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  1. Wu X, Sivakumar M, Lim SS, Wu T, Heng PC
    Ultrason Sonochem, 2024 Feb;103:106782.
    PMID: 38309050 DOI: 10.1016/j.ultsonch.2024.106782
    This study investigates a prospective and straightforward method for producing graphene material derived from biomass, examining the influence of plant cell composition and functions. The experimental outcomes highlight ultrasound's crucial role in synthesizing graphene material sourced from biomass. Ultrasound, a pivotal element in the experiment, significantly affects graphene production from biomass by working synergistically with the liquid components in the solvent system. Notably, the ethanol content reduces the solution's surface tension, facilitating the effective dispersion of biochar and graphene oxide sheets throughout the process. Simultaneously, the water content maintains the solution's polarity, enhancing the cavitation effect induced by ultrasound. Biomass-derived graphene is exfoliated utilizing an ultrasonic bath system (134.4 W, 40 kHz, 0.5 W/cm2) from biochar. The as-synthesized graphene oxide exhibits a structure comprising a few layers while remaining intact, featuring abundant functional groups. Interestingly, the resulting product displays nanopores with an approximate diameter of 100 nm. These nanopores are attributed to preserving specific cell structures, particularly those with specialized cell wall structures or secondary metabolite deposits from biomass resources. The study's findings shed light on the impact of cellular structure on synthesizing graphene material sourced from biomass, emphasizing the potential application of ultrasound as a promising approach in graphene production.
  2. He WH, Feng XX, Wu X, Zhai XH, Li YY, Zhang B, et al.
    Trop Biomed, 2020 Dec 01;37(4):871-876.
    PMID: 33612740 DOI: 10.47665/tb.37.4.871
    To evaluate the inhibitory effects of drugs on the growth of Babesia gibsoni, relative quantification real-time PCR method was developed in this study. The 18S rRNA gene was used as a target gene for the 2-ΔΔCt method analysis. Additionally, chicken RNA was added to the parasitized blood before total RNA extraction. The chicken β-actin gene was selected as an internal control gene for the 2-ΔΔCt method analysis. The 100 µL parasitized blood samples with different percentages of parasitized erythrocytes (PPEs) (3%, 1.5%, 0.75%, 0.375% and 0.1875%) were prepared for relative quantification of B. gibsoni. Regression analysis results revealed significant linear relationships between the relative quantification value and parasitemia. 18S rRNA gene expression was significantly decreased after treatment with diminazene aceturate and artesunate in vitro drug sensitivity test. This result suggested that this relative quantification real-time PCR method can be used to evaluate the effects of drug inhibition.
  3. Tong JB, Sanjiv R, Elderdery A, Wu X, Rajesh R, Suresh Kumar S, et al.
    Med J Malaysia, 2023 Jul;78(4):534-540.
    PMID: 37518929
    INTRODUCTION: The meniscus plays an important role in maintaining homeostasis to facilitate the normal function of the knee joint. It is one of the most commonly injured areas of the knee joint. Meniscal-related injuries can lead to significantly decreased athletic ability, and their incidence has increased yearly. It has been found that most meniscal injuries are irreparable, and meniscectomy can increase the predisposition to knee osteoarthritis. Tissue engineering technology on meniscus repairing and transplantation has received widespread attention recently. This review aimed to analyse the scientific literature regarding the potential applications of tissue engineering on meniscus repairing and transplantation procedures.

    METHOD AND MATERIALS: The electronic search was carried out using PubMed/MEDLINEⓇdatabases with the keywords "tissue engineering AND meniscus" spanning the period of publications from Jan 1980 until Dec 2022.

    RESULTS: The literature search identified 405 references in PubMed/MEDLINE, and 179 were selected following the eligibility requirements. The research analysis showed that the existing meniscal tissue engineering studies used a wide variety of seed cells, cytokines, bioactive materials and 3D structures. Each showed distinct advantages and disadvantages in terms of biocompatibility, degradability, mechanical strength, porosity, and etc. It was noted that 3D printing technology is promising for tissue engineering meniscus research. In addition, the optimal use of compression and hydrostatic pressure to markedly improve the functional properties of tissue-engineering meniscal can serve as an useful strategy.

    CONCLUSION: This review analysed the different approaches employed for meniscus tissue engineering and regeneration. Meniscal tissue engineering still faces several major challenges in terms of seed cells, choice of materials and 3D printing strategies, which should be effectively overcome to harness the full potential of this technology.

  4. Wu X, Li C, Zhou Z, Nie X, Chen Y, Zhang Y, et al.
    Int J Adv Manuf Technol, 2021;117(9-10):2565-2600.
    PMID: 34465936 DOI: 10.1007/s00170-021-07854-1
    Cutting fluid has cooling and lubricating properties and is an important part of the field of metal machining. Owing to harmful additives, base oils with poor biodegradability, defects in processing methods, and unreasonable emissions of waste cutting fluids, cutting fluids have serious pollution problems, which pose challenges to global carbon emissions laws and regulations. However, the current research on cutting fluid and its circulating purification technique lacks systematic review papers to provide scientific technical guidance for actual production. In this study, the key scientific issues in the research achievements of eco-friendly cutting fluid and waste fluid treatment are clarified. First, the preparation and mechanism of organic additives are summarized, and the influence of the physical and chemical properties of vegetable base oils on lubricating properties is analyzed. Then, the process characteristics of cutting fluid reduction supply methods are systematically evaluated. Second, the treatment of oil mist and miscellaneous oil, the removal mechanism and approach of microorganisms, and the design principles of integrated recycling equipment are outlined. The conclusion is concluded that the synergistic effect of organic additives, biodegradable vegetable base oils and recycling purification effectively reduces the environmental pollution of cutting fluids. Finally, in view of the limitations of the cutting fluid and its circulating purification technique, the prospects of amino acid additive development, self-adapting jet parameter supply system, matching mechanism between processing conditions and cutting fluid are put forward, which provides the basis and support for the engineering application and development of cutting fluid and its circulating purification.
  5. Ghazalli N, Wu X, Walker S, Trieu N, Hsin LY, Choe J, et al.
    Stem Cells Dev, 2018 07 01;27(13):898-909.
    PMID: 29717618 DOI: 10.1089/scd.2017.0160
    Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known. In this study, we aim to identify small molecules that affect immature beta cells. A cell-based assay, using pancreatic beta-like cells derived from murine embryonic stem (ES) cells harboring a transgene containing an insulin 1-promoter driven enhanced green fluorescent protein reporter, was used to screen a compound library (NIH Clinical Collection-003). Cortisone, a glucocorticoid, was among five positive hit compounds. Quantitative reverse transcription-polymerase chain reaction analysis revealed that glucocorticoids enhance the gene expression of not only insulin 1 but also glucose transporter-2 (Glut2; Slc2a2) and glucokinase (Gck), two molecules important for glucose sensing. Mifepristone, a pharmacological inhibitor of glucocorticoid receptor (GR) signaling, reduced the effects of glucocorticoids on Glut2 and Gck expression. The effects of glucocorticoids on ES-derived cells were further validated in immature primary islets. Isolated islets from 1-week-old mice had an increased Glut2 and Gck expression in response to a 4-day treatment of exogenous hydrocortisone in vitro. Gene deletion of GR in beta cells using rat insulin 2 promoter-driven Cre crossed with GRflox/flox mice resulted in a reduced gene expression of Glut2, but not Gck, and an abrogation of insulin secretion when islets were incubated in 0.5 mM d-glucose and stimulated by 17 mM d-glucose in vitro. These results demonstrate that glucocorticoids positively regulate glucose sensors in immature murine beta-like cells.
  6. Zhang X, Wu X, Centeno A, Ryan MP, Alford NM, Riley DJ, et al.
    Sci Rep, 2016;6:23364.
    PMID: 26997140 DOI: 10.1038/srep23364
    Copper zinc tin sulfide (CZTS) is a promising material for harvesting solar energy due to its abundance and non-toxicity. However, its poor performance hinders their wide application. In this paper gold (Au) nanoparticles are successfully incorporated into CZTS to form Au@CZTS core-shell nanostructures. The photocathode of Au@CZTS nanostructures exhibits enhanced optical absorption characteristics and improved incident photon-to-current efficiency (IPCE) performance. It is demonstrated that using this photocathode there is a significant increase of the power conversion efficiency (PCE) of a photoelectrochemical solar cell of 100% compared to using a CZTS without Au core. More importantly, the PCE of Au@CZTS photocathode improved by 15.8% compared to standard platinum (Pt) counter electrode. The increased efficiency is attributed to plasmon resonance energy transfer (PRET) between the Au nanoparticle core and the CZTS shell at wavelengths shorter than the localized surface plasmon resonance (LSPR) peak of the Au and the semiconductor bandgap.
  7. Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, et al.
    Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
    PMID: 25489084 DOI: 10.1073/pnas.1406199111
    Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
  8. Guo J, Wu X, Too CL, Yin F, Lu X, He J, et al.
    PLoS One, 2012;7(7):e41228.
    PMID: 22829930 DOI: 10.1371/journal.pone.0041228
    OBJECTIVES: Dendritic cell immunoreceptor (DCIR) has been implicated in development of autoimmune disorders in rodent and DCIR polymorphisms were associated with anti-citrullinated proteins antibodies (ACPA)-negative rheumatoid arthritis (RA) in Swedish Caucasians. This study was undertaken to further investigate whether DCIR polymorphisms are also risk factors for the development of RA in four Asian populations originated from China and Malaysia.

    METHODS: We genotyped two DCIR SNPs rs2377422 and rs10840759 in Han Chinese population (1,193 cases, 1,278 controls), to assess their association with RA. Subsequently, rs2377422 was further genotyped in three independent cohorts of Malaysian-Chinese subjects (MY_Chinese, 254 cases, 206 controls), Malay subjects (MY_ Malay, 515 cases, 986 controls), and Malaysian-Indian subjects (MY_Indian, 378 cases, 285 controls), to seek confirmation of association in various ethnic groups. Meta-analysis was preformed to evaluate the contribution of rs2377422 polymorphisms to the development of ACPA-negative RA in distinct ethnic groups. Finally, we carried out association analysis of rs2377422 polymorphisms with DCIR mRNA expression levels.

    RESULTS: DCIR rs2377422 was found to be significantly associated with ACPA -negative RA in Han Chinese (OR 1.92, 95% CI 1.27-2.90, P=0.0020). Meta-analysis confirms DCIR rs2377422 as a risk factor for ACPA-negative RA across distinct ethnic groups (OR(overall) =1.17, 95% CI 1.06-1.30, P=0.003). The SNP rs2377422 polymorphism showed significant association with DCIR mRNA expression level, i.e. RA-risk CC genotype exhibit a significant increase in the expression of DCIR (P=0.0023, Kruskal-Wallis).

    CONCLUSIONS: Our data provide evidence for association between DCIR rs2377422 and RA in non-Caucasian populations and confirm the influence of DCIR polymorphisms on RA susceptibility, especially on ACPA-negative RA.
  9. Chornokur G, Lin HY, Tyrer JP, Lawrenson K, Dennis J, Amankwah EK, et al.
    PLoS One, 2015;10(6):e0128106.
    PMID: 26091520 DOI: 10.1371/journal.pone.0128106
    BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk.

    METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.

    RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).

    CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.

  10. Earp M, Tyrer JP, Winham SJ, Lin HY, Chornokur G, Dennis J, et al.
    PLoS One, 2018;13(7):e0197561.
    PMID: 29979793 DOI: 10.1371/journal.pone.0197561
    Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
  11. Wu X, Zhang W, Li Y, Zheng L, Liu J, Jiang Y, et al.
    PLoS One, 2024;19(1):e0295118.
    PMID: 38166098 DOI: 10.1371/journal.pone.0295118
    BACKGROUND: As an important factor affecting personal health, anxiety has always been valued by people. Prior research has consistently shown that personality traits is associated with anxiety level,but little is known about the inner mechanism of this relationship. To fill the gap, the present research aims to explore the chain mediating role of general self-efficacy and academic burnout in the relationship between big five personality and anxiety.

    METHODS: This cross-sectional study was performed from September to November 2022. Self-reported questionnaires including the Big Five Personality Questionnaire, General Self-Efficacy Scale, College Student's academic burnout Scale, Generalized Anxiety Scale and demographic characteristics were distributed to 2505 college students in a university in Hebei Province, of which 2,471 were valid. Statistical analysis was carried out through SPSS26.0 and SPSS PROCESS macro.

    RESULTS: Results showed four of the big five personality characters (i.e., extraversion, agreeableness, conscientiousness, and openness) were negatively correlated with anxiety. Neuroticism was positively correlated with anxiety. Moreover, general self-efficacy was found to be negatively correlated with academic burnout and anxiety; academic burnout was positively correlated with anxiety. Finally, general self-efficacy and academic burnout mediated the relationship between personality traits (i.e., extraversion, agreeableness, neuroticism, openness) and anxiety.

    CONCLUSIONS: Personality traits (i.e., extraversion, agreeableness, neuroticism, and openness) could influence anxiety through the chain mediating effects of general self-efficacy and academic burnout. Interventions focusing on anxiety reduction may be successful in increasing general self-efficacy and decreasing students' academic burnout.

  12. Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  13. Xia W, Tang N, Kord-Varkaneh H, Low TY, Tan SC, Wu X, et al.
    Pharmacol Res, 2020 11;161:105113.
    PMID: 32755613 DOI: 10.1016/j.phrs.2020.105113
    BACKGROUND AND AIM: Previous studies lack consistent conclusions as to whether astaxanthin is actually linked to various health benefits as claimed. Here, we attempt to unravel the association of astaxanthin consumption with selected health benefits by performing a systematic review and meta-analysis.

    METHODS: Online literature search databases including Scopus, Web of Science, PubMed/Medline, Embase and Google Scholar were searched to discover relevant articles available up to 17 March 2020. We used mean changes and SD of the outcomes to assess treatment response from baseline and mean difference, and 95 % CI were calculated to combined data and assessment effect sizes in astaxanthin and control groups.

    RESULTS: 14 eligible articles were included in the final quantitative analysis. Current study revealed that astaxanthin consumption was not associated with FBS, HbA1c, TC, LDL-C, TG, BMI, BW, DBP, and SBP. We did observe an overall increase in HDL-C (WMD: 1.473 mg/dl, 95 % CI: 0.319-2.627, p = 0.012). As for the levels of CRP, only when astaxanthin was administered (i) for relatively long periods (≥ 12 weeks) (WMD: -0.528 mg/l, 95 % CI: -0.990 to -0.066), and (ii) at high dose (> 12 mg/day) (WMD: -0.389 mg/dl, 95 % CI: -0.596 to -0.183), the levels of CRP would decrease.

    CONCLUSION: In summary, our systematic review and meta-analysis revealed that astaxanthin consumption was associated with increase in HDL-C and decrease in CRP. Significant associations were not observed for other outcomes.

  14. Haw YH, Lai KW, Chuah JH, Bejo SK, Husin NA, Hum YC, et al.
    PeerJ Comput Sci, 2023;9:e1325.
    PMID: 37346512 DOI: 10.7717/peerj-cs.1325
    Oil palm is a key agricultural resource in Malaysia. However, palm disease, most prominently basal stem rot caused at least RM 255 million of annual economic loss. Basal stem rot is caused by a fungus known as Ganoderma boninense. An infected tree shows few symptoms during early stage of infection, while potentially suffers an 80% lifetime yield loss and the tree may be dead within 2 years. Early detection of basal stem rot is crucial since disease control efforts can be done. Laboratory BSR detection methods are effective, but the methods have accuracy, biosafety, and cost concerns. This review article consists of scientific articles related to the oil palm tree disease, basal stem rot, Ganoderma Boninense, remote sensors and deep learning that are listed in the Web of Science since year 2012. About 110 scientific articles were found that is related to the index terms mentioned and 60 research articles were found to be related to the objective of this research thus included in this review article. From the review, it was found that the potential use of deep learning methods were rarely explored. Some research showed unsatisfactory results due to limitations on dataset. However, based on studies related to other plant diseases, deep learning in combination with data augmentation techniques showed great potentials, showing remarkable detection accuracy. Therefore, the feasibility of analyzing oil palm remote sensor data using deep learning models together with data augmentation techniques should be studied. On a commercial scale, deep learning used together with remote sensors and unmanned aerial vehicle technologies showed great potential in the detection of basal stem rot disease.
  15. Abd Wahab NH, Hasikin K, Wee Lai K, Xia K, Bei L, Huang K, et al.
    PeerJ Comput Sci, 2024;10:e1943.
    PMID: 38686003 DOI: 10.7717/peerj-cs.1943
    BACKGROUND: Maintaining machines effectively continues to be a challenge for industrial organisations, which frequently employ reactive or premeditated methods. Recent research has begun to shift its attention towards the application of Predictive Maintenance (PdM) and Digital Twins (DT) principles in order to improve maintenance processes. PdM technologies have the capacity to significantly improve profitability, safety, and sustainability in various industries. Significantly, precise equipment estimation, enabled by robust supervised learning techniques, is critical to the efficacy of PdM in conjunction with DT development. This study underscores the application of PdM and DT, exploring its transformative potential across domains demanding real-time monitoring. Specifically, it delves into emerging fields in healthcare, utilities (smart water management), and agriculture (smart farm), aligning with the latest research frontiers in these areas.

    METHODOLOGY: Employing the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) criteria, this study highlights diverse modeling techniques shaping asset lifetime evaluation within the PdM context from 34 scholarly articles.

    RESULTS: The study revealed four important findings: various PdM and DT modelling techniques, their diverse approaches, predictive outcomes, and implementation of maintenance management. These findings align with the ongoing exploration of emerging applications in healthcare, utilities (smart water management), and agriculture (smart farm). In addition, it sheds light on the critical functions of PdM and DT, emphasising their extraordinary ability to drive revolutionary change in dynamic industrial challenges. The results highlight these methodologies' flexibility and application across many industries, providing vital insights into their potential to revolutionise asset management and maintenance practice for real-time monitoring.

    CONCLUSIONS: Therefore, this systematic review provides a current and essential resource for academics, practitioners, and policymakers to refine PdM strategies and expand the applicability of DT in diverse industrial sectors.

  16. Hampras SS, Sucheston-Campbell LE, Cannioto R, Chang-Claude J, Modugno F, Dörk T, et al.
    Oncotarget, 2016 10 25;7(43):69097-69110.
    PMID: 27533245 DOI: 10.18632/oncotarget.10215
    BACKGROUND: Regulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.

    METHODS: In a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.

    RESULTS: The most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).

    CONCLUSIONS: Common inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

  17. Li P, Huang W, Chen Y, Aslam MS, Cheng W, Huang Y, et al.
    Neural Plast, 2023;2023:1474841.
    PMID: 37179843 DOI: 10.1155/2023/1474841
    PURPOSE: To explore the therapeutic efficiency of acupuncture and the related molecular mechanism of neural plasticity in depression.

    METHODS: Chronic unpredictable mild stress- (CUMS-) induced rats were established for the depression animal model. There were a total of four rat groups, including the control group, the CUMS group, the CUMS+acupuncture group, and the CUMS+fluoxetine group. The acupuncture group and the fluoxetine group were given a 3-week treatment after the modeling intervention. The researcher performed the open-field, elevated plus maze, and sucrose preference tests to evaluate depressive behaviors. The number of nerve cells, dendrites' length, and the prefrontal cortex's spine density were detected using Golgi staining. The prefrontal cortex expression, such as BDNF, PSD95, SYN, and PKMZ protein, was detected using the western blot and RT-PCR.

    RESULTS: Acupuncture could alleviate depressive-like behaviors and promote the recovery of the neural plasticity functions in the prefrontal cortex, showing the increasing cell numbers, prolonging the length of the dendrites, and enhancing the spine density. The neural plasticity-related proteins in the prefrontal cortex, including BDNF, PSD95, SYN, and PKMZ, were all downregulated in the CUMS-induced group; however, these effects could be partly reversed after being treated by acupuncture and fluoxetine (P < 0.05).

    CONCLUSION: Acupuncture can ameliorate depressive-like behaviors by promoting the recovery of neural plasticity functions and neural plasticity-related protein upregulation in the prefrontal cortex of CUMS-induced depressed rats. Our study provides new insights into the antidepressant approach, and further studies are warranted to elucidate the mechanisms of acupuncture involved in depression treatment.

  18. Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, et al.
    Nat Genet, 2015 Feb;47(2):164-71.
    PMID: 25581431 DOI: 10.1038/ng.3185
    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
  19. Wu X, Azizan EAB, Goodchild E, Garg S, Hagiyama M, Cabrera CP, et al.
    Nat Genet, 2023 Jun;55(6):1009-1021.
    PMID: 37291193 DOI: 10.1038/s41588-023-01403-0
    Aldosterone-producing adenomas (APAs) are the commonest curable cause of hypertension. Most have gain-of-function somatic mutations of ion channels or transporters. Herein we report the discovery, replication and phenotype of mutations in the neuronal cell adhesion gene CADM1. Independent whole exome sequencing of 40 and 81 APAs found intramembranous p.Val380Asp or p.Gly379Asp variants in two patients whose hypertension and periodic primary aldosteronism were cured by adrenalectomy. Replication identified two more APAs with each variant (total, n = 6). The most upregulated gene (10- to 25-fold) in human adrenocortical H295R cells transduced with the mutations (compared to wildtype) was CYP11B2 (aldosterone synthase), and biological rhythms were the most differentially expressed process. CADM1 knockdown or mutation inhibited gap junction (GJ)-permeable dye transfer. GJ blockade by Gap27 increased CYP11B2 similarly to CADM1 mutation. Human adrenal zona glomerulosa (ZG) expression of GJA1 (the main GJ protein) was patchy, and annular GJs (sequelae of GJ communication) were less prominent in CYP11B2-positive micronodules than adjacent ZG. Somatic mutations of CADM1 cause reversible hypertension and reveal a role for GJ communication in suppressing physiological aldosterone production.
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