B lymphocyte-induced maturation protein-1 (Blimp-1) serves as a master regulator of the development and function of antibody-producing B cells. Given that its function in T lymphocytes has been ...identified within the past decade, we review recent findings with emphasis on its role in coordinated control of gene expression during the development, differentiation, and function of T cells. Expression of Blimp-1 is mainly confined to activated T cells and is essential for the production of interleukin (IL)-10 by a subset of forkhead box (Fox)p3
regulatory T cells with an effector phenotype. Blimp-1 is also required to induce cell elimination in the thymus and critically modulates peripheral T cell activation and proliferation. In addition, Blimp-1 promotes T helper (Th) 2 lineage commitment and limits Th1, Th17 and follicular helper T cell differentiation. Furthermore, Blimp-1 coordinates with other transcription factors to regulate expression of IL-2, IL-21 and IL-10 in effector T lymphocytes. In CD8
T cells, Blimp-1 expression is distinct in heterogeneous populations at the stages of clonal expansion, differentiation, contraction and memory formation when they encounter antigens. Moreover, Blimp-1 plays a fundamental role in coordinating cytokine receptor signaling networks and transcriptional programs to regulate diverse aspects of the formation and function of effector and memory CD8
T cells and their exhaustion. Blimp-1 also functions as a gatekeeper of T cell activation and suppression to prevent or dampen autoimmune disease, antiviral responses and antitumor immunity. In this review, we discuss the emerging roles of Blimp-1 in the complex regulation of gene networks that regulate the destiny and effector function of T cells and provide a Blimp-1-dominated transcriptional framework for T lymphocyte homeostasis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Summary
Background
Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations.
Aims
To explore genetic variants associated with chronic HBV infection.
Methods
The ...study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole‐genome genotyping by Axiom‐Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method.
Results
Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10−35) was significantly associated with HBV chronicity (Pcorrected < 8.6 × 10−8). Imputation analyses showed that HLA‐DPA1*02:02 and HLA‐DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09‐1.89) and 1.61 (1.29‐2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA‐DRB1*13:02, HLA‐DQA1* 01:02 and HLA‐DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17‐0.58), 0.70 (0.56‐0.87) and 0.33 (0.18‐0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein.
Conclusions
HLA class II variants are relevant for chronicity after HBV acquisition.
To perform a meta‐analysis to compare the efficacy and safety of diode laser transscleral cyclophotocoagulation (TSCPC) and cyclocryotherapy (CCT) in the treatment of intractable glaucoma. Systemic ...searches of the Ovid MEDLINE, EMBASE, and Cochrane Library databases yielded experimental and observational comparative studies. TSCPC and CCT efficacy and safety outcomes were compared. Subgroup analyses of participant ethnicity, preoperative intraocular pressure (IOP) level, and underlying causes of glaucoma were conducted. The pooled effects were computed using the random‐effects model. The meta‐analysis included nine studies totalling 668 eyes. There was no statistically significant difference between the TSCPC and CCT groups in the IOP reduction (IOPR%), decrease in antiglaucoma medications, the operative success rate with or without medications, or retreatment rate in the efficacy analysis. In the subgroup analysis, CCT had a better IOP‐lowering effect among non‐Asian participants and a non‐inferior IOPR% to TSCPC among Asian participants. TSCPC and CCT were associated with similar rates of deterioration in visual acuity, postoperative visual analog scale, and other analysed postoperative complications in the safety analysis. In both groups, severe complications were uncommon. Diode laser TSCPC and CCT had nearly equivalent clinical efficacy in treating intractable glaucoma, while CCT demonstrated a better IOP‐lowering effect in non‐Asian. Both cyclodestructive procedures have a comparable safety profile.
Electrochromic devices (ECDs) play an important role in smart window applications for blocking heat from sunlight. Tungsten trioxide (WO3) is one of the best candidates for making electrochromic ...films. Current manufacturing processes are, however, costly, have long processing time, and often use non-eco-friendly precursors. Here an alternative facile method integrating electro-exploding wire and spray coating techniques is demonstrated for applications in large size ECDs. The electro-exploding wire technique is used to synthesize WO3 nanomaterials (NMs) in deionized water. The varied size distribution of WO3 NMs is achieved by changing the exploding voltage. The NMs are characterized by X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). The exploding voltage of 36 V is selected to generate WO3 NMs in a wide size distribution for making porous WO3 films. Subsequently, spray coating is used to disperse WO3 NM suspension on the ITO/glass substrate to form an electrochromic film. The films are characterized by scanning electron microscopy (SEM) and by cycle voltammetry, chronoamperometry, and chronocoulometry measurements in dilute sulfuric acid. The WO3 NM films prepared at a high exploding voltage and a high substrate temperature present a higher electrochemical stability. Considering porosity and electrochemical stability, WO3 NMs exploded at 36 V are used to prepare WO3 films on substrates heated at 300 °C. The electrochromic WO3 film can be operated for over 1000 cycles. We demonstrate an ECD with an area of 15 × 15 cm2 and propose a way to make large size ECDs with low cost and eco-friendly processes.
Display omitted
•The preparation of WO3 nanomaterials is simply done in water. It's a completely green technology. The following spray coating is also carried out by the suspension of WO3 nanomaterials in water.•The size “distribution” of the nanomaterials can be tuned using the exploding voltage thus the optimal size distribution for preparing a better porous film structure can be selected.•The porosity of the electrochromic film can be adjusted by using different size distribution of electro-exploded nanomaterials.•The large-size electrochromic device of 15 cm by 15 cm is prepared with 125-μm thick, PMMA-based LiClO4 electrolyte.•The ECD shows a large transmittance different of 55.4% between the colored and the bleached states for light of 633 nm in wavelength.
Let the sun shine in: Highly efficient and stable polymer bulk‐heterojunction solar cells can be achieved by the incorporation of vertically oriented, cross‐linked polymer nanorods (see picture). The ...device exhibits a record power conversion efficiency of 7.3 %.
Background and Aim
A large genetic effect of a novel gallstone‐associated genetic variant, the hepatocyte nuclear factor 4α (HNF4A) rs1800961 polymorphism, has been identified through recent ...genome‐wide association studies. However, this effect has not been validated in Asian populations. We investigated the association between the rs1800961 variant and gallstones among a Taiwanese population.
Methods
A total of 20 405 participants aged between 30 and 70 years voluntarily enrolled in the Taiwan Biobank. Self‐report questionnaires, physical examinations, biochemical tests, and genotyping were used for analysis. The association of the HNF4A rs1800961 variant and other metabolic risks with gallstone disease was analyzed using multiple logistic regression models.
Results
The minor T allele of HNF4A rs1800961 was associated with an increased risk of gallstone, and the association remained significant even after adjustment for other risk factors including age, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and cigarette smoking (adjusted odds ratio OR = 1.90, 95% confidence interval CI = 1.31 to 2.75) in male participants. When further stratified by BMI and age, the lithogenic effect was the most significant in male participants with obesity (adjusted OR = 3.55, 95% CI = 1.92 to 6.56) and who were younger (adjusted OR = 2.45, 95% CI = 1.49 to 4.04).
Conclusion
The novel gallstone‐associated HNF4A rs1800961 variant was associated with the risk of gallstone in the Taiwanese men. Screening for the rs1800961 polymorphism may be particularly useful in assessing the risk of gallstone formation in younger or obese men.
Precision therapy for lung cancer requires comprehensive genomic analyses. Specific effects of targeted therapies have been reported in Asia populations, including Taiwanese, but genomic studies have ...rarely been performed in these populations.
We enrolled 72 patients with non-small cell lung cancer, of whom 61 had adenocarcinoma, 10 had squamous cell carcinoma, and 1 had combined adenocarcinoma and squamous cell carcinoma. Whole-exome or targeted gene sequencing was performed. To identify trunk mutations, we performed whole-exome sequencing in two tumor regions in four patients.
Nineteen known driver mutations in EGFR, PIK3CA, KRAS, CTNNB1, and MET were identified in 34 of the 72 tumors evaluated (47.22%). A comparison with the Cancer Genome Atlas dataset showed that EGFR was mutated at a much higher frequency in our cohort than in Caucasians, whereas KRAS and TP53 mutations were found in only 5.56% and 25% of our Taiwanese patients, respectively. We also identified new mutations in ARID1A, ARID2, CDK12, CHEK2, GNAS, H3F3A, KDM6A, KMT2C, NOTCH1, RB1, RBM10, RUNX1, SETD2, SF3B1, SMARCA4, THRAP3, TP53, and ZMYM2. Moreover, all ClinVar pathogenic variants were trunk mutations present in two regions of a tumor. RNA sequencing revealed that the trunk or branch genes were expressed at similar levels among different tumor regions.
We identified novel variants potentially associated with lung cancer tumorigenesis. The specific mutation pattern in Taiwanese patients with non-small cell lung cancer may influence targeted therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Periodontal disease may drive a systemic inflammatory response that triggers migraine; however, the association between periodontal disease and migraine has rarely been investigated in a ...community‐based setting.
Methods
This cross‐sectional study included 66,109 participants aged 30 to 70 years from Taiwan Biobank (TWB). A structured questionnaire was administered to participants, who were also subjected to whole‐genome single nucleotide polymorphism genotyping using the customized Axiom–TWB array. To identify subjects with periodontal disease and migraine, the computerized linkage of data obtained from TWB and the National Health Insurance Research Database was performed. Participants were evaluated for their genetic predisposition to migraine using a polygenic risk score. We examined and estimated the magnitude of associations between periodontal disease and migraine.
Results
In this study, 4618 (4618/66,109; 7%) participants with migraine and 61,491 (61,491/66,109; 83%) participants without migraine were included. Participants with migraine exhibited a higher prevalence of periodontal disease than participants without migraine (4324/4618; 94% vs. 56,036/61,491; 91%). A significant positive association was observed between periodontal disease and migraine, with an adjusted odds ratio (ORadj) of 1.40 (95% confidence interval CI = 1.24–1.59; p < 0.001). The association remained consistent even after excluding participants with other comorbidities (ORadj = 1.34; 95% CI = 1.16–1.55; p < 0.001). Moreover, the positive association between periodontal disease and migraine remained significant across the subgroups of age, sex, other comorbidities, and classified polygenic risk scores of migraine, with the ORadj ranging from 1.26 to 1.78.
Conclusions
A significant positive association was observed between periodontal disease and migraine. Future studies need to explore the biological mechanisms of how periodontal disease might affect migraine.
Objectives
Cognitive impairment and change are a focus of research into late‐life depression. The aims of this 5‐year prospective study were (1) to observe cognitive status change; (2) to investigate ...the rate and risk ratio of dementia or cognitive decline; and (3) to examine the cognitive domain predictors for conversion to dementia within 5 years among a clinical cohort with remitted major depressive disorder (MDD).
Methods
The study cohort included 130 elderly persons with late‐life remitted MDD and 100 normal controls. Comprehensive neuropsychological tests were conducted to determine cognitive domain status. Diagnoses of mild cognitive impairment (MCI) and dementia were made at baseline and at a follow‐up visit at the 5‐year point. In total, 98 cases and 55 normal controls completed the 5‐year follow‐up assessment.
Results
Of the study cohort with late‐life remitted MDD, 28.6% had MCI and 25.5% developed dementia within 5 years. Patients with late‐life remitted MDD had an approximate 3 times higher risk of subsequent cognitive decline as compared with the normal controls. Information‐processing speed (p = 0.009) and memory (p = 0.041) could predict subsequent progression to dementia within 5 years among patients with MDD.
Conclusions
This study demonstrated that compared with the general elderly population, elderly patients with depression have more significant impairment in cognitive function after 5 years. Further, we found that in depressed patients, deficits in information‐processing speed and memory domains were highly suggestive of progression to dementia within 5 years.
Key points
Elderly patients with depression had higher risk of subsequent cognitive decline.
In elder patients with remitted major depressive disorder (MDD), deficits in information‐processing speed and memory domains were highly suggestive of progression to dementia within 5 years.
A series of dialkylated dithienothiophenoquinoids (DTTQs), end‐functionalized with dicyanomethylene units and substituted with different alkyl chains, are synthesized and characterized. Facile ...one‐pot synthesis of the dialkylated DTT core is achieved, which enables the efficient realization of DTTQs as n‐type active semiconductors for solution‐processable organic field effect transistors (OFETs). The molecular structure of hexyl substituted DTTQ‐6 is determined via single‐crystal X‐ray diffraction, revealing DTTQ is a very planar core. The DTTQ cores form a “zig‐zag” linking layer and the layers stack in a “face‐to‐face” arrangement. The very planar core structure, short core stacking distance (3.30 Å), short intermolecular SN distance (2.84 Å), and very low lying lowest unoccupied molecular orbital energy level of −4.2 eV suggest that DTTQs should be excellent electron transport candidates. The physical and electrochemical properties as well as OFETs performance and thin film morphologies of these new DTTQs are systematically studied. Using a solution‐shearing method, DTTQ‐11 exhibits n‐channel transport with the highest mobility of up to 0.45 cm2 V−1 s−1 and a current ON/OFF ratio (ION/IOFF) greater than 105. As such, DTTQ‐11 has the highest electron mobility of any DTT‐based small molecule semiconductors yet discovered combined with excellent ambient stability. Within this family, carrier mobility magnitudes are correlated with the alkyl chain length of the side chain substituents of DTTQs.
Dialkylated dithienothiophenoquinoids (DTTQs) with different alkyl chains and end‐functionalized with dicyanomethylene groups are investigated for organic field effect transistors (OFETs) applications. Remarkably, solution‐sheared DTTQ‐11 OFETs yield the highest mobility of 0.45 cm2 V−1 s−1, good long‐term environmental stability, and electrical stability, which is attractive for solution‐processable n‐type organic semiconductor applications.
PDF
