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  1. Bao R, Liu M, Wang D, Wen S, Yu H, Zhong Y, et al.
    Front Pharmacol, 2019;10:1464.
    PMID: 31920654 DOI: 10.3389/fphar.2019.01464
    Background:Eurycoma longifolia is a tropical medicinal plant belonging to Simaroubaceae distributed in South East Asia. The stems are traditionally used for the treatment of sexual insufficiency, fever, hypertension, and malaria. Furthermore, it has antidiabetic and anticancer activities. Recently, it has been reported to reduce uric acid, but the mechanism is unclear. Hypothesis/Purpose: The aim of this study is to explore the effect and mechanism of E. longifolia stem 70% ethanol extract (EL) and its active compounds on uric acid excretion. Study Design and Methods: Potassium oxonate (PO) induced hyperuricemia rats model and adenine-PO induced hyperuricemia mice model were used to evaluate the effects of EL. Ultraperformance liquid chromatography was used to determine the levels of plasma or serum uric acid and creatinine. Hematoxylin-eosin staining was applied to observe kidney pathological changes, and western blot was applied to detect protein expression levels of uric acid transporters. Effects of constituents on urate uptake were tested in hURAT1-expressing HEK293T cells. Results: EL significantly reduced serum and plasma uric acid levels at dosages of 100, 200, and 400 mg/kg in hyperuricemia rats and mice, increased the clearance rate of uric acid and creatinine, and improved the renal pathological injury. The protein expression levels of urate reabsorption transporter 1 (URAT1) and glucose transporter 9 were down-regulated, while sodium-dependent phosphate transporter 1 and ATP-binding cassette transporter G2 were up-regulated in the kidney after EL treatment. The quassinoids isolated from EL showed inhibitory effects on urate uptake in hURAT1-expressing HEK293T cells, and the effect of eurycomanol was further confirmed in vivo. Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.
  2. Zhang Y, Knibbe R, Sunarso J, Zhong Y, Zhou W, Shao Z, et al.
    Adv Mater, 2017 Dec;29(48).
    PMID: 28628239 DOI: 10.1002/adma.201700132
    Solid-oxide fuel cells (SOFCs) are electricity generators that can convert the chemical energy in various fuels directly to the electric power with high efficiency. Recent advances in materials and related key components for SOFCs operating at ≈500 °C are summarized here, with a focus on the materials, structures, and techniques development for low-temperature SOFCs, including the analysis of most of the critical parameters affecting the electrochemical performance of the electrolyte, anode, and cathode. New strategies, such as thin-film deposition, exsolution of nanoparticles from perovskites, microwave plasma heating, and finger-like channeled electrodes, are discussed. These recent developments highlight the need for electrodes with higher activity and electrolytes with greater conductivity to generate a high electrochemical performance at lower temperatures.
  3. Sun Y, Zhong Y, Sun W, Chu L, Long J, Fan XW
    Front Public Health, 2023;11:1167234.
    PMID: 37521991 DOI: 10.3389/fpubh.2023.1167234
    BACKGROUND: Adolescent depression has become a leading problem around the world, especially as the COVID-19 pandemic has remained prevalent and heavily influenced people's mental health. While gender difference has always been a topic in the field of psychiatry, there are cultural differences across the world that must be taken into account. The current study is examining gender differences in symptoms of Chinese adolescents with depression.

    METHODS: The sample was obtained from a total of 574 adolescent patients (172 males and 402 females) diagnosed with depression following the DSM-IV/ICD-10 diagnostic criteria; patients who also had other severe mental or physical illnesses were excluded. The ages of participants ranged from 10 to 19 years. Additionally, independent t-test and one-way ANOVA were used to examine differences in symptoms between different gender and age groups. The LPA was used to examine whether females and males were having different patterns of symptoms.

    RESULTS: Our analysis showed that compared to males, females exhibited higher rates of depression and more severe depressive symptoms across age groups. Likewise, the analysis also revealed an earlier onset of depression among Chinese adolescents compared to that in Western countries in previous studies. Finally, the LPA showed that mild to moderate depression was predominant in male patients, while severe depression was predominant in female patients.

    CONCLUSION: This study highlights the gender differences in the prevalence and severity of depressive symptoms in Chinese adolescents. The current study highlighted the importance of gender equality and developing gender-friendly interventions in maintaining the overall mental health of adolescents in China.

  4. Yu J, Zhong Y, Wu X, Sunarso J, Ni M, Zhou W, et al.
    Adv Sci (Weinh), 2018 Sep;5(9):1800514.
    PMID: 30250794 DOI: 10.1002/advs.201800514
    Hydrogen production from renewable electricity relies upon the development of an efficient alkaline water electrolysis device and, ultimately, upon the availability of low cost and stable electrocatalysts that can promote oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Normally, different electrocatalysts are applied for HER and OER because of their different reaction intermediates and mechanisms. Here, the synthesis of a heterostructured CoP@a-CoOx plate, which constitutes the embedded crystalline cobalt phosphide (CoP) nanoclusters and amorphous cobalt oxides (CoOx) nanoplates matrix, via a combined solvothermal and low temperature phosphidation route is reported. Due to the presence of synergistic effect between CoP nanoclusters and amorphous CoOx nanoplates in the catalyst, created from the strong nanointerfaces electronic interactions between CoP and CoOx phases in its heterostructure, this composite displays very high OER activity in addition to favorable HER activity that is comparable to the performance of the IrO2 OER benchmark and approached that of the Pt/C HER benchmark. More importantly, an efficient and stable alkaline water electrolysis operation is achieved using CoP@a-CoOx plate as both cathode and anode as evidenced by the obtainment of a relatively low potential of 1.660 V at a 10 mA cm-2 current density and its marginal increase above 1.660 V over 30 h continuous operation.
  5. Xie M, Zhong Y, Xue Q, Wu M, Deng X, O Santos H, et al.
    Exp Gerontol, 2020 07 15;136:110949.
    PMID: 32304719 DOI: 10.1016/j.exger.2020.110949
    BACKGROUND AND AIM: Inconsistencies exist with regard to the influence of dehydroepiandrosterone (DHEA) supplementation on insulin-like growth factor 1 (IGF-1) levels. The inconsistencies could be attributed to several factors, such as dosage, gender, and duration of intervention, among others. To address these inconsistencies, we conducted a systematic review and meta-analysis to combine findings from randomized controlled trials (RCTs) on this topic.

    METHODS: Electronic databases (Scopus, PubMed/Medline, Web of Science, Embase and Google Scholar) were searched for relevant literature published up to February 2020.

    RESULTS: Twenty-four qualified trials were included in this meta-analysis. It was found that serum IGF-1 levels were significantly increased in the DHEA group compared to the control (weighted mean differences (WMD): 16.36 ng/ml, 95% CI: 8.99, 23.74; p = .000). Subgroup analysis revealed that a statistically significant increase in serum IGF-1 levels was found only in women (WMD: 23.30 ng/ml, 95% CI: 13.75, 32.87); in participants who supplemented 50 mg/d DHEA (WMD: 15.75 ng/ml, 95% CI: 7.61, 23.89); in participants undergoing DHEA intervention for >12 weeks (WMD: 17.2 ng/ml, 95% CI: 8.02, 26.22); in participants without an underlying comorbidity (WMD: 19.11 ng/ml, 95% CI: 10.69, 27.53); and in participants over the age of 60 years (WMD: 19.79 ng/ml, 95% CI: 9.86, 29.72).

    CONCLUSION: DHEA supplementation may increase serum IGF-I levels especially in women and older subjects. However, further studies are warranted before DHEA can be recommended for clinical use.

  6. Yan L, Yu J, Zhong Y, Gu Y, Ma Y, Li W, et al.
    J Nanosci Nanotechnol, 2020 03 01;20(3):1605-1612.
    PMID: 31492322 DOI: 10.1166/jnn.2020.17340
    The present study focuses on the microstructural and bioactive properties evolution in selective laser melting (SLM) β titanium alloys. We have applied cross-scan strategy for improving mechanical properties and lower elastic modulus of SLMed Ti-20Mg-5Ta alloys which has been shown to be altering the microstructure and refining the grain size. The cross-scan strategy can refine the microstructure and induce various deformation textures in contrast to the conventional scan strategy. The microstructures of Ti-20Mg-5Ta alloys indicate that the cross-scan strategy will yield the best mechanical properties and lower elastic modulus. The corrosion behavior of the Ti-20Mg-5Ta alloys was studied during immersion in an acellular simulated body fluid (SBF) at 37±0.50 °C for 28 days. Both the mechanical and bioactive properties showed that the novel Ti-20Mg-5Ta alloys should be ideal for bone implants.
  7. Rothan HA, Zhong Y, Sanborn MA, Teoh TC, Ruan J, Yusof R, et al.
    Antiviral Res, 2019 11;171:104590.
    PMID: 31421166 DOI: 10.1016/j.antiviral.2019.104590
    Two major flaviviruses, dengue virus (DENV) and Zika virus (ZIKV), cause severe health and economic burdens worldwide. Recently, genome-wide screenings have uncovered the importance of regulators of the Hrd1 ubiquitin ligase-mediated endoplasmic reticulum (ER)-associated degradation (ERAD) pathway for flavivirus replication in host cells. Here we report the identification of the compound Bardoxolone methyl (CDDO-me) as a potent inhibitor of the Hrd1 ubiquitin ligase-mediated ERAD, which possesses a broad-spectrum activity against both DENV and ZIKV. Cellular thermal shift assay (CETSA) suggested that CDDO-me binds to grp94, a key component of the Hrd1 pathway, at a low nanomolar concentration, whereas interaction was not detected with its paralog Hsp90. CDDO-me and the grp94 inhibitor PU-WS13 substantially suppressed DENV2 replication and the cytopathic effects caused by DENV and ZIKV infection. The antiviral activities of both compounds were demonstrated for all four DENV serotypes and four ZIKV strains in multiple human cell lines. This study defines grp94 as a crucial host factor for flavivirus replication and identified CDDO-me as a potent small molecule inhibitor of flavivirus infection. Inhibition of grp94 may contribute to the antiviral activity of CDDO-me. Further investigation of grp94 inhibitors may lead to a new class of broad-spectrum anti-flaviviral medications.
  8. Peng W, Mao P, Liu L, Chen K, Zhong Y, Xia W, et al.
    Complement Ther Med, 2020 Jan;48:102241.
    PMID: 31987255 DOI: 10.1016/j.ctim.2019.102241
    OBJECTIVE: Glucose disorders and dyslipidemia are closely associated with obesity and metabolic disease. The purpose of this study was to investigate the effect of Carnosine supplementation on lipid profile, fasting blood glucose, HbA1C and Insulin resistance.

    METHOD: MEDLINE/PubMed, Scopus and Web of sciences were investigated to identify relevant articles up to June 2019. The search strategy combined the Medical Subject Heading and Title and/or abstract keywords. The combined effect sizes were calculated as weight mean difference (WMD) using the random-effects model. Between study heterogeneity was evaluated by the Cochran's Q test and I2.

    RESULTS: Four RCTs studies investigated Carnosine use versus any control for at least 2 weeks were identified and analyzed. Overall results from the random-effects model on included studies, with 184 participants, indicated that carnosine intervention reduced HbA1C levels in intervention vs control groups (WMD: -0.92 %, 95 % CI: -1.20, -0.63, I2:69 %). Four studies, including a total of 183 participants, reported TG changes as an outcome measure variable, but combined results did not show significant reduction in this outcome (WMD: -14.46 mg/dl, 95 % CI: -29.11, 0.19, I2:94 %). Furthermore, combined results did not show any significant change in HOMA-IR, Cholesterol, fasting blood sugar, or HDL-C.

    CONCLUSION: Carnosine supplementation results in a decrease in HbA1C, but elicits no effect on HOMA-IR, Cholesterol, fasting blood sugar, TG and HDL-C. Future studies with a larger sample sizes, varied doses of carnosine, and population-specific sub-groups are warranted to confirm, and enhance, the veracity of our findings.

  9. Zhong Y, Tan GW, Bult J, Veltmaat N, Plattel W, Kluiver J, et al.
    BMC Cancer, 2024 Apr 02;24(1):407.
    PMID: 38566053 DOI: 10.1186/s12885-024-12191-z
    BACKGROUND: Primary central nervous system lymphoma (PCNSL) are rare mature B-cell lymphoproliferative diseases characterized by a high incidence of MYD88 L265P and CD79B Y196 hotspot mutations. Diagnosis of PCNSL can be challenging. The aim of the study was to analyze the detection rate of the MYD88 L265P and CD79B Y196 mutation in cell free DNA (cfDNA) in plasma of patients with PCNSL.

    METHODS: We analyzed by digital droplet PCR (ddPCR) to determine presence of the MYD88 L265P and CD79B Y196 hotspot mutations in cfDNA isolated from plasma of 24 PCNSL patients with active disease. Corresponding tumor samples were available for 14 cases. Based on the false positive rate observed in 8 healthy control samples, a stringent cut-off for the MYD88 L265P and CD79B Y196 mutation were set at 0.3% and 0.5%, respectively.

    RESULTS: MYD88 L265P and CD79B Y196 mutations were detected in 9/14 (64%) and 2/13 (15%) tumor biopsies, respectively. In cfDNA samples, the MYD88 L265P mutation was detected in 3/24 (12.5%), while the CD79B Y196 mutation was not detected in any of the 23 tested cfDNA samples. Overall, MYD88 L265P and/or CD79B Y196 were detected in cfDNA in 3/24 cases (12.5%). The detection rate of the combined analysis did not improve the single detection rate for either MYD88 L265P or CD79B Y196.

    CONCLUSION: The low detection rate of MYD88 L265P and CD79B Y196 mutations in cfDNA in the plasma of PCNSL patients argues against its use in routine diagnostics. However, detection of MYD88 L265P by ddPCR in cfDNA in the plasma could be considered in challenging cases.

  10. Ge L, Li B, Li G, Wang X, Cheong KY, Peng Y, et al.
    J Phys Chem Lett, 2023 Jan 19;14(2):592-597.
    PMID: 36633457 DOI: 10.1021/acs.jpclett.2c03637
    This paper presents a fabricated solar-blind phototransistor based on hydrogen-terminated diamond. The phototransistor shows a large photocurrent and enhancement of responsivity over conventional two-terminal diamond-based photodetector. These enhancement effects are owing to the internal gain of the phototransistor. The fabricated phototransistor exhibits a high photoresponsivity (R) of 2.16 × 104 A/W and a detectivity (D*) of 9.63 × 1011 jones, with gate voltage (VG) and drain voltage of approximately -1.5 V and -5 V, respectively, under 213 nm light illumination. Even at ultralow operating voltage of -0.01 V, the device records satisfactory performance with R and D* of 146.7 A/W and 6.19 × 1010 jones, respectively. By adjusting the VG, photocurrent generation in the device can be continuously tuned from the fast photoconductive effect to the optical gating effect with high optical gain. When VG increases from 1.4 to 2.4 V, the decay time decreases from 1512.0 to 25.5 ms. Therefore, responsivity, dark current, Iphoto/Idark, and decay time of the device can be well tuned by VG.
  11. Du Y, Zhen F, Ding S, Zhong Y, Li P, Zhan K, et al.
    PMID: 39540851 DOI: 10.1021/acsami.4c15588
    Effective heat redistribution in specific directions is vital for advanced thermal management, significantly enhancing device performance by optimizing spatial heat configurations. We have designed and fabricated a hierarchical fibrous membrane that enables precise heat directing. By integrating hierarchical structure design with the anisotropic thermal conductivity of two-dimensional (2D) materials, we developed a fibrous membrane for anisotropic heat transfer. Such a structure is fabricated by aligning a 1D structured fiber in the 2D plane to achieve anisotropy at each scale level. The fiber units, where 2D nanosheets circumferentially and axially aligned, achieved a high axial thermal conductivity of 16.8 W·m-1·K-1 and advanced heat directing ability, confirmed by characterizations and simulations. The assembled membrane demonstrated an exceptional tensile strength (365 MPa) and high thermal conductivity (10.5 W·m-1·K-1) along the fiber axis. Our membranes are seen as a refined model for thermal management materials, combining the benefits of heat spreaders and thermal interface materials, thus being proficient in directing heat along programmed pathways. A practical wireless charging cooling demonstration illustrated this. Our methodology also proved versatile with different 2D fillers and various geometries. This research presents a method to achieve precise heat directing at the material's level, facilitating the systematic design of thermal management in electronics.
  12. Ooi JD, Jiang JH, Eggenhuizen PJ, Chua LL, van Timmeren M, Loh KL, et al.
    Nat Commun, 2019 07 29;10(1):3392.
    PMID: 31358739 DOI: 10.1038/s41467-019-11255-0
    Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409-428), can induce anti-MPO autoimmunity. The peptide (6PGD391-410) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD391-410, or with S. aureus containing a plasmid expressing 6PGD391-410, develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD391-410 is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD391-410 antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.
  13. Leung D, Chua GT, Mondragon AV, Zhong Y, Nguyen-Ngoc-Quynh L, Imai K, et al.
    Front Immunol, 2020;11:1605.
    PMID: 32903579 DOI: 10.3389/fimmu.2020.01605
    Background: The Asia Pacific Society for Immunodeficiencies (APSID) conducted nine primary immunodeficiency (PID) Schools in 5 years since inauguration to provide PID care training for early career physicians in Asia Pacific, a region with divergent needs in PID resources and training. Objective: To identify differences in PID patient care resource and training needs across Asia Pacific and propose a corresponding action plan. Methods: The Human Development Index (HDI) indicates the degree of socio-economic development in each country/region. Information related to investigations and learning issues were extracted from the abstracts and personal statements from all Schools and mapped onto resource and training needs. Correlations between HDI and country/region-specific parameters were tested by two-tailed Pearson correlation. Results: A total of 427 abstracts were received in nine Schools between 2015 and 2020, predominantly on immunodeficiencies affecting cellular and humoral immunity. Genetic confirmation was described in 61.8% of abstracts, and its absence negatively correlated with HDI (r = -0.696, p = 0.004). Essential immunologic and genetic tests were not available in 25.4 and 29.5% of abstracts, respectively, and their absence negatively correlated with HDI (r = -0.788, p < 0.001; r = -0.739, p = 0.002). HDI positively correlated with average testing level (r = 0.742, p = 0.002). Cases from medium-HDI countries/regions focused on learning how to investigate a patient for PIDs in cases of severe or atypical infections, whereas those from very-high-HDI countries/regions, from which most faculty members originated, listed hematopoietic stem cell transplantation and gene therapy, newborn screening, and research as learning issues more frequently. Conclusion: There are unique HDI-related PID resource and training needs in each country/region. APSID proposes HDI group-specific strategies to improve PID care and education in her member countries/regions. Further quantitative analysis of needs in PID care in Asia Pacific is needed for lobbying governments to increase their support for PID care and research.
  14. Chan CM, Abdul Latiff AH, Noh LM, Ismail IH, Abd Hamid IJ, Liew WK, et al.
    Front Immunol, 2023;14:1209315.
    PMID: 37529038 DOI: 10.3389/fimmu.2023.1209315
    INTRODUCTION: With increased diagnostic capabilities and treatment modalities in the field of primary immunodeficiencies (PID), many pediatric patients survive beyond childhood and experience a change of care to the adult-oriented healthcare system. Unfortunately, the transition pathways for PID are less clearly defined, resulting in deterioration of quality of care in adulthood. Hence, this is the first regional study to address PID clinicians' opinions on practices and challenges of transition care in 7 Southeast Asia (SEA) countries.

    METHODS: We adopted a cross-sectional study design through an online survey platform to enquire opinions of transition practices from expert representatives in 7 SEA countries.

    RESULTS: Regionally, 3 out 7 countries reported having no practice of transition care. Among cited challenges were reluctant adaptation by patients and caregivers to unfamiliarized adult healthcare systems, inadequate ratio of adult immunologists to patients and lack of facilities for transfer.

    DISCUSSION AND CONCLUSION: Our study provides evidence to advocate policy makers on the importance of standardized integration of transition practice towards betterment of transiting PID patients into adulthood.

  15. Zhong Y, Chu C, Myers JA, Gilbert GS, Lutz JA, Stillhard J, et al.
    Nat Commun, 2021 May 25;12(1):3137.
    PMID: 34035260 DOI: 10.1038/s41467-021-23236-3
    Arbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) associations are critical for host-tree performance. However, how mycorrhizal associations correlate with the latitudinal tree beta-diversity remains untested. Using a global dataset of 45 forest plots representing 2,804,270 trees across 3840 species, we test how AM and EcM trees contribute to total beta-diversity and its components (turnover and nestedness) of all trees. We find AM rather than EcM trees predominantly contribute to decreasing total beta-diversity and turnover and increasing nestedness with increasing latitude, probably because wide distributions of EcM trees do not generate strong compositional differences among localities. Environmental variables, especially temperature and precipitation, are strongly correlated with beta-diversity patterns for both AM trees and all trees rather than EcM trees. Results support our hypotheses that latitudinal beta-diversity patterns and environmental effects on these patterns are highly dependent on mycorrhizal types. Our findings highlight the importance of AM-dominated forests for conserving global forest biodiversity.
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