activity against multiple RNA viruses. Here, we expand the evaluation of remdesivir’s antiviral activity to members of the families Flaviviridae, Picornaviridae, Filoviridae, Orthomyxoviridae, and Hepadnaviridae. Using cell-based assays, we show that remdesivir can inhibit infection of flaviviruses (such as dengue 1–4, West Nile, yellow fever, Zika viruses), picornaviruses (such as enterovirus and rhinovirus), and filoviruses (such as various Ebola, Marburg, and Sudan virus isolates, including novel geographic isolates), but is ineffective or is significantly less effective against orthomyxoviruses (influenza A and B viruses), or hepadnaviruses B, D, and E. In addition, remdesivir shows no antagonistic effect when combined with favipiravir, another broadly acting antiviral nucleoside analog, and has minimal interaction with a panel of concomitant medications. Our data further support remdesivir as a broad-spectrum antiviral agent that has the potential to address multiple unmet medical needs, including those related to antiviral pandemic preparedness.

Abstract Measuring sailing ship plumes provides comprehensive and real‐time emission data. However, accurately tracking and measuring ship plumes still requires research. This study describes a tracking and measurement method of ship plumes using an unmanned aerial vehicle (UAV). A UAV ship exhaust measurement system and monitoring process were developed. Data from an automatic identification system (AIS) was used to improve the Gaussian plume diffusion model to facilitate the initial location of the plume on sailing ships. Based on the real‐time gas measurement values obtained by the UAV, the UAV flight method was optimized to accurately track and measure the ship's plume. The Pudong Maritime Safety Administration used this system in 2019 to effectively monitor the plumes of 27 sailing ships as part of maritime law enforcement. Consequently, four cases of excessive fuel sulphur content (FSC) were detected in situ for the first time, indicating that China's maritime authorities can use the technology to supervise and control the FSC of sailing ships.

Abstract Background To retrospectively investigate the success rate of primary-molar pulpectomy performed under general anaesthesia and the potential risk factors that affect the 24-month success rate. Methods The case data and two-year follow-up records of children (aged 3–6 years) who received pulpectomy in primary molars performed under general anaesthesia were reviewed and assessed. Potential risk factors included age, gender, decayed-missing-filled teeth, endodontic diagnosis, tooth location, and postobturation sealing of the pulp chamber floor with MTA. With a two-year follow-up period, the outcomes of all the primary molars were classified into success and failure. Survival analysis was used to assess the outcomes. The Kaplan–Meier method was used to analyse the success rate. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the potential risk factors associated with the overall survival of primary molars. Results A total of 410 teeth from 163 children (88 boys and 75 girls) were included in this study. The overall two-year success rate was 66.1% for all primary molars. The mean overall survival time for this study was 22.1 (95% CI, 21.73‒22.48) months. Multivariate Cox regression analysis demonstrated that endodontic diagnosis (irreversible pulpitis or periapical periodontitis), tooth location (maxillary or mandibular primary molar), and postobturation sealing of the pulp chamber floor (MTA or no-MTA) were significant risk factors for overall survival in this study (P .05). Conclusions When compared to teeth diagnosed with irreversible pulpitis, those with periapical periodontitis failed more frequently. Postobturation sealing of the pulp chamber floor with MTA improved the success rate of pulpectomy in primary molars, especially when the inflammation did not spread to the periradicular area.

Arabidopsis SPINDLY (SPY) is a nucleocytoplasmic protein O-fucosyltransferase. Here, the authors present a crystal structure of Arabidopsis SPY/GDP complex, reveal SPY’s substrate recognition and enzyme mechanism, and provide insights into the glycan donor substrate selection in GT41 proteins.

Distinct SARS-CoV-2 Omicron sublineages have evolved showing increased fitness and immune evasion than the original Omicron variant BA.1. Here, we report the neutralization activity of sera from BNT162b2 vaccinated individuals or unimmunized Omicron BA.1-infected individuals against Omicron sublineages and “Deltacron” variant (XD). BNT162b2 post-dose 3 immune sera neutralized USA-WA1/2020, Omicron BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and XD-spike SARS-CoV-2s with geometric mean titres (GMTs) of 1335, 393, 298, 315, 216, 103, and 301, respectively; thus, BA.4/5 SARS-CoV-2 spike variant showed the highest propensity to evade vaccine neutralization compared to the original Omicron variants BA.1. BA.1-convalescent sera neutralized USA-WA1/2020, BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and Deltacron-spike SARS-CoV-2s with GMTs of 15, 430, 110, 109, 102, 25, and 284, respectively. The unique mutation F486V in the BA.4/5 spike contributes to the increased evasion of antibody neutralization by sublineage BA.4/5. The low neutralization titres of vaccinated sera or convalescent sera from BA.1 infected individuals against the emerging and rapidly spreading Omicron BA.4/5 variants provide important results for consideration in the selection of an updated vaccine in the current Omicron wave.Trial registration: ClinicalTrials.gov; identifier: NCT04368728.

In this paper, we investigated the influence of calcium (Ca) on the electrochemical and corrosion properties of Al–Mg–Sn–Ga alloys in neutral and alkaline electrolytes, respectively. Results indicate that Ca element promotes the uniform dissolution of the anode and improve its discharge efficiency. The peak energy densities of the Al-0.5Mg-0.1Sn-0.05Ga-0.1Ca alloy in neutral and alkaline solutions are 3361 and 3581 Wh kg−1, respectively. Compared with calcium-free alloy, the increase is 5.3% and 26.5%, respectively. Additionally, the severe intergranular corrosion behavior of Al-0.5Mg-0.1Sn-0.05Ga alloy can be significantly inhibited by adding Ca element under alkaline conditions. Therefore, the addition of Ca element further optimizes the discharge performance of Al–Mg–Sn–Ga-based anodes and enhances its environmental adaptability.

Abstract Background The mechanistic target of rapamycin (mTOR) signal pathway plays a critical regulating role in the occurrence and development of cataract. However, the role of mTORC1 downstream proteins, including ribosomal protein S6K (RP-S6K), eukaryotic initiation factor 4E-binding protein (EIF4EBP), eukaryotic initiation factor 4G (EIF-4G), eukaryotic initiation factor 4E (EIF-4E), and eukaryotic initiation factor 4A (EIF-4A), in regulating cataract development is still unknown. Herein, we conducted a mendelian randomization (MR) study to understand the function of mTORC1 signaling in the process of cataract development. Results The causal estimate was evaluated with inverse-variance weighted (IVW) estimate, weighted median estimator, MR-Egger and MR robust adjusted profile score (MR. RAPS). The single-nucleotide polymorphisms (SNPs), P

Bispecific antibodies can have advantages compared to antibody cocktails. Here, the authors engineer and characterize two different approaches for generating bispecific SARS-CoV-2 specific antibodies and find that only one design increases antigen-binding and virus neutralizing activities.

High-throughput double cone specimens were used to study the influence of Mo on the microstructure evolution of Al–Cu–Mg–Ag alloy under a wide range of strain along the axis. The microstructure evolution was characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and electron backscatter diffraction (EBSD). Results demonstrated that Al6(Fe, Mn, Mo) dispersoids formed in the Al–Cu–Mg–Ag alloy with the addition of 0.2% Mo during double-step homogenization. Meanwhile, rod-like Al20Cu2Mn3 and disk-like Al6(Fe, Mn, Mo) dispersoids segregated to opposite distribution in interdendritic regions and dendrite cores, respectively, which obviously eliminated the dispersoid-free zones and intragranular sparse regions. With different effective strains along the axis, Al6(Fe, Mn, Mo) dispersoids obviously reduced the transformation from Low-angle grain boundaries to High-angle grain boundaries. The nucleation and growth of dynamic recrystallization grains were effectively inhibited by the coupling of Al20Cu2Mn3 and Al6(Fe, Mn, Mo) dispersoids due to the obstruction of dislocation movement.

Abstract The etiology and mechanism causing Meniere’s disease (MD) are not understood. The present study investigated the possible molecular mechanism of autoimmunity and autoinflammation associated with MD. Thirty-eight patients with definite MD and 39 normal volunteers were recruited, and 48 human cytokines/chemokines were quantified. In patients with MD pure tone audiograms, tympanograms and standard blood tests were performed. The mean hearing loss in the worse ear was 44.1 dB nHL. Compared to the referents, the concentrations of TNFα, IL1α, IL8, CTACK, MIP1α, MIP1β, G-CSF, and HGF in the sera of patients with MD were significantly elevated, while those of TRAIL and PDGFBB were significantly decreased. The area under the receiver operating characteristic curve (AUC) showed that G-CSF, MIP1α, and IL8 were above 0.8 and could be used to diagnose MD (p

Background Uncertainty exists regarding the pain scores and the success rate of intraligamentary anesthesia compared to other infiltration anesthesia. Based on the conditions of clinical anesthesia techniques, we conducted a systematic review and meta-analysis to compare the efficacy of intraligamentary anesthesia with other infiltration anesthesia. Methods The search was carried out in PubMed Central, Cochrane Central Register of Controlled Trials, MEDLINE (via OVID), Embase (via OVID), and Scopus from the inception to March 26, 2023. Results Seven eligible randomized controlled trials were included in the meta-analysis. The results indicated no significant difference in the success rate (RR = 0.96; 95% CI [0.81–1.14]; p = 0.65; I2= 73%) and visual analog scale (VAS) during dental procedures (MD = 3.81; 95% CI [−0.54–8.16]; p = 0.09; I2= 97%) between intraligamentary anesthesia and other infiltration anesthesia. However, intraligamentary anesthesia exhibited a higher VAS score during injection than other infiltration anesthesia (MD = 8.83; 95% CI [4.86–12.79]; p

Background: Almost all patients treated with androgen deprivation therapy (ADT) eventually develop castration-resistant prostate cancer (CRPC). Our research aims to elucidate the potential biomarkers and molecular mechanisms that underlie the transformation of primary prostate cancer into CRPC.Methods: We collected three microarray datasets (GSE32269, GSE74367, and GSE66187) from the Gene Expression Omnibus (GEO) database for CRPC. Differentially expressed genes (DEGs) in CRPC were identified for further analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Weighted gene coexpression network analysis (WGCNA) and two machine learning algorithms were employed to identify potential biomarkers for CRPC. The diagnostic efficiency of the selected biomarkers was evaluated based on gene expression level and receiver operating characteristic (ROC) curve analyses. We conducted virtual screening of drugs using AutoDock Vina. In vitro experiments were performed using the Cell Counting Kit-8 (CCK-8) assay to evaluate the inhibitory effects of the drugs on CRPC cell viability. Scratch and transwell invasion assays were employed to assess the effects of the drugs on the migration and invasion abilities of prostate cancer cells.Results: Overall, a total of 719 DEGs, consisting of 513 upregulated and 206 downregulated genes, were identified. The biological functional enrichment analysis indicated that DEGs were mainly enriched in pathways related to the cell cycle and metabolism. CCNA2 and CKS2 were identified as promising biomarkers using a combination of WGCNA, LASSO logistic regression, SVM-RFE, and Venn diagram analyses. These potential biomarkers were further validated and exhibited a strong predictive ability. The results of the virtual screening revealed Aprepitant and Dolutegravir as the optimal targeted drugs for CCNA2 and CKS2, respectively. In vitro experiments demonstrated that both Aprepitant and Dolutegravir exerted significant inhibitory effects on CRPC cells (p < 0.05), with Aprepitant displaying a superior inhibitory effect compared to Dolutegravir.Discussion: The expression of CCNA2 and CKS2 increases with the progression of prostate cancer, which may be one of the driving factors for the progression of prostate cancer and can serve as diagnostic biomarkers and therapeutic targets for CRPC. Additionally, Aprepitant and Dolutegravir show potential as anti-tumor drugs for CRPC.