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1.
Designing electrolytes and interphases for high-energy lithium batteries.
Wan, H, Xu, J, Wang, C
Nature reviews. Chemistry. 2024;(1):30-44
Abstract
High-energy and stable lithium-ion batteries are desired for next-generation electric devices and vehicles. To achieve their development, the formation of stable interfaces on high-capacity anodes and high-voltage cathodes is crucial. However, such interphases in certain commercialized Li-ion batteries are not stable. Due to internal stresses during operation, cracks are formed in the interphase and electrodes; the presence of such cracks allows for the formation of Li dendrites and new interphases, resulting in a decay of the energy capacity. In this Review, we highlight electrolyte design strategies to form LiF-rich interphases in different battery systems. In aqueous electrolytes, the hydrophobic LiF can extend the electrochemical stability window of aqueous electrolytes. In organic liquid electrolytes, the highly lithiophobic LiF can suppress Li dendrite formation and growth. Electrolyte design aimed at forming LiF-rich interphases has substantially advanced high-energy aqueous and non-aqueous Li-ion batteries. The electrolyte and interphase design principles discussed here are also applicable to solid-state batteries, as a strategy to achieve long cycle life under low stack pressure, as well as to construct other metal batteries.
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Characterization of skin barrier defects using infrared spectroscopy in patients with atopic dermatitis.
Williams, SF, Wan, H, Chittock, J, Brown, K, Wigley, A, Cork, MJ, Danby, SG
Clinical and experimental dermatology. 2024;(5):466-477
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Abstract
BACKGROUND Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC). OBJECTIVES To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity. METHODS We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped. RESULTS Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465 cm-1 (full width half maximum) and 1340 cm-1 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = -0.59, carboxylate peak area r = -0.50). CONCLUSIONS ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies.
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The effect of subcutaneous Lixisenatide on weight loss in patients with type 2 Diabetes Mellitus: Systematic review and Meta-Analysis of randomized controlled trials.
Sheng, L, Deng, M, Li, X, Wan, H, Lei, C, Prabahar, K, Hernández-Wolters, B, Kord-Varkaneh, H
Diabetes research and clinical practice. 2024;:111617
Abstract
BACKGROUND The impacts of subcutaneous Lixisenatide on body weight in patients with type 2 DM, remain inadequately understood; consequently, this systematic review and meta-regression analysis of randomized controlled trials (RCTs) was conducted to evaluate the influence of subcutaneous Lixisenatide administration on BW and BMI values in individuals with Type 2 diabetes. METHODS A comprehensive literature search was conducted across four databases, spanning from their inception to February 2023. We computed effect sizes employing the random-effects model and reported results in terms of weighted mean differences (WMD) along with their corresponding 95% confidence intervals (CI). RESULTS 23 articles with 26 RCT arms were included in the meta-analysis. The combined findings from a random-effects model demonstrated a significant reduction in body weight (WMD: -0.97 kg, 95 % CI: -1.10, -0.83, p < 0.001) and BMI (WMD: -0.48 kg/m2, 95 % CI: -0.67, -0.29, P < 0.001) after subcutaneous administration of Lixisenatide. Furthermore, a more pronounced reduction in body weight was discovered in RCTs lasting less than 24 weeks (WMD: -1.56 kg, 95 % CI: -2.91, -0.20, p < 0.001), employing a daily dosage of subcutaneous Lixisenatide lower than 19 µg per day (WMD: -1.94 kg, 95 % CI: -2.54, -1.34, p < 0.001) and with a mean participant age of 60 years or more (WMD: -1.86 kg, 95 % CI: -3.16, -0.57, p = 0.005). CONCLUSIONS Lixisenatide was found to significantly decrease BW and BMI in patients with type 2 DM and could be considered as a therapeutic option for those suffering from weight gain caused by other anti-diabetic agents. However, while prescribing Lixisenatide, careful consideration of patient-specific factors is recommended.
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Effectiveness of an evidence-based swallowing facilitation strategy for patients undergoing radiotherapy for head and neck cancer: a study protocol for a randomised controlled trial.
Zhang, Y, Zhu, Y, Wan, H
BMJ open. 2024;(1):e072859
Abstract
INTRODUCTION Dysphagia emerges as a frequent, persistent and enduring aftermath in individuals undergoing radiotherapy for head and neck cancer (HNC). Timely intervention becomes imperative to ameliorate prolonged dysphagia and curtail related complications. Among the evidence-grounded tactics, preventive swallowing training and proficient feeding management stand out as pivotal measures for precluding and mitigating dysphagia. However, past inquiries that amalgamated these dual interventions exhibited heterogeneous quality due to their restricted participant cohorts and a dearth of uniform, systematic and practicable procedural benchmarks. METHOD/DESIGN This randomised, parallel-controlled study enrols 94 patients diagnosed with HNC, who are undergoing radiotherapy either with or without concurrent chemotherapy. The patients will be randomly assigned to either the intervention group, which will receive a facilitation strategy to enhance swallowing function in conjunction with standard care, or the control group, which will receive typical radiotherapy care. Patient assessments will be conducted at three distinct time points: at the onset of radiotherapy (baseline), at the conclusion of radiotherapy and 3 months postradiotherapy. The primary outcome will revolve around measuring swallowing function, while secondary outcomes will encompass swallowing-related quality of life and nutritional status. ETHICS AND DISSEMINATION This research initiative received endorsement from the Shanghai Proton Heavy Ion Hospital Ethics Committee on 2 December 2 (Approval Number 2210-59-01). Throughout the recruitment process, patients will be acquainted with the primary aims and scope of the study. Their participation will be a voluntary choice, demonstrated by their informed consent form signatures. The outcomes of this study will be disseminated through publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER Clinical Trials.gov, ChiCTR2300067550, registered 11 January 2023.
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Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases.
Ban, XX, Wan, H, Wan, XX, Tan, YT, Hu, XM, Ban, HX, Chen, XY, Huang, K, Zhang, Q, Xiong, K
Current medical science. 2024;(1):28-50
Abstract
Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.
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Mechanisms of Ferritinophagy and Ferroptosis in Diseases.
Li, S, Huang, P, Lai, F, Zhang, T, Guan, J, Wan, H, He, Y
Molecular neurobiology. 2024;(3):1605-1626
Abstract
The discovery of the role of autophagy, particularly the selective form like ferritinophagy, in promoting cells to undergo ferroptosis has inspired us to investigate functional connections between diseases and cell death. Ferroptosis is a novel model of procedural cell death characterized by the accumulation of iron-dependent reactive oxygen species (ROS), mitochondrial dysfunction, and neuroinflammatory response. Based on ferroptosis, the study of ferritinophagy is particularly important. In recent years, extensive research has elucidated the role of ferroptosis and ferritinophagy in neurological diseases and anemia, suggesting their potential as therapeutic targets. Besides, the global emergence and rapid transmission of COVID-19, which is caused by SARS-CoV-2, represents a considerable risk to public health worldwide. The potential involvement of ferroptosis in the pathophysiology of brain injury associated with COVID-19 is still unclear. This review summarizes the pathophysiological changes of ferroptosis and ferritinophagy in neurological diseases, anemia, and COVID-19, and hypothesizes that ferritinophagy may be a potential mechanism of ferroptosis. Advancements in these fields will enhance our comprehension of methods to prevent and address neurological disorders, anemia, and COVID-19.
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Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials.
Orkin, C, Molina, JM, Cahn, P, Lombaard, J, Supparatpinyo, K, Kumar, S, Campbell, H, Wan, H, Teal, V, Jin Xu, Z, et al
The lancet. HIV. 2024;(2):e75-e85
Abstract
BACKGROUND In two phase 3 trials for first-line therapy in adults with HIV-1, doravirine showed non-inferior efficacy, a favourable safety profile, and a superior lipid profile to darunavir and efavirenz through to 48 and 96 weeks. Here we report 192-week results from both studies. METHODS DRIVE-FORWARD and DRIVE-AHEAD are multicentre, double-blind, randomised, active comparator-controlled, phase 3 trials of first-line antiretroviral treatment in adults with HIV-1. Eligible participants (aged ≥18 years) were naive to antiretroviral therapy, had plasma HIV-1 RNA 1000 copies per mL or more at screening, had no known resistance to any of the trial drugs, and had creatinine clearance 50 mL per min or more. DRIVE-FORWARD was conducted at 125 sites in 15 countries and compared doravirine (100 mg) with ritonavir-boosted darunavir (ritonavir [100 mg] and darunavir [800 mg]), each administered orally once daily with two nucleoside or nucleotide reverse transcriptase inhibitors (tenofovir disoproxil fumarate [300 mg] and emtricitabine [200 mg] or abacavir sulfate [600 mg] and lamivudine [300 mg]). DRIVE-AHEAD was conducted at 126 sites in 23 countries and compared doravirine (100 mg), lamivudine (300 mg), and tenofovir disoproxil fumarate (300 mg) with that of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), all administered orally once daily. DRIVE-FORWARD enrolment was between Dec 1, 2014, and June 1, 2020, and DRIVE-AHEAD enrolment was between June 10, 2015, and Aug 10, 2020. After the 96-week double-blind phase, eligible participants could enter an open-label extension and either continue doravirine or switch from comparator to doravirine for an additional 96 weeks. Efficacy (HIV-1 RNA <50 copies per mL) and safety assessments (adverse events and changes in laboratory parameters) were pooled. The DRIVE-FORWARD and DRIVE-AHEAD trials were registered with ClinicalTrials.gov, NCT02275780 and NCT02403674. FINDINGS Of 1494 participants treated in the double-blind phase (1261 [84%] male and 233 [16%] female), 550 continued doravirine and 502 switched to doravirine in the extension. Using the FDA snapshot approach, HIV-1 RNA less than 50 copies per mL was maintained in 457 (83%) of 550 participants who continued doravirine and 404 (80%) of 502 participants who switched to doravirine. Protocol-defined virological failure and development of resistance were low, occurring mainly before week 96. Two (<1%) of 550 participants who continued doravirine reported serious drug-related adverse events, and three (1%) who continued doravirine and one (<1%) of 502 who switched to doravirine discontinued due to drug-related adverse events. Participants continuing or switching to doravirine showed generally favourable lipid profiles, little weight gain, and small decreases in estimated glomerular filtration rates, with no discontinuations due to increased creatinine or renal adverse events. INTERPRETATION Favourable efficacy and safety profiles for doravirine at week 96 were maintained through to week 192 in participants who continued or switched to doravirine, supporting use of doravirine for long-term first-line HIV-1 treatment and for virologically suppressed adults switching therapy. FUNDING Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.
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Research Progress on the Role of Sirtuin 1 in Cerebral Ischemia.
Fangma, Y, Wan, H, Shao, C, Jin, L, He, Y
Cellular and molecular neurobiology. 2023;(5):1769-1783
Abstract
A significant amount of evidence from the past few years has shown that Sirtuin 1 (SIRT1), a histone deacetylase dinucleotide of nicotinamide adenine dinucleotide (NAD+) is closely related to the cerebral ischemia. Several potential neuroprotective strategies like resveratrol, ischemia preconditioning, and caloric restriction exert their neuroprotection effects through SIRT1-related signaling pathway. However, the potential mechanisms and neuroprotection of SIRT1 in the process of cerebral ischemia injury development and recovery have not been systematically elaborated. This review summarized the the deacetylase activity and distribution of SIRT1 as well as analyzed the roles of SIRT1 in astrocytes, microglia, neurons, and brain microvascular endothelial cells (BMECs), and the molecular mechanisms of SIRT1 in cerebral ischemia, providing a theoretical basis for exploration of new therapeutic target in future.
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TMEM16A ion channel: A novel target for cancer treatment.
Li, S, Wang, Z, Geng, R, Zhang, W, Wan, H, Kang, X, Guo, S
Life sciences. 2023;:122034
Abstract
Cancer draws attention owing to the high morbidity and mortality. It is urgent to develop safe and effective cancer therapeutics. The calcium-activated chloride channel TMEM16A is widely distributed in various tissues and regulates physiological functions. TMEM16A is abnormally expressed in several cancers and associate with tumorigenesis, metastasis, and prognosis. Knockdown or inhibition of TMEM16A in cancer cells significantly inhibits cancer development. Therefore, TMEM16A is considered as a biomarker and therapeutic target for some cancers. This work reviews the cancers associated with TMEM16A. Then, the molecular mechanism of TMEM16A overexpression in cancer was analyzed, and the possible signal transduction mechanism of TMEM16A regulating cancer development was summarized. Finally, TMEM16A inhibitors with anticancer effect and their anticancer mechanism were concluded. We hope to provide new ideas for pharmacological studies on TMEM16A in cancer.
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Molnupiravir for the treatment of COVID-19 in immunocompromised participants: efficacy, safety, and virology results from the phase 3 randomized, placebo-controlled MOVe-OUT trial.
Johnson, MG, Strizki, JM, Brown, ML, Wan, H, Shamsuddin, HH, Ramgopal, M, Florescu, DF, Delobel, P, Khaertynova, I, Flores, JF, et al
Infection. 2023;(5):1273-1284
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Abstract
PURPOSE Immunocompromised patients have a potentially increased risk for progression to severe COVID-19 and prolonged replication of SARS-CoV-2. This post hoc analysis examined outcomes among immunocompromised participants in the MOVe-OUT trial. METHODS In phase 3 of MOVe-OUT, non-hospitalized at-risk adults with mild-to-moderate COVID-19 were randomized to receive molnupiravir 800 mg or placebo twice daily for 5 days. Immunocompromised participants were identified based on prior/concomitant medications and/or medical history. All-cause hospitalization/death, adverse events, SARS-CoV-2 titers, infectivity, and RNA sequences were compared between immunocompromised participants who received molnupiravir or placebo and with non-immunocompromised participants. RESULTS Fifty-five of 1408 participants were considered immunocompromised. Compared to placebo, fewer molnupiravir-treated immunocompromised participants were hospitalized/died through Day 29 (22.6% [7/31] vs. 8.3% [2/24]), with fewer adverse events (45.2% [14/31] vs. 25.0% [6/24]). A larger mean change from baseline in SARS-CoV-2 RNA was observed with molnupiravir compared to placebo in non-immunocompromised participants (least squares mean [LSM] difference Day 5: - 0.31, 95% confidence interval [CI] - 0.47 to - 0.15), while the mean change was comparable between treatment groups in immunocompromised participants (LSM difference Day 5: 0.23, 95% CI - 0.71 to 1.17). Molnupiravir treatment was associated with increased clearance of infectious virus. Increased errors in viral nucleotide sequences in post-baseline samples compared to placebo support molnupiravir's mechanism of action and were not associated with observation of novel treatment-emergent amino acid substitutions in immunocompromised participants. CONCLUSION Although the study population was small, these data suggest that molnupiravir treatment for mild-to-moderate COVID-19 in non-hospitalized immunocompromised adults is efficacious and safe and quickly reduces infectious SARS-CoV-2. GOV REGISTRATION NUMBER NCT04575597.