We present geochronological, geochemical, whole-rock Sr–Nd and zircon Hf–isotopic data for late Paleozoic volcanic rocks from the Daheshen Formation in central Jilin Province, northeastern China, and ...constrain the petrogenesis of the volcanic rocks and late Paleozoic tectonic evolution of the northern margin of the Northern China Craton, which is regarded as the eastern segment of the Central Asian Orogenic Belt (CAOB). Lithologically, the Daheshen Formation is composed mainly of rhyolite, rhyolitic tuff, dacite and andesite, with minor basalt. The zircons from three rhyolites, two dacites, one rhyolitic tuff and one basalt are euhedral–subhedral, display oscillatory zoning and have high Th/U ratios (0.50–2.28), implying a magmatic origin. LA–ICP-MS zircon U–Pb age data indicate that the volcanic rocks from the Daheshen Formation formed during Late Carboniferous–Early Permian time (302–299Ma). Geochemically, late Paleozoic volcanic rocks have SiO2=52.13–81.77wt.% and K2O=0.86–6.88wt.%, belonging to mid-K to high-K calc-alkaline series. These rocks are characterized by enrichment in large ion lithophile elements (LILEs) and light rare earth elements (LREEs), and depletion in high field strength elements (HFSEs, such as Nb, Ta, and Ti) and heavy rare earth elements (HREEs), with affinities to igneous rocks forming in an active continental margin setting. All volcanic rocks have depleted Nd isotopic compositions (εNd(t)=+2.4 to +2.5 for the basalts and +5.8 to +7.1 for the andesites and dacites, respectively). In situ Hf isotopic results of zircon from the rhyolites show that they have εHf(t)=−1.1 to +10.6. All these geochemical features indicate that the andesites, dacites, and rhyolites likely originated from the partial melting of Meso-Neoproterozoic accreted lower crust (Hf and Nd model ages (TDM2) of 1384–662Ma and 1061–800Ma, respectively). In contrast, the basalts were derived from the partial fusion of a depleted lithospheric mantle that had subsequently been metasomatized by subducted slab-derived fluids. These data, along with the regional geological investigations, suggest that the generation of late Paleozoic volcanic rocks from the Daheshen Formation was related to southward subduction of the Paleo-Asian oceanic plate beneath the northern margin of the North China Craton. This also indicates that the Paleo-Asian Ocean may have not closed before the Early Permian.
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•The volcanic rocks in the northern margin of the NCC formed in 302–299Ma.•Different origins of the basalts and the intermediate to acidic volcanics•The volcanic rocks formed in an active continental margin setting.•The Paleo-Asian Ocean had not been closed before the Early Permian.
To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress ...of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% 95% CI, 55.4-74.7%); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% 95% CI, 27.3-70.6%). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.
•Blautia-deficient microbiota and reduced fecal butyrate level in PD patients, and negatively associated with the PD severity.•B. producta (as a producing-butyrate bacteria) supplementation inhibited ...neuroinflammation of in PD mice.•We identified a key pathway regulated by butyrate, RAS related pathway, and RAS-NF-κB pathway in PD patients was changed.•B. producta-derived butyrate causally inhibited activation of microglia of PD by regulating RAS-NF-κB pathway.•These findings provide insights into the causally relationship between specific members of the microbiota and PD.
Parkinson's disease (PD) is intricately linked to abnormal gut microbiota, yet the specific microbiota influencing clinical outcomes remain poorly understood. Our study identified a deficiency in the microbiota genus Blautia and a reduction in fecal short-chain fatty acid (SCFA) butyrate level in PD patients compared to healthy controls. The abundance of Blautia correlated with the clinical severity of PD. Supplementation with butyrate-producing bacterium B. producta demonstrated neuroprotective effects, attenuating neuroinflammation and dopaminergic neuronal death in mice, consequently ameliorating motor dysfunction. A pivotal inflammatory signaling pathway, the RAS-related pathway, modulated by butyrate, emerged as a key mechanism inhibiting microglial activation in PD. The change of RAS-NF-κB pathway in PD patients was observed. Furthermore, B. producta-derived butyrate demonstrated the inhibition of microglial activation in PD through regulation of the RAS-NF-κB pathway. These findings elucidate the causal relationship between specific gut microbiota and PD, presenting a novel microbiota-based treatment perspective for PD.
Hepatitis C virus (HCV) reinfections after successful treatment with direct-acting antivirals (DAAs) pose a significant challenge to HCV elimination, especially among high-risk people living with HIV ...(PLWH). In this study, PLWH who had achieved HCV viral clearance with DAAs were included between January 2018 and June 2021. PLWH having acquired HCV infections after 2017 were classified as "recent-infection group," and those before 2017 as "remote-infection group," and the incidences of HCV reinfection were compared between two groups. Clinical and behavioural characteristics were evaluated to identify associated factors with HCV reinfection. A total of 284 PLWH were included: 179 in the recent-infection group and 105 in the remote-infection group. After a median follow-up of 2.32 years (interquartile range IQR, 0.13-3.94), the overall incidence of HCV reinfection was 5.8 per 100 person-years of follow-up (PYFU). The incidence in the recent-infection group was significantly higher than that in the remote-infection group (9.8 vs. 0.4 per 100 PYFU, p < 0.001). The leading HCV genotypes before DAA treatment were genotypes 2 (31.0%), 1b (26.8%), and 6 (21.8%); however, genotype 6 (58.8%) became predominant upon reinfection. Younger age (adjusted odds ratio aOR per 1-year increase, 0.95; 95% CI, 0.90-0.99), condomless receptive anal sex (aOR, 14.5; 95% CI, 2.37-88.8), rimming (aOR, 3.87; 95% CI, 1.14-13.1), and recent syphilis (aOR, 2.73; 95% CI, 1.26-5.91) were linked to HCV reinfections. In conclusion, PLWH acquiring HCV after 2017 had a significantly higher risk for sexually-transmitted HCV reinfections. The predominance of HCV genotype 6 reinfections suggests possible on-going clustered HCV infections among at-risk PLWH.
While some evidence has suggested the benefits of co-formulated bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) in improving the quality of life of people living with HIV (PLWH), ...patient-reported outcome studies that focus on Asian population remain scarce. We aimed to determine the changes in HIV-related symptom burden in virally-suppressed PLWH switching to B/F/TAF in a real-world setting.
PLWH on stable antiretroviral therapy (ART) for ≥6 months with plasma HIV RNA <200 copies/mL who decided to switch to B/F/TAF were eligible for the study. Participants’ experience with 20 symptoms were assessed using HIV Symptom Index at baseline and weeks 24 and 48. Responses were dichotomized in two ways: 1) present vs. not present; and 2) bothersome vs. not bothersome, and compared across time points.
Six hundred and thirty participants (prior regimen, 94.4% integrase inhibitor-based) who completed week 48 visit were included in the analysis. Forty-eight weeks after switching to B/F/TAF, six symptoms were significantly less prevalent, and seven symptoms were significantly less bothersome. Improvement was more pronounced in participants whose prior regimen was elvitegravir-based versus dolutegravir-based. Logistic regression results showed that prior dolutegravir-based ART and pre-existing diabetes independently predicted improvement in diarrhea/loose bowels and muscle aches/joint pain, respectively. Despite the overall improvement, some symptoms persisted in a substantial proportion of participants.
Virally-suppressed PLWH might benefit from a regimen switch to B/F/TAF to reduce the prevalence and level of bother of HIV-related symptoms. Nevertheless, additional multidisciplinary interventions are warranted to further alleviate the symptom burden of PLWH.
To establish a clinically applicable neuroimaging-guided diagnostic support system that uses near-infrared spectroscopy (NIRS) for differential diagnosis at the individual level among major ...depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ).
A total of 192 participants were recruited, including 40 patients with MDD, 38 patients with BPD, 65 patients with SZ, and 49 healthy individuals. We analyzed the spatiotemporal characteristics of hemodynamic responses in the frontotemporal cortex during a verbal fluency test (VFT) measured by NIRS to assess the accuracy of single-subject classification for differential diagnosis among the three psychiatric disorders. The optimal threshold of the frontal centroid value (54 seconds) was utilized on the basis of the findings of the Japanese study.
The application of the optimal threshold of the frontal centroid value (54 seconds) allowed for the accurate differentiation of patients with unipolar MDD (72.5%) from BPD (78.9%) or SZ (84.6%).
These results suggest that the NIRS-aided differential diagnosis of major psychiatric disorders can be a promising biomarker in Taiwan. Future multi-site studies are needed to validate our findings.
•We used NIRS signals for differential diagnosis among major depressive disorder (MDD), bipolar disorder (BPD), and schizophrenia (SZ).•NIRS could accurately differentiate patients with MDD (72.5%) from BPD (78.9%) or SZ (84.6%).•Our results indicated that NIRS could be a promising biomarker in psychiatric clinical practice.
Cdk1 (cyclin-dependent kinase 1) is critical regulator of the G2-M checkpoint. Cyclin-dependent kinase pathways are considered possible targets for cancer treatment; however, the prognostic role of ...Cdk1 in colorectal cancer is still controversial. Therefore, we attempted to determine the impact of Cdk1 on the clinical outcome of colorectal cancer patients to further identify its role in colorectal cancer.
Cdk1 immunoreactivity was analyzed by immunohistochemistry (IHC) in 164 cancer specimens from primary colorectal cancer patients. The medium follow-up time after surgery was 3.7 years (range: 0.01 to 13.10 years). The prognostic value of Cdk1 on overall survival was determined by Kaplan-Meier analysis and Cox proportional hazard models.
All samples displayed detectable Cdk1 expression with predominant location in the cytoplasm and nucleus. A high Cdk1 nuclear/cytoplasmic (N/C) expression ratio was correlated with poor overall survival (5-year survival rate: 26.3% vs 46.9%, N/C ratio ≥1.5 vs N/C ratio <1.5, log-rank p = 0.027). Accordingly, a Cdk1 N/C expression ratio ≥1.5 was identified as an independent risk factor by multivariate analysis (hazard ratio = 1.712, P = 0.039).
We suggest that Cdk1 N/C expression ratio determined by IHC staining could be an independent prognostic marker for colorectal cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Sequential addition of tenofovir disoproxil fumarate (TDF) is often needed for patients coinfected with HIV and hepatitis B virus (HBV) who develop HBV resistance to lamivudine after combination ...antiretroviral therapy (cART) containing only lamivudine for HBV. We aimed to assess the virological response of HBV to add-on TDF in patients coinfected with lamivudine-resistant HBV.
Between November 2010 and December 2014, 33 HIV/HBV-coinfected patients with lamivudine-resistant HBV and 56 with lamivudine-susceptible HBV were prospectively included. TDF plus lamivudine was used to substitute zidovudine or abacavir plus lamivudine contained in cART in patients with lamivudine-resistant HBV infection, while patients with lamivudine-susceptible HBV infection received TDF plus lamivudine as backbone of cART. Serial determinations of plasma HBV DNA load, HBV serologic markers, and liver and renal functions were performed after initiation of TDF-containing cART.
Of 89 patients included, 38.6% tested positive for HBV envelope antigen (HBeAg) at baseline. The plasma HBV DNA level at enrollment of lamivudine-resistant and lamivudine-susceptible group were 6.1 ± 2.2 log10 and 6.0 ± 2.2 log10 copies/mL, respectively (p = 0.895). The cumulative percentage of HBV viral suppression in lamivudine-resistant and lamivudine-susceptible group was 81.8% and 91.1% at 48 weeks, respectively (p = 0.317), which increased to 86.7% and 96.2% at 96 weeks, respectively (p = 0.185). At 48 weeks, 11 patients testing HBeAg-positive at baseline failed to achieve viral suppression. In multivariate analysis, the only factor associated with failure to achieve viral suppression at 48 weeks was higher HBV DNA load at baseline (odds ratio, per 1-log10 copies/mL increase, 1.861; 95% CI, 1.204-2.878). At 48 weeks, HBeAg seroconversion was observed in 5 patients (1 in the lamivudine-resistant group and 4 in the lamivudine-susceptible group; p = 0.166). During the study period, HBsAg levels decreased over time, regardless of lamivudine resistance. Loss of HBsAg was observed in 3 (3.4%) patients in the lamivudine-susceptible group.
Add-on TDF-containing cART in patients coinfected with lamivudine-resistant HBV achieved a similar rate of HBV viral suppression compared to TDF-containing cART as initial regimen in patients coinfected with lamivudine-susceptible HBV. A higher baseline HBV DNA load and HBeAg positivity were associated with failure to achieve HBV viral suppression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We report on a highly stable p-type Mn 3 O 4 flexible gas sensor for room-temperature detection of O 3 . The Mn 3 O 4 film is deposited by the successive ionic layer adsorption and reaction (SILAR) ...method at low temperatures and photochemically activated by an ultraviolet light-emitting diode at room temperature. The Mn 3 O 4 gas sensor exhibits gas response, response time, and recovery time of 1.65, 159, and 130 s, respectively, against 5 ppm O 3 gas at a UV intensity of 20 mW/cm 2 . It enables high selectivity for O 3 gas against various toxic gases even at room temperature. Moreover, the flexible gas sensor exhibits negligible degradation over 60 days and folds reproducibly after repeated bending for 300 cycles. These results strongly support that a Mn 3 O 4 film deposited by SILAR is a good candidate for room-temperature flexible gas sensors for the applications of wearable devices.
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