Assessment of causal associations between uric acid and 25-hydroxyvitamin D levels

BackgroundPrevious observational studies have revealed the association between serum uric acid and 25-hydroxyvitamin D. However, the causality and the direction of the associations remain unknown. Thus, we performed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal association between uric acid and 25-hydroxyvitamin D and to determine the direction of the association.MethodBased on the summary-level GWAS data from large genome-wide association studies, several steps were taken in our analysis to select eligible single-nucleotide polymorphisms (SNPs), which were strongly related to exposure as the instrumental variables. We used different analytical methods, such as inverse-variance weighting (IVW) method, weighted median, MR-Egger regression, and weighted mode method, to make our result more robust and reliable. The IVW method was used as the primary analysis. The Cochran’s Q test, MR-Egger intercept test, MR-PRESSO method, and “leave-one-out” sensitivity analysis was performed to evaluate the heterogeneities, horizontal pleiotropy, and robustness of the results. MR analyses were also conducted using genetic risk scores (GRS) as instrumental variables in both directions by using the same summary-level GWAS data.ResultsOur two-sample MR analysis suggested a causal association of genetically predicted uric acid on 25-hydroxyvitamin D [IVW method: β(SE), −0.0352(0.0149); p = 0.0178], which suggested that a per mg/dl increase in uric acid was associated with a decrease of 0.74 nmol/L of 25-hydroxyvitamin D, and the above results remained stable in the sensitivity analysis. By contrast, four MR methods suggested no causal relationship of 25-hydroxyvitamin D on serum uric acid [IVW β(SE), 0.0139 (0.0635); p = 0.826; MR-Egger β(SE), 0.0671 (0.108); p = 0.537; weighted median β(SE), 0.0933 (0.0495); p = 0.0598; weighted mode β(SE), 0.0562 (0.0463); p = 0.228, respectively]. After excluding the SNPs, which were associated with confounding factors and outlier SNPs, the IVW method suggested that there was still no causal association of 25-hydroxyvitamin D on serum uric acid. The GRS approach showed similar results.ConclusionsSerum uric acid may causally affect the 25-hydroxyvitamin D levels, whereas the causal role of 25-hydroxyvitamin D on uric acid was not supported in our MR analysis. Our findings suggest that increased levels of uric acid should prompt investigation for vitamin D deficiency

Templated-Construction of Hollow MoS2 Architectures with Improved Photoresponses

: Despite the outstanding optoelectronic properties of MoS2 and its analogues, synthesis of such materials with desired features including fewer layers, arbitrary hollow structures, and particularly specifically customized morphologies, via inorganic reactions has always been challenging. Herein, using predesigned lanthanide-doped upconversion luminescent materials (e.g., NaYF4:Ln) as templates, arbitrary MoS2 hollow structures with precisely defined morphologies, widely variable dimensions, and very small shell thickness (≈2.5 nm) are readily constructed. Most importantly, integration of the near-infrared-responsive template significantly improves the photoresponse of up to 600 fold in device made of NaYF4:Yb/Er@MoS2 compared with that of MoS2 nanosheets under 980 nm laser illumination. Multichannel optoelectronic device is further fabricated by simply changing luminescent ions in the template, e.g., NaYF4:Er@MoS2, operating at 1532 nm light excitation with a 276-fold photoresponse enhancement. The simple chemistry, easy operation, high reliability, variable morphologies, and wide universality represent the most important advantages of this novel strategy that has not been accessed before

THE PREVENTIVE EFFECT AND ENHANCE IMMUNITY FUNCTION OF BU-ZHONG-YI-QIWAN ON S180 TUMOR MICE.

Background: To evaluate the preventive effect and enhance immunity functions of Bu-zhong-yi-qi wan in vivo. Materials and Methods: S180 tumor mice model was established by subcutaneous injection a dose of 0.2 ml (1×107/ml) at the right oxter. The inhibitory rates, spleen indexes and thymus indexes were calculated. Splenic lymphocyte proliferative activity assay and phagocytosis activity of peritoneal macrophages were done. Interferon (IFN-γ), interleukin (IL-2) and tumor necrotic factor (TNF-α) in serum were detected. Results: In the S180 tumor-bearing mice, Bu-zhong-yi-qi wan with medium-dose (975 mg/kg, 100 mg/l) had potent preventive effect and anti-tumor effect, macrophage phagocytosis and Con A-stimulated splenocyte proliferation were increased as compared with model control treatment. Bu-zhong-yi-qi wan could take part in the immune response by promoting the proliferation and differentiation of Tcells, increasing the activity of the macrophages, inducing the generation of cell factor IL-2, TNF-α, IFN-γ. Conclusion: It proved that Bu-zhong-yi-qi wan of medium-dose had great preventive effect and could enhance immunity function

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

Excitation-Controlled Host–Guest Multicolor Luminescence in Lanthanide-Doped Calcium Zirconate for Information Encryption

Efficient control over lanthanide luminescence by regulating excitations offers a real-time and reversible luminescence-managing strategy, which is of great importance and highly desirable for various applications, including multicolor display and information encryption. Herein, we studied the crystal structure, luminescence properties, and mechanisms of undoped and Tb3+/Eu3+-doped CaZrO3 in detail. The intrinsic purple-blue luminescence from host CaZrO3 and the introduced green/red luminescence from guest dopants Tb3+/Eu3+ were found to have different excitation mechanisms and, therefore, different excitation wavelength ranges. This enables the regulation of luminescent color through controlling the excitation wavelengths of Tb3+/Eu3+-doped CaZrO3. Furthermore, preliminary applications for information encryption with these materials were demonstrated using portable UV lamps of 254 and 302 nm. This study not only promotes the development of multicolor luminescence regulation in fixed-composition materials, but also advances the practical applications of lanthanide luminescent materials in visually readable, high-level anti-counterfeiting and information encryption

Analysis of clinical characteristics of 25 patients with hypereosinophilia complicated with peripheral arterial occlusion

Objective To improve the understanding of hypereosinophilia(HE) rarely complicated with peripheral arterial occlusion. Methods Among 555 inpatients with HE from Peking Union Medical College Hospital from April 2012 to October 2021, 25 cases complicated with peripheral artery occlusion were involved according to the inclusion and exclusion criteria. The initial clinical features, symptoms of arterial occlusion and organ involvement of the 25 patients were summarized. After age and gender matching, 34 HE patients without peripheral artery occlusion as the control group. Clinical manifestations, treatment and prognosis of the two groups were compared. Results All patients were male, with an average of (44.5±16.2) years old. The main involved arteries included ulnar artery, radial artery, tibial artery and peroneal artery. The IgA level and involvement of skin and peripheral nerves in the case group were significantly higher than that in control group(P＜0.05). 76% and 80% of the patients in the case group received anticoagulant therapy or antiplatelet therapy, respectively, 20% received steroid pulse therapy and 64% received immunosuppressive therapy, above which were significantly higher than that in control group(P＜0.05). As indicated by eosinophil level, 68% and 48% of patients in the two groups achieved complete remission, respectively. Conclusions The skin and peripheral nervous system are the most commonly involved organs in HE patients complicated with peripheral arterial occlusion, and administration of steroids and immunosuppressive medicines may lead to good prognosis

Association between Coffee Consumption, Caffeine Intake, and Metabolic Syndrome Severity in Patients with Self-Reported Rheumatoid Arthritis: National Health and Nutrition Examination Survey 2003–2018

Rheumatoid arthritis (RA) is chronic inflammatory disease. Although coffee impacts metabolism, no evidence has shown an association between coffee consumption and decreased risk for developing metabolic syndrome (MetS) among RA patients. Hence, we examined the association between coffee consumption and metabolic syndrome severity among 1094 participants with self-reported RA. Accordingly, patients with MetS z-scores of p = 0.04). Subgroup analysis showed that in the low-risk group, daily intake of p = 0.003), scores (p = 0.03). Coffee intake was associated with low body mass index (p = 0.03 for 0–2 cups per day; p = 0.02 for >2 cups per day) and low HOMA-IR (β, −2.62; 95%CI, −5.13 to −0.11; p = 0.04). Our study suggests that coffee, but not decaffeinated coffee consumption and total caffeine intake, is associated with MetS severity in RA

Air-conditioning use behaviors when elevated air movement is available

Many experimental studies demonstrated that elevating indoor temperatures to 28 or 30°C is comfortable if fans are used, while this elevation often is not applied in practice. This study aims to investigate AC thermostat use behaviors when elevated air movement is available, as well as to provide insights at guiding occupants to select warmer environments without reducing their comfort. 20 subjects participated in a series of tests at three initial ambient temperatures (26, 28, and 30°C) with different settings of an AC thermostat and a ceiling fan: (1) a free-controlled thermostat without a fan, (2) a free-controlled thermostat with a free-controlled fan, (3) a free-controlled thermostat with an always-on fan (controllable but not allowed to turn off), (4) a limited thermostat (no lower than 28°C) with a free-controlled fan, and (5) a limited thermostat with an always-on fan. The results show that without the ceiling fan, subjects used AC to lower indoor temperatures to 25.7°C. When the fan was available (free-controlled), they did not only rely on lowering the AC set-point alone but also turned on the fan immediately when starting using AC. This behavior ended a final ambient temperature up to 27.4°C. Under always-on fan conditions, the fan was running at a high speed at the beginning of using AC. Although subjects turned down the fan speed, the final fan speeds were about doubled the speeds as compared with free-controlled fan conditions. This higher initial speed by the always-on fan made subjects select higher indoor temperatures: at the 28°C initial temperature, there was no further lowering of ambient temperatures; at the 30°C initial temperature, the final temperatures were 28.6 and 28.9°C for the free-controlled and limited AC test conditions, about a 3-K set-points extension compared with the no-fan condition. Further, despite different conditions, more than 90% of subjects had comfortable feelings, which indicates that people with adjustable AC prefer a constant thermal perception rather than a constant ambient temperature. Therefore, the strategy of using fans before AC should be adopted to guide people actively to select higher AC set-point temperatures

Air-conditioning use behaviors when elevated air movement is available

Many experimental studies demonstrated that elevating indoor temperatures to 28 or 30°C is comfortable if fans are used, while this elevation often is not applied in practice. This study aims to investigate AC thermostat use behaviors when elevated air movement is available, as well as to provide insights at guiding occupants to select warmer environments without reducing their comfort. 20 subjects participated in a series of tests at three initial ambient temperatures (26, 28, and 30°C) with different settings of an AC thermostat and a ceiling fan: (1) a free-controlled thermostat without a fan, (2) a free-controlled thermostat with a free-controlled fan, (3) a free-controlled thermostat with an always-on fan (controllable but not allowed to turn off), (4) a limited thermostat (no lower than 28°C) with a free-controlled fan, and (5) a limited thermostat with an always-on fan. The results show that without the ceiling fan, subjects used AC to lower indoor temperatures to 25.7°C. When the fan was available (free-controlled), they did not only rely on lowering the AC set-point alone but also turned on the fan immediately when starting using AC. This behavior ended a final ambient temperature up to 27.4°C. Under always-on fan conditions, the fan was running at a high speed at the beginning of using AC. Although subjects turned down the fan speed, the final fan speeds were about doubled the speeds as compared with free-controlled fan conditions. This higher initial speed by the always-on fan made subjects select higher indoor temperatures: at the 28°C initial temperature, there was no further lowering of ambient temperatures; at the 30°C initial temperature, the final temperatures were 28.6 and 28.9°C for the free-controlled and limited AC test conditions, about a 3-K set-points extension compared with the no-fan condition. Further, despite different conditions, more than 90% of subjects had comfortable feelings, which indicates that people with adjustable AC prefer a constant thermal perception rather than a constant ambient temperature. Therefore, the strategy of using fans before AC should be adopted to guide people actively to select higher AC set-point temperatures

FGF-2 Transcriptionally Down-Regulates the Expression of BNIP3L via PI3K/Akt/FoxO3a Signaling and Inhibits Necrosis and Mitochondrial Dysfunction Induced by High Concentrations of Hydrogen Peroxide in H9c2 Cells

Background/Aims: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress. However, the mechanisms by which FGF-2 rescues the myocardium from oxidative stress damage in cardiovascular disease remain unclear. The present study explored the protective effects of FGF-2 in the H2O2-induced necrosis of H9C2 cardiomyocytes as well as the possible signaling pathways involved. Methods: Necrosis of H9c2 cardiomyocytes was induced by H2O2 and assessed using a Cell Counting Kit-8 (CCK8) assay and flow cytometry analysis. The cells were pretreated with the PI3K/Akt inhibitor Wortmannin to investigate the possible involvement of the PI3K/Akt pathway in the protection by FGF-2. The levels of Akt, p-Akt, FoxO3a, p-FoxO3a, and BNIP3L were detected by Western blot. Chromatin immuno-precipitation (ChIP) analysis was used to test whether FoxO3a binds directly to the BNIP3L promoter region. A luciferase assay was used to study the effects of FoxO3a on BNIP3L gene promoter activity. Mitochondrial ΔΨM was quantified using tetramethylrhodamine methyl ester perchlorate (TMRM). The mitochondrial oxygen consumption rate (OCR) was assessed with a Seahorse XF24 Analyzer. Results: Treatment with H2O2 decreased the phosphorylation of Akt and FoxO3a, and it induced the nuclear localization of FoxO3a and the necrosis of H9c2 cells. These effects of H2O2 were abrogated by pretreatment with FGF-2. Furthermore, the protective effects of FGF-2 were abolished by the PI3K/Akt inhibitor Wortmannin. ChIP analyses indicated that FoxO3a binds directly to the BNIP3L promoter region. Using a luciferase assay, we further observed that FoxO3a increased BNIP3L gene promoter activity. As expected, overexpression of BNIP3L in H9C2 cardiomyoblast cells reduced the cardioprotection of FGF-2 in H2O2-induced necrosis and mitochondrial dysfunction. Conclusions: The present data suggest that FGF-2 protects against H2O2-induced necrosis of H9C2 cardiomyocytes via the activation of the PI3K/Akt/FoxO3a pathway. Moreover, the present results demonstrate that FoxO3a is an important transcription factor that acts by binding to the promoter and promoting the transcription of BNIP3L, and it contributes to the necrosis and mitochondrial dysfunction induced by H2O2 in H9c2 cardiomyoblast cells