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Objective: To (1) determine how intended users interact with and use the BD Odon Device in simulation, (2) use these findings to alter progressively the design of the BD Odon Device and (3) validate that these changes have improved the ability of practitioners to use the BD Odon Device.Design: Human factors evaluation study.Setting: Simulation suite designed to mimic delivery room.Population or Sample: Three hundred and ninety simulated operative births, performed by 100 practising clinicians.Methods: Simulated operative vaginal births performed using the BD Odon Device and the device Instructions for use were subjected to three formative human factors evaluations and one human factors validation test. Following each evaluation, findings were reviewed and the design of the BD Odon Device and Instructions for use were modified.Main Outcome Measures: Successful performance of an operative vaginal birth using the BD Odon Device in accordance with provided training and Instructions for use.Results: Using version two of the BD Odon Device, and following exposure to face-to-face training and written instructions, 25% of accouchers were able successfully to perform a simulated operative vaginal birth. In the final evaluation, following device design and training material alterations, all accouchers were able successfully to perform a simulated operative vaginal birth using version four of the BD Odon Device.Conclusions: Human factors evaluations have enabled a multi-professional device and training materials design team to alter the design of the BD Odon Device and the Instructions for use in an evidence-based fashion. This process has resulted in a device which has a predictable and likely safe pattern of use.Tweetable Abstract: Human Factors evaluations help make the BD Odon Device safe and usable for clinical practice. [ABSTRACT FROM AUTHOR]

It is known that apolipoprotein E (ApoE) is essential for normal lipid metabolism. ApoE is the major apolipoprotein in the central nervous system and plays a key role in neurobiology by mediating the transport of cholesterol, phospholipids, and sulfatides. We therefore examined APOE epsilon2, epsilon3, and epsilon4 knock-in mice, using electrospray ionization mass spectrometry to determine if APOE genotype or age leads to altered levels in the brain of a number of glycerophospholipids (phosphatidylinositol, PI; phosphatidylethanolamine, PE; phosphatidic acid, PA, phosphatidylserine, PS; phosphatidylcholine, PC), sphingolipids (sphingomyelin, SM; ceramide, Cer), cholesterol, and triacylglycerols. We observed slight changes within individual PI, PE, PC, Cer, and SM lipid levels in APOE epsilon2 and epsilon4 mice compared to APOE epsilon3 mice. However, overall, we did not observe any major effects in APOE epsilon4 knock-in mice for the levels of the glycerophospholipids measured, as compared to APOE epsilon2 and epsilon3 mice. Our findings indicate that variations in ApoE isoforms do not per se affect bulk lipid homeostasis in the brain. These findings indicate that APOE epsilon4 is not associated with disturbances in brain sterol or sphingolipids in the absence of environmental factors. [ABSTRACT FROM AUTHOR]

The pursuit of translational biomarkers is complex due to the heterogeneous human pathophysiology, but critical for disease diagnosis, prognosis, monitoring therapeutic efficacy, and for patient stratification. In HIV-associated neurocognitive impairment (NCI), biomarkers that delineate the trajectory of neuropathogenesis and neurocognitive sequelae are critical, particularly considering confounders such as substance use, including Methamphetamine (METH). METH use is a significant health concern among persons living with HIV (PWH), aggravating cognitive deficits and neuroinflammation despite of antiretrovirals, introducing elements in the microenvironment that are fundamentally differerent in relation to non-METH users, such as high levels of dopamine (DA) affecting HIV-innate immune targets. Yet, current biomarkers do not detect these differences. We hypothesized that predefined DA-induced signatures detectable in peripheral blood leukocytes, can distinguish HIV+ METH users compared to HIV-negative or PWH that are non METH users. The elevated expression of CD8A, CREBBP, CCL5, and combinations of dopaminergic pathway transcripts clustered METH users with detectable CSF viral load and major depressive disorder (MDD), indicating neuroimmune-mechanistic links. Cathecol-o-methyltransferase (COMT) gene polymorphisms affecting DA metabolism improved the identification of PWH using METH with biomarkers. The results indicate that underlying immunedopaminergic mechanisms provide signatures and genotypes that can identify PWH that are METH users and their attributes., Competing Interests: The authors of the manuscript “Identifying Methamphetamine Use Predictors in HIV Infection: Immune-Dopaminergic Signatures in Peripheral Leukocytes and the Role of COMT Genotype” have no conflicts of interest to declare., (© 2024 The Authors.)

Parkinson's disease (PD) is a common motor neurodegenerative disease that still lacks effective therapeutic options. Previous studies have reported that lactoferrin exhibited neuroprotective effects in cellular and animal models of PD, typically induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP + ) synthetic toxin. However, the neuroprotective capacity of lactoferrin in the rotenone-induced cellular model of PD remains relatively less established. Unlike MPTP/MPP + , rotenone is a naturally occurring environmental toxin known to induce chronic toxicity and increase the risk of PD in humans. In this study, we constructed a cellular model of PD by differentiating SH-SY5Y neuroblastoma cells with retinoic acid into mature dopaminergic neurons with increased β-tubulin III and tyrosine hydroxylase expression, followed by 24 h of rotenone exposure. Using this cellular model of PD, we showed that lactoferrin (1-10 µg/ml) pre-treatment for 48 h decreased loss of cell viability, mitochondrial membrane potential impairment, reactive oxygen species generation and pro-apoptotic activities (pan-caspase activation and nuclear condensation) in cells exposed to rotenone (1 and 5 µM) using biochemical assays, Hoechst 33342 staining and immunocytochemical techniques. We further demonstrated that 48 h of lactoferrin (10 µg/ml) pre-treatment decreased Bax:Bcl2 ratio and p42/44 mitogen-activated protein kinase expression but increased pAkt expression in 5 µM rotenone-exposed cells. Our study demonstrates that lactoferrin neuroprotective capacity is present in the rotenone-induced cellular model of PD, further supporting lactoferrin as a potential PD therapeutic that warrants further studies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study investigated osteoporosis risk factors among older Asian men with type-2 diabetes mellitus, hypertension, or hyperlipidaemia in primary care. Advanced age, dementia, depression, and polypharmacy were associated with higher risks for osteoporosis. Screening strategies targeting these factors are crucial for improving bone health as part of comprehensive preventive care., Purpose: Asian patients with type-2 diabetes mellitus (T2DM), hypertension, or hyperlipidaemia (DHL) are predominantly managed in primary care. They are also at risk of osteoporosis, but men are often under-screened and under-treated for this preventable bone disorder. This study aimed to identify the clinical characteristics and risk factors of osteoporosis among older men with DHL in primary care for early intervention., Methods: This retrospective study included men aged 65 years and older managed in public primary care clinics for their DHL between 1st July 2017 and 30th June 2018. Demographic, clinical, laboratory, and imaging data were extracted from their electronic medical records based on their International Classification of Diseases-10 (ICD-10) diagnosis codes. Descriptive statistical analyses, with statistical significance set at p < 0.05, were conducted, followed by generalized estimating equation (GEE) modelling., Results: Medical records of 17,644 men (83.1% Chinese, 16.9% minority ethnic groups, median age 71 years) were analysed. 2.3% of them had diagnosis of osteoporosis, 0.15% had fragility fracture, and 26.0% of those diagnosed with osteoporosis were treated with bisphosphonates. Their mean HbA1c was 6.9%; mean systolic and diastolic blood pressure were 133 and 69 mmHg. The GEE model showed that age (OR = 1.07, 95%CI = 1.05-1.09, p < 0.001), dementia (OR = 2.24, 95%CI = 1.33-3.77, p = 0.002), depression (OR = 2.38, 95%CI = 1.03-5.50, p = 0.043), and polypharmacy (OR = 6.85, 95%CI = 3.07-15.26, p < 0.001) were significantly associated with higher risks for osteoporosis., Conclusion: Age, dementia, depression, and polypharmacy are associated with osteoporosis risks in men with DHL. Strategies to incorporate osteoporosis screening among older men with these risk factors are needed to improve their bone health., (© 2024. The Author(s).)

Pain on the dorsal side of the wrist is a common clinical presentation, comparable to pain experienced on the ulnar and radial aspects of the wrist. The dorsal wrist region has distinct anatomical features and is associated with a wide spectrum of pathologies, including conditions affecting the bones, cartilage, ligaments, and tendons. Accurate diagnosis often depends on imaging techniques such as radiographs and ultrasound, with a growing trend towards the use of magnetic resonance imaging (MRI) for more detailed assessment of complex cases. The role of imaging in diagnosing dorsal wrist pain is expected to expand further in the future. To the best of our knowledge, there has not been a comprehensive review paper that specifically addresses the imaging findings related to dorsal wrist pain. This review aims to fill that gap by discussing the imaging characteristics of both common and uncommon pathologies that can cause dorsal wrist pain. It provides an overview of the most appropriate imaging modalities to evaluate various causes of dorsal wrist pain, highlights key imaging findings, and discusses differential diagnoses. By doing so, this review seeks to enhance the understanding and interpretation of imaging results, ultimately aiding in the accurate diagnosis and management of dorsal wrist pain. This comprehensive approach underscores the critical role of advanced imaging in contemporary clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-420/coif). J.F.G. serves as an unpaid editorial board member of Quantitative Imaging in Medicine and Surgery. The other authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4 + T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-β) plus IL-4 activates pSmad3-Ser 213 and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-β-activated kinase 1 (TAK1) and nuclear factor κB (NF-κB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Glycogen storage, conversion and utilization in astrocytes play an important role in brain energy metabolism. The conversion of glycogen to lactate through glycolysis occurs through the coordinated activities of various enzymes and inhibition of this process can impair different brain processes including formation of long-lasting memories. To replenish depleted glycogen stores, astrocytes undergo glycogen synthesis, a cellular process that has been shown to require transcription and translation during specific stimulation paradigms. However, the detail nuclear signaling mechanisms and transcriptional regulation during glycogen synthesis in astrocytes remains to be explored. In this report, we study the molecular mechanisms of vasoactive intestinal peptide (VIP)-induced glycogen synthesis in astrocytes. VIP is a potent neuropeptide that triggers glycogenolysis followed by glycogen synthesis in astrocytes. We show evidence that VIP-induced glycogen synthesis requires CREB-mediated transcription that is calcium dependent and requires conventional Protein Kinase C but not Protein Kinase A. In parallel to CREB activation, we demonstrate that VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei. Transcriptome profiles of VIP-induced astrocytes identified robust CREB transcription, including a subset of genes linked to glucose and glycogen metabolism. Finally, we demonstrate that VIP-induced glycogen synthesis shares similar as well as distinct molecular signatures with glucose-induced glycogen synthesis, including the requirement of CREB-mediated transcription. Overall, our data demonstrates the importance of CREB-mediated transcription in astrocytes during stimulus-driven glycogenesis., (© 2024. The Author(s).)

Many tissue-specific adult stem cell lineages maintain a balance between proliferation and differentiation. Here, we study how the H3K4me3 methyltransferase Set1 regulates early-stage male germ cells in Drosophila. Early-stage germline-specific knockdown of Set1 results in temporally progressive defects, arising as germ cell loss and developing into overpopulated early-stage germ cells. These germline defects also impact the niche architecture and cyst stem cell lineage non-cell-autonomously. Additionally, wild-type Set1, but not the catalytically inactive Set1, rescues the Set1 knockdown phenotypes, highlighting the functional importance of the methyltransferase activity of Set1. Further, RNA-sequencing experiments reveal key signaling pathway components, such as the JAK-STAT pathway gene Stat92E and the BMP pathway gene Mad, which are upregulated upon Set1 knockdown. Genetic interaction assays support the functional relationships between Set1 and JAK-STAT or BMP pathways, as both Stat92E and Mad mutations suppress the Set1 knockdown phenotypes. These findings enhance our understanding of the balance between proliferation and differentiation in an adult stem cell lineage. The phenotype of germ cell loss followed by over-proliferation when inhibiting a histone methyltransferase also raises concerns about using their inhibitors in cancer therapy., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Background/Objectives : This study determined the effects of 60 min or 30 min Pilates program on cervicothoracic alignment, muscular strength, and endurance in university students with upper-crossed syndrome (UCS). Methods : Twenty-six university students with UCS were randomly allocated into 60 min Pilates (60 PG, n = 9), 30 min Pilates (30 PG, n = 9), and control (CG, n = 8) groups. The 60 and 30 PG students participated in the Pilates program, focusing on relaxation, stability, mobility, and strengthening of the cervical, thoracic, and scapular muscles for 60 or 30 min per session, twice a week, for 12 weeks. Cervicothoracic alignment was measured using BodyStyle to determine craniovertebral angle (CVA), forward shoulder angle (FSA), head position angle (HPA), head tilt angle (HTA), and kyphosis angle (KA). We measured the muscular strength and endurance of the shoulder on the dominant side. Results : After the intervention, CVA, HPA, HTA, and KA significantly improved in the 60 and 30 PG (all p < 0.01) but not in the CG ( p > 0.05). There were no significant differences between the 60 and 30 PG at 4, 8, and 12 weeks. Shoulder strength differed between shoulder flexion and horizontal abduction ( p < 0.01). Shoulder endurance differed between extension, flexion, and horizontal abduction ( p < 0.05, p < 0.01, and p < 0.001, respectively). Conclusions : This study confirmed the effectiveness of the Pilates program in improving cervicothoracic sagittal alignment and shoulder muscular function in university students with UCS. Additionally, the effects of participating in 60 and 30 min Pilates programs were found to be equivalent. Therefore, encouraging busy university students to participate in at least 30 min of the Pilates program is important.

Halophilic bacteria are extremophiles that thrive in saline environment. Their ability to withstand such harsh conditions makes them an ideal choice for industrial applications such as lignocellulosic biomass degradation. In this study, a halophilic bacterium with the ability to produce extracellular cellulases and hemicellulases, designated as Nesterenkonia sp. CL21, was isolated from mangrove sediment in Tanjung Piai National Park, Malaysia. Thus far, studies on lignocellulolytic enzymes concerning bacterial species under this genus are limited. To gain a comprehensive understanding of its lignocellulose-degrading potential, the whole genome was sequenced using the Illumina NovaSeq 6000 platform. The genome of strain CL21 was assembled into 25 contigs with 3,744,449 bp and a 69.74% GC content and was predicted to contain 3,348 coding genes. Based on taxonomy analysis, strain CL21 shares 73.8 to 82.0% average nucleotide identity with its neighbouring species, below the 95% threshold, indicating its possible status as a distinct species in Nesterenkonia genus. Through in-depth genomic mining, a total of 81 carbohydrate-active enzymes were encoded. Among these, 24 encoded genes were identified to encompass diverse cellulases (GH3), xylanases (GH10, GH11, GH43, GH51, GH127 and CE4), mannanases (GH38 and GH106) and pectinases (PL1, PL9, and PL11). The production of lignocellulolytic enzymes was tested in the presence of several substrates. This study revealed that strain CL21 can produce a diverse array of enzymes which are active at different time points. By combining experimental data with genomic information, the ability of strain CL21 to produce lignocellulolytic enzymes has been elucidated, with potential applications in biorefinery industry., (© 2024. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

The mammalian SWI/SNF-like BAF complexes play critical roles during animal development and pathological conditions. Previous gene deletion studies and characterization of human gene mutations implicate that the complexes both repress and activate a large number of genes. However, the direct function of the complexes in cells remains largely unclear due to the relatively long-term nature of gene deletion or natural mutation. Here we generate a mouse line by knocking in the auxin-inducible degron tag (AID) to the Smarca4 gene, which encodes BRG1, the essential ATPase subunit of the BAF complexes. We show that the tagged BRG1 can be efficiently depleted by osTIR1 expression and auxin treatment for 6 to 10 h in CD4 + T cells, hepatocytes, and fibroblasts isolated from the knock-in mice. The acute depletion of BRG1 leads to decreases in nascent RNAs and RNA polymerase II binding at a large number of genes, which are positively correlated with the loss of BRG1. Further, these changes are correlated with diminished accessibility at DNase I Hypersensitive Sites (DHSs) and p300 binding. The acute BRG1 depletion results in three major patterns of nucleosome shifts leading to narrower nucleosome spacing surrounding transcription factor motifs and at enhancers and transcription start sites (TSSs), which are correlated with loss of BRG1, decreased chromatin accessibility and decreased nascent RNAs. Acute depletion of BRG1 severely compromises the Trichostatin A (TSA) -induced histone acetylation, suggesting a substantial interplay between the chromatin remodeling activity of BRG1 and histone acetylation. Our data suggest BRG1 mainly plays a direct positive role in chromatin accessibility, RNAPII binding, and nascent RNA production by regulating nucleosome positioning and facilitating transcription factor binding to their target sites., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) pose significant burdens on individuals and society, necessitating accurate prediction methods. Machine learning (ML) algorithms utilizing electronic health records and survey data offer promising tools for forecasting these conditions. However, potential bias and inaccuracies inherent in subjective survey responses can undermine the precision of such predictions. This research investigates the reliability of five prominent ML algorithms-a Convolutional Neural Network (CNN), Random Forest, XGBoost, Logistic Regression, and Naive Bayes-in predicting MDD and GAD. A dataset rich in biomedical, demographic, and self-reported survey information is used to assess the algorithms' performance under different levels of subjective response inaccuracies. These inaccuracies simulate scenarios with potential memory recall bias and subjective interpretations. While all algorithms demonstrate commendable accuracy with high-quality survey data, their performance diverges significantly when encountering erroneous or biased responses. Notably, the CNN exhibits superior resilience in this context, maintaining performance and even achieving enhanced accuracy, Cohen's kappa score, and positive precision for both MDD and GAD. This highlights the CNN's superior ability to handle data unreliability, making it a potentially advantageous choice for predicting mental health conditions based on self-reported data. These findings underscore the critical importance of algorithmic resilience in mental health prediction, particularly when relying on subjective data. They emphasize the need for careful algorithm selection in such contexts, with the CNN emerging as a promising candidate due to its robustness and improved performance under data uncertainties.

Introduction: Self-efficacy in individuals optimizes their hypertension management. Electronic patient portals are being increasingly used to support chronic disease management, as they raise the health literacy of patients and enable them in self-management. However, the association between the use of patient portals and self-efficacy in hypertension management remains unclear. The study aimed to determine the association between self-efficacy among patients with hypertension who are managed in primary care and their demographic characteristics and usage patterns of patient portals., Method: A cross-sectional survey was conducted at a public primary care clinic in urban Singapore. Multi-ethnic adult patients with hypertension were invited to participate in a self-administered electronic questionnaire. Chi-square test was performed for bivariate analysis; adjusted logistic regression models were used for factors with P value <.1., Results: A total of 310 patients (66.8% Chinese, 55.5% males, mean age of 63.1 years) completed the survey. Patient portal users had higher self-efficacy scores than non-users (mean score=63 vs 60, maximum = 80, P  = .011). The factors associated with increased patient portal access included younger age <65 years (absolute odds ratio [AOR] = 2.634, 95%CI = 1.432-4.847; P  = .002), monthly income >$5000 (AOR = 2.324, 95%CI = 1.104-4.892; P  = .026), and post-secondary education level (AOR = 3.128, 95%CI = 1.675-5.839; P  < .001). Most patients (93.1%) used the portal to check medical appointments but only1.3% of them used it to record home blood pressure measurements (HBPM)., Conclusions: Patient portal usage was associated with higher self-efficacy scores in patients with hypertension. These users were younger, more educated, and earned more than the non-users, but only 1.3% of them used it for HBPM documentation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background & Objectives: Despite much clinical and laboratory research that has been performed to explore the mechanisms of Parkinson's disease (PD), its pathogenesis remains elusive to date. Therefore, this study aimed to identify possible regulators of neurodegeneration by performing microarray analysis of the zebrafish PD model's brain following rotenone exposure., Methods: A total of 36 adult zebrafish were divided into two groups: control (n = 17) and rotenonetreated (n = 19). Fish were treated with rotenone water (5 μg/L water) for 28 days and subjected to locomotor behavior analysis. Total RNA was extracted from the brain tissue after rotenone treatment. The cDNA synthesized was subjected to microarray analysis and subsequently validated by qPCR., Results: Administration of rotenone has significantly reduced locomotor activity in zebrafish (p < 0.05), dysregulated dopamine-related gene expression ( dat, th1 , and th2, p < 0.001), and reduced dopamine level in the brain (p < 0.001). In the rotenone-treated group, genes involved in cytotoxic T lymphocytes ( gzm3, cd8a, p < 0.001) and T cell receptor signaling ( themis, lck, p < 0.001) were upregulated significantly. Additionally, gene expression involved in microgliosis regulation ( tyrobp, p < 0.001), cellular response to IL-1 ( ccl34b4, il2rb, p < 0.05), and regulation of apoptotic process ( dedd1, p < 0.001) were also upregulated significantly., Conclusion: The mechanisms of T cell receptor signaling, microgliosis regulation, cellular response to IL-1, and apoptotic signaling pathways have potentially contributed to PD development in rotenonetreated zebrafish., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neomicrocalamus and Temochloa are closely related to bamboo genera. However, when considered with newly discovered and morphologically similar material from China and Vietnam, the phylogenetic relationship among these three groups was ambiguous in the analyses based on DNA regions. Here, as a means of investigating the relationships among the three bamboo groups and exploring potential sources of genomic conflicts, we present a phylogenomic examination based on the whole plastome, single-nucleotide polymorphism (SNP), and single-copy nuclear (SCN) gene datasets. Three different phylogenetic hypotheses were found. The inconsistency is attributed to the combination of incomplete lineage sorting and introgression. The origin of newly discovered bamboos is from introgressive hybridization between Temochloa liliana (which contributed 80.7% of the genome) and Neomicrocalamus prainii (19.3%), indicating that the newly discovered bamboos are closer to T. liliana in genetics. The more similar morphology and closer distribution elevation also imply a closer relationship between Temochloa and newly discovered bamboos., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cai, Niu, Zhang, Tong, Vu, Goh, Sungkaew, Teerawatananon and Xia.)

Background: Total wrist replacement (TWR) is rarely done in the Asia-Pacific region. The aim of this study is to report the surgical outcomes and experience of TWR in patients with advanced arthritis. Methods: This is a retrospective review of all TWR patients in the Department of Orthopaedics and Traumatology, Prince of Wales Hospital, Hong Kong, which is a university tertiary centre, from January 2004 to March 2023. Recorded demographic parameters include gender, age upon surgery, pathology, types of implants and follow-up period. The surgical outcome parameters include range of motion, grip strength, wrist function assessment, radiological and clinical complications and any related secondary operations. Postoperative X-ray and clinical notes were reviewed. All wrist function assessments were performed by specialised occupational therapists according to protocol. Results: The study included a total of 12 wrists of 10 patients, all Chinese-Asian, with a mean age of 61.4 years at surgery. Larsen grade V arthritis constituted 50% and grade IV 16.7% of the patients, amongst which 33% had volar subluxation. The mean follow-up period was 97.4 months (21-205 months). The mean grip strength was 64.2% of the unaffected side. The mean postoperative Disabilities of Arm, Shoulder and Hand (DASH) score was 41.12% and patient-rated wrist/hand evaluation (PRWE) score 18.0. Complication incidence was 16.67% for loosening, 8.3% for metallosis and 8.3% for infection. One patient required conversion to total wrist arthrodesis due to metallosis. No patient suffered from dislocation, periprosthetic fracture and infection. Conclusions: TWR is an effective and safe alternative to total wrist arthrodesis with comparable outcomes. Our series outcomes are satisfactory and in line with literature. With meticulous soft tissue release and balancing, volar subluxation can also be corrected and may not be a contraindication. Level of Evidence: Level IV (Therapeutic).

Fractionation behaviors of Cu and Zn isotopes have been increasingly studied at the field scale, but those in various redox conditions of groundwater contaminated with petroleum and treated by oxidation have not been assessed. In this study, δ 65 Cu and δ 66 Zn as well as δ 34 S SO4 and Δδ 18 O SO4-H2O were assessed in wells undergoing contamination by total petroleum hydrocarbons (TPH) and oxidation using H 2 O 2 in 2021 and 2022. High δ 34 S SO4 and relevant parameters (e.g., dissolved sulfide and HCO 3 - ) indicated the occurrence of sulfate reduction. The plot of δ 65 Cu versus δ 34 S SO4 effectively indicated precipitation of Cu sulfides and their reoxidation at oxidation wells. Although the plot of δ 66 Zn versus δ 34 S SO4 could also indicate reoxidation of Zn sulfides, the Zn isotopic fingerprint of sulfide precipitation may have been masked by fractionation by sorption. The advantage of using δ 65 Cu in the redox reactions resulted from the wider range of δ 65 Cu owing to the redox behavior of Cu. The plot combining isotopic fractionations of Cu and S can assist in assessing sulfide precipitation and oxidative treatment in TPH-contaminated groundwater., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The advancements in microscopic techniques have stimulated great interest in the muscular and neural architectures of invertebrates, specifically using muscle and neural structures to infer phylogenetic relationships. Here, we provide the data on the development of the muscular and nervous systems during the larval development of stalked barnacle, Octolasmis angulata using the phalloidin F-actin and immunohistochemical labelling (e.g. acetylated α-tubulin and serotonin) and confocal laser scanning microscopy analysis. All naupliar stages shared the same muscle and neural architectures with only the discrepancy in size. The nauplii have a complex muscle arrangement in their feeding apparatus and naupliar appendages. Most naupliar muscles undergo histolyse during the cyprid metamorphosis. The cyprid muscles form beneath the head shield at the end of nauplius VI. The naupliar and cyprid central nervous systems exhibit the typical tripartite brain comprising the protocerebrum, deutocerebrum and tritocerebrum. The serotonin-like immunoreactivity is mainly found in the naupliar brain, mandibular ganglia, cyprid brain and posterior ganglia. Our study revealed that numerous muscle and neural architectures in the naupliar and cyprids have phylogenetic significance, but future studies on the myoanatomy and neuroanatomy of other barnacle species are necessary to determine the homology of these structures., Competing Interests: Declaration of competing interest The authors declare no competing financial interests or personal relationships., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Malaysia is home to a number of hot springs that are rich in microbial diversity including the photosynthetic cyanobacteria. Although this microbial community has been characterised based on metagenomics approach, the culturable thermophilic isolates have not been isolated and characterised extensively. Compared to the mesophiles, information on plant growth promoting (PGP) properties of these thermophiles remain largely untapped. As the amount of arable land for microbial bioprospecting is decreasing due to extensive human activities, the search for alternative source for microbial strains with PGP properties is important for the development of potential biofertilisers. This study sought to isolate and characterise culturable cyanobacteria strains from two local hot springs - Sungai Klah (SK) and Lubuk Timah (LT) located in Perak using morphological and molecular methods. The IAA production from the axenic cultures were measured. The PGP properties were also measured by priming the rice seeds with cyanobacterial water extracts. A total of six strains were isolated from both hot springs. Strains LTM and LTW from LT were identified as Leptolyngbya sp. whereas strains SEM, SEH, STH and STM were identified as Thermosynechococcus elongatus . All six strains produced IAA ranged from 670.10 pg/μL to 2010 pg/μL. The water extracts were found to increase the seed amylase activity of the rice seeds from 5th day of germination (DAG) to 10th DAG. In general, the IAA production and increased seed amylase activity might have contributed in enhancing the longest root length, shoot length and root-to-shoot (RS) ratio. To conclude, the thermophilic cyanobacteria from hot springs can be further exploited as a novel source of PGP microbes for the development of biofertilsers., (© Penerbit Universiti Sains Malaysia, 2023.)

Hand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC (45.5% similarity), DE, EF, GH and HI loops, VP2 EF loop and VP3 GH loop (91.3% similarity) were substituted with corresponding CV-A16 loops. Only ChiE71-1-BC, ChiE71-1-EF, ChiE71-1-GH and ChiE71-3-GH were viable. EV-A71 and CV-A16 antiserum neutralized ChiE71-1-BC and ChiE71-1-EF. Mice immunized with inactivated ChiE71 elicited high IgG, IFN-γ, IL-2, IL-4 and IL-10. Neonatal mice receiving passive transfer of WT EV-A71, ChiE71-1-EF and ChiE71-1-BC immune sera had 100%, 80.0% and no survival, respectively, against lethal challenges with EV-A71, suggesting that the substituted CV-A16 loops disrupted EV-A71 immunogenicity. Passive transfer of CV-A16, ChiE71-1-EF and ChiE71-1-BC immune sera provided 40.0%, 20.0% and 42.9% survival, respectively, against CV-A16. One-day-old neonatal mice immunized with WT EV-A71, ChiE71-1-BC, ChiE71-1-EF and CV-A16 achieved 62.5%, 60.0%, 57.1%, and no survival, respectively, after the EV-A71 challenge. Active immunization using CV-A16 provided full protection while WT EV-A71, ChiE71-1-BC and ChiE71-1-EF immunization showed partial cross-protection in CV-A16 lethal challenge with survival rates of 50.0%, 20.0% and 40%, respectively. Disruption of a capsid loop could affect virus immunogenicity, and future vaccine design should include conservation of the enterovirus capsid loops.

The local signaling mechanism which directly assembles and maintains glutamatergic synapses has not been well understood. Glutamatergic synapses are made of presynaptic and postsynaptic compartments with distinct sets of proteins. The planar cell polarity (PCP) pathway is highly conserved and responsible for establishing and maintaining the cell and tissue polarity along the tissue plane. The six core PCP proteins form antagonizing complexes within the cells and asymmetric intercellular complexes across neighboring cells which regulate cell-cell interactions during planar polarity signaling. Accumulating evidence suggests that the PCP proteins play essential roles in glutamatergic synapse assembly, maintenance and function in the brain. This review summarizes the key evidence that PCP proteins may be responsible for the formation and stability of the vast majority of the glutamatergic synapses in hippocampus and medial prefrontal cortex, the progress in understanding the mechanisms of how PCP proteins assemble and maintain glutamatergic synapses and initial insights on how disruption of the function of the PCP proteins can lead to neurodegenerative, neurodevelopmental and neuropsychiatric disorders. The PCP proteins may be the missing pieces of a long-standing puzzle and filling this gap of knowledge may provide the basis for understanding many unsolved questions in synapse biology., (© 2023 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Remote epitaxy is a promising technology that has recently attracted considerable attention, which enables the growth of thin films that copy the crystallographic characteristics of the substrate through two-dimensional material interlayers. The grown films can be exfoliated to form freestanding membranes, although it is often challenging to apply this technique if the substrate materials are prone to damage under harsh epitaxy conditions. For example, remote epitaxy of GaN thin films on graphene/GaN templates has not been achieved by a standard metal-organic chemical vapor deposition (MOCVD) method due to such damages. Here, we report GaN remote heteroepitaxy on graphene/AlN templates by MOCVD and investigate the influence of surface pits in AlN on the growth and exfoliation of GaN thin films. We first show the thermal stability of graphene before GaN growth, based on which two-step growth of GaN on graphene/AlN is developed. The GaN samples are successfully exfoliated after the first step of the growth at 750 °C, whereas the exfoliation failed after the second step at 1050 °C. In-depth analysis confirms that the pits in AlN templates lead to the degradation of graphene near the area and thus the alteration of growth modes and the failure of exfoliation. These results exemplify the importance of chemical and topographic properties of growth templates for successful remote epitaxy. It is one of the key factors for III-nitride-based remote epitaxy, and these results are expected to be of great help in realizing complete remote epitaxy using only MOCVD.

Herein, a novel combination of Mg- and Ga-co-doped ZnO (MGZO)/Li-doped graphene oxide (LGO) transparent electrode (TE)/electron-transporting layer (ETL) has been applied for the first time in Cu 2 ZnSn(S,Se) 4 (CZTSSe) thin-film solar cells (TFSCs). MGZO has a wide optical spectrum with high transmittance compared to that with conventional Al-doped ZnO (AZO), enabling additional photon harvesting, and has a low electrical resistance that increases electron collection rate. These excellent optoelectronic properties significantly improved the short-circuit current density and fill factor of the TFSCs. Additionally, the solution-processable alternative LGO ETL prevented plasma-induced damage to chemical bath deposited cadmium sulfide (CdS) buffer, thereby enabling the maintenance of high-quality junctions using a thin CdS buffer layer (≈30 nm). Interfacial engineering with LGO improved the V oc of the CZTSSe TFSCs from 466 to 502 mV. Furthermore, the tunable work function obtained through Li doping generated a more favorable band offset in CdS/LGO/MGZO interfaces, thereby, improving the electron collection. The MGZO/LGO TE/ETL combination achieved a power conversion efficiency of 10.67%, which is considerably higher than that of conventional AZO/intrinsic ZnO (8.33%)., (© 2023 Wiley-VCH GmbH.)

High-frequency stimulation (HFS) is a promising therapy for patients with depression. However, the mechanisms underlying the HFS-induced antidepressant-like effects on susceptibility and resilience to depressive-like behaviors remain obscure. Given that dopaminergic neurotransmission has been found to be disrupted in depression, we investigated the dopamine(DA)-dependent mechanism of the antidepressant-like effects of HFS of the prelimbic cortex (HFS PrL). We performed HFS PrL in a rat model of mild chronic unpredictable stress (CUS) together with 6-hydroxydopamine lesioning in the dorsal raphe nucleus (DRN) and ventral tegmental area (VTA). Animals were assessed for anxiety, anhedonia, and behavioral despair. We also examined levels of corticosterone, hippocampal neurotransmitters, neuroplasticity-related proteins, and morphological changes in dopaminergic neurons. We found 54.3% of CUS animals exhibited decreased sucrose consumption and were designated as CUS-susceptible, while the others were designated CUS-resilient. HFS PrL in both the CUS-susceptible and CUS-resilient animals significantly increased hedonia, reduced anxiety, decreased forced swim immobility, enhanced hippocampal DA and serotonin levels, and reduced corticosterone levels when compared with the respective sham groups. The hedonic-like effects were abolished in both DRN- and VTA-lesioned groups, suggesting the effects of HFS PrL are DA-dependent. Interestingly, VTA-lesioned sham animals had increased anxiety and forced swim immobility, which was reversed by HFS PrL. The VTA-lesioned HFS PrL animals also had elevated DA levels, and reduced p-p38 MAPK and NF-κB levels when compared to VTA-lesioned sham animals. These findings suggest that HFS PrL in stressed animals leads to profound antidepressant-like responses possibly through both DA-dependent and -independent mechanisms.

Adult stem cells undergo asymmetric cell divisions to produce 2 daughter cells with distinct cell fates: one capable of self-renewal and the other committed for differentiation. Misregulation of this delicate balance can lead to cancer and tissue degeneration. During asymmetric division of Drosophila male germline stem cells (GSCs), preexisting (old) and newly synthesized histone H3 are differentially segregated, whereas old and new histone variant H3.3 are more equally inherited. However, what underlies these distinct inheritance patterns remains unknown. Here, we report that the N-terminal tails of H3 and H3.3 are critical for their inheritance patterns, as well as GSC maintenance and proper differentiation. H3 and H3.3 differ at the 31st position in their N-termini with Alanine for H3 and Serine for H3.3. By swapping these 2 amino acids, we generated 2 mutant histones (i.e., H3A31S and H3.3S31A). Upon expressing them in the early-stage germline, we identified opposing phenotypes: overpopulation of early-stage germ cells in the H3A31S-expressing testes and significant germ cell loss in testes expressing the H3.3S31A. Asymmetric H3 inheritance is disrupted in the H3A31S-expressing GSCs, due to misincorporation of old histones between sister chromatids during DNA replication. Furthermore, H3.3S31A mutation accelerates old histone turnover in the GSCs. Finally, using a modified Chromatin Immunocleavage assay on early-stage germ cells, we found that H3A31S has enhanced occupancy at promoters and transcription starting sites compared with H3, while H3.3S31A is more enriched at transcriptionally silent intergenic regions compared to H3.3. Overall, these results suggest that the 31st amino acids for both H3 and H3.3 are critical for their proper genomic occupancy and function. Together, our findings indicate a critical role for the different amino acid composition of the N-terminal tails between H3 and H3.3 in an endogenous stem cell lineage and provide insights into the importance of proper histone inheritance in specifying cell fates and regulating cellular differentiation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Background: This study aims to look at the intermediate-term clinical, functional and radiological outcomes of patients with enchondroma in hand treated with osteoscopic-assisted curettage and artificial bone substitute or bone graft. The addition of osteoscopy allows direct visualisation of the bone cavity during and after curettage of tumour tissue without the need of creating a large opening in the bone cortex. This could lead to better clearance of tumour tissue and lower risk of iatrogenic fracture. Methods: A total of 11 patients who received surgery from December 2013 to November 2020 were retrospectively reviewed. All cases had histological diagnosis of enchondroma. Patients with a follow-up period of less than 3 months were excluded. The mean duration of follow-up was 20.9 months. For the clinical outcome, we measured the total active motion (TAM) and graded with Belsky score grip strength. For the functional outcome, the Quick Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) score was used. For the radiological outcome, we evaluated the X-ray for bone cavity filling defect, new bone formation according to the system proposed by Tordai. Results: The mean TAM of patients was 257º. A total of 60% patients had Belsky score grading excellent, 40% patients had Belsky score grading good. The mean percentage of grip strength compared with the contralateral side was 86.2%. The mean QuickDASH score was 7.7. For the wound aesthetic rating by patients, 81.8% patients reported as excellent. For the radiological outcome, the postoperative X-ray of all patients showed bone filling defect less than 3 mm. The mean time to complete bone consolidation was 3.8 months. None of the patients showed any radiological signs of recurrence. Conclusions: Our study showed that patients with enchondromas in hand treated with this minimally invasive method demonstrated good functional and radiological outcome. Its application may also be extended into treating other benign bone lesions in hand. Level of Evidence: Level IV (Therapeutic).

Recent advancements in lactoferrin research have uncovered that lactoferrin does function not only as an antimicrobial protein but also as an immunomodulatory, anticancer, and neuroprotective agent. Focusing on neuroprotection, this literature review delineates how lactoferrin interacts in the brain, specifically its neuroprotective effects and mechanisms against Alzheimer's and Parkinson's diseases (AD and PD), the two most common neurodegenerative diseases. The neuroprotective pathways involving surface receptors (heparan sulfate proteoglycan (HSPG) and lactoferrin receptor (LfR)), signaling pathways (extracellular regulated protein kinase-cAMP response element-binding protein (ERK-CREB) and phosphoinositide 3-kinase/Akt (PI3K/Akt)), and effector proteins (A disintegrin and metalloprotease10 (ADAM10) and hypoxia-inducible factor 1α (HIF-1α)) in cortical/hippocampal and dopaminergic neurons are described. These cellular effects of lactoferrin are likely responsible for attenuating cognitive and motor deficits, amyloid-β and α-synuclein accumulation, and neurodegeneration in animal and cellular models of AD and PD. This review also discusses the inconsistent findings related to the neuroprotective effects of lactoferrin against AD. Overall, this review contributes to the existing literature by clarifying the potential neuroprotective effects and mechanisms of lactoferrin in the context of AD and PD neuropathology.

Introduction: Regional analgesia techniques have been increasingly used for post-operative pain management following mastectomy. We aim to evaluate analgesic benefits of pectoral nerve (PECS2) block incorporated as part of the enhanced recovery after surgery (ERAS) protocol in patients undergoing mastectomy in University Malaya Medical Centre, Malaysia., Material and Methods: A single centre, cohort study evaluating 335 women who have undergone unilateral mastectomy between January 2017 and March 2020 in Malaysia. Regional anaesthesia were given pre-operatively via ultrasound guided pectoral and intercostal nerves block (PECSII)., Results: Utilization of regional anaesthesia increased from 11% in 2017 to 43% in 2020. Types and duration of surgeries were comparable. Opiod consumption was 3 mg lower in those who had PECS2 block ((27 [24-30] mg), in comparison with those who received general anaesthesia only (30 [26-34] mg), p < 0.001, and length of stay was half a day shorter in the regional anaesthesia group and these were statistically significant. However, pain score (2 [1-3]; 2 [1-3], p=0.719) and post-operative nausea and vomiting (PONV) (32.6-32.5%, p = 0.996) were similar., Conclusion: This study highlights the importance of PECS2 block as a component of ERAS protocol for mastectomy in an Asian hospital. This study also inferred that patients may be safely discharged within 24 h of surgery and therefore, same day surgery may be feasible in selected group of patients undergoing mastectomy and this could imply overall cost benefits., (© 2023. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

This systematic review assesses if positive psychology interventions (PPI) are more effective than other active psychological interventions for increasing the well-being of depressed adults. A review of randomised trials that compared PPI to other active interventions was conducted. A systematic search was undertaken using PsycInfo, PubMed, EMBASE, Web of Science, Scopus, CINAHL, two trial registries, and a manual search. The outcomes were happiness and depression. Ten studies, totalling 1341 participants, were included in the review. The small effect sizes for depression (Hedge's g = 0.15) and happiness (Hedge's g = 0.20) favoured PPI but were not significant, indicating no difference between PPI and other active interventions for the outcomes. Heterogeneity was high mainly due to differences in trial implementation. Risks of bias ranged from moderate to high. The results should be interpreted with caution because of the small number of included studies, high heterogeneity, and presence of bias. Protocol Registration Number PROSPERO CRD42019152513., Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-022-00598-z., Competing Interests: Conflict of interestNo conflicts of interest to report., (© The Author(s) 2022.)

SARS-CoV-2 virus continues to evolve and mutate causing most of the mutated variants resist to many of the therapeutic monoclonal antibodies (mAbs). Despite several mAbs retained neutralizing capability for Omicron BA.1 and BA.2, reduction in neutralization potency was reported. Hence, effort of searching for mAb that is broader in neutralization breadth without losing the neutralizing ability is continued. MW06 was reported with capability in neutralizing most of the variants of concern (VOC) and it binds to the conserved region (left flank) near epitope mAb sotrovimab (S309). In this study, binding affinity of mAb MW06 and its cocktail formulation with MW05 for receptor binding domain (RBD) SARS-CoV-2 virus was investigated under molecular dynamics simulations (MDs). Binding free energies computed by Molecular Mechanics Generalised Born Surface Area (MM-GBSA) algorithm predicted the binding affinity of MW06 for RBD BA.1 (-53 kcal/mol) as strong as RBD wildtype (-58 kcal/mol) while deterioration was observed for RBD BA.2 (-43 kcal/mol). Alike S309 and MW06, simulated cocktail mAb (MW05 and MW06)-RBD interactions suggested the neutralizing capability of the cocktail formulation for RBD BA.1 and BA.2 reduced. Meanwhile, residue pairs that favour the communication between the mAb and RBD have been identified by decomposing the free energy per pairwise residue basis. Apart from understanding the effects of mutation occurred in the RBD region on human angiotensin-converting enzyme 2 (hACE2) binding, impact of heavily mutated RBD on mAb-RBD interactions was investigated in this study as well. In addition to energetic profile obtained from MDs, plotting the dynamics cross-correlation map of the mAb-RBD complex under elastic network model (ENM) was aimed to understand the cross-correlations between residue fluctuations. It allows simple and rapid analysis on the motions or dynamics of the protein residues of mAbs and RBD in complex. Protein residues having correlated motions are normally part of the structural domains of the protein and their respective motions and protein function are related. Motion of mutated RBD residues and mAb residues was less correlated while their respective interactions energy computed to be higher. The combined techniques of MDs and ENM offered simplicity in understanding dynamics and energy contribution that explain binding affinity of mAb-RBD complexes., (© 2023 The Authors.)

Background: The research on surgical outcomes of hemiarthroplasty and reverse total shoulder arthroplasty using allograft-prosthesis composites for the proximal humeral oncologic condition is still scarce. Therefore, this study aimed to compare surgical outcomes of shoulder joint reconstruction with hemiarthroplasty and reverse total shoulder arthroplasty using allograft-prosthesis composites for tumors of the proximal humerus., Methods: Eleven patients underwent hemiarthroplasty or reverse total shoulder arthroplasty using allograft-prosthesis composites for tumors of the proximal humerus between July 2011 and April 2018 were reviewed. Radiographic analysis for bone union of allograft-host bone junction, implant loosening, stress shielding and shoulder dislocation or subluxation was performed. Functional outcomes were evaluated using visual analog scales for pain, range of motion, Simple Shoulder Test score and Musculoskeletal Tumor Society score. Furthermore, oncologic outcome and complications were also assessed, respectively., Results: There were five patients with hemiarthroplasty (mean age, 23.2 years) and six patients with reverse total shoulder arthroplasty (mean age, 46.8 years, P = 0.05). Radiographically, there were no events associated with implant loosening, stress shielding and shoulder dislocation or subluxation in the two groups. There were no differences in functional outcomes between the two groups. There was no local recurrence in entire cohort. In the hemiarthroplasty group, one patient was required revision surgery to reverse total shoulder arthroplasty at postoperative 6 years due to rotator cuff dysfunction. In the reverse total shoulder arthroplasty group, one patient showed the fracture occurred at allograft-host bone junction at postoperative 6 months., Conclusions: Surgical outcomes of hemiarthroplasty with allograft-prosthesis composites were not inferior to reverse total shoulder arthroplasty when applied in properly selected patients. The authors recommended that hemiarthroplasty with allograft-prosthesis composites could be used for young age patients without glenoid metastasis involvement, and reverse total shoulder arthroplasty with allograft-prosthesis composites could be used for patients with old age or metastatic bone tumors., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this study, Hovenia dulcis fruit fermented vinegar (HFV) was produced by the two-step fermentation of the H. dulcis fruit. The bioactivities before and after fermentation were compared. During the two-stage fermentation, the highest total acidity (4.99%) in the H. dulcis fruit extract juice was determined to be 16°Bx. During fermentation, the acetic acid content increased from 54.45 to 5404.30 mg%, and the fructose level in the HFV decreased from 130.68 to 54.91 mg%. The levels of DPPH and ABTS ·+ free radicals scavenging activities, reducing power, hydrogen peroxide scavenging and β-carotene bleaching activities were found to be increased in HFV as compared to before fermentation. Furthermore, the serum alcohol and acetaldehyde levels were reduced significantly in HFV compared to before fermentation. This study shows that HFV enhances the antioxidant and alcohol degradation activities and can potentially be used as a functional drink to prevent hangovers., Competing Interests: Conflict of interestAll authors of the article declare no conflict of interest., (© The Korean Society of Food Science and Technology 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Interleukin-9 (IL-9)-producing CD4 + T helper cells (Th9) have been implicated in allergy/asthma and anti-tumor immunity, yet molecular insights on their differentiation from activated T cells, driven by IL-4 and transforming growth factor-beta (TGF-β), is still lacking. Here we show opposing functions of two transcription factors, D-binding protein (DBP) and E2F8, in controlling Th9 differentiation. Specifically, TGF-β and IL-4 signaling induces phosphorylation of the serine 213 site in the linker region of the Smad3 (pSmad3L-Ser 213 ) via phosphorylated p38, which is necessary and sufficient for Il9 gene transcription. We identify DBP and E2F8 as an activator and repressor, respectively, for Il9 transcription by pSmad3L-Ser 213 . Notably, Th9 cells with siRNA-mediated knockdown for Dbp or E2f8 promote and suppress tumor growth, respectively, in mouse tumor models. Importantly, DBP and E2F8 also exhibit opposing functions in regulating human TH9 differentiation in vitro. Thus, our data uncover a molecular mechanism of Smad3 linker region-mediated, opposing functions of DBP and E2F8 in Th9 differentiation., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The exploration and identification of safe and effective vaccines for the SARS-CoV-2 pandemic have captured the world's attention and remains an ongoing issue due to concerns of balancing protection against emerging variants of concern while also generating long-lasting immunity. Here, we report the synthesis of a novel messenger ribonucleic acid encoding the spike protein in a lipid nanoparticle formulation (STI-7264) that generates robust humoral and cellular immunity following immunization of C57Bl6 mice. In an effort to improve immunity, a clinically focused lymphatic drug delivery device (MuVaxx) was engineered to modulate immune cells at the injection site (epidermis and dermis) and draining lymph node (LN) and tested to measure adaptive immunity. Using MuVaxx, immune responses were elicited and maintained at a 10-fold dose reduction compared to traditional intramuscular (IM) administration as measured by anti-spike antibodies, cytokine-producing CD8 T cells, neutralizing antibodies against the Washington (wild type) strain and South African (Beta) variants, and LN-resident spike-specific memory B cells. Remarkably, a 4-fold-elevated T cell response was observed in MuVaxx-administered vaccination compared to that of IM-administered vaccination. Thus, these data support further investigation into STI-7264 and lymphatic-mediated delivery using MuVaxx for SARS-CoV-2 and VoC vaccines., (© The Author(s) (2022). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, CEMCS, CAS.)

Cell-to-cell variation in gene expression is a widespread phenomenon, which may play important roles in cellular differentiation, function, and disease development 1-9 . Chromatin is implicated in contributing to the cellular heterogeneity in gene expression 10-16 . Fully understanding the mechanisms of cellular heterogeneity requires simultaneous measurement of RNA and occupancy of histone modifications and transcription factors on chromatin due to their critical roles in transcriptional regulation 17,18 . We generally term the occupancy of histone modifications and transcription factors as Chromatin occupancy. Here, we report a technique, termed scPCOR-seq (single-cell Profiling of Chromatin Occupancy and RNAs Sequencing), for simultaneously profiling genome-wide chromatin protein binding or histone modification marks and RNA expression in the same cell. We demonstrated that scPCOR-seq can profile either H3K4me3 or RNAPII and RNAs in a mixture of human H1, GM12878 and 293 T cells at a single-cell resolution and either H3K4me3, RNAPII, or RNA profile can correctly separate the cells. Application of scPCOR-seq to the in vitro differentiation of the erythrocyte precursor CD36 cells from human CD34 stem or progenitor cells revealed that H3K4me3 and RNA exhibit distinct properties in clustering cells during differentiation. Overall, our work provides a promising approach to understand the relationships among different omics layers., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Topoisomerase 3β (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation-enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is partly linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B-TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity., (Published by Oxford University Press on behalf of Nucleic Acids Research 2022.)