Sedimentary ancient DNA reveals past ecosystem and biodiversity changes on the Tibetan Plateau: Overview and prospects

Alpine ecosystems on the Tibetan Plateau are being threatened by ongoing climate warming and intensified human activities. Ecological time-series obtained from sedimentary ancient DNA (sedaDNA) are essential for understanding past ecosystem and biodiversity dynamics on the Tibetan Plateau and their responses to climate change at a high taxonomic resolution. Hitherto only few but promising studies have been published on this topic. The potential and limitations of using sedaDNA on the Tibetan Plateau are not fully understood. Here, we (i) provide updated knowledge of and a brief introduction to the suitable archives, region-specific taphonomy, state-of-the-art methodologies, and research questions of sedaDNA on the Tibetan Plateau; (ii) review published and ongoing sedaDNA studies from the Tibetan Plateau; and (iii) give some recommendations for future sedaDNA study designs. Based on the current knowledge of taphonomy, we infer that deep glacial lakes with freshwater and high clay sediment input, such as those from the southern and southeastern Tibetan Plateau, may have a high potential for sedaDNA studies. Metabarcoding (for microorganisms and plants), metagenomics (for ecosystems), and hybridization capture (for prehistoric humans) are three primary sedaDNA approaches which have been successfully applied on the Tibetan Plateau, but their power is still limited by several technical issues, such as PCR bias and incompleteness of taxonomic reference databases. Setting up high-quality and open-access regional taxonomic reference databases for the Tibetan Plateau should be given priority in the future. To conclude, the archival, taphonomic, and methodological conditions of the Tibetan Plateau are favorable for performing sedaDNA studies. More research should be encouraged to address questions about long-term ecological dynamics at ecosystem scale and to bring the paleoecology of the Tibetan Plateau into a new era

A High-Performance Synthetic Jet Piezoelectric Air Pump with Petal-Shaped Channel

The synthetic jet piezoelectric air pump is a potential miniature device for electronic cooling. In order to improve the performance of the device, a small-sized synthetic jet piezoelectric air pump is proposed in this work, which is mainly characterized by petal-shaped inlet channels. First, the structure and working principle of the piezoelectric vibrator and the proposed pump are analyzed. Then, three synthetic jet piezoelectric air pumps with different inlet channels are compared. These inlets are the direct channels, the diffuser/nozzle channels, and the petal-shaped channels, respectively. Furthermore, the performance of the synthetic jet piezoelectric air pump with the petal-shaped inlet channels is optimized by orthogonal tests. Finally, the simulation was used to investigate the heat dissipation capability of the synthetic jet piezoelectric pump. The experimental results show that among the three inlet channels, the petal-shaped channel can greatly improve the performance of the pump. The unoptimized pump with petal-shaped channels has a maximum flow rate of 1.8929 L/min at 100 V, 3.9 kHz. Additionally, the optimized pump with petal-shaped channels reaches a maximum flow rate of 3.0088 L/min at 100 V, 3.7 kHz, which is 58.95% higher than the unoptimized one. The proposed synthetic jet piezoelectric air pump greatly improves the output performance and has the advantages of simple structure, low cost, and easy integration. The convective heat transfer coefficient of the synthetic jet piezoelectric pump is 28.8 W/(m2·°C), which can prove that the device has a better heat dissipation capability

Fuel Economy Improvement of a Heavy-Duty Powertrain by Using Hardware-in-Loop Simulation and Calibration

Fuel economy efficiency is one of the most important parameters for vehicle powertrains, which is of particular interest for heavy-duty powertrain calibration. Conventionally, this work relies heavily on road tests, which cost more and may lead to long duration product development cycles. The paper proposes a novel hardware-in-loop modeling and calibration method to work it out. A dSPACE hardware-based test bench was successfully established and validated, which is valuable for a more efficient and easier shift schedule in calibration. Meanwhile, a real-time dynamic powertrain model, including a diesel engine, torque converter, gear box and driver model was built. Typical driving cycles that both velocity and slope information were constructed for different road conditions. A basic economic shift schedule was initially calculated and then optimal calibrated by the test bench. The results show that there is an optimal relationship between an economic shift schedule and speed regulation. By matching the best economic shift schedule regulation to different road conditions; the fuel economy of vehicles can be improved. In a smooth driving cycle; when the powertrain applies a larger speed regulation such as 12% and the corresponding shift schedule; the fuel consumption is smaller and is reduced by 13%. In a complex driving cycle, when the powertrain applies a smaller speed regulation such as 5% along with the corresponding shift schedule; the fuel consumption is smaller and is reduced by 5%. The method thus can provide guidance for economic calibration experiments of off-road heavy-duty vehicles

Drug resistance evolution in patients with human immunodeficiency virus-1 under long-term antiretroviral treatment-failure in Yunnan Province, China

Abstract Background Understanding the prevalence and evolution of HIV-1 drug resistance (DR) and associated mutation patterns is critical to implementing free antiretroviral therapy in Yunnan, the first antiretroviral treatment location in China. Here We provide a basis for understanding the occurrence and development of HIV-1 resistance in Yunnan and a theoretical foundational for strategy to delay HIV-1 drug resistance and achieve successful individualized treatment. Methods Plasma samples from different cities/prefectures were collected at Yunnan Provincial Hospital of Infectious Disease from January 2010 to September 2016, and those from drug-resistant individuals were genotyped using in-house assays, 88 patients were selected for the study who had been on treatment for ≥6 months (and for whom drug resistance was then measured), and each patient had at least 3 genotype resistance tests and who were enrolled to analyze mutation and evolution of HIV resistance. Results 264 Pol sequences of 88 patients were obtained. Drug resistance levels to eight drugs increased to varying degrees with prolonged treatment. Resistance to efavirenz (EFV) and etravirine (ETR) showed the highest change, comparisons of resistant changes to second and first and to third and second agents showed altered level of drug resistance were 25 and 20 cases, 28 and 18 cases, respectively. The smallest change was Lopinavir/Ritonavir (LPV/r) present 2 and 3 cases; Resistance to lamivudine (3TC) and lopinavir/ritonavir (LPV/r) was high among patients detected thrice, whereas other drugs were distributed in all resistance levels. M184 V/I (26.14%), T69S (11.36%), and T215Y/I (10.23%) mutations were the most common in nucleoside reverse transcriptase inhibitors (NRTIs), and K103 N/R/S (21.59%), V179D/E (20.45%) in Non-NRTIs (NNRTIs). Furthermore, L10 V/F/I (6.82%), A71V (4.55%), and I54V (4.55%) mutations were common in protease inhibitors (PIs). Conclusions We found dynamic genotypic changes in HIV-1 drug-resistance in Yunnan, with prolonged treatment, and drug resistance was inevitable. However, resistance to different drugs occurred at varying times, and mutation site emergence was the main cause. These findings enhance our understanding of evolution and regulation, and are valuable for developing HIV-1 DR prevention strategies in Yunnan

Ga₂O₃ Schottky Avalanche Solar-Blind Photodiode with High Responsivity and Photo-to-Dark Current Ratio

Solar-blind photodetectors have attracted extensive attention due to their advantages such as ultra-low background noise and all-weather. In this study, the planar Ti/Ga2O3/Au Schottky avalanche photodetector (APD) is fabricated based on β-Ga2O3 epitaxial film on the sapphire substrate grown by metal–organic chemical vapor deposition. The Schottky APD exhibits a high responsivity of 9780.23 A W−1, an ultrahigh photo-to-dark current ratio of 1.88 × 107, an external quantum efficiency of 4.77 × 106%, a specific detectivity of 9.48 × 1014 Jones, with an ultrahigh gain of 1 × 106 under 254 nm light illumination at 60 V reverse bias, indicating high application potential for solar-blind imaging. The superior photoresponse performances ascribe to the effective carrier avalanche multiplication, which contributes to the high photocurrent, and the high quality Schottky junction depletion, which leads to the low dark current.</p

Early Initiation of ARV During Pregnancy to Move towards Virtual Elimination of Mother-to-Child-Transmission of HIV-1 in Yunnan, China.

To identify factors associated with mother-to-child-transmission and late access to prevention of maternal to child transmission (PMTCT) services among HIV-infected women; and risk factors for infant mortality among HIV-exposed infants in order to assess the feasibility of virtual elimination of vertical transmission and pediatric HIV in this setting.Observational study evaluating the impact of a provincial PMTCT program.The intervention was implemented in 26 counties of Yunnan Province, China at municipal and tertiary health care settings. Log linear regression models with generalized estimating equations were used to identify unadjusted and adjusted correlates for late ARV intervention and MTCT. Cox proportional hazard models with robust sandwich estimation were applied to examine correlates of infant mortality.Mother-to-child- transmission rate of HIV was controlled to 2%, with late initiation of maternal ARV showing a strong association with vertical transmission and infant mortality. Risk factors for late initiation of maternal ARV were age, ethnicity, education, and having a husband not tested for HIV. Mortality rate among HIV-exposed infants was 2.9/100 person-years. In addition to late initiation of maternal ARV, ethnicity, low birth weight and preterm birth were associated with infant mortality.This PMTCT program in Yunnan achieved low rates of MTCT. However the infant mortality rate in this cohort of HIV-exposed children was almost three times the provincial rate. Virtual elimination of MTCT of HIV is an achievable goal in China, but more attention needs to be paid to HIV-free survival

Prevalence and Clinical Impact of Human Pegivirus-1 Infection in HIV-1-Infected Individuals in Yunnan, China

Human Pegivirus-1 (HPgV-1) may have a beneficial impact on disease progression in human immunodeficiency virus-1 (HIV-1) infection. However, analysis of the genotypic diversity of HPgV-1 and its relevance to the progression of HIV-1 disease remains limited. A total of 1062 HIV-1-infected individuals were recruited in all sixteen prefectures of Yunnan province, China. The reverse transcription nested polymerase chain reaction (RT-nPCR), phylogenetic analyses, and clinical data analyses were used to detect HPgV-1 infection, determine genotype, and analyze HPgV-1 genotype impact on HIV-1 disease progression. The overall positive rate of HPgV-1 RNA was 23.4% (248/1062), and the frequency of HPgV-1 infection in injecting drug users (IDUs) (28.5%, 131/460) was significantly higher than in heterosexuals (19.4%, 117/602). Multiple genotypes were identified in 212 subjects with successful sequencing for the E2 gene, including genotype 7 (55.7%), genotype 3 (34.9%), genotype 4 (4.7%), genotype 2 (3.3%), and an unclassified group (1.4%). Moreover, genotype 7 predominated in IDUs, whereas genotype 3 was the most common in heterosexuals. Our results revealed that HPgV-1 genotype 7 groups exhibited significantly lower HIV-1 viral load and higher CD4+ cell counts. This finding suggests that HPgV-1 genotype 7 may be associated with a better progression of HIV-1 disease

sj-pdf-1-jcb-10.1177_0271678X231219115 - Supplemental material for Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X231219115 for Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway by Danyang Liu, Tao Wang, Xingqi Zhao, Juan Chen, Tianqi Yang, Yi Shen and Yu-Dong Zhou in Journal of Cerebral Blood Flow & Metabolism</p

Antitumor and off-target effects of cholesterol-conjugated let-7a mimics in an orthotopic hepatocellular carcinoma xenograft nude mouse model

Objective:. To explore the antitumor and potential off-target effects of systemically delivered cholesterol-conjugated let-7a mimics (Chol-let-7a) and control mimics (Chol-miRCtrl) on hepatocellular carcinoma in vivo. Methods:. The antitumor effects of two intravenous dosing regimens of Chol-let-7a on heptocellular carcinoma growth were compared using an orthotopic xenograft mouse model. Off-targets were analyzed with histopathological and ultrapathological features of heparenal tissue and cells in the Chol-let-7a-, Chol-miRCtrl-, and saline-treated (blank) xenograft mice and normal control mice. Then, let-7a abundance in orthotopic tumors, corresponding paracancerous hepatic tissue, and normal liver tissue from healthy nude mice was examined by reverse transcription-polymerase chain reaction. The distribution of Chol-let-7a and Chol-miRCtrl in vivo was examined by whole-animal imaging and frozen-sections observation. The experiments were approved by the Institutional Research Board of Peking Union Medical College Hospital. Results:. Continuous treatment with Chol-let-7a resulted in tumors that were 35.86% and 40.02% the size of those in the Chol-miRCtrl and blank xenograft group (P < 0.01 and P < 0.01, respectively), while intermittent dosing with Chol-let-7a resulted in tumors that were 65.42% and 56.66% the size of those in the Chol-miRCtrl and the blank control group, respectively (P < 0.05 and P < 0.05). In addition, some histopathological and ultrapathological features were only observed after treatment with the two cholesterol-conjugated molecules, however mild with intermittent dosing Chol-let-7a treatment, such as diffuse sinusoidal dilation and edema, primarily around the centrolobular vein in heptic tissues; mild hypercellularity with dilated capillary lumens in the renal tissue; and some organelle abnormalities found in heptic and renal cells. Furthermore, whole-animal imaging showed that Chol-let-7a and Chol-miRCtrl were predominantly distributed in the liver, kidney, and bladder regions after injection, and that the concentration of Chol-let-7a and Chol-miRCtrl in the kidney and the bladder decreased much slowly in the xenograft animals, especially in the Chol-miRCtrl group. Finally, RT-PCR analysis showed that let-7a levels were significantly increased in Chol-let-7a-treated xenografts compared with Chol-miRCtrl group (P=0.003) and blank xenograft group (P=0.001); however, the level was only equivalent to 50.6% and 40.7% of that in paracancerous hepatic tissue and hepatic tissue in normal mice, respectively. Conclusions:. Chol-let-7a, administered either continuously or intermittently, showed effective antitumor efficacy. Chol-let-7a had some off-target effects, such as mild acute hepatitis-like inflammation and non-specific drug-induced kidney injury. The intermittent dosing regimen resulted in less damage than the continuous regimen, while maintaining relatively satisfactory antitumor efficacy, which could be useful for the investigation and possible clinical use of miRNA treatment regimens in the future