Fluoride-induced hypertension by regulating RhoA/ROCK pathway and phenotypic transformation of vascular smooth muscle cells: In vitro and in vivo evidence.

Fluoride exposure has been implicated as a potential risk factor for hypertension, but the underlying mechanisms remain unclear. This study investigated the role of the RhoA/ROCK signaling pathway in fluoride-induced hypertension. Male Wistar rats were divided into different groups and exposed to varying concentrations of sodium fluoride (NaF) or sodium chloride (NaCl) via drinking water. The rats' blood pressure was measured, and their aortic tissue was utilized for high-throughput sequencing analysis. Additionally, rat and A7r5 cell models were established using NaF and/or Fasudil. The study evaluated the effects of fluoride exposure on blood pressure, pathological changes in the aorta, as well as the protein/mRNA expression levels of phenotypic transformation indicators (a-SMA, calp, OPN) in vascular smooth muscle cells (VSMCs), along with the RhoA/ROCK signaling pathway (RhoA, ROCK1, ROCK2, MLC/p-MLC). The results demonstrated that fluoride exposure in rats led to increased blood pressure. High-throughput sequencing analysis revealed differential gene expression associated with vascular smooth muscle contraction, with the RhoA/ROCK signaling pathway emerging as a key regulator. Pathological changes in the rat aorta, such as elastic membrane rupture and collagen fiber deposition, were observed following NaF exposure. However, fasudil, a ROCK inhibitor, mitigated these pathological changes. Both in vitro and in vivo models confirmed the activation of the RhoA/ROCK signaling pathway and the phenotypic transformation of VSMCs from a contractile to a synthetic state upon fluoride exposure. Fasudil effectively inhibited the activities of ROCK1 and ROCK2 and attenuated the phenotypic transformation of VSMCs. In conclusion, fluoride has the potential to induce hypertension through the activation of the RhoA/ROCK signaling pathway and phenotypic changes in vascular smooth muscle cells. These results provide new insights into the mechanism of fluoride-induced hypertension.

TRANSPARENT TESTA GLABRA1 Regulates High-Intensity Blue Light-Induced Phototropism by Reducing CRYPTOCHROME1 Levels.

The asymmetrical distribution of auxin supports high intensity blue light (HBL)-mediated phototropism. Flavonoids, secondary metabolites induced by blue light and TRANSPARENT TESTA GLABRA1 (TTG1), alter auxin transport. However, the role of TTG1 in HBL-induced phototropism in Arabidopsis (Arabidopsis thaliana) remains unclear. We found that TTG1 regulates HBL-mediated phototropism. HBL-induced degradation of CRYPTOCHROME 1 (CRY1) was repressed in ttg1-1, and depletion of CRY1 rescued the phototropic defects of the ttg1-1 mutant. Moreover, overexpression of CRY1 in a cry1 mutant background led to phototropic defects in response to HBL. These results indicated that CRY1 is involved in the regulation of TTG1-mediated phototropism in response to HBL. Further investigation showed that TTG1 physically interacts with CRY1 via its N-terminus and that the added TTG1 promotes the dimerization of CRY1. The interaction between TTG1 and CRY1 may promote HBL-mediated degradation of CRY1. TTG1 also physically interacted with blue light inhibitor of cryptochrome 1 (BIC1) and Light-Response Bric-a-Brack/Tramtrack/Broad 2 (LRB2), and these interactions either inhibited or promoted their interaction with CRY1. Exogenous gibberellins (GA) and auxins, two key plant hormones that crosstalk with CRY1, may confer the recovery of phototropic defects in the ttg1-1 mutant and CRY1-overexpressing plants. Our results revealed that TTG1 participates in the regulation of HBL-induced phototropism by modulating CRY1 levels, which are coordinated with GA or IAA signaling.

Proactive consultation of laboratory medicine increased diagnostic rate of multiple myeloma: One single center's 12-year experience.

Multiple myeloma (MM) was one of the hardest cancers to diagnose because of numerous nonspecific symptoms, leading to diagnostic delay. Proactive consultation of laboratory medicine (PCLM) could help timely diagnosis of blood cancers, avoiding diagnostic delay. This study aimed to evaluate the effect of PCLM on diagnosis and outcomes in MM. This retrospective study was conducted in newly diagnosed MM patients from 2011 to 2022. Implementation of PCLM initiated in 2015 with a laboratory-oriented algorithm. The annual diagnostic rate, patient demographics, the time intervals from symptom onset to diagnosis and to treatment, and clinical outcomes were analyzed. A total of 134 patients were newly diagnosed during the study interval. The diagnostic rate increased from 4.65 ±â€…1.59 to 7.43 ±â€…1.52 per million patient-visits after implementation of PCLM. The median time interval from symptom onset to diagnosis was significantly shortened after implementation of PCLM (50 days with interquartile range [IQR]: 24-136 days vs 150 days with IQR: 41-385 days, P = .003). Besides, the 1-year survival was significantly higher in patients diagnosed as MM after implementation of PCLM (72.4% vs 51.7%, P = .035). Implementation of PCLM not only increased diagnostic rate of MM and improved outcomes, but also raise awareness for MM and promote multidisciplinary collaboration in healthcare.

Revisiting the association between vitamin D deficiency and active tuberculosis: A prospective case-control study in Taiwan.

BACKGROUND: To revisit the association between vitamin D deficiency (VDD, defined as serum 25(OH)D < 20 ng/ml) and incident active tuberculosis (TB), after two potentially underpowered randomized trials showed statistically non-significant 13%-22% decrease in TB incidence in vitamin D supplementation groups. METHODS: We prospectively conducted an age/sex-matched case-control study that accounting for body-mass index (BMI), smoking, and other confounding factors to examine the association between VDD and active TB among non-HIV people in Taiwan (latitude 24°N), a high-income society which continues to have moderate TB burden. RESULTS: We enrolled 62 people with incident active TB and 248 people in control group. The TB case patients had a significantly higher proportion of VDD compared to the control group (51.6% vs 29.8%, p = 0.001). The 25(OH)D level was also significantly lower in TB patients compared to control group (21.25 ± 8.93 ng/ml vs 24.45 ± 8.36 ng/ml, p = 0.008). In multivariable analysis, VDD (adjusted odds ratio [aOR]: 3.03, p = 0.002), lower BMI (aOR: 0.81, p < 0.001), liver cirrhosis (aOR: 8.99, p = 0.042), and smoking (aOR: 4.52, p = 0.001) were independent risk factors for incident active TB. CONCLUSIONS: VDD is an independent risk factor for incident active TB. Future randomized trials examining the effect of vitamin D supplementation on TB incidence should focus on people with a low BMI or other risk factors to maximize the statistical power.

Quantitative assessment of background parenchymal enhancement is associated with lifetime breast cancer risk in screening MRI.

OBJECTIVES: To compare the quantitative background parenchymal enhancement (BPE) in women with different lifetime risks and BRCA mutation status of breast cancer using screening MRI. MATERIALS AND METHODS: This study included screening MRI of 535 women divided into three groups based on lifetime risk: nonhigh-risk women, high-risk women without BRCA mutation, and BRCA1/2 mutation carriers. Six quantitative BPE measurements, including percent enhancement (PE) and signal enhancement ratio (SER), were calculated on DCE-MRI after segmentation of the whole breast and fibroglandular tissue (FGT). The associations between lifetime risk factors and BPE were analyzed via linear regression analysis. We adjusted for risk factors influencing BPE using propensity score matching (PSM) and compared the BPE between different groups. A two-sided Mann-Whitney U-test was used to compare the BPE with a threshold of 0.1 for multiple testing issue-adjusted p values. RESULTS: Age, BMI, menopausal status, and FGT level were significantly correlated with quantitative BPE based on the univariate and multivariable linear regression analyses. After adjusting for age, BMI, menopausal status, hormonal treatment history, and FGT level using PSM, significant differences were observed between high-risk non-BRCA and BRCA groups in PEFGT (11.5 vs. 8.0%, adjusted p = 0.018) and SERFGT (7.2 vs. 9.3%, adjusted p = 0.066). CONCLUSION: Quantitative BPE varies in women with different lifetime breast cancer risks and BRCA mutation status. These differences may be due to the influence of multiple lifetime risk factors. Quantitative BPE differences remained between groups with and without BRCA mutations after adjusting for known risk factors associated with BPE. CLINICAL RELEVANCE STATEMENT: BRCA germline mutations may be associated with quantitative background parenchymal enhancement, excluding the effects of known confounding factors. This finding can provide potential insights into the cancer pathophysiological mechanisms behind lifetime risk models. KEY POINTS: Expanding understanding of breast cancer pathophysiology allows for improved risk stratification and optimized screening protocols. Quantitative BPE is significantly associated with lifetime risk factors and differs between BRCA mutation carriers and noncarriers. This research offers a possible understanding of the physiological mechanisms underlying quantitative BPE and BRCA germline mutations.

Functional identification of specialized diterpene synthases from Chamaecyparis obtusa and C. obtusa var. formosana to illustrate the putative evolution of diterpene synthases in Cupressaceae.

Chamaecyparis obtusa and C. obtusa var. formosana of the Cupressaceae family are well known for their fragrance and excellent physical properties. To investigate the biosynthesis of unique diterpenoid compounds, diterpene synthase genes for specialized metabolite synthesis were cloned from C. obtusa and C. obtusa var. formosana. Using an Escherichia coli co-expression system, eight diterpene synthases (diTPSs) were characterized. CoCPS and CovfCPS are class II monofunctional (+)-copalyl diphosphate synthases [(+)-CPSs]. Class I monofunctional CoLS and CovfLS convert (+)-copalyl diphosphate [(+)-CPP] to levopimaradiene, CoBRS, CovfBRS1, and CovfBRS3 convert (+)-CPP to (-)-beyerene, and CovfSDS converts (+)-CPP to (-)-sandaracopimaradiene. These enzymes are all monofunctional diterpene syntheses in Cupressaceae family of gymnosperm, and differ from those in Pinaceae. The discovery of the enzyme responsible for the biosynthesis of tetracyclic diterpene (-)-beyerene was characterized for the first time. Diterpene synthases with different catalytic functions exist in closely related species within the Cupressaceae family, indicating that this group of monofunctional diterpene synthases is particularly prone to the evolution of new functions and development of species-specific specialized diterpenoid constituents.

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.

Comparative study on chain conformations, physicochemical and rheological properties of three acidic polysaccharides from Opuntia dillenii Haw. fruits.

In this study, three acidic polysaccharides (OFPP-1, OFPP-2 and OFPP-3) were isolated from the pulps of Opuntia dillenii Haw. fruits, and their chain conformations, physicochemical and rheological properties were investigated. The molecular weight and conformational parameters (Mw, Mn, Mz, Rg and Rh) of OFPPs in 0.1 M NaNO3 solution were detected by HPSEC-MALLS-RI. In addition, based on the parameters ρ and v, it was concluded that these three polysaccharide chains exhibited sphere-like conformation in 0.1 M NaNO3 solution, which was consistent with AFM and TEM observations. Furthermore, the Congo Red experiment showed that OFPP-2 had a triple-helix structure, which may be conducive to its biological activity. This study also found that OFPPs were semi-crystalline structures with high thermal and pH stability. The rheological analyses indicated that the apparent viscosity of OFPPs solutions exhibited concentration-, temperature-, and pH-dependence, and the viscoelasticity of them was affected by molecular characteristics and concentration. The results of this study are helpful to elucidate the structure-activity relationship of OFPPs. Moreover, this study can provide theoretical reference for the application of OFPPs as bioactive ingredients or functional materials in the food, pharmaceutical and cosmetic industries and the development and utilization of the O. dillenii Haw. fruits resource.

Antifungal Activity of Cedrol from Cunninghamia lanceolate var. konishii against Phellinus noxius and Its Mechanism.

Phellinus noxius is a highly destructive fungus that causes brown root disease in trees, leading to decay and death. In Taiwan, five prized woods-Taiwania cryptomerioides, Calocedrus macrolepis var. formosana, Cunninghamia lanceolata var. konishii, Chamaecyparis formosensis, and Chamaecyparis obtusa var. formosana-are known for their fragrance and durability. This study aims to explore the anti-brown-root-rot-fungus activity of Cunninghamia lanceolata var. konishii (CL) essential oil (CLOL) and its primary components, while also delving into their mechanisms of action and inhibition pathways. The essential oil (CLOL) from CL wood demonstrated significant efficacy against P. noxius, with an inhibitory concentration (IC50) of 37.5 µg/mL. Cedrol, the major component (78.48%) in CLOL, emerged as a potent antifungal agent, surpassing the reference drug triflumizole. Further assays with cedrol revealed a stronger anti-brown-root-disease activity (IC50 = 15.7 µg/mL) than triflumizole (IC50 = 32.1 µg/mL). Scanning electron microscopy showed deformation and rupture of fungal hyphae treated with CLOL and cedrol, indicating damage to the fungal cell membrane. Cedrol-induced oxidative stress in P. noxius was evidenced by increased reactive oxygen species (ROS) levels, leading to DNA fragmentation, mitochondrial membrane potential reduction, and fungal apoptosis through the mitochondrial pathway. Gel electrophoresis confirmed cedrol-induced DNA fragmentation, whereas TUNEL staining demonstrated increased apoptosis with rising cedrol concentrations. Moreover, protein expression analysis revealed cedrol-triggered release of cytochrome c, activation of caspase-9, and subsequent caspase-3 activation, initiating a caspase cascade reaction. This groundbreaking study establishes cedrol as the first compound to induce apoptosis in P. noxius while inhibiting its growth through oxidative stress, an increase in mitochondrial membrane permeability, and activation of the mitochondrial pathway. The findings offer compelling evidence for cedrol's potential as an effective antifungal agent against the destructive brown root disease caused by P. noxius.

Transformation from zero tolerance to living with COVID-19 in New Taipei City, Taiwan. Experience of the FEMH "home-hotel-hospital" care model.

In March 2022, local cases of COVID-19 infections of the Omicron variant were identified in Taiwan. In response to impending community transmission, the "Home-Hotel-Hospital" (3H) care model was implemented by the Far Eastern Memorial Hospital (FEMH). It established the first remote home care center in Taiwan and two quarantine centers in two hotels. The hospital focused on care for critical COVID-19 patients, community screening, and telehealth care. The home care call center evaluated and triaged up to 104,244 cases and provided remote home care for 96,894 cases within the first three months; in 2022, it provided home care to 107,095 patients. The two quarantine hotels admitted a total of 1834 individuals. A total of 3796 COVID-19 patients were admitted to the hospital-367 in intensive care. The telehealth outpatient clinic-including the online video clinic-served 25,775 cases; 21.5% (n = 5544) of them were prescribed oral anti-viral medications. In 2022, the FEMH prescribed oral anti-viral therapies to a total of 12,571 cases. The FEMH 3H care model not only enabled non-critical patients to recover at home, but also provided severely ill patients access to timely in-hospital care. In the future, this model will continue to play a significant role in COVID-19 management.

Early HIV diagnosis enhances quality-adjusted life expectancy of men who have sex with men living with HIV: A population-based cohort study in Taiwan.

BACKGROUND: Whether early HIV diagnosis is beneficial for HIV patients themselves remains uncertain, given the stigma and social discrimination associated with an HIV diagnosis. This study aimed to measure the impact of early HIV diagnosis on quality-adjusted life expectancy (QALE) in comparison with late HIV diagnosis, from real-world data in Taiwan under universal access to antiretroviral therapy (ART). METHODS: This population-based cohort study included 14,570 men who have sex with men (MSM) in the national HIV registry and a quasi-random sample (n = 127) of MSM patients to measure quality of life using the EQ-5D health utility instrument. We integrated quality of life data into the extrapolated cohort survival curve to estimate the QALE in patients with early versus late HIV diagnosis (≤30 days before AIDS diagnosis). Loss-of-QALE were estimated by comparing the cohort with age-, sex-, and calendar-year-matched referents simulated from vital statistics. Difference-in-differences was estimated to quantify the effect of early HIV diagnosis. RESULTS: Early HIV diagnosis is associated with a loss-of-life expectancy of 3.11 years, with an average health utility of 0.95, in contrast to those diagnosed late (loss-of-life expectancy 8.47 years, with an average health utility of 0.86). After integration of survival and life quality, early HIV diagnosis results in a reduction of loss-of-QALE by 8.28 quality-adjusted life years among MSM living with HIV. CONCLUSIONS: Under universal access to ART, early HIV diagnosis is highly beneficial for people living with HIV themselves, with a net gain of 8.28 healthy life years compared with those diagnosed late.

Single center experience using stereotactic body radiation therapy (SBRT) on orthotopic liver transplant protocol for unresectable cholangiocarcinoma.

PURPOSE: To evaluate tolerability, pathologic response, and disease outcomes utilizing pre-operative stereotactic body radiation therapy (SBRT) followed by consolidation chemotherapy (CHT) prior to orthotopic liver transplant (OLT) in unresectable cholangiocarcinoma (CCA). METHODS: This was a retrospective chart review of patients treated on OLT protocol at a single tertiary center from 2012 to 2019. Patients received pre-operative SBRT (40-50 Gy in 5 fractions) followed by CHT until progression or OLT. Progression-free survival (PFS) and overall survival (OS) were compared via log-rank test and Cox proportional hazards regression. RESULTS: 26 patients (84.6% hilar, 15.4% intrahepatic) were identified for analysis. Eight patients (30.8%) patients developed acute toxicity after SBRT, mostly grade 1 nausea. Nine (34.6%) patients underwent OLT of which 4 (44.4%) achieved a pathologic complete response (pCR). Five (55.6%) OLT patients, including 2 pCR, developed recurrence at a median time of 49.9 weeks after OLT. 3-year OS for the OLT and dropout cohort was 75% and 9%, respectively (p < 0.0001). OS in hilar tumors only was statistically different for those that achieved a pCR (p = 0.014). CONCLUSIONS: Pre-operative SBRT is a well-tolerated and effective radiation technique as part of OLT protocol for unresectable CCA and conferred in a pCR rate of 44% within our cohort.

Unveiling the LncRNA-miRNA-mRNA Regulatory Network in Arsenic-Induced Nerve Injury in Rats through High-Throughput Sequencing.

Arsenic is a natural toxin which is widely distributed in the environment, incurring diverse toxicities and health problems. Previous studies have shown that long non-coding RNAs (LncRNAs) are also reported to contribute to As-induced adverse effects. LncRNAs are involved in the development of nerve injury, generally acting as sponges for microRNAs (miRNAs). This study aimed to investigate the competitive endogenous RNA (ceRNA) regulatory networks associated with arsenic-induced nerve damage. A total of 40 male Wistar rats were exposed to different doses of arsenic for 12 weeks, and samples were collected for pathological observation and high-throughput sequencing. The ceRNA network was constructed using Cytoscape, and key genes were identified through the PPI network and CytoHubba methods. A real-time quantitative PCR assay was performed to validate gene expression levels. The results showed that subchronic exposure to arsenic in drinking water resulted in pathological and ultrastructural damage to the hippocampal tissue, including changes in neuron morphology, mitochondria, and synapses. Exposure to arsenic results in the dysregulation of LncRNA and mRNA expression in the hippocampal tissues of rats. These molecules participated in multiple ceRNA axes and formed a network of ceRNAs associated with nerve injury. This study also verified key molecules within the ceRNA network and provided preliminary evidence implicating the ENRNOT-00000022622-miR-206-3p-Bdnf axis in the mechanism of neural damage induced by arsenic in rats. These findings provide novel insights into the underlying mechanism of nervous system damage induced by arsenic exposure.

Subchronic Arsenic Exposure Induces Behavioral Impairments and Hippocampal Damage in Rats.

This study investigated the effects of subchronic arsenic exposure on behavior, neurological function, and hippocampal damage in rats. Thirty-two male Wistar rats were divided into four groups and exposed to different concentrations of arsenic in their drinking water for 12 weeks, while weekly water intake and body weight were recorded. Various neurobehavioral tests were conducted, evaluating overall activity levels, exploratory behavior, short-term memory, spatial learning and memory, anxiety-like behavior, and depressive-like states. Arsenic levels in urine, serum, and brain tissue were measured, and histopathological analysis assessed hippocampal damage using hematoxylin and eosin staining. The results demonstrated that arsenic exposure did not significantly affect overall activity or exploratory behavior. However, it impaired short-term memory and spatial learning and memory functions. Arsenic-exposed rats exhibited increased anxiety-like behavior and a depressive-like state. Arsenic levels increased dose-dependently in urine, serum, and brain tissue. The histopathological examinations revealed significant hippocampal damage, including neuronal shrinkage, cell proliferation, irregular structure, disordered arrangement, and vacuolation. These findings emphasize the importance of understanding the impact of arsenic exposure on behavior and brain health, highlighting its potential neurological consequences.

Hydrogen peroxide mediates high-intensity blue light-induced hypocotyl phototropism of cotton seedlings.

Phototropism is a classic adaptive growth response that helps plants to enhance light capture for photosynthesis. It was shown that hydrogen peroxide (H2O2) participates in the regulation of blue light-induced hypocotyl phototropism; however, the underlying mechanism is unclear. In this study, we demonstrate that the unilateral high-intensity blue light (HBL) could induce asymmetric distribution of H2O2 in cotton hypocotyls. Disruption of the HBL-induced asymmetric distribution of H2O2 by applying either H2O2 itself evenly on the hypocotyls or H2O2 scavengers on the lit side of hypocotyls could efficiently inhibit hypocotyl phototropic growth. Consistently, application of H2O2 on the shaded and lit sides of the hypocotyls led to reduced and enhanced hypocotyl phototropism, respectively. Further, we show that H2O2 inhibits hypocotyl elongation of cotton seedlings, thus supporting the repressive role of H2O2 in HBL-induced hypocotyl phototropism. Moreover, our results show that H2O2 interferes with HBL-induced asymmetric distribution of auxin in the cotton hypocotyls. Taken together, our study uncovers that H2O2 changes the asymmetric accumulation of auxin and inhibits hypocotyl cell elongation, thus mediating HBL-induced hypocotyl phototropism.

Savinin Triggers Programmed Cell Death of Ray Parenchyma Cells in Heartwood Formation of Taiwania cryptomerioides Hayata.

The purpose of this study was to investigate the relationship between lignan biosynthesis and programmed cell death (PCD) of ray parenchyma cells during the heartwood formation of Taiwania (Taiwania cryptomerioides Hayata). Since the PCD of ray parenchyma cells and the synthesis of lignans are the two main processes involved in the formation of heartwood, both of which need to be completed through gene regulation. Based on the results of genomics and bioinformatics analysis, that the PCD of tracheids are induced by genotoxic, and the PCD of ray parenchyma cells is induced by biological factors, such as fungi, bacteria, and viruses, which could induce oxidative stress. According to the results of time-of-flight secondary ion mass spectrometry (ToF-SIMS) analysis, lignans are produced in ray parenchyma cells, and the accumulation of savinin and its downstream lignans might be the cause of PCD in ray parenchyma cells. An in vitro experiment further confirmed that the accumulation of savinin could cause protoplasts of Taiwania's xylem to produce taiwanin A, which is the marker of heartwood formation in Taiwania. Resulting in an increase in reactive oxygen species (ROS) content, which could induce oxidative stress in ray parenchyma cells and potentially lead to PCD. Based on these findings, we conclude that accumulation of savinin could be induced PCD of ray parenchyma cells in heartwood formation in Taiwania.

CircSOBP suppresses the progression of glioma by disrupting glycolysis and promoting the MDA5-mediated immune response.

Glioma, an aggressively growing and highly malignant brain tumor, poses substantial therapeutic challenges due to its resistance to radiotherapy and chemotherapy. Recent research has identified circRNAs as pivotal players in glioma formation and development. However, the roles of circRNA in the metabolic and immune regulation of glioma are unclear. In this study, circSOBP expression was significantly downregulated in glioma cells and specimens. Functionally, enhanced circSOBP expression mitigated cell proliferation, invasion, migration, and glycolysis in gliomas. Mechanistically, circSOBP inhibited glycolysis and activated the MDA5-mediated IKKε/TBK1/IRF3 signaling pathway by binding TKFC proteins. Furthermore, the elevated levels of IFN-I induced by the MDA5 pathway increased the number and activity of CD8+ T and NK cells in the immune response of the animal models. In summary, our findings have emphasized the critical role of circSOBP in binding and modulating TKFC protein, offering potential therapeutic avenue for targeting glioma metabolism and immunological reprogramming.

Estimating Time-Varying Treatment Switching Effect Using Accelerated Failure Time Model with Application to Vascular Access for Hemodialysis.

Vascular access for hemodialysis is of paramount importance. Although studies have found that central venous catheter (CVC) is often associated with poor outcomes and switching to arteriovenous fistula (AVF) and arteriovenous grafts (AVG) is beneficial, it has not been fully elucidated how the effect of switching of access on outcomes changes over time and whether the effect depends on switching time. In this paper we propose to relate the observed survival time for patients without access change and the counterfactual time for patients with access change using an AFT model with time-varying effects. The flexibility of AFT model allows us to account for baseline effect and the prognostic effect from covariates at access change while estimating the effect of access change. The effect of access change overtime is modeled nonparametrically using a cubic spline function. Simulation studies show excellent performance. Our methods are applied to investigate the effect of vascular access change over time in dialysis patients. It is concluded that the benefit of switching from CVC to AVG depends on the time of switching, the sooner the better.

Monoterpene synthases contribute to the volatile production in tana (Zanthoxylum ailanthoides) through indigenous cultivation practices.

Tana (Zanthoxylum ailanthoides), a perennial deciduous species in the Rutaceae family, possesses leaves with a unique fragrance that indigenous peoples incorporate into their traditional cuisine. In Kalibuan, the cultivated tana trees were pruned repeatedly to maintain a shorter height, which led to the growth of new leaves that were spicier and pricklier. Tana leaves contain a range of volatile terpenoids, and the pungent aroma may arise from the presence of monoterpenoids. To gain insight into the biosynthetic pathway, five candidate monoterpene synthase genes were cloned and characterized using a purified recombinant protein assay. The main product of Za_mTPS1, Za_mTPS2, and Za_mTPS5 is sabinene, geraniol, and (E)-ß-ocimene, respectively. The main product of Za_mTPS3 and Za_mTPS4 is linalool. Real-time PCR analysis revealed that Za_mTPS1 and Za_mTPS5 are expressed at higher levels in prickly leaves of cultivated tana, suggesting that they may contribute to the distinctive aroma of this plant.

Diagnostic performance of GenBody COVID-19 rapid antigen test for laboratory and non-laboratory medical professionals in real practice: A retrospective study.

Point-of-care tests for coronavirus disease 2019 (COVID-19) antigen detection have been widely used for rapid diagnosis in various settings. However, research on the diagnostic performance of the COVID-19 antigen test performed by non-laboratory personnel is limited. In this study, we aimed to elucidate the diagnostic performance of GenBody COVID-19 rapid antigen between laboratory professionals and non-laboratory staff. We retrospectively analyzed the data of patients who underwent both GenBody COVID-19 rapid antigen testing and reverse transcription polymerase chain reaction (RT-PCR) between November 01, 2021, and June 30, 2022. The diagnostic performance of the antigen test was compared between laboratory and non-laboratory operators, using RT-PCR as the gold standard. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy were calculated and sensitivity analysis was performed based on the PCR cycle threshold (Ct) value. Of the 11,963 patients, 1273 (10.6%) tested positive using real-time RT-PCR. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, positive predictive value, negative predictive value, and accuracy of the GenBody COVID-19 rapid antigen test with 95% confidence interval were 79.92% (77.26%-82.39%), 99.23% (98.73%-99.57%), 103.25 (62.31-171.11), 0.2 (0.18-0.23), 510.18 (299.81-868.18), 98.11% (96.91%-98.85%), 90.75% (89.64%-91.75%) and 92.76% (91.76%-93.67%), respectively, for non-laboratory staff and 79.80% (74.78%-84.22%), 99.99% (99.94%-100.00%), 6983.92 (983.03-49617.00), 0.2 (0.16-0.25), 34566.45 (4770.30-250474.46) 99.58% (97.09%-99.94%), 99.32% (99.15%-99.46%), and 99.33% (99.13%-99.48%), respectively, for laboratory staff. Notably, when the PCR Ct value exceeded 25, the sensitivity of both the groups decreased to < 40%. The diagnostic performance of GenBody COVID-19 rapid antigen performed by non-laboratory staff was comparable to that of laboratory professionals. However, it should be noted that the sensitivity of the antigen tests decreased when the PCR Ct value exceeded 25. Overall, the GenBody COVID-19 antigen test is a viable option for non-laboratory staff during an epidemic.