Publications by authors named "Yang Ma"

192 Publications

Predictive Value of CHADS -VASc-HSF Score for Severity of Acute Coronary Syndrome.

Clin Appl Thromb Hemost 2022 Jan-Dec;28:10760296211073969

117914Chengde Medical University Affiliated Hospital, Chengde, HeBei, 067000, China.

CHADS and CHADS-VASc scores have been used to assess the prognostic risk of thromboembolism in non-valvular atrial fibrillation patients. Recent studies have shown the utility of CHADS and CHADS-VASc scores for evaluating the severity of coronary artery disease (CAD). The newly defined CHADS-VASc-HSF score evaluates atherosclerosis and is associated with CAD severity. This study investigated the association between the CHADS-VASc-HSF score and acute coronary syndrome (ACS) severity as assessed by the Gensini score and the number of vessels. Furthermore, this study also compared the diagnostic value of the CHADS, CHA2 DS2-VASc, and CHADS-VASc-HSF score for ACS. A total of 2367 eligible inpatients (ACS group [ = 2030]; non-CAD group [ = 337]) were consecutively enrolled in this study. Receiver operating characteristic curve diagnostic tests and logistic regression models were used to analyze the risk factors for ACS. The CHADS, CHADS-VASc, and CHADS-VASc-HSF scores were significantly higher in the ACS group than those in the control group. After adjusting for numerous traditional CAD risk factors, an increased CHADS-VASc-HSF score was found to be an independent risk factor for patients with ACS (odds ratio 1.401, 95% confidence interval 1.044, -1.879;  < 0.05). A newly diagnosed CHADS-VASc-HSF score predicts the severity of ACS.
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http://dx.doi.org/10.1177/10760296211073969DOI Listing
January 2022

Energy-Efficient Trajectory Optimization for UAV-Based Hybrid FSO/RF Communications with Buffer Constraints.

Entropy (Basel) 2021 Nov 28;23(12). Epub 2021 Nov 28.

Key Laboratory of Broadband Wireless Communication and Sensor Network Technology, Nanjing University of Posts and Telecommunications, Nanjing 210003, China.

This paper focuses on an unmanned aerial vehicle (UAV) assisted hybrid free-space optical (FSO)/radio frequency (RF) communication system. Considering the rate imbalance between the FSO and RF links, a buffer is employed at the UAV. Initially, theoretical models of energy consumption and throughput are obtained for the hybrid system. Based on these models, the theoretical expression of the energy efficiency is derived. Then, a nonconvex trajectory optimization problem is formulated by maximizing the energy efficiency of the hybrid system under the buffer constraint, velocity constraint, acceleration constraint, start-end position constraint, and start-end velocity constraint. By using the sequential convex optimization and first-order Taylor approximation, the nonconvex problem is transformed into a convex one. An iterative algorithm is proposed to solve the problem. Numerical results verify the efficiency of the proposed algorithm and also show the effects of buffer size on a UAV's trajectory.
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http://dx.doi.org/10.3390/e23121596DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699851PMC
November 2021

Modulating autophagy by strontium-doped micro/nano rough titanium surface for promotion of osteogenesis and inhibition of osteoclastogenesis.

Colloids Surf B Biointerfaces 2022 Feb 27;210:112246. Epub 2021 Nov 27.

Zhejiang University, Stomatology Hospital, Department of Prosthodontics, School of Stomatology, Zhejiang University School of Medicine, Clinical Research Center for Oral Diseases of Zhejiang Province, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310006. Electronic address:

Although it has been demonstrated that implant surfaces treated with strontium (Sr) promote osseointegration, the underlying intracellular mechanism remains unknown. Autophagy is a vital intracellular degradation mechanism that plays an essential role in maintaining bone homeostasis. Therefore, while designing implant biomaterials, it is critical to consider the autophagy mechanism. In this study, we fabricated Sr-doped micro/nano rough titanium implant surface by hydrothermal treatment (SLA+Sr). The in vitro results revealed that the SLA+Sr surface promoted osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via autophagy activation. The SLA+Sr surface, on the other hand, inhibited osteoclast differentiation by downregulating autophagy. Additionally, in vivo, the SLA+Sr implant improved osseointegration, inhibited osteoclastogenesis, and upregulated autophagy levels in surrounding bone tissue cells. Our findings established a novel centralized mechanism by which SLA+Sr regulated osteogenesis and osteoclastogenesis during the osseointegration process through autophagy regulation. Moreover, endowing implants with the ability to modulate autophagy may be a promising strategy for enhancing implant osseointegration in the future translational medicine field.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112246DOI Listing
February 2022

Study on the associated factors of turnover intention among emergency nurses in China and the relationship between major factors.

Int Emerg Nurs 2022 Jan 1;60:101106. Epub 2021 Dec 1.

School of Public Health and Management, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing 400016, China. Electronic address:

Background: In China, the demand for emergency medical services is increasing. However, there is a shortage of nurses and a high turnover rate. The study has three purposes: (1) to investigate the turnover intention of emergency nurses in China; (2) to analyze the associated factors of turnover intention; and (3) to clarify the relationship between work stress, job burnout, perceived organization support, job satisfaction and turnover intention.

Methods: A cross-sectional study was conducted to investigate 56 hospitals with independent emergency departments in Chongqing. A total of 522 emergency nurses were included. Descriptive statistics, One-way analysis of variance, Pearson correlated analysis and a mediation regression analysis were used to analyze the turnover intention, associated factors, and the relationship between the major study variables.

Results: The score of turnover intention was 2.38 ± 0.57, and the proportion of nurses with high turnover intention was 40.61%. Age, working years in emergency department (ED), marital status, employment forms, professional title, promotion opportunities, weekly working hours, monthly night shifts and exposure to workplace violence during the year influenced turnover intention of emergency nurses. Work stress and job burnout were positively correlated with turnover intention (r = 0.189, r = 0.391), while perceived organization support and job satisfaction were negatively correlated with turnover intention (r = - 0.349, r = - 0.485). perceived organization support plays a mediating role between work stress and job burnout, between work stress and job satisfaction, and between work stress and turnover intention.

Conclusion: Work stress, job burnout, perceived organization support and job satisfaction are important associated factors of emergency nurses' turnover intention in China. It is suggested to take intervention measures to reduce work stress and job burnout and to improve perceived organization support and job satisfaction.
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http://dx.doi.org/10.1016/j.ienj.2021.101106DOI Listing
January 2022

Analysis of a more sustainable method for recycling waste lead batteries: Surface renewal promotes desulfurization agent regeneration.

Waste Manag 2022 Jan 24;137:319-328. Epub 2021 Nov 24.

Department of Environment and Resources, Xiangtan University, Xiangtan 411105, PR China.

The traditional sodium desulfurization process for waste lead-acid batteries is beneficial to the environment; however, it is limited by poor economic viability as the cost of desulfurizer is much higher than the value of desulfurization by-products. This study proposes a new closed-loop pre-desulfurization process for lead paste, which consumes only lime as the indirect desulfurizer, produces sodium sulfate as a by-product, and regenerates sodium hydroxide as the direct desulfurizer. The concentration of prepared sodium hydroxide reached 2.57 mol/L when the reaction was conducted at room temperature for 2.0 h, with a sodium oxalate: calcium oxide molar ratio of 1:1.3, a CaO: water mass ratio of 1:6, and magnetic stirring at 600 rpm. Cost estimation and economic analyses were also conducted. The cost of lead paste generated by this new pre-desulfurization process was 37.62 dollars/ton lower than traditional high-temperature smelting, and 44.42 dollars/ton lower than direct sodium pre-desulfurization. Thus, this process provides a practical and feasible clean recycling method for waste lead-acid batteries with significant environmental and economic benefits.
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http://dx.doi.org/10.1016/j.wasman.2021.11.011DOI Listing
January 2022

Differences in Multi-Faceted Lifestyles in Response to the COVID-19 Pandemic and Their Association with Depression and Quality of Life of Older Adults in South Korea: A Cross-Sectional Study.

Nutrients 2021 Nov 17;13(11). Epub 2021 Nov 17.

Department of Occupational Therapy, College of Software and Digital Healthcare Convergence, Yonsei University, Wonju 26493, Korea.

Background: The World Health Organization declared COVID-19 a global pandemic on 11 March 2020, due to the number of newly reported confirmed cases and the rapid increase in deaths. Therefore, countries around the world limited their population to policies such as "social distancing" or "staying at home" to prevent the spread of the virus. The purpose of this study was to evaluate differences in lifestyle pre and post the outbreak COVID-19 among older adults in South Korea and to identify the impact of lifestyle differences on depression and quality of life.

Methods: An online single questionnaire covering sociodemographic data, lifestyle details, depression status, and quality of life level was distributed using mailing lists and social media. To assess lifestyles differences in older people pre and post the outbreak of COVID-19 pandemic, the online single questionnaire was used post COVID-19 pandemic. Based on the participants' memories, they responded lifestyles at two time points (pre and post COVID-19 pandemic).

Results: The results showed that there was a significant decrease in physical activity and activity participation during the pandemic. In terms of nutrition, there was no statistically significant change pre and post the outbreak COVID-19, except for the intake of protein, fat, and vitamins. Additionally, the results showed that the resulting lifestyle differences seem to have had a negative impact on depression and quality of life among older adults in South Korea.

Conclusion: There was a significant difference the lifestyle patterns among the participants in South Korea between the current period and pre COVID-19 pandemic. Additionally, it is observed that these differenced lifestyles were associated with depression and quality of life among the participants. Our findings may help to develop public health programs that support healthy lifestyles in pandemic conditions.
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http://dx.doi.org/10.3390/nu13114124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8625190PMC
November 2021

Giant oscillatory Gilbert damping in superconductor/ferromagnet/superconductor junctions.

Sci Adv 2021 Nov 26;7(48):eabh3686. Epub 2021 Nov 26.

International Center for Quantum Materials, School of Physics, Peking University, Beijing 100871, China.

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abh3686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626077PMC
November 2021

Evidence for anisotropic spin-triplet Andreev reflection at the 2D van der Waals ferromagnet/superconductor interface.

Nat Commun 2021 Nov 18;12(1):6725. Epub 2021 Nov 18.

International Center for Quantum Materials, School of Physics, Peking University, 100871, Beijing, P. R. China.

Fundamental symmetry breaking and relativistic spin-orbit coupling give rise to fascinating phenomena in quantum materials. Of particular interest are the interfaces between ferromagnets and common s-wave superconductors, where the emergent spin-orbit fields support elusive spin-triplet superconductivity, crucial for superconducting spintronics and topologically-protected Majorana bound states. Here, we report the observation of large magnetoresistances at the interface between a quasi-two-dimensional van der Waals ferromagnet FeTaS and a conventional s-wave superconductor NbN, which provides the possible experimental evidence for the spin-triplet Andreev reflection and induced spin-triplet superconductivity at ferromagnet/superconductor interface arising from Rashba spin-orbit coupling. The temperature, voltage, and interfacial barrier dependences of the magnetoresistance further support the induced spin-triplet superconductivity and spin-triplet Andreev reflection. This discovery, together with the impressive advances in two-dimensional van der Waals ferromagnets, opens an important opportunity to design and probe superconducting interfaces with exotic properties.
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http://dx.doi.org/10.1038/s41467-021-27041-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602320PMC
November 2021

LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer.

Front Oncol 2021 22;11:719855. Epub 2021 Sep 22.

Pancreatic Disease Center, Department of General Surgery, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. and sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.
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http://dx.doi.org/10.3389/fonc.2021.719855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494469PMC
September 2021

Network pharmacology-based prediction of the active compounds and mechanism of Buyang Huanwu Decoction for ischemic stroke.

Exp Ther Med 2021 Oct 23;22(4):1050. Epub 2021 Jul 23.

College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi 712046, P.R. China.

Buyang Huanwu Decoction (BYHWD) is used to promote blood circulation and is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used to treat ischemic stroke are not well understood. The current study aimed to identify the potential active components of BYHWD and explore its mechanism using network pharmacology and bioinformatics analyses. The compounds of BYHWD were obtained from public databases. Oral bioavailability and drug-likeness were screened using the absorption, distribution, metabolism and excretion (ADME) criteria. Components of BYHWD, alongside the candidate targets of each component and the known therapeutic targets of ischemic stroke were collected. A network of target gene compounds and cerebral ischemia compounds was established using network pharmacology data sources. The enrichment of key targets and pathways was analyzed using STRING and DAVID databases. Moreover, three of key targets [IL6, VEGFA and hypoxia-inducible-factor-1α (HIF-1α)] were verified using western blot analysis. Network analysis determined 102 compounds in seven herbal medicines that were subjected to ADME screening. A total of 42 compounds as well as 79 genes formed the principal pathways associated with ischemic stroke. The 16 key compounds identified were baicalein, beta-carotene, baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, bifendate, formononetin, calycosin, astragaloside IV, stigmasterol, sitosterol, Z-ligustilide, and dihydrocapsaicin. The core genes in this network were IL6, TNF, VEGFA, HIF-1α, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. Furthermore, the TNF, IL17, apoptosis, PI3K-Akt, toll-like receptor, MAPK, NF-κB and HIF-1 signaling pathways were identified to be associated with ischemic stroke. Compared with the control group (no treatment), BYHWD significantly inhibited the expression of IL6 and increase the expression of HIF-1α and VEGFA. Network pharmacology analyses can help to reveal close interactions between multi-components and multi-targets and enhance understanding of the potential effects of BYHWD on ischemic stroke.
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http://dx.doi.org/10.3892/etm.2021.10484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353622PMC
October 2021

Targeted inhibition of GRK2 kinase domain by CP-25 to reverse fibroblast-like synoviocytes dysfunction and improve collagen-induced arthritis in rats.

Acta Pharm Sin B 2021 Jul 23;11(7):1835-1852. Epub 2021 Jan 23.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei 230032, China.

Rheumatoid arthritis (RA) is an autoimmune disease and is mainly characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS). The up-regulated cellular membrane expression of G protein coupled receptor kinase 2 (GRK2) of FLS plays a critical role in RA progression, the increase of GRK2 translocation activity promotes dysfunctional prostaglandin E4 receptor (EP4) signaling and FLS abnormal proliferation. Recently, although our group found that paeoniflorin-6'--benzene sulfonate (CP-25), a novel compound, could reverse FLS dysfunction GRK2, little is known as to how GRK2 translocation activity is suppressed. Our findings revealed that GRK2 expression up-regulated and EP4 expression down-regulated in synovial tissues of RA patients and collagen-induced arthritis (CIA) rats, and prostaglandin E2 (PGE2) level increased in arthritis. CP-25 could down-regulate GRK2 expression, up-regulate EP4 expression, and improve synovitis of CIA rats. CP-25 and GRK2 inhibitors (paroxetine or GSK180736A) inhibited the abnormal proliferation of FLS in RA patients and CIA rats by down-regulating GRK2 translocation to EP4 receptor. The results of microscale thermophoresis (MST), cellular thermal shift assay, and inhibition of kinase activity assay indicated that CP-25 could directly target GRK2, increase the protein stability of GRK2 in cells, and inhibit GRK2 kinase activity. The docking of CP-25 and GRK2 suggested that the kinase domain of GRK2 might be an important active pocket for CP-25. G201, K220, K230, A321, and D335 in kinase domain of GRK2 might form hydrogen bonds with CP-25. Site-directed mutagenesis and co-immunoprecipitation assay further revealed that CP-25 down-regulated the interaction of GRK2 and EP4 controlling the key amino acid residue of Ala321 of GRK2. Our data demonstrate that FLS proliferation is regulated by GRK2 translocation to EP4. Targeted inhibition of GRK2 kinase domain by CP-25 improves FLS function and represents an innovative drug for the treatment of RA by targeting GRK2.
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http://dx.doi.org/10.1016/j.apsb.2021.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8343125PMC
July 2021

Multigene Combined Detection by RT-qPCR Using Cytological Specimens.

Acta Cytol 2021 3;65(5):393-402. Epub 2021 Aug 3.

Department of Cytology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Objective: The aim of the study was to investigate the mutation status of multiple driver genes by RT-qPCR and their significance in advanced lung adenocarcinoma using cytological specimens.

Materials And Methods: 155 cytological specimens that had been diagnosed with lung adenocarcinoma in the Fourth Hospital of Hebei Medical University were selected from April to November 2019. The cytological specimens included serous cavity effusion and fine-needle aspiration biopsies. Among cytological specimens, 108 cases were processed by using the cell block method (CBM), and 47 cases were processed by the disposable membrane cell collector method (MCM) before DNA/RNA extraction. Ten drive genes of EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET were combined detected at one step by the amplification refractory mutation system and ABI 7500 RT-qPCR.

Results: The purity of RNA (p = 0.005) and DNA (p = 0.001) extracted by using the MCM was both significantly higher than that extracted by using the CBM. Forty-seven cases of fresh cell specimens processed by the MCM all succeeded in multigene detections, while of 108 specimens processed by the CBM, 6 cases failed in multigene detections. Among 149 specimens, single-gene mutation rates of EGFR, ALK, ROS1, RET, HER2, MET, KRAS, NRAS, BRAF, and PIK3CA mutations were 57.71%, 6.04%, 3.36%, 2.68%, 2.01%, 2.01%, 1.34%, 0.67%, 0% and 0% respectively, and 6 cases including 2 coexistence mutations. We found that mutation status was correlated with gender (p = 0.047), but not correlated with age (p = 0.141) and smoking status (p = 0.083). We found that the EGFR mutation status was correlated with gender (p = 0.003), age (p = 0.015) and smoking habits (p = 0.007), and ALK mutation status was correlated with age (p = 0.002).

Conclusion: Compared with the CBM, the MCM can improve the efficiency of DNA/RNA extraction and PCR amplification by removing impurities and enriching tumor cells. And we speculate that the successful detection rate of fresh cytological specimens was higher than that of paraffin-embedded specimens. EGFR, ALK, and ROS1 mutations were the main driver mutations in patients with advanced lung adenocarcinoma. We speculate that EGFR and ALK are more prone to concomitant mutations, respectively. Targeted therapies for patients with coexisting mutations need further study.
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http://dx.doi.org/10.1159/000514821DOI Listing
September 2021

Genetic Continuity of Bronze Age Ancestry with Increased Steppe-Related Ancestry in Late Iron Age Uzbekistan.

Mol Biol Evol 2021 Oct;38(11):4908-4917

Key Laboratory of Vertebrate Evolution and Human Origins, Institute of Vertebrate Paleontology and Paleoanthropology, Center for Excellence in Life and Paleoenvironment, Chinese Academy of Sciences, Beijing, China.

Although Uzbekistan and Central Asia are known for the well-studied Bronze Age civilization of the Bactria-Margiana Archaeological Complex (BMAC), the lesser-known Iron Age was also a dynamic period that resulted in increased interaction and admixture among different cultures from this region. To broaden our understanding of events that impacted the demography and population structure of this region, we generated 27 genome-wide single-nucleotide polymorphism capture data sets of Late Iron Age individuals around the Historical Kushan time period (∼2100-1500 BP) from three sites in South Uzbekistan. Overall, Bronze Age ancestry persists into the Iron Age in Uzbekistan, with no major replacements of populations with Steppe-related ancestry. However, these individuals suggest diverse ancestries related to Iranian farmers, Anatolian farmers, and Steppe herders, with a small amount of West European Hunter Gatherer, East Asian, and South Asian Hunter Gatherer ancestry as well. Genetic affinity toward the Late Bronze Age Steppe herders and a higher Steppe-related ancestry than that found in BMAC populations suggest an increased mobility and interaction of individuals from the Northern Steppe in a Southward direction. In addition, a decrease of Iranian and an increase of Anatolian farmer-like ancestry in Uzbekistan Iron Age individuals were observed compared with the BMAC populations from Uzbekistan. Thus, despite continuity from the Bronze Age, increased admixture played a major role in the shift from the Bronze to the Iron Age in southern Uzbekistan. This mixed ancestry is also observed in other parts of the Steppe and Central Asia, suggesting more widespread admixture among local populations.
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http://dx.doi.org/10.1093/molbev/msab216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8557446PMC
October 2021

Human population history at the crossroads of East and Southeast Asia since 11,000 years ago.

Cell 2021 07 24;184(14):3829-3841.e21. Epub 2021 Jun 24.

Yunnan Institute of Cultural Relics and Archaeology, Kunming 650118, China; Yunnan Key Laboratory of Earth System Science, Yunnan University, Kunming 650500, China. Electronic address:

Past human genetic diversity and migration between southern China and Southeast Asia have not been well characterized, in part due to poor preservation of ancient DNA in hot and humid regions. We sequenced 31 ancient genomes from southern China (Guangxi and Fujian), including two ∼12,000- to 10,000-year-old individuals representing the oldest humans sequenced from southern China. We discovered a deeply diverged East Asian ancestry in the Guangxi region that persisted until at least 6,000 years ago. We found that ∼9,000- to 6,000-year-old Guangxi populations were a mixture of local ancestry, southern ancestry previously sampled in Fujian, and deep Asian ancestry related to Southeast Asian Hòabìnhian hunter-gatherers, showing broad admixture in the region predating the appearance of farming. Historical Guangxi populations dating to ∼1,500 to 500 years ago are closely related to Tai-Kadai and Hmong-Mien speakers. Our results show heavy interactions among three distinct ancestries at the crossroads of East and Southeast Asia.
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http://dx.doi.org/10.1016/j.cell.2021.05.018DOI Listing
July 2021

Investigation of the Multi-Target Mechanism of Guanxin-Shutong Capsule in Cerebrovascular Diseases: A Systems Pharmacology and Experimental Assessment.

Front Pharmacol 2021 13;12:650770. Epub 2021 May 13.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Guanxin-Shutong capsule (GXSTC), a combination of Mongolian medicines and traditional herbs, has been clinically proven to be effective in treating cerebrovascular diseases (CBVDs). However, the underlying pharmacological mechanisms of GXSTC in CBVDs remain largely unknown. In this study, a combination of systems pharmacology and experimental assessment approach was used to investigate the bioactive components, core targets, and possible mechanisms of GXSTC in the treatment of CBVDs. A total of 15 main components within GXSTC were identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) and a literature research. Fifty-five common genes were obtained by matching 252 potential genes of GXSTC with 462 CBVD-related genes. Seven core components in GXSTC and 12 core genes of GXSTC on CBVDs were further determined using the protein-protein interaction (PPI) and component-target-pathway (C-T-P) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results predicted that the molecular mechanisms of GXSTC on CBVDs were mainly associated with the regulation of the vascular endothelial function, inflammatory response, and neuronal apoptosis. Molecular docking results suggested that almost all of core component-targets have an excellent binding activity (affinity < -5 kcal/mol). More importantly, in middle cerebral artery occlusion (MCAO) -injured rats, GXSTC significantly improved the neurological function, reduced the infarct volume, and decreased the percentage of impaired neurons in a dose-dependent manner. Western blotting results indicated that GXSTC markedly upregulated the expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS), while downregulating the expression of cyclooxygenase-2 (COX-2) and transcription factor AP-1 (c-Jun) in MCAO-injured rats. These findings confirmed our prediction that GXSTC exerts a multi-target synergetic mechanism in CBVDs by maintaining vascular endothelial function, inhibiting neuronal apoptosis and inflammatory processes. The results of this study may provide a theoretical basis for GXSTC research and the clinical application of GXSTC in CBVDs.
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http://dx.doi.org/10.3389/fphar.2021.650770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155632PMC
May 2021

CtBP2 confers protection against oxidative stress through interactions with NRF1 and NRF2.

Biochem Biophys Res Commun 2021 07 27;562:146-153. Epub 2021 May 27.

Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

While molecular oxygen is essential for aerobic organisms, its utilization is inseparably connected with generation of oxidative insults. To cope with the detrimental aspects, cells evolved antioxidative defense systems, and insufficient management of the oxidative insults underlies the pathogenesis of a wide range of diseases. A battery of genes for this antioxidative defense are regulated by the transcription factors nuclear factor-erythroid 2-like 1 and 2 (NRF1 and NRF2). While the regulatory steps for the activation of NRFs have been investigated with particular emphasis on nuclear translocation and proteosomal degradation, unknown redundancy may exist considering the indispensable nature of these defense systems. Here we unraveled that C-terminal binding protein 2 (CtBP2), a transcriptional cofactor with redox-sensing capability, is an obligate partner of NRFs. CtBP2 forms transcriptional complexes with NRF1 and NRF2 that is required to promote the expression of antioxidant genes in response to oxidative insults. Our findings illustrate a basis for understanding the transcriptional regulation of antioxidative defense systems that may be exploited therapeutically.
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http://dx.doi.org/10.1016/j.bbrc.2021.05.069DOI Listing
July 2021

The pathogenesis, models and therapeutic advances of primary biliary cholangitis.

Biomed Pharmacother 2021 Aug 25;140:111754. Epub 2021 May 25.

Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, China. Electronic address:

Primary biliary cholangitis (PBC) is an autoimmune disease characterized by the destruction of intrahepatic small bile ducts and the presence of antimitochondrial antibody (AMA), eventually progresses to liver fibrosis and cirrhosis. Genetic predisposition and environmental factors are involved in the occurrence of PBC, and the epitopes exposure and the imbalance of autoimmune tolerance are the last straw. The apoptosis of biliary epithelial cell (BEC) leads to the release of autoantigen epitopes, which activate the immune system, and the disorder of innate and adaptive immunity eventually leads to the start of disease. Animal models have unique advantages in investigating the pathogenesis and drug exploitation of PBC. Multiple models have been reported, and spontaneous model and induced model have been widely used in relevant research of PBC in recent years. Currently, the only drugs licensed for PBC are ursodesoxycholic acid (UDCA) and obeticholic acid (OCA). In the last few years, as the learned more about the pathogenesis of PBC, more and more targets have been discovered, and multiple targeted drugs are being in developed. In this review, the pathogenesis, murine models and treatment strategies of PBC were summarized, and the current research status was discussed to provide insights for the further study of PBC.
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http://dx.doi.org/10.1016/j.biopha.2021.111754DOI Listing
August 2021

[Cannulation of the Portal Vein during Endoscopic Retrograde Cholangiopancreatography in a Patient with Choledocholithiasis].

Korean J Gastroenterol 2021 05;77(5):253-257

Department of Internal Medicine, Presbyterian Medical Center, Jeonju, Korea.

Cannulation of the portal vein is a rare complication of ERCP. This paper reports a case of portal vein catheterization during ERCP in a patient with choledocholithiasis. A 62-year-old man was admitted to the Presbyterian Medical Center with right upper quadrant pain and jaundice. ERCP was performed under the suspicion of obstructive jaundice caused by a radiolucent stone. Bile duct cannulation using a pull-type papillotome was attempted, but it failed. After needle-knife fistulotomy, wire-guided cannulation was performed successfully, and 10 mL contrast was injected. On the other hand, the fluoroscopy image showed that the contrast medium disappeared very quickly. Pure blood was collected when the catheter was aspirated to identify the bile reflux, indicating possible cannulation of the portal vein. The procedure was terminated immediately and abdominal computed tomography showed air in the portal vein. One day after, a follow-up CT scan showed no air in the portal vein. The patient underwent repeated ERCP, and the common bile duct was cannulated. In most cases, isolated portal vein cannulation does not result in severe morbidity. However, it is important to aware of this rare complication so that no further invasive procedure is performed on the patient.
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http://dx.doi.org/10.4166/kjg.2021.030DOI Listing
May 2021

The Impact of Pine Wood Nematode Infection on the Host Fungal Community.

Microorganisms 2021 Apr 22;9(5). Epub 2021 Apr 22.

Collaborative Innovation Center of Sustainable Forestry in Southern China, College of Forestry, Nanjing Forestry University, Nanjing 210037, China.

Pine wilt disease (PWD), caused by pinewood nematode (PWN) , is globally one of the most destructive diseases of pine forests, especially in China. However, little is known about the effect of PWD on the host microbiome. In this study, the fungal community and functional structures in the needles, roots, and soil of and around naturally infected by PWN were investigated by using high-throughput sequencing coupled with the functional prediction (FUNGuild). The results showed that fungal richness, diversity, and evenness in the needles of diseased trees were significantly lower than those of healthy ones ( < 0.05), whereas no differences were found in the roots and soil. Principal coordinate analysis (PCoA) showed that the fungal community and functional structures significantly differed only in the needles of diseased and healthy trees, but not in the soil and roots. Functionally, the saprotrophs had a higher abundance in the needles of diseased trees, whereas symbiotrophs abundance was higher in the needles of healthy trees (linear discriminant analysis (LDA) > 2.0, < 0.05). These results indicated that PWN infection primarily affected the fungal community and functional structures in the needles of . , but not the roots and soil.
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http://dx.doi.org/10.3390/microorganisms9050896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146488PMC
April 2021

Associations between floods and bacillary dysentery cases in main urban areas of Chongqing, China, 2005-2016: a retrospective study.

Environ Health Prev Med 2021 Apr 19;26(1):49. Epub 2021 Apr 19.

School of Public Health and Management, Research Center for Medicine and Social Development, Innovation Center for Social Risk Governance in Health, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.

Background: Understanding the association between floods and bacillary dysentery (BD) incidence is necessary for us to assess the health risk of extreme weather events. This study aims at exploring the association between floods and daily bacillary dysentery cases in main urban areas of Chongqing between 2005 and 2016 as well as evaluating the attributable risk from floods.

Methods: The association between floods and daily bacillary dysentery cases was evaluated by using distributed lag non-linear model, controlling for meteorological factors, long-term trend, seasonality, and day of week. The fraction and number of bacillary dysentery cases attributable to floods was calculated. Subgroup analyses were conducted to explore the association across age, gender, and occupation.

Results: After controlling the impact of temperature, precipitation, relative humidity, long-term trend, and seasonality, a significant lag effect of floods on bacillary dysentery cases was found at 0-day, 3-day, and 4-day lag, and the cumulative relative risk (CRR) over a 7-lag day period was 1.393 (95%CI 1.216-1.596). Male had higher risk than female. People under 5 years old and people aged 15-64 years old had significantly higher risk. Students, workers, and children had significantly higher risk. During the study period, based on 7-lag days, the attributable fraction of bacillary dysentery cases due to floods was 1.10% and the attributable number was 497 persons.

Conclusions: This study confirms that floods can increase the risk of bacillary dysentery incidence in main urban areas of Chongqing within an accurate time scale, the risk of bacillary dysentery caused by floods is still serious. The key population includes male, people under 5 years old, students, workers, and children. Considering the lag effect of floods on bacillary dysentery, the government and public health emergency departments should advance to the emergency health response in order to minimize the potential risk of floods on public.
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http://dx.doi.org/10.1186/s12199-021-00971-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056597PMC
April 2021

Impact of the COVID-19 pandemic on the lifestyle, mental health, and quality of life of adults in South Korea.

PLoS One 2021 26;16(2):e0247970. Epub 2021 Feb 26.

Department of Occupational Therapy, Yonsei University, Wonju, South Korea.

Objective: The COVID-19 pandemic continues to pose significant challenges to nations. The Korean government aimed to mitigate the spread of COVID-19 through stay-at-home strategies and maintaining social distance, which are likely to result in major changes in the lifestyle, mental health, and quality of life of citizens. This study aimed to investigate the impact of the COVID-19 pandemic on these factors in Koreans over 20 years old.

Methods: The study sample consisted of 104 adults in South Korea aged over 20 years. An online survey was conducted between August and October 2020, in which participants were asked to complete the Yonsei Lifestyle Profile to assess lifestyle changes, the Center for Epidemiological Studies-Depression Scale, and the World Health Organization Quality of Life Scale abbreviated version. To investigate the changes in people's lifestyles, depression, and quality of life post COVID-19, descriptive statistics were calculated for these indicators before and after the onset of the pandemic. The p-value was two-sided, and values <0.05, were regarded as statistically significant.

Results: There was a significant decline in physical and other meaningful activities, including activities of daily living, leisure, social activity, and education. However, there were no significant changes in nutrition, except in the consumption of carbohydrates and minerals. Participants reported that their quality of life and mental health had decreased after the pandemic struck.

Conclusions: We obtained novel data on the changes in the lifestyle, mental health, and quality of life of South Korean adults before and after the onset of the pandemic. The results of our study may assist health policymakers and practitioners in the development of health education or relevant interventions to deal with the pandemic situation as well as future crises.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247970PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909697PMC
March 2021

Using Disposable Membrane Cell Collector to Enrich Lung Adenocarcinoma Cells in Bloody Pleural Effusion for Anaplastic Lymphoma Kinase Fusion Gene Detection.

Acta Cytol 2021 25;65(3):235-241. Epub 2021 Feb 25.

Department of Cytology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Purpose: For anaplastic lymphoma kinase (ALK) gene detection, the centrifugal sedimentation method (CSM) and cell block method (CBM) are commonly used to process samples of bloody pleural effusions (BPEs). However, in practice, the impurity content in the processed samples often affects the results and even leads to the detection failure. The purpose of this study was to establish a cell enrichment method (CEM) by using a disposable membrane cell collector to remove blood and inflammatory cells and enrich lung adenocarcinoma cells in BPE for more efficient RNA extraction and ALK gene detection.

Materials And Methods: CEM proposed in this study and the traditional CSM and CBM were used to treat BPE samples collected from 37 lung adenocarcinoma patients. A DeNovix DS-11 ultraviolet spectrophotometer was used to measure the concentration and purity of extracted RNA. Amplification refractory mutation systems (ARMS) and ABI 7500 fluorescence qPCR were used to detect ALK gene. Through statistical analysis, the CEM was compared with the CSM and CBM in RNA concentration, purity, and ALK gene detection results.

Results: The concentration of RNA extracted by using the CEM was significantly higher than that extracted by using the CBM and CSM (p < 0.001). The purity of RNA extracted by using the CEM was significantly higher than that by the other 2 methods (p = 0.011, p = 0.005). ALK gene testing with PCR was successful in all the samples using the CEM, but 2 cases by the CSM and 1 case by the CBM failed.

Conclusions: Using the disposable membrane cell collector to process BPE of lung adenocarcinoma patients for RNA extraction and ALK gene detection is more effective and successful compared with the traditional methods, and it is suggested to be further applied and popularized in clinical practice.
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http://dx.doi.org/10.1159/000512868DOI Listing
June 2021

Response of soil NO emission and nitrogen utilization to organic matter in the wheat and maize rotation system.

Sci Rep 2021 02 23;11(1):4396. Epub 2021 Feb 23.

Department of Soil and Water Resources, Institute of Industrial and Forage Crops, Hellenic Agricultural Organization-"Demeter", 41335, Larissa, Greece.

The appropriate nitrogen (N) fertilizer regulator could increase N utilization of crops and reduce N losses in the North China Plain. We investigated the effects of reduced inorganic-N rate combined with an organic fertilizer on nitrous oxide (NO) emissions in winter wheat and summer maize rotation system. Simultaneously studied the effect of different treatments on N use efficiency (NUE), N balance and net income. After reducing the amount of nitrogen fertilizer in the wheat-corn rotation system, the results showed that the cumulative emission of soil NO from the RN40% + HOM [40% of RN (recommended inorganic-N rate) with homemade organic matter] treatment was 41.0% lower than that of the RN treatment. In addition, the N production efficiency, agronomic efficiency, and apparent utilization were significantly increased by 50.2%, 72.4% and 19.5% than RN, respectively. The use of RN40% + HOM resulted in 22.0 and 30.1% lower soil N residual and N losses as compared with RN. After adding organic substances, soil NO cumulative emission of RN40% + HOM treatment decreased by 20.9% than that of the HAN (zinc and humic acid urea at the same inorganic-N rate of RN) treatment. The N production efficiency, N agronomic efficiency and NUE of RN40% + HOM treatment were 36.6%, 40.9% and 15.3% higher than HAN's. Moreover, soil residual and apparent loss N were 23.3% and 18.0% less than HAN's. The RN40% + HOM treatment appears to be the most effective as a fertilizer control method where it reduced N fertilizer input and its loss to the environment and provided the highest grain yield.
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http://dx.doi.org/10.1038/s41598-021-83832-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902846PMC
February 2021

Two-dimensional superconductivity and anisotropic transport at KTaO (111) interfaces.

Science 2021 02 21;371(6530):716-721. Epub 2021 Jan 21.

Materials Science Division, Argonne National Laboratory, Lemont, IL 60439, USA.

The distinctive electronic structure found at interfaces between materials can allow unconventional quantum states to emerge. Here we report on the discovery of superconductivity in electron gases formed at interfaces between (111)-oriented KTaO and insulating overlayers of either EuO or LaAlO The superconducting transition temperature, as high as 2.2 kelvin, is about one order of magnitude higher than that of the LaAlO/SrTiO system. Notably, similar electron gases at KTaO (001) interfaces remain normal down to 25 millikelvin. The critical field and current-voltage measurements indicate that the superconductivity is two-dimensional. In EuO/KTaO (111) samples, a spontaneous in-plane transport anisotropy is observed before the onset of superconductivity, suggesting the emergence of a distinct "stripe"-like phase, which is also revealed near the critical field.
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http://dx.doi.org/10.1126/science.aba5511DOI Listing
February 2021

P2X7 receptor activation aggravates NADPH oxidase 2-induced oxidative stress after intracerebral hemorrhage.

Neural Regen Res 2021 Aug;16(8):1582-1591

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Oxidative stress is a crucial pathological process that contributes to secondary injury following intracerebral hemorrhage. P2X7 receptor (P2X7R), which is activated by the abnormal accumulation of extracellular ATP, plays an important role in the regulation of oxidative stress in the central nervous system, although the effects of activated P2X7R-associated oxidative stress after intracerebral hemorrhage remain unclear. Mouse models of intracerebral hemorrhage were established through the stereotactic injection of 0.075 U VII collagenase into the right basal ganglia. The results revealed that P2X7R expression peaked 24 hours after intracerebral hemorrhage, and P2X7R expressed primarily in neurons. The inhibition of P2X7R, using A438079 (100 mg/kg, intraperitoneal), reduced nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression and malondialdehyde generation, increased superoxide dismutase and glutathione/oxidized glutathione levels, and alleviated neurological damage, brain edema, and apoptosis after intracellular hemorrhage. The P2X7R inhibitor A438079 (100 mg/kg, intraperitoneal injection) inhibited the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and nuclear factor kappa-B (NF-κB) after intracerebral hemorrhage. Blocking ERK1/2 activation, using the ERK1/2 inhibitor U0126 (2 µg, intraventricular injection), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation after intracellular hemorrhage. Similarly, the inhibition of NF-κB, using the NF-κB inhibitor JSH-23 (3.5 µg, intraventricular), reduced the level of NOX2-mediated oxidative stress induced by P2X7R activation. Finally, GSK2795039 (100 mg/kg, intraperitoneal), a NOX2 antagonist, attenuated P2X7R-mediated oxidative stress, neurological damage, and brain edema after intracerebral hemorrhage. The results indicated that P2X7R activation aggravated NOX2-induced oxidative stress through the activation of the ERK1/2 and NF-κB pathways following intracerebral hemorrhage in mice. The present study was approved by the Ethics Committee of Huazhong University of Science and Technology, China (approval No. TJ-A20160805) on August 26, 2016.
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http://dx.doi.org/10.4103/1673-5374.303036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323669PMC
August 2021

Z-Guggulsterone alleviated oxidative stress and inflammation through inhibiting the TXNIP/NLRP3 axis in ischemic stroke.

Int Immunopharmacol 2020 Dec 28;89(Pt B):107094. Epub 2020 Oct 28.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Ischemic stroke is a serious and life-threatening cerebrovascular thrombotic disease; however, the therapeutic strategy is limited for the complicated mechanism and narrow therapeutic window. Our previous study suggested that Z-Guggulsterone (Z-GS), an active component derived from myrrh, is a good candidate for cerebral injury. The object of this study is to investigate the exact mechanisms of Z-GS in cerebral ischemic stroke. Rats were used to conduct middle cerebral artery occlusion (MCAO) model and were treated with different dosage of Z-GS. Morphological results showed that Z-GS significantly alleviated neurological deficits, infarct volume and histopathological damage in MCAO rats. A total of 8276 differentially expressed genes were identified based on microarray analysis. Oxidation-reduction process and inflammatory response were enriched as the significant gene ontology items. TXNIP and NLRP3 were screened as the potential target genes by Series Test of Cluster (STC) analysis. The results were validated by immunohistochemistry and immunofluorescence staining. Besides, Z-GS successfully inhibited oxidative stress and inflammatory response in oxygen-glucose deprivation (OGD) treated neurons. Knockdown of TXNIP significantly decreased the expression of NLRP3 in OGD-induced neurons. In addition, Z-GS treatment scarcely changed the expressions of NLRP3 in siRNA-TXNIP pretreated cells compared with the siRNA-TXNIP alone treatment group, suggesting that the neuroprotective effect of Z-GS was dependent on TXNIP-NLRP3 axis. Taken together, this study revealed that Z-GS exerted neuroprotective property through alleviated oxidative stress and inflammation via inhibiting the TXNIP/NLRP3 axis. Z-GS could be considered as a promising candidate for the treatment of ischemic stroke.
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http://dx.doi.org/10.1016/j.intimp.2020.107094DOI Listing
December 2020

Denisovan DNA in Late Pleistocene sediments from Baishiya Karst Cave on the Tibetan Plateau.

Science 2020 10;370(6516):584-587

Key Laboratory of Vertebrate Evolution and Human Origins of Chinese Academy of Sciences, Institute of Vertebrate Paleontology and Paleoanthropology, CAS, Beijing 100044, China.

A late Middle Pleistocene mandible from Baishiya Karst Cave (BKC) on the Tibetan Plateau has been inferred to be from a Denisovan, an Asian hominin related to Neanderthals, on the basis of an amino acid substitution in its collagen. Here we describe the stratigraphy, chronology, and mitochondrial DNA extracted from the sediments in BKC. We recover Denisovan mitochondrial DNA from sediments deposited ~100 thousand and ~60 thousand years ago (ka) and possibly as recently as ~45 ka. The long-term occupation of BKC by Denisovans suggests that they may have adapted to life at high altitudes and may have contributed such adaptations to modern humans on the Tibetan Plateau.
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http://dx.doi.org/10.1126/science.abb6320DOI Listing
October 2020

A Network Pharmacology Technique to Investigate the Synergistic Mechanisms of and in Treatment of Cardio-Cerebral Vascular Diseases.

Evid Based Complement Alternat Med 2020 5;2020:6937186. Epub 2020 Oct 5.

College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, China.

Objective: This study is aimed to analyze the active ingredients, drug targets, and related pathways in the combination of (SM) and (RP) in the treatment of cardio-cerebral vascular diseases (CCVDs).

Method: The ingredients and targets of SM and RP were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and the disease targets were obtained from Therapeutic Target Database (TTD), National Center for Biotechnology Information (NCBI), and Online Mendelian Inheritance in Man (OMIM) Database. The synergistic mechanisms of the SM and RP were evaluated by gene ontology (GO) enrichment analyses and Kyoto encyclopedia of genes and genomes (KEGG) path enrichment analyses.

Result: A total of 61 active ingredients and 58 common targets were identified in this study. KEGG pathway enrichment analysis results showed that SM- and RP-regulated pathways were mainly inflammatory processes, immunosuppression, and cardiovascular systems. The component-target-pathway network indicated that SM and RP exert a synergistic mechanism for CCVDs through PTGS2 target in PI3k-Akt, TNF, and Jak-STAT signaling pathways.

Conclusion: In summary, this study clarified the synergistic mechanisms of SM and RP, which can provide a better understanding of effect in the treatment of CCVDs.
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http://dx.doi.org/10.1155/2020/6937186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566220PMC
October 2020

GTPases Arf5 and Arl2 function partially distinctly during oocyte meiosis.

J Cell Biochem 2021 02 27;122(2):198-208. Epub 2020 Sep 27.

Nanjing Medical University, Nanjing, Jiangsu, China.

Mammalian female meiosis must be tightly regulated to produce high-quality mature oocytes for subsequent regular fertilization and healthy live birth of the next generation. GTPases control many important signal pathways involved in diverse cellular activities. ADP-ribosylation factor family members (Arfs) in mice possess GTPase activities, and some members have been found to function in meiosis. However, whether other Arfs play a role in meiosis is unknown. In this study, we found that Arl2 and Arf5 are the richest among Arfs in mouse oocytes, and they are more abundant in oocytes than in granular cells. Furthermore, Arl2 and Arf5 depletion both impeded meiotic progression, but by affecting spindles and microfilaments, respectively. Moreover, Arl2 and Arf5 depletion both significantly increased regular reactive oxygen species levels and decreased mitochondrial membrane potential and autophagy, indicating that oocyte quality was damaged by Arl2 and Arf5 depletion. These results suggest that Arl2 and Arf5 are two novel essential GTPases required for oocyte meiosis and quality control.
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http://dx.doi.org/10.1002/jcb.29839DOI Listing
February 2021
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