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Biomedical subjects

Wei Jin

Publications and source records attributed to Wei Jin.

At least 19 recordsLinked to original sources

Single-cell expression quantitative trait locus Mendelian randomization reveals immune cell-specific causal regulatory networks and actionable targets in polycystic ovary syndrome.

ObjectiveTo systematically investigate whether the pathogenesis of polycystic ovary syndrome (PCOS) is causally related to dysregulated gene expression in specific immune cell subsets, and to evaluate the potential of these causal genes as actionable drug targets.MethodsThis study employed a two-sample Mendelian randomization (MR) framework using publicly available genome-wide association study (GWAS) summary statistics. The participant data included 797 PCOS cases and 140,558 controls (no direct patient recruitment was involved). Instrumental variables were derived from high-resolution immune cell-specific single-cell expression quantitative trait locus (sc-eQTL) data (OneK1K project) across 14 immune cell types. Primary analyses utilized the inverse-variance weighted (IVW) method. Shared causal variants were validated using Bayesian colocalization. Phenome-wide association analysis (PheWAS), external transcriptomic dataset validation (GSE8157), and DrugBank database screening were conducted for pleiotropy assessment and drug repositioning.ResultsMR analysis revealed genome-wide significant causal associations for GLIPR1 in non-classical monocytes (Mono NC) and XBP1 in CD4+ effector memory T cells (CD4 ET) with PCOS risk. Higher GLIPR1 expression was associated with a decreased PCOS risk (OR = 0.669, P = 4.34×10-6), whereas higher XBP1 expression was associated with an increased risk (OR = 1.406, P = 9.53×10-8). Colocalization analysis confirmed that GLIPR1 shares a causal variant with PCOS (PP.H4 = 96.73%). PheWAS and external validation confirmed the safety profile and significant upregulation (P = 0.03) of GLIPR1. Drug repositioning identified SOT-107, a Phase III protein therapy drug, as a potential interacting agent for GLIPR1.ConclusionsThis sc-eQTL MR study reveals immune cell-specific causal regulatory networks in PCOS. GLIPR1 in non-classical monocytes represents a high-confidence protective target, while XBP1 provides suggestive evidence for immune-mediated pathogenesis. The candidate drug SOT-107 highlights theoretical repositioning opportunities, though rigorous preclinical validation remains required.

Female↗

Identification and prognosis of low office and ambulatory blood pressure in patients with heart failure.

BACKGROUND: Low blood pressure (BP) limits the up-titration of guideline-directed medical therapies (GDMTs) and predicts poor outcomes in heart failure (HF). We assessed the value of ambulatory BP&#xa0;monitoring (ABPM) in detecting&#xa0;low BP and its impact on GDMTs optimization and prognosis in HF. METHODS: In&#xa0;491 HF patients initiating GDMTs from the Risk Evaluation and Management in Heart Failure (REM-HF) study since April 2018 to December 2022, ABPM was measured&#xa0;in addition to office BP. Participants were classified as sustained low systolic BP (SBP) (24-hour and office SBP < 120&#x2009;mmHg), masked low SBP (24-hour SBP < 120&#x2009;mmHg, office SBP &#x2265; 120&#x2009;mmHg), and no low SBP. The primary outcome was a composite of all-cause mortality and HF rehospitalization. GDMTs target dose achievement was assessed at 3 months. Logistic regression and&#xa0;Cox regression models were used to assess GDMTs optimization and outcomes across SBP groups. RESULTS: Sustained, masked, and no low SBP were observed in 25.3%, 30.8%, and 44.0% of patients, respectively. Both sustained (OR 2.36, 95%CI 1.25-4.47) and masked low SBP (OR 2.32, 95%CI 1.11-4.87) groups were associated with lower likelihood of achieving GDMTs target doses. Over a median 21-month follow-up, all-cause mortality and HF rehospitalization rates were higher in sustained (HR 2.45, 95% CI 1.56-3.86) and masked low SBP (HR 1.68, 95% CI 1.08-2.62) groups. No difference was found in the target dose achievement and outcomes between the two low SBP groups. CONCLUSION: Sustained and masked low SBP were common in HF and both associated with GDMTs intolerance and adverse outcomes.

Humans↗

Fusion splicing small-core photonic crystal fibers and single-mode fibers by repeated arc discharges.

We demonstrate a novel method for low-loss splicing small-core photonic crystal fibers (PCFs) and single-mode fibers (SMFs) by repeated arc discharges using a conventional fusion splicer. An optimum mode field match at the interface of PCF-SMF and an adiabatic mode field variation in the longitudinal direction of the small-core PCF can be achieved by repeated arc discharges applied over the splicing joint to gradually collapse the air holes of the small-core PCF. This method is simple and offers a practical solution for light coupling between small-core PCFs and SMFs.

Journal Article↗

Highly sensitive long-period fiber-grating strain sensor with low temperature sensitivity.

A long-period fiber-grating sensor with a high strain sensitivity of -7.6 pm/microepsilon and a low temperature sensitivity of 3.91 pm/ degrees C is fabricated by use of focused CO(2) laser beam to carve periodic grooves on a large- mode-area photonic crystal fiber. Such a strain sensor can effectively reduce the cross-sensitivity between strain and temperature, and the temperature-induced strain error obtained is only 0.5 microepsilon/ degrees C without using temperature compensation.

Journal Article↗

CO2 laser-grooved long period fiber grating temperature sensor system based on intensity modulation.

A long period fiber grating (LPFG) temperature sensor system based on intensity modulation is developed. The LPFG employed is fabricated by the use of a focused CO2 laser beam to carve periodic grooves on the fiber. The temperature measurement resolution of up to 0.1 degrees C has been obtained within the temperature range between 20 degrees C and 100 degrees C. The system uses a simple intensity measurement method and exhibits the advantages of convenient intensity measurement, double temperature sensitivity, high resolution, simple configuration, and low cost.

Journal Article↗

Development of high-performance liquid chromatographic fingerprint for the quality control of Rheum tanguticum Maxim. ex Balf.

A novel, accurate and valid fingerprint method was developed by using high-performance liquid chromatography-photodiode array detection (HPLC-DAD) to control the quality of Rheum tanguticum Maxim. ex Balf. By comprehensively comparing chromatograms of all samples, our result revealed that the chromatographic fingerprint we developed combining similarity evaluation could efficiently identify and distinguish raw materials of R. tanguticum from different sources. Besides, 21 characteristic peaks in chromatogram of R. tanguticum were unambiguously confirmed by comparison of reference compounds based on their retention time (t(R)) and UV spectra.

Chromatography, High Pressure Liquid↗

Measuring optical fiber length by use of a short-pulse optical fiber ring laser in a self-injection seeding scheme.

A method for measuring the length of an optical fiber by use of an optical fiber ring laser pulse source is proposed and demonstrated. The key element of the optical fiber ring laser is a gain-switched Fabry-Perot laser diode operated in a self-injection seeding scheme. This method is especially suitable for measuring a medium or long fiber, and a resolution of 0.1 m is experimentally achieved. The measurement is implemented by accurately determining the pulse frequency that can maximize the output power of the fiber ring laser. The measurement results depend only on the refractive index of the fiber corresponding to this single wavelength, instead of the group index of the fiber, which represents a great advantage over both optical time-domain reflectometry and optical low-coherence reflectometry methods.

Journal Article↗

Photopolymer microtips for efficient light coupling between single-mode fibers and photonic crystal fibers.

A novel method for light coupling between single-mode fibers (SMFs) and small-core photonic crystal fibers (PCFs) is demonstrated. The method is based on growing photopolymer microtips directly on the end faces of SMFs. The shape and size of the tips can be controlled by adjusting the laser power and the exposure time for polymerization to match the mode field to the small-core PCFs. A 5 dB improvement in coupling efficiency between a SMF and a commercial small-core, highly nonlinear PCF is experimentally demonstrated. This compact and efficient butt-coupling method is particularly suitable for PCF gas sensor applications.

Journal Article↗

Increase of CD4(+)CD25(+) T cells in Smad3(-/-) mice.

AIM: To investigate the changes of lymphocyte subpopulations, especially CD4(+)CD25(+) T regulatory cells in Smad3(-/-) mice. METHODS: Hematological changes and changes of lymphocyte subpopulations were detected in Smad3(-/-) mice using cell counter and flow cytometry, respectively, and compared to their littermate controls. RESULTS: The numbers of neutrophils and lymphocytes in peripheral blood were significantly increased in Smad3(-/-) mice compared to littermate controls. CD19(+) expressing cells in blood and spleen, and CD8(+) T cells in thymus were all markedly decreased in Smad3(-/-) mice. More important, Smad3(-/-) mice had an increased population of CD4(+)CD25(+) T cells in peripheral lymphoid tissues, including thymus, spleen, and lymph nodes. CONCLUSION: These observations suggest that the changes of lymphocyte subpopulations might play a role in susceptibility to inflammation of Smad3(-/-) mice.

Animals↗

Regulation of T cell development by the deubiquitinating enzyme CYLD.

T cell receptor signaling is essential for the generation and maturation of T lymphocyte precursors. Here we identify the deubiquitinating enzyme CYLD as a positive regulator of proximal T cell receptor signaling in thymocytes. CYLD physically interacted with active Lck and promoted recruitment of active Lck to its substrate, Zap70. CYLD also removed both Lys 48- and Lys 63-linked polyubiquitin chains from Lck. Because of a cell-autonomous defect in T cell development, CYLD-deficient mice had substantially fewer mature CD4(+) and CD8(+) single-positive thymocytes and peripheral T cells.

Animals↗

Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim.

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, promotes invasion, metastasis, and growth and survival of malignant cells and confers resistance to some chemotherapeutic drugs. However, the molecular mechanisms underlying the actions of EMMPRIN are not fully understood. In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage, and to explore the signaling pathways involved. We found that in the absence of attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed less compact aggregates with larger surface area and less fibronectin matrix assembly, had higher viability, and were resistant to anoikis. Knockdown of EMMPRIN expression by RNA interference (small interfering RNA or short hairpin RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase-3, increased DNA fragmentation, and decreased cellular viability. Furthermore, we observed that the accumulation of Bim, a proapoptotic BH3-only protein, was reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression elevated Bim protein levels and enhanced cellular sensitivity to anoikis. Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive to anoikis. These results indicated that expression of EMMPRIN protects cancer cells from anoikis and that this effect is mediated at least in part by a MAP kinase-dependent reduction of Bim. Because anoikis deficiency is a key feature of neoplastic transformation and invasive growth of epithelial cancer cells, our study on the role of EMMPRIN in anoikis resistance and the mechanism involved underscores the potential of EMMPRIN expression as a prognostic marker and novel target for cancer therapy.

Anoikis↗

Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin.

Glyceryl trinitrate (GTN), also known as nitroglycerin, has been used to treat angina and heart failure for more than 130 years. Recently, it was shown that mitochondrial aldehyde dehydrogenase-2 (ALDH2) is responsible for formation of NO, the metabolite needed for GTN efficacy. In the present study, we show that the common G-to-A polymorphism in exon 12 of ALDH2--resulting in a Glu504Lys replacement that virtually eliminates ALDH2 activity in both heterozygotes and homozygotes--is associated with a lack of efficacy of sublingual GTN in Chinese subjects. We also show that the catalytic efficiency (Vmax/Km) of GTN metabolism of the Glu504 protein is approximately 10-fold higher than that of the Lys504 enzyme. We conclude that the presence of the Lys504 allele contributes in large part to the lack of an efficacious clinical response to nitroglycerin; we recommend that this genetic factor be considered when administering nitroglycerin to patients, especially Asians, 30-50% of whom possess the inactive ALDH2*2 mutant allele.

Administration, Sublingual↗

Phosphorylation of NF-kappaB1/p105 by oncoprotein kinase Tpl2: implications for a novel mechanism of Tpl2 regulation.

The oncoprotein kinase Tpl2 plays an essential role in macrophage activation by the bacterial component lipopolysaccharide (LPS). In response to LPS stimulation, Tpl2 phosphorylates a downstream kinase, MEK1, leading to the activation of ERK signaling pathway. Recent studies demonstrate that the NF-kappaB1 precursor protein p105 functions as an inhibitor of Tpl2 and that the LPS-stimulated Tpl2 activation requires p105 degradation. However, how p105 inhibits the signaling function of Tpl2 is not completely understood. We show here that p105 does not inhibit the intrinsic kinase activity of Tpl2. When complexed with p105, Tpl2 remains catalytically active and uses p105 as a substrate. However, the p105-bound Tpl2 is unable to phosphorylate its physiological target, MEK1. These findings suggest that p105 functions as a competitive inhibitor of Tpl2 that blocks its access by MEK1.

Amino Acid Sequence↗

Two new phenolic glycosides from the barks of Hydnocarpus annamensis and their anti-inflammatory and anti-oxidation activities.

Two new phenolic glycosides 1 and 2 were isolated from the barks of Hydnocarpus annamensis, along with eighteen known compounds. The structures of all compounds were deduced using spectroscopic methods. Anti-inflammatory and anti-oxidation activities were evaluated. Among the isolates, compounds 1, 5, 15 and 17 exhibited COX-2 inhibitory activities, with an inhibitory rate of 60.3 - 63.4 % at 10 microM. Compounds 7, 12, 13 and 20 showed anti-oxidation capacities in the DPPH free-radical assay, with a scavenging effect of 60.9 - 69.4 % at 50 microM, and 18.5 - 34.6 % at 10 microM.

Animals↗

Municipal wastewater treatment by moving-bed-biofilm reactor with diatomaceous earth as carriers.

This study was conducted to examine the feasibility of using a moving-bed-biofilm reactor with internal circulation through aeration for the treatment of municipal wastewater. The attached film was a mixed-microorganism consortium, which used composite-refined-diatomaceous earth as novel biomass carriers to form a diatomaceous-earth-moving-bed-biofilm-reactor (DEMBBR) process. The startup of laboratory-scale, continuous-flow reactor was successfully achieved without seeding activated sludge. The DEMBBR process removed chemical oxygen demand, total phosphorus, ammonium-nitrogen, and turbidity at the highest rate of 88.5, 83, 92.3, and 96.7%, respectively, with a hydraulic retention time of only 2.5 hours. The DEMBBR was less affected by interruption and adverse operation conditions than the conventional-activated-sludge reactor. Thus, the DEMBBR could be proposed to be a cost-effective, small-wastewater-treatment-process unit.

Biofilms↗

Use of surgical videos for realistic simulation of surgical procedures.

One of the major challenges in the development of virtual environments for medical simulations is photorealistic rendering, permitting high fidelity visual effects and user interaction. Digitized videos recorded from the laparoscopic camera are a rich source of information about surgical scenarios. How to fully utilize the information is important for improving the realism of the simulated scenarios. In reality, the camera viewpoint changes frequently and even for the same viewpoint, the scene is dynamic due to rhythmic heartbeat. Hence, the results of classical texture mapping are usually visually unappealing as they fail to capture the pulsatile effect, as well as other global illumination properties of the scene. In this paper we present a hybrid technique to improve the photorealistic rendering of the virtual surgery scenarios by spatio-temporally utilizing videos recorded during actual surgical procedures.

Computer Simulation↗

[Raising fat content in transgenic rice by anti-PEP gene transformation].

Gene for phosphoenolpyruvate carboxylase (PEPCase) was incorporated in antisense orientation into genome of japonica rice variety Xiushui 11 through Agrobacterium tumefaciens-mediated transformation of mature seeds-derived embryogenic calli, and a total of 95 transgenic plants were regenerated, which were confirmed by histochemical detection of GUS activity (Fig.2), PCR assay (Fig.3) and Southern hybridization analysis (Fig.4). The transgene was inherited by the T1 progeny and Mendelian 3:1 segregation ratio was observed in most transgenic lines. It was found that the fat content of hulled grains of T2 transgenic lines was 0.37 +/- 0.12 per cent higher than that of the control, most of which were statistically very significant (Table 2).

Agrobacterium tumefaciens↗

[Treatment of male adrenogenital syndrome (report of 17 cases)].

OBJECTIVE: To discuss the treatment of male adrenogenital syndrome. METHODS: The clinical data of 17 patients with male adrenogenital syndrome, including 15 cases of congenital adrenal hyperplasia (CAH) and 2 cases of adrenocortical tumors, were analyzed retrospectively. The patients with 21-hydroxylase deficiency (21-OHD) and 11beta-hydroxylase deficiency (11beta-OHD) were treated with adrenocortical hormone, those with 17-hydroxylase deficiency (17-OHD) received sexual glands excision and estrogen besides adrenocortical hormone, and those with adrenocortical tumors underwent surgical removal. RESULTS: Sexual precocity symptoms disappeared and abnormal laboratory results returned to normal in 5 of the 21-OHD patients, who adhered to hormone treatment, and height growth was improved in the other 2, who received the medicine at an early age. The testicular adrenal rest (TAR) tumor was reduced dramatically in 1 case of 21-OHD after treatment. A left TAR found in another 21-OHD patient who discontinued the hormone therapy became softened after the resumption. Sperm could be seen in the semen of 3 21-OHD patients, but in small quantity and of poor quality. One 11beta-OHD patient with sexual precocity symptoms and hypertension became normal after the hormone treatment, and six 17-OHD patients maintained their female sexuality after the hormone treatment and operation. No relapse was found after resection of the adrenocortical tumors. CONCLUSION: Adrenocortical hormone therapy helps improve the height growth and testicular function of CAH patients, and surgical removal is necessary for adrenocortical tumors.

Adolescent↗