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Objective: To better understand the clinical phenotype of Ménière's disease (MD), we examined family history, thyroid disorder, migraine, and associated disorders in complaints of people living with MD. Method: We designed the study as a retrospective and examined data gathered from 912 participants with MD. Their data were originally collected by the Finnish Ménière Federation (FMF). The survey data included individual case histories for environmental factors, comorbidities, disease-specific complaints, impact-related questions, cognitive complaints, health-related quality of life (HRQoL), and sense of coherence (SOC). Results: We observed significant differences between those with and without sporadic occurrence, family history, thyroid disorder, and migraine-associated complaints. Family history explained 20% of variability in patient complaints. Patients with a family history of MD whose disease started at younger age experienced balance problems, more severe vertigo spells, more severe vestibular drop attacks (VDA), and less nausea, although they had good SOC. Thyroid disorder explained 14% of variability in patient complaints. MD patients with a thyroid disorder comorbidity suffered more often from constant dizziness, balance problems, greater impact of hearing problems, cognitive complaints, and poor HRQoL. Migraine explained 12% of variability in patients’ complaints and was associated with poor SOC and cognitive balance problems. MD patients with both thyroid disorder and migraine used antidepressants more often than other groups. Logistic regression analysis showed comorbidities of ischemic brain disorder (among 7.1%), kidney insufficiency (among 1.2%), and diabetes (among 7.3%) had statistically significant but restricted association with balance and gait problems, VDA, and reduced HRQoL. Conclusions: Family history of MD and thyroid disorder or migraine comorbidities in MD influence the complaint pattern and partially explain complex symptom profiles, including symptoms of cognitive problems. Confounders play a minimal role in complaint profile and impact of MD whereas comorbidities influence the complaint structure and partly explain the complex symptom profile in MD.

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.

Abstract Aurora-B is a kinase that regulates spindle assembly and kinetochore-microtubule (KT-MT) attachment during mitosis and meiosis. SUMOylation is involved in the oocyte meiosis regulation through promoting spindle assembly and chromosome segregation, but its substrates to support this function is still unknown. It is reported that Aurora-B is SUMOylated in somatic cells, and SUMOylated Aurora-B contributes the process of mitosis. However, whether Aurora-B is SUMOylated in oocytes and how SUMOylation of Aurora-B impacts its function in oocyte meiosis remain poorly understood. In this study, we report that Aurora-B is modified by SUMOylation in mouse oocytes. The results show that Aurora-B colocalized and interacted with SUMO-2/3 in mouse oocytes, confirming that Aurora-B is modified by SUMO-2/3 in this system. Compared with that in young mice, the protein expression of SUMO-2/3 decreased in the oocytes of aged mice, indicating that SUMOylation might be related to mouse aging. Overexpression of Aurora-B SUMOylation site mutants, Aurora-BK207R and Aurora-BK292R, inhibited Aurora-B recruitment and first polar body extrusion, disrupting localization of gamma tubulin, spindle formation and chromosome alignment in oocytes. The results show that it was related to decreased recruitment of p-HDAC6 which induces the high stability of whole spindle microtubules including the microtubules of both correct and wrong KT-MT attachments though increased acetylation of microtubules. Therefore, our results corroborate the notion that Aurora-B activity is regulated by SUMO-2/3 in oocytes, and that SUMOylated Aurora B plays an important role in spindle formation and chromosome alignment.

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: 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.

A novel bifunctional single-sheet electromagnetic surface is proposed in this paper. To alleviate the mutual coupling of the two functions, an equivalent series circuit for linear-to-linear polarization conversion and an equivalent parallel circuit for filtering property are cascaded. Thanks to the combination of different equivalent circuits and the displacement of the resonating parts of two functions, the proposed electromagnetic surface demonstrates filtering and polarization conversion properties in adjacent frequency bands. When the unit cell is periodically arranged to constitute a finite metasurface, more than 6 dB RCS reduction is obtained from 7.7 GHz to 22.8 GHz. The physical mechanism reveals that the low RCS property of the metasurface is in virtue of both scattering field cancellation and transmission. The simple structure, relatively small cell size and good performance of the metasurface suggest it may be a promising candidate as antenna radome. Moreover, the proposed integration method of different functions in one surface makes the design of multifunctional electromagnetic surface easier and faster.

Plant stress responses are important mechanisms that allow plants to adapt and survive in a dynamic and often challenging climatic conditions. In nature, plants encounter a wide range of stressors, including both biotic and abiotic factors, which can negatively impact their growth, development, and overall fitness. Plants therefore need to develop coping mechanisms to these stressors. Key players in these regulatory processes include transcription factors, kinases, and various signalling molecules. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play a pivotal role in plant stress tolerance. MiRNAs are increasingly recognized as key players in orchestrating how plants and other organisms adapt to a multitude of environmental stresses. However, little is still known on the function of miRNAs in plant responses to multiple stresses. This systematic review aimed to provide a comprehensive overview and analysis of the current state of knowledge regarding the role of microRNAs (miRNAs) in plant responses to multiple stresses under the changing environmental. The review paper has synthesized the existing research, highlighted key findings, and offered insights into the significance of miRNAs in enhancing plant resilience to various environmental stressors. It has concluded that the exploration of microRNAs (miRNAs) in the context of enhancing plant resilience to multiple stresses has yielded valuable insights into the intricacies of plant stress responses and the potential applications of these small regulatory molecules in agriculture for improved productivity under different stress conditions.

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 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.

Anxiety disorders are the most common mental illnesses and are often overlooked in primary care settings, with delays in initial treatment and significant impairment on patients' social function and quality of life. In 2023, the U.S. Preventive Services Task Force (USPSTF) published a recommendation statement on adult anxiety disorder screening in JAMA, along with the latest evidence report and systematic review results. The USPSTF suggests screening for anxiety in adults, including pregnant and postpartum women. However, current evidence on the risks and benefits of screening for anxiety in older adults is insufficient to determine the pros and cons of screening. This article combines the USPSTF statement with domestic and international research to provide an overview of several aspects: the current state of adult anxiety disorders domestically and internationally, a summary of the USPSTF recommendation statement, risk factors, early screening tools and their pros and cons, treatment, and the value of the statement for general practice guidance.

Background With the change of disease spectrum and the development of modern medical model, traditional Chinese medicine (TCM) is playing an important role in disease prevention, health care and rehabilitation. It is necessary to further promote the development of prevention of disease in TCM and vigorously promote the unique role of TCM in maintaining and promoting people's health. However, popularization and education of the concept of prevention of disease in TCM among community residents remains unclear. Objective To understand the overall awareness, trust, and adoption behavior of prevention of disease in TCM of community residents in Guangzhou, and explore the influencing factors of community residents' trust in prevention of disease in TCM services. Methods From April to August 2022, a stratified cluster sampling method was used to interview 652 community residents from 12 streets in 4 administrative regions of Guangzhou city based on geographic location (central city, urban-rural areas, and suburbs) and economic factors by questionnaires. The survey included residents' basic information, awareness and access to knowledge of prevention of disease in TCM, as well as their demand, utilization and trust in it. The influencing factors of community residents' trust in prevention of disease in TCM services were explored by binary Logistic regression analysis. Results Among the 652 community residents, 67.79% (442/652) were aware of prevention of disease in TCM, 77.91% (508/652) trusted prevention of disease in TCM services, 69.63% (454/652) had received traditional TCM physiotherapy, and only 6.59% (43/652) had received prevention of disease in TCM services more than 4 times in the past year. Univariate correlation analysis showed that age (χ2=9.218), household type (χ2=19.356), marriage status (χ2=2.490), occupation (χ2=17.889), and medical insurance payment type (χ2=13.516) were influencing factors of residents' trust in prevention of disease in TCM services. Binary Logistic regression analysis showed that household type (non-agricultural, agricultural to resident, and non-agricultural to resident) was an influential factor for community residents' trust in prevention of disease in TCM services (OR=2.646, 5.593, 10.502) . Conclusion The overall awareness (67.79%) and trust (77.91%) of prevention of disease in TCM among community residents in Guangzhou are relatively high, but the actual number of services received is insufficient, with a phenomenon of knowledge-attitude-practice separation. Community residents with non-agricultural household type have a higher level of trust, while those with agricultural household type have a lower level of trust. During popularization and services of prevention of disease in TCM, it is necessary to fully utilize the residents' preferred forms, as well as to target specific groups, so as to cultivate the health habits of prevention of disease in community residents.

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 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.

Osmanthus fragrans is an ethylene-sensitive flower, and flower senescence was mediated by ethylene-responsive transcription factors (OfERFs). A total of 227 OfERFs were identified from O. fragrans, which were classified into five subfamilies: AP2 (35), DREB (57), ERF (125), RAV (6), and Soloist (4). Gene composition and structural analysis indicate that members of different subfamilies have different gene structures and conserved domains. Their gene promoter contains various functional responsive elements, including auxin, jasmonic acid, and other responsive elements. Among them, 124 OfAP2/ERF genes have expressed at any stage of flowering, and 10 of them may play roles in flowering or senescence. By comparative transcriptome analysis, OfAP2/ERFs affected by ethephon (ETH) and 5′-azacytidine (Aza) treatment were divided into three categories, which have various target gene sets. Importantly, these target gene sets participate in similar or different biological processes and metabolic pathways, suggesting that ethylene and DNA hypomethylation have crosstalk and a unique mechanism in regulating the flower senescence of O. fragrans. Co-expression analysis revealed that several key OfAP2/ERFs played a central role in organic acid metabolism and biosynthesis of branched-chain amino acids (BcAAs), among which OfERF017 was selected for further functional analysis. Overexpression of OfERF017 leads to significant enrichment of genes in organic acid metabolism pathways, which leads to a decrease in organic acid levels and promoting the flower senescence of O. fragrans. Together, these results give insights into the characteristics and functional analysis of OfAP2/ERF genes in O. fragrans.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon compound that is generated during combustion processes, and is present in various substances such as foods, tobacco smoke, and burning emissions. BaP is extensively acknowledged as a highly carcinogenic substance to induce multiple forms of cancer, such as lung cancer, skin cancer, and stomach cancer. Recently it is shown to adversely affect the reproductive system. Nevertheless, the potential toxicity of BaP on oocyte quality remains unclear. In this study, we established a BaP exposure model via mouse oral gavage and found that BaP exposure resulted in a notable decrease in the ovarian weight, number of GV oocytes in ovarian, and oocyte maturation competence. BaP exposure caused ribosomal dysfunction, characterized by a decrease in the expression of RPS3 and HPG in oocytes. BaP exposure also caused abnormal distribution of the endoplasmic reticulum (ER) and induced ER stress, as indicated by increased expression of GRP78. Besides, the Golgi apparatus exhibited an abnormal localization pattern, which was confirmed by the GM130 localization. Disruption of vesicle transport processes was observed by the abnormal expression and localization of Rab10. Additionally, an enhanced lysosome and LC3 fluorescence intensity indicated the occurrence of protein degradation in oocytes. In summary, our results suggested that BaP exposure disrupted the distribution and functioning of organelles, consequently affecting the developmental competence of mouse oocytes.

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.

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.

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.

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

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.

BackgroundOutside of pregnancy, intuitive eating (IE) is associated with lower body weight, blood glucose, and higher positive mood. However, little was known about the relationship between IE and anxiety-depression in the GDM population. Thus, this study aimed to investigate the association of IE with anxiety and depression, pregnancy weight and pregnancy blood glucose in the first and second GDM visit.MethodsData from 310 pregnant women with GDM from the Fujian Maternal and Child Health Hospital Trial (Approval Number: 2020Y9133) were analyzed. IE was assessed using the Intuitive Eating Scale-2 subscales of Eating for Physiological Reasons rather than Emotional Reasons (EPR), Relying on Hunger and Satiety Cues (RHSC) and Body-Food Choice Consistency (B-FCC). Observations included weight, body mass index (BMI), fasting plasma glucose (FPG) and 2-h postprandial blood glucose; the Hospital Anxiety and Depression Scale (HADS) was used to assess the level of anxiety and depression in pregnant women with GDM. Linear regression analysis was used to assess the correlation between IE and anxiety, depression, pregnancy blood glucose and weight.ResultsThe cross-sectional analysis showed that the EPR eating behavior was negatively correlated with anxiety and depression, and the B-FCC eating behavior was negatively correlated with depression at both the first and second GDM visit; in addition, the B-FCC eating behavior was associated with lower BMI in the third trimester (all p

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.

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.

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.

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.

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.

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.

Perinatal mental disorders are one of the most common disorders during pregnancy and may lead to adverse maternal and offspring outcomes. There is an increasing number of women currently at risk for emotional problems such as anxiety and depression during pregnancy and childbirth, and women with previous mental disorders are also at risk of relapse during pregnancy. At the same time, the lack of clinical guidelines for the diagnosis and treatment of perinatal mental disorders has made the work of clinicians even more challenging. The expert writing group integrated the latest medical evidence and clinical practice in related fields at home and abroad to form the expert consensus, consisting of the epidemiology and pathogenesis, clinical manifestations, clinical evaluation, diagnosis, treatment and management of perinatal mental disorders, which can provide reference and guidance for practical clinical work. The consensus advocates comprehensive, whole-process, hierarchical, multidisciplinary and collaborative diagnosis and treatment, to help frontline clinicians screen, rationally assess and clinically diagnose perinatal pregnant women as soon as possible, as well as provide necessary psychological interventions and clinical medication for them.

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.

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.

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.

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.

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.

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.

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 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.

Abstract ADP‐ribosylation factor 1 (Arf1) is a small GTPase belonging to the Arf family. As a molecular switch, Arf1 is found to regulate retrograde and intra‐Golgi transport, plasma membrane signaling, and organelle function during mitosis. This study aimed to explore the noncanonical roles of Arf1 in cell cycle regulation and cytoskeleton dynamics in meiosis with a mouse oocyte model. Arf1 accumulated in microtubules during oocyte meiosis, and the depletion of Arf1 led to the failure of polar body extrusion. Unlike mitosis, it finds that Arf1 affected Myt1 activity for cyclin B1/CDK1‐based G2/M transition, which disturbed oocyte meiotic resumption. Besides, Arf1 modulated GM130 for the dynamic changes in the Golgi apparatus and Rab35‐based vesicle transport during meiosis. Moreover, Arf1 is associated with Ran GTPase for TPX2 expression, further regulating the Aurora A–polo‐like kinase 1 pathway for meiotic spindle assembly and microtubule stability in oocytes. Further, exogenous Arf1 mRNA supplementation can significantly rescue these defects. In conclusion, results reported the noncanonical functions of Arf1 in G2/M transition and meiotic spindle organization in mouse oocytes.