Publications by authors named "Wei Yang"

3,498 Publications

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miR-526b-3p inhibits lung cancer cisplatin-resistance and metastasis by inhibiting STAT3-promoted PD-L1.

Cell Death Dis 2021 Jul 28;12(8):748. Epub 2021 Jul 28.

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China.

Chemotherapy remains the primary treatment of advanced solid cancer, including lung cancer. However, as first-line treatment, cisplatin-based therapy is restricted by the frequent development of drug resistance. Increasing data showed that the programmed cell death protein ligand 1 (PD-L1) plays a vital role in regulating cisplatin resistance. However, the underlying mechanisms are not fully understood. We found that miR-526b-3p expression declined while PD-L1 was elevated in cisplatin-resistant lung cancer compared to that in cisplatin-sensitive lung cancer by analyzing clinical samples. Significantly, miR-526b-3p was associated with response to cisplatin negatively. We further demonstrated that miR-526b-3p reversed cisplatin resistance, suppressed metastasis, and activated CD8+ T cells in a STAT3/PD-L1-dependent manner. Thus, our findings extended the knowledge of PD-L1-mediated cisplatin resistance of lung cancer. In addition, the introduction of miR-526b-3p provided a new clue to improve the anti-tumor effects of the combination of immunotherapy and chemotherapy.
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http://dx.doi.org/10.1038/s41419-021-04033-8DOI Listing
July 2021

Network pharmacology and molecular docking analysis on mechanisms of Tibetan Hongjingtian () in the treatment of COVID-19.

J Med Microbiol 2021 Jul;70(7)

Key Laboratory of Molecular Mechanism and Intervention Research for Plateau Diseases of Tibet Autonomous Region, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, PR China.

Coronavirus disease 2019 (COVID-19) is a highly contagious disease and ravages the world. We proposed that might have potential value in the treatment of COVID-19 patients by regulating the immune response and inhibiting cytokine storm. We aimed to explore the potential molecular mechanism for () against the immune regulation of COVID-19, and to provide a referenced candidate Tibetan herb () to overcome COVID-19. Components and targets of were retrieved from the TCMSP database. GO analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment were built by R bioconductor package to explore the potential biological effects for targets of . The -compound-target network, target pathway network and protein-protein interaction (PPI) network were constructed using Cytoscape 3.3.0. Autodock 4.2 and Discovery Studio software were applied for molecular docking. Four bioactive components (quercetin, kaempferol, kaempferol-3-O-α-l-rhamnoside and tamarixetin) and 159 potential targets of were identified from the TCMSP database. The result of GO annotation and KEGG-pathway-enrichment analyses showed that target genes of were associated with inflammatory response and immune-related signalling pathways, especially IL-17 signalling pathway, and TNF signalling pathway. Targets-pathway network and PPI network showed that IL-6, IL-1B and TNF-α were considered to be hub genes. Molecular docking showed that core compound (quercetin) had a certain affinity with IL-1β, IL-6 and TNF-α. might play an anti-inflammatory and immunoregulatory role in the cytokine storm of COVID-19.
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http://dx.doi.org/10.1099/jmm.0.001374DOI Listing
July 2021

MicroRNA-181b Serves as a Circulating Biomarker and Regulates Inflammation in Heart Failure.

Dis Markers 2021 1;2021:4572282. Epub 2021 Jul 1.

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Street Harbin, Heilongjiang, China 150001.

Heart failure (HF) is the typical terminal stage of cardiac diseases involving inflammatory states. The function of microRNAs (miRNAs) in the progress of HF remains poorly understood. In this study, real-time PCR results showed a decreased expression of miRNA-181b (miR-181b) in HF patients compared with healthy individuals. Besides, miR-181b expressions were negatively correlated with hypersensitive C-reactive protein (hsCRP) levels in the serum of HF patients. Receiver operator characteristic (ROC) curve analysis showed that miR-181b was a diagnostic predictor of HF, and the area under the curve was 0.970 (DCM-induced HF group) and 0.962 (ICM-induced HF group). Strikingly, in HF rats induced by isoproterenol (ISO), the expression of miR-181b of heart tissue was suppressed before tumor necrosis factor-alpha (TNF-), interleukin-1 (IL-1), and interleukin-6 (IL-6) increase, as revealed by western blot and real-time PCR. Besides, the overexpression of miR-181b also decreased the expression of TNF-, IL-1, and IL-6 in lipopolysaccharide- (LPS-) induced neonatal cardiomyocytes. In conclusion, our results revealed that miR-181b might be a potential biomarker for HF and provided a novel target for anti-inflammatory therapy.
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http://dx.doi.org/10.1155/2021/4572282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270725PMC
July 2021

Loss of KMT2C reprograms the epigenomic landscape in hPSCs resulting in NODAL overexpression and a failure of hemogenic endothelium specification.

Epigenetics 2021 Jul 24:1-19. Epub 2021 Jul 24.

Department of Pediatrics, Division of Pediatric Hematology and Oncology, Washington University in St Louis School of Medicine, St. Louis, Missouri, United States.

Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. In isogenic KO hPSCs, we found genome-wide differences in histone modifications at active and poised enhancers, leading to gene expression profiles akin to mesendoderm rather than mesoderm highlighted by a significant increase in NODAL expression and WNT inhibition, ultimately resulting in a lack of hemogenic endothelium specification. These unbiased multi-omic results provide new evidence for germline mechanisms increasing risk of early leukaemogenesis.
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http://dx.doi.org/10.1080/15592294.2021.1954780DOI Listing
July 2021

Effect of dihydropyridine enrichment in the microstructure of the palisade layer on the stability of fat nano-emulsions.

J Pharm Sci 2021 Jul 22. Epub 2021 Jul 22.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, Guangdong, China; Department of Clinical Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou510080,Guangdong, China. Electronic address:

Relationship between the stability of fat nano-emulsions and the incorporated drug at the molecular level are rarely known. Herein,fat nano-emulsions containing dihydropyridine drugs were prepared and the microstructure of their palisade layers were investigated.The prepared 1.0 mg/mL nimodipine nano-emulsion was found to contain 65.50% drug in the palisade layer. The increasing drug concentration led to a decrease-increase-decrease trend in centrifugal stability constant, particle size and proton nuclear magnetic resonance (H NMR) signal intensity of the lecithin trimethyl ammonium group in the nimodipine and felodipine nano-emulsions. The H NMR spectra of test solutions including nano-emulsionssuggests that increasing drugs penetrated into the palisade layer, resulting in the lecithin arrangement from loose to tight, and then from monolayer to bilayer. Nimodipine and felodipine nano-emulsions showed two valley values at concentrations of 0.15 and 0.75 mg/mL, and 0.30 and 0.90 mg/mL respectively, which indicated that the nano-emulsion has two more stable states corresponding to the tightly arranged mono- and bi-palisade layer. These two concentrations are positively correlated with lipophilicity of nimodipine and felodipine. Further, nimodipine liposomes were prepared to validatethe effect of drugs on the arrangement of lecithin in the palisade layer. H NMR characterizations of the liposomes showed a similar profile to that of nano-emulsions. These results demonstrated that the increasing drug concentration could cause a rearrangement of lecithin in the palisade layer, thus affecting emulsion stability.
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http://dx.doi.org/10.1016/j.xphs.2021.07.013DOI Listing
July 2021

Protein Kinase CK2 Regulates B Cell Development and Differentiation.

J Immunol 2021 Aug 23;207(3):799-808. Epub 2021 Jul 23.

Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294; and.

Protein kinase CK2 (also known as Casein Kinase 2) is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α') and two regulatory CK2β subunits. CK2 is overexpressed and overactive in B cell acute lymphoblastic leukemia and diffuse large B cell lymphomas, leading to inappropriate activation of the NF-κB, JAK/STAT, and PI3K/AKT/mTOR signaling pathways and tumor growth. However, whether CK2 regulates normal B cell development and differentiation is not known. We generated mice lacking CK2α specifically in B cells (using CD19-driven Cre recombinase). These mice exhibited cell-intrinsic expansion of marginal zone B cells at the expense of transitional B cells, without changes in follicular B cells. Transitional B cells required CK2α to maintain adequate BCR signaling. In the absence of CK2α, reduced BCR signaling and elevated Notch2 signaling activation increased marginal zone B cell differentiation. Our results identify a previously unrecognized function for CK2α in B cell development and differentiation.
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http://dx.doi.org/10.4049/jimmunol.2100059DOI Listing
August 2021

Dysregulation of the Adaptive Immune System in Patients With Early-Stage Parkinson Disease.

Neurol Neuroimmunol Neuroinflamm 2021 Jul 22;8(5). Epub 2021 Jul 22.

From the Department of Cell, Developmental and Integrative Biology (Z.Y., W.Y., H.W., E.N.B., H.Q.), Department of Neurology (M.N.D., D.G.S.), and Department of Biostatistics (G.R.C.), University of Alabama at Birmingham.

Objective: To determine the activation status and cytokine profiles of CD4 T cells, CD8 T cells, and CD19 B cells from patients with early-stage Parkinson disease (PD) compared with healthy controls (HCs).

Methods: Peripheral blood samples from 41 patients with early-stage PD and 40 HCs were evaluated. Peripheral blood mononuclear cells were analyzed by flow cytometry for surface markers and intracellular cytokine production. Correlations of immunologic changes and clinical parameters were analyzed.

Results: Adaptive immunity plays a role in the pathogenesis of PD, yet the contribution of T cells and B cells, especially cytokine production by these cells, is poorly understood. We demonstrate that naive CD4 and naive CD8 T cells are significantly decreased in patients with PD, whereas central memory CD4 T cells are significantly increased in patients with PD. Furthermore, IL-17-producing CD4 Th17 cells, IL-4-producing CD4 Th2 cells, and IFN-γ-producing CD8 T cells are significantly increased in patients with PD. Regarding B cells, we observed a decrease in naive B cells and an increase in nonswitched memory and double-negative B cells. As well, TNF-α-producing CD19 B cells were significantly increased in patients with PD. Notably, some of the changes observed in CD4 T cells and B cells were associated with clinical motor disease severity.

Conclusions: These findings suggest that alterations in the adaptive immune system may promote clinical disease in PD by skewing to a more proinflammatory state in the early-stage PD patient cohort. Our study may shed light on potential immunotherapies targeting dysregulated CD4 T cells, CD8 T cells, and CD19 B cells in patients with PD.
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http://dx.doi.org/10.1212/NXI.0000000000001036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299515PMC
July 2021

AIRE-overexpressing BMDCs suppress T cells through ICOSL to prevent and attenuate autoimmune diabetes in NOD mice.

Int Immunopharmacol 2021 Jul 19;99:107979. Epub 2021 Jul 19.

Department of Immunology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China. Electronic address:

The strong genetic association between autoimmune regulator (AIRE) and autoimmune diseases indicates its critical role in immune tolerance. AIRE deficiency is thought to promote the development of follicular helper T (T) cells, which are considered to be essential in B cell proliferation. Excessive T cell generation is a key step towards the development of autoimmune diseases, including type 1 diabetes. However, the potential mechanism by which AIRE contributes to the generation and function of the T cell population has remained elusive. We show that AIRE reduced T cell generation by inhibiting the expression of inducible costimulatory ligand (ICOSL), interleukin (IL)-6 and IL-27 in dendritic cells (DCs). To understand the precise impact of AIRE-overexpressing bone marrow-derived DCs (AIRE-BMDCs) on type 1 diabetes progression and the associated molecular mechanisms, we transferred AIRE-BMDCs to recipient NOD mice and found that transplantation of AIRE-BMDCs can prevent or delay the onset of diabetes, attenuate diabetes after the establishment of overt hyperglycaemia, and lead to the inhibition of autoreactive pathological T cells and germinal centre (GC) B cells. To further determine the potential mechanism underlying this T cell depletion, BMDCs were cotransferred with recombinant mouse ICOSL (ICOSLG protein). We demonstrated that NOD mice were more susceptible to diabetes when they received AIRE-BMDCs and ICOSLG than when they received only mock-vehicle BMDCs (GFP-BMDCs). In addition, we did not observe the reversal of diabetes in any mice subjected to this cotransfer system. A single cycle of ICOSLG treatment temporarily promoted T cell proliferation and GC development. Our results reveal a mechanistic role of AIRE-BMDCs in the initiation of T cell differentiation, and the AIRE-mediated decrease in ICOSL expression in BMDCs plays a critical role. The effect of decreased ICOSL expression in type 1 diabetes will guide the design and evaluation of parallel studies in patients.
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http://dx.doi.org/10.1016/j.intimp.2021.107979DOI Listing
July 2021

Adventitious root primordia formation and development in the stem of var. slip.

Plant Signal Behav 2021 Jul 21:1949147. Epub 2021 Jul 21.

College of Landscape Architecture-Sichuan Agricultural University, Chengdu- Sichuan, China.

There are about 4-6 slips on a fruit, and they are good materials for effective regeneration of var. . Adventitious root (AR) induction is essential for the propagation of slips. Growth regulator treatment, and culture medium are imperative factors that affect slip growth and rooting. In order to screen the optimal methods for slips rooting and reveal the anatomic procedure of slip rooting, this study induced slip rooting by different treatment of growth regulator, culture medium, observed the slip stem structure, AR origination and formation procedure through paraffin sections. The results showed that, slip cuttings treated with 100 mg/L of Aminobenzotriazole (ABT) for 6 hrs, cultured in river sand: coconut chaff: garden soil 2:2:1 medium is the optimal method for rooting. The proper supplementary of ABT can enhance the soluble sugar content, soluble protein content, polyphenol oxidase (PPO) activity and peroxidase (POD) enzyme activity, which resulted in the improvement of rooting. The slip stem structure is quite different from other monocots, which consists of epidermis, cortex, and stele with vascular tissues distributed in the cortex and stele. The AR primordia originates from the parenchyma cells located on the borderline between the cortex and stele. The vascular tissues in the AR develop and are connected with vascular tissue of the stem before the AR grew out the stem. The number of primary xylem poles in AR is about 30.
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http://dx.doi.org/10.1080/15592324.2021.1949147DOI Listing
July 2021

Single-cell Long Non-coding RNA Landscape of T Cells in Human Cancer Immunity.

Genomics Proteomics Bioinformatics 2021 Jul 17. Epub 2021 Jul 17.

Translational Medicine Collaborative Innovation Center, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518020, China; Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen 518020, China. Electronic address:

The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 libraries of T cells across three cancer types, we provide the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novo transcriptome assembly and obtained a novel lncRNA catalog containing 9433 genes. This increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNAs were identified. They associated with effector, exhausted, and regulatory T cell states. 84 of them were functionally annotated based on the co-expression network, indicating that lncRNAs might broadly participate in the regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.
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http://dx.doi.org/10.1016/j.gpb.2021.02.006DOI Listing
July 2021

SARS-CoV-2: from its discovery to genome structure, transcription, and replication.

Cell Biosci 2021 Jul 19;11(1):136. Epub 2021 Jul 19.

Tumor Virus RNA Biology Section, HIV DRP, National Cancer Institute, NIH, Frederick, MD, USA.

SARS-CoV-2 is an extremely contagious respiratory virus causing adult atypical pneumonia COVID-19 with severe acute respiratory syndrome (SARS). SARS-CoV-2 has a single-stranded, positive-sense RNA (+RNA) genome of ~ 29.9 kb and exhibits significant genetic shift from different isolates. After entering the susceptible cells expressing both ACE2 and TMPRSS2, the SARS-CoV-2 genome directly functions as an mRNA to translate two polyproteins from the ORF1a and ORF1b region, which are cleaved by two viral proteases into sixteen non-structural proteins (nsp1-16) to initiate viral genome replication and transcription. The SARS-CoV-2 genome also encodes four structural (S, E, M and N) and up to six accessory (3a, 6, 7a, 7b, 8, and 9b) proteins, but their translation requires newly synthesized individual subgenomic RNAs (sgRNA) in the infected cells. Synthesis of the full-length viral genomic RNA (gRNA) and sgRNAs are conducted inside double-membrane vesicles (DMVs) by the viral replication and transcription complex (RTC), which comprises nsp7, nsp8, nsp9, nsp12, nsp13 and a short RNA primer. To produce sgRNAs, RTC starts RNA synthesis from the highly structured gRNA 3' end and switches template at various transcription regulatory sequence (TRS) sites along the gRNA body probably mediated by a long-distance RNA-RNA interaction. The TRS motif in the gRNA 5' leader (TRS) is responsible for the RNA-RNA interaction with the TRS upstream of each ORF and skipping of the viral genome in between them to produce individual sgRNAs. Abundance of individual sgRNAs and viral gRNA synthesized in the infected cells depend on the location and read-through efficiency of each TRS. Although more studies are needed, the unprecedented COVID-19 pandemic has taught the world a painful lesson that is to invest and proactively prepare future emergence of other types of coronaviruses and any other possible biological horrors.
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http://dx.doi.org/10.1186/s13578-021-00643-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287290PMC
July 2021

Redox-Mediated Artificial Non-Enzymatic Antioxidant MXene Nanoplatforms for Acute Kidney Injury Alleviation.

Adv Sci (Weinh) 2021 Jul 17:e2101498. Epub 2021 Jul 17.

College of Polymer Science and Engineering, Sichuan University, State Key Laboratory of Polymer Materials Engineering, Chengdu, Sichuan, 610065, China.

Acute kidney injury (AKI), as a common oxidative stress-related renal disease, causes high mortality in clinics annually, and many other clinical diseases, including the pandemic COVID-19, have a high potential to cause AKI, yet only rehydration, renal dialysis, and other supportive therapies are available for AKI in the clinics. Nanotechnology-mediated antioxidant therapy represents a promising therapeutic strategy for AKI treatment. However, current enzyme-mimicking nanoantioxidants show poor biocompatibility and biodegradability, as well as non-specific ROS level regulation, further potentially causing deleterious adverse effects. Herein, the authors report a novel non-enzymatic antioxidant strategy based on ultrathin Ti C -PVP nanosheets (TPNS) with excellent biocompatibility and great chemical reactivity toward multiple ROS for AKI treatment. These TPNS nanosheets exhibit enzyme/ROS-triggered biodegradability and broad-spectrum ROS scavenging ability through the readily occurring redox reaction between Ti C and various ROS, as verified by theoretical calculations. Furthermore, both in vivo and in vitro experiments demonstrate that TPNS can serve as efficient antioxidant platforms to scavenge the overexpressed ROS and subsequently suppress oxidative stress-induced inflammatory response through inhibition of NF-κB signal pathway for AKI treatment. This study highlights a new type of therapeutic agent, that is, the redox-mediated non-enzymatic antioxidant MXene nanoplatforms in treatment of AKI and other ROS-associated diseases.
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http://dx.doi.org/10.1002/advs.202101498DOI Listing
July 2021

Interplay and cooperation between SREBF1 and master transcription factors regulate lipid metabolism and tumor-promoting pathways in squamous cancer.

Nat Commun 2021 07 16;12(1):4362. Epub 2021 Jul 16.

Department of Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63), a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC.
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http://dx.doi.org/10.1038/s41467-021-24656-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285542PMC
July 2021

BI-RADS Ultrasound Lexicon Descriptors and Stromal Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer.

Acad Radiol 2021 Jul 13. Epub 2021 Jul 13.

Department of Breast Imaging, Unit 1350, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Increased levels of stromal tumor-infiltrating lymphocytes (sTILs) have recently been considered a favorable independent prognostic and predictive biomarker in triple-negative breast cancer (TNBC). The purpose of this study was to determine the relationship between BI-RADS (Breast Imaging Reporting and Data System) ultrasound lexicon descriptors and sTILs in TNBC.

Materials And Methods: Patients with stage I-III TNBC were evaluated within a single-institution neoadjuvant clinical trial. Two fellowship-trained breast radiologists used the BI-RADS ultrasound lexicon to assess pretreatment tumor shape, margin, echo pattern, orientation, posterior features, and vascularity. sTILs were defined as low <20 or high ≥20 on the pretreatment biopsy. Fisher's exact tests were used to assess the association between lexicon descriptors and sTIL levels.

Results: The 284 patients (mean age 52 years, range 24-79 years) were comprised of 68% (193/284) with low-sTIL tumors and 32% (91/284) with high-sTIL tumors. TNBC tumors with high sTILs were more likely to have the following features: (1) oval/round shape than irregular shape (p = 0.003), (2) circumscribed or microlobulated margins than spiculated, indistinct, or angular margins (p = 0.0005); (3) complex cystic and solid pattern than heterogeneous pattern (p = 0.006); and (4) posterior enhancement than shadowing (p = 0.002). There was no significant association between sTILs and descriptors for orientation and vascularity (p = 0.06 and p = 0.49, respectively).

Conclusion: BI-RADS ultrasound descriptors of the pretreatment appearance of a TNBC tumor can be useful in discriminating between tumors with low and high sTIL levels. Therefore, there is a potential use of ultrasound tumor characteristics to complement sTILs when used as stratification factors in treatment algorithms for TNBC.
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http://dx.doi.org/10.1016/j.acra.2021.06.007DOI Listing
July 2021

Analysis of Estimated and Measured Glomerular Filtration Rates and the CKD-EPI Equation Race Coefficient in the Chronic Renal Insufficiency Cohort Study.

JAMA Netw Open 2021 Jul 1;4(7):e2117080. Epub 2021 Jul 1.

Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.17080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283556PMC
July 2021

Catastrophic health expenditure and mental health in the older Chinese population: The moderating role of social health insurance.

Authors:
Wei Yang Bo Hu

J Gerontol B Psychol Sci Soc Sci 2021 Jul 13. Epub 2021 Jul 13.

Care Policy and Evaluation Centre (CPEC), Department of Health Policy, The London School of Economics and Political Science.

Objectives: Catastrophic health expenditure (CHE) has considerable effects on household living standards, but little is known regarding the relationships between CHE and people's mental health. Using China as an example, this study examines the association between CHE and mental health and investigates whether the association differs between those with and without social health insurance (SHI).

Methods: The data came from three waves of the China Health and Retirement Longitudinal Study (CHARLS 2011, 2013, and 2015, N = 13,166). We focused on older people aged 60 and above. We built panel data regression and quantile regression models to analyse the data.

Results: Incurring CHE is significantly associated with poor mental health. The association is weakened among older people receiving SHI, which indicates that SHI has a protective effect. Moreover, the association between CHE and mental health and the protective effect of SHI are stronger among those with mild or moderate mental health problems.

Discussion: Our findings provide empirical evidence that encourages the integration of psychologically informed approaches in health services. We also urge governments in low- and middle-income countries to consider more generous health financing mechanisms for older people with greater healthcare needs.
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http://dx.doi.org/10.1093/geronb/gbab130DOI Listing
July 2021

Food insecurity during the COVID-19 pandemic: evidence from a survey of low-income Americans.

Food Secur 2021 Jul 7:1-19. Epub 2021 Jul 7.

Department of Agricultural Economics and Agribusiness, University of Arkansas, Fayetteville, AR USA.

The COVID-19 pandemic significantly increased food insecurity despite emergency legislation that put more resources into food assistance programs, increased unemployment benefits, and provided stimulus payments. We conducted a survey in the US on food insecurity among low-income Americans during the early months of the pandemic. While we cannot estimate causal effects, we are able to show important associations between food insecurity and nutritional and economic assistance that highlight the need to ensure that those newly at risk for food insecurity are able to connect to resources. For example, our results indicate that those who lost jobs due to the pandemic reported the highest level of food insecurity and also the lowest engagement with food assistance programs. The SNAP expansion appears to be important only among groups with higher levels of income stability including non-minority households and those not experiencing a job loss. Thus, the SNAP expansion may not have had a meaningful impact on those most at risk for food insecurity. Finally, our data highlight the importance of school meal programs during normal times. Those who took advantage of school meals before the outbreak are more likely to have experienced food insecurity during the pandemic-related school closures.
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http://dx.doi.org/10.1007/s12571-021-01189-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262589PMC
July 2021

Inner workings of RAG recombinase and its specialization for adaptive immunity.

Curr Opin Struct Biol 2021 Jul 7;71:79-86. Epub 2021 Jul 7.

Laboratory of Molecular Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

RAG1/2 (RAG) is an RNH-type DNA recombinase specially evolved to initiate V(D)J gene rearrangement for generating the adaptive immune response in jawed vertebrates. After decades of frustration with little mechanistic understanding of RAG, the crystal structure of mouse RAG recombinase opened the flood gates in early 2015. Structures of three different chordate RAG recombinases, including protoRAG, and the evolutionarily preceding transib transposase have been determined in complex with various DNA substrates. Biochemical studies along with the abundant structural data have shed light on how RAG has evolved from an ordinary transposase to a specialized recombinase in initiating gene rearrangement. RAG has also become one of the best characterized RNH-type recombinases, illustrating how a single active site can cleave the two antiparallel DNA strands of a double helix.
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http://dx.doi.org/10.1016/j.sbi.2021.05.014DOI Listing
July 2021

Metagenomic Next-Generation Sequencing for the Diagnosis of Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients: A Retrospective Study.

Infect Dis Ther 2021 Sep 10;10(3):1733-1745. Epub 2021 Jul 10.

Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, 410008, People's Republic of China.

Introduction: This study aimed to evaluate the utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus-infected patients.

Methods: We conducted a retrospective study. A total of 60 non-human immunodeficiency virus-infected PJP patients and 134 patients diagnosed with non-PJP pneumonia were included. P. jirovecii and other co-pathogens identified by mNGS in bronchoalveolar lavage fluid and/or blood samples were analyzed. Using clinical composite diagnosis as the reference standard, we compared the diagnostic performance of mNGS in PJP with conventional methods, including Gomori methenamine silver staining and serum (1,3)-β-D-glucan. Modifications of antimicrobial treatment for PJP patients after the report of mNGS results were also reviewed.

Results: mNGS reached a sensitivity of 100% in diagnosing PJP, which was remarkably higher than Gomori methenamine silver staining (25.0%) and serum (1,3)-β-D-glucan (67.4%). The specificity of mNGS (96.3%) significantly surpassed serum (1,3)-β-D-glucan (81.4%). Simultaneous mNGS of bronchoalveolar lavage fluid and blood samples was performed in 21 out of 60 PJP patients, and it showed a concordance rate of 100% in detecting P. jirovecii. Besides, mNGS showed good performance in identifying co-pathogens of PJP patients, among which cytomegalovirus and Epstein-Barr virus were most commonly seen. Initial antimicrobial treatment was modified in 71.7% of PJP patients after the report of mNGS results.

Conclusion: mNGS is a useful diagnostic tool with good performance for the diagnosis of PJP and the detection of co-pathogens. mNGS of bronchoalveolar lavage fluid and/or blood samples is suggested in patients with presumptive diagnosis of PJP. Blood samples may be a good alternative to bronchoalveolar lavage fluid for mNGS when bronchoscopic examination is not feasible.
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http://dx.doi.org/10.1007/s40121-021-00482-yDOI Listing
September 2021

Light, strong, and stable nanoporous aluminum with native oxide shell.

Sci Adv 2021 Jul 9;7(28). Epub 2021 Jul 9.

Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016, PR China.

Aluminum (Al) metal is highly reactive but has excellent corrosion resistance because of the formation of a self-healing passive oxide layer on the surface. Here, we report that this native aluminum oxide shell can also stabilize and strengthen porous Al when the ligament (strut) size is decreased to the submicron or nanometer scale. The nanoporous Al with native oxide shell, which is a nanoporous Al-AlO core-shell composite self-organized in a galvanic replacement reaction, is nonflammable under ambient conditions and stable against coarsening near melting temperatures. This material is stronger than conventional foams of similar density consisting of pure Al or Al-based composites, and also lighter and stronger than most nanoporous metals reported previously. Its light weight, high strength, and excellent stability warrant the explorations of functional and structural applications of this material, if more efficient and scalable synthesis processes are developed in the future.
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http://dx.doi.org/10.1126/sciadv.abb9471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270488PMC
July 2021

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin.

Evid Based Complement Alternat Med 2021 18;2021:6610793. Epub 2021 Jun 18.

Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong, China.

Introduction: Forsythin is the main ingredient of and is widely used in treatment of fever, viral cold, gonorrhea, and ulcers clinically. This study aimed to evaluate the potential genetic toxicity of forsythin and its safety for human use.

Methods: Based on the Good Laboratory Practice regulations and test guidelines, the genetic toxicity of forsythin was assessed by the Ames test, chromosome aberration (CA) test, and bone marrow micronucleus (MN) test in vivo. In the Ames test, five strains of were exposed to different concentrations of forsythin in the presence or absence of the S9 mixture, and then, the number of His + revertant colonies was counted. In the CA test, Chinese hamster lung (CHL) fibroblast cells were treated with different concentrations of forsythin, mitomycin C, or cyclophosphamide in the presence or absence of the S9 mixture, and the chromosomal aberrations were determined. In the MN test, bone marrow was isolated from the mice with different treatments, and the ratios of polychromatic erythrocytes (PCE) and erythrocytes (PCE/(PCE + NCE)) were measured. Finally, beagle dogs were divided into four groups (negative control, low dose, medium dose, and high dose groups), and then, a telemetry system was used to evaluate the safe use of forsythin.

Results: Ames test results showed that the number of colonies in all test strains with different treatments showed no significantly dose-dependent increase in the presence or absence of the S9 mixture ( > 0.05). In the CA test, the number of cells with aberrations in the CHL fibroblast cells treated with low, medium, and high doses of forsythin for 24/48 h in the absence of the S9 mixture was, respectively, 5.0/2.5, 4.5/1.5, and 5.0/5.0, and in the presence of the S9 mixture, the number was, respectively, 5.0, 5.0, and 4.5. These results showed that there was no significant difference compared to the negative control group either in the presence (2.0) or in the absence (4.0/2.5 for 24/48 h) of the S9 mixture ( > 0.05). The MN test showed that the values of PCE/(PCE + NCE) in the negative, positive controls, and forsythin treatment groups were all more than 20%, which indicated that forsythin had no cytotoxicity. Additionally, no significant toxicological effects of forsythin on blood pressure, respiration, temperature, electrocardiogram, and other physiological indicators in the conscious beagle dogs of different groups were observed by the telemetry method.

Conclusion: Our findings showed that forsythin has low probability of genetic toxicity and no significant toxicological effects, which implied that forsythin is suitable for further development and potential application.
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http://dx.doi.org/10.1155/2021/6610793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233079PMC
June 2021

Erratum: Long noncoding RNA LINC01123 promotes the proliferation and invasion of hepatocellular carcinoma cells by modulating the miR-34a-5p/TUFT1 axis: Erratum.

Int J Biol Sci 2021 8;17(9):2336-2337. Epub 2021 Jun 8.

Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang 310014, China.

[This corrects the article DOI: 10.7150/ijbs.45457.].
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http://dx.doi.org/10.7150/ijbs.61069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241735PMC
June 2021

Organic Cation Transporters are Involved in Fluoxetine Transport Across the Blood-Brain Barrier in Vivo and in Vitro.

Curr Drug Deliv 2021 Jul 8. Epub 2021 Jul 8.

Zhejiang Key Laboratory of Neuropsychiatric Drug Research, Hangzhou Medical College (Zhejiang Academy of Medical Sciences), No.182, Tianmu Shan Road, 310013 Hangzhou, China.

Background: The research and development of drugs for the treatment of central nervous system diseases faces many challenges at present. One of the most important questions to be answered is, how does the drug cross the blood-brain barrier to get to the target site for pharmacological action. Fluoxetine is widely used in clinical antidepressant therapy. However, the mechanism by which fluoxetine passes through the BBB also remains unclear. Under physiological pH conditions, fluoxetine is an organic cation with a relatively small molecular weight (<500), which is in line with the substrate characteristics of organic cation transporters (OCTs). Therefore, this study aimed to investigate the interaction of fluoxetine with OCTs at the BBB and BBB-associated efflux transporters. This is of great significance for fluoxetine to better treat depression. Moreover, it can provide a theoretical basis for clinical drug combinations.

Methods: In vitro BBB model was developed using human brain microvascular endothelial cells (hCMEC/D3), and the cellular accumulation was tested in the presence or absence of transporter inhibitors. In addition, an in vivo trial was performed in rats to investigate the effect of OCTs on the distribution of fluoxetine in the brain tissue. Fluoxetine concentration was determined by a validated UPLC-MS/MS method.

Results: The results showed that amantadine (an OCT1/2 inhibitor) and prazosin (an OCT1/3 inhibitor) significantly decreased the cellular accumulation of fluoxetine (P <.001). Moreover, we found that N-methylnicotinamide (an OCT2 inhibitor) significantly inhibited the cellular uptake of 100 and 500 ng/mL fluoxetine (P <.01 and P <.05 respectively). In contrast, corticosterone (an OCT3 inhibitor) only significantly inhibited the cellular uptake of 1000 ng/mL fluoxetine (P <.05). The P-glycoprotein (P-gp) inhibitor, verapamil, and the multidrug resistance resistance-associated proteins (MRPs) inhibitor, MK571, significantly decreased the cellular uptake of fluoxetine. However, intracellular accumulation of fluoxetine was not significantly changed when fluoxetine was incubated with the breast cancer resistance protein (BCRP) inhibitor Ko143. Furthermore, in vivo experiments proved that corticosterone and prazosin significantly inhibited the brain-plasma ratio of fluoxetine at 5.5 h and 12 h, respectively.

Conclusion: OCTs might play a significant role in the transport of fluoxetine across the BBB. In addition, P-gp, BCRP, and MRPs seemed not to mediate the efflux transport of fluoxetine.
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http://dx.doi.org/10.2174/1567201818666210708122326DOI Listing
July 2021

Discovery of a potent and selective inhibitor of histone lysine demethylase KDM4D.

Eur J Med Chem 2021 Jun 26;223:113662. Epub 2021 Jun 26.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan, 610041, China. Electronic address:

Histone lysine demethylase 4D (KDM4D) plays an important role in the regulation of tumorigenesis, progression and drug resistance and has been considered a potential target for cancer treatment. However, there is still a lack of potent and selective KDM4D inhibitors. In this investigation, we report a new class of KDM4D inhibitors containing the 2-(aryl(pyrrolidine-1-yl)methyl)phenol scaffold, identified through AlphaLisa-based screening, structural optimization, and structure-activity relationship analyses. Among these inhibitors, 24s was the most potent, with an IC value of 0.023 ± 0.004 μM. This compound exhibited more than 1500-fold selectivity towards KDM4D versus KDM4A as well as other JMJD subfamily members, indicating good selectivity for KDM4D. Kinetic analysis indicated that 24s did not occupy the 2-oxoglutarate binding pocket. In an in vitro assay, 24s significantly suppressed the proliferation and migration of colorectal cancer (CRC) cells. Overall, this study has identified a good tool compound to explore the biological function of KDM4D and a good lead compound for drug discovery targeting KDM4D.
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http://dx.doi.org/10.1016/j.ejmech.2021.113662DOI Listing
June 2021

Overexpression of miR-122 Impairs Intestinal Barrier Function and Aggravates Acute Pancreatitis by Downregulating Occludin Expression.

Biochem Genet 2021 Jul 7. Epub 2021 Jul 7.

Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, No. 189, Chaoyang Road, Kunshan, 215300, Jiangsu Province, People's Republic of China.

Acute pancreatitis (AP) causes intestinal barrier damage, resulting in systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors affecting AP severity and mortality. Here, we studied the mechanism of miR-122 in regulating intestinal barrier function in AP. AP rat model was constructed via intraperitoneal injection of ketamine, and primary intestinal epithelial cells were isolated from rats for in vitro studies. HE staining was used to assess pathological alterations of pancreas and intestines tissues. Inflammatory factors were detected by ELISA assay. qRT-PCR and WB were used to detect the expressions of miR-122 and occluding, respectively. Then dual-luciferase reporter assay, intestinal permeability test, and cell permeability were performed in vivo and in vitro to probe the molecular mechanism of miR-122 in regulating intestinal barrier function in AP. The expression of miR-122 was upregulated in AP rats, while the expression of occludin was downregulated, and the intestinal permeability was increased in AP rats and primary intestinal epithelial cells isolated from rats. Inhibition of miR-122 regulated intestinal barrier function through mediating occludin expression. miR-122 regulated intestinal barrier function to affect AP through mediating occludin expression in vivo. These results provided evidence that miR-122 overexpression impaired intestinal barrier function via regulation of occludin expression, thus promoting AP progression.
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http://dx.doi.org/10.1007/s10528-021-10106-2DOI Listing
July 2021

Base-Resolution Analysis of Deoxyuridine at the Genome Scale Based on the Artificial Incorporation Modified Nucleobase.

ACS Cent Sci 2021 Jun 28;7(6):973-979. Epub 2021 Apr 28.

College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, 430072 Hubei, China.

Deamination of cytosine and dUMP misincorporation have been found to be capable of producing uracil in the genome. This study presents the AI-seq (artificial incorporation modified nucleobase for sequencing), a "base substitution", which not only is capable of profiling uracil at single-nucleotide resolution and showing its centromeric enrichment but could also reveal that the identified uracil sites are derived from cytosine deamination. All the results indicate the potential biological significance of uracil as the epigenetic modification.
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http://dx.doi.org/10.1021/acscentsci.0c01504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227591PMC
June 2021

A new application of terahertz time-domain absorption spectra in luminescent complexes: characterization of the C-Hπ weak interactions in Cu(I) complexes.

Dalton Trans 2021 Jul;50(29):10214-10224

Faculty of Food Science and Technology, Suzhou Polytechnical Institute of Agriculture, Suzhou 215008, P. R. China.

Six Cu(i) complexes, [Cu(2,3-f)(bdppmapy)]BF4 (1), [Cu(2,3-f)(bdppmapy)]ClO4 (2), [Cu(2,3-f)(bdppmapy)]CF3SO3 (3), [Cu(imidazo[4,5-f])(bdppmapy)]BF4 (4), [Cu(imidazo[4,5-f])(bdppmapy)]ClO4 (5), and [Cu(imidazo[4,5-f])(bdppmapy)]CF3SO3·MeOH (6·MeOH) (bdppmapy = N,N-bis[(diphenylphosphino)methyl]-2-pyridinamine, 2,3-f = pyrazine[2,3-f][1,10]-phenanthroline, and imidazo[4,5-f] = 1H-imidazo[4,5-f][1,10]-phenanthroline), have been synthesized to explore the effects of counteranions on their crystal structures, photophysical properties, and terahertz (THz) spectra. Time-dependent density functional theory (TD-DFT) shows that the luminescence performance of these complexes is attributed to the metal-to-ligand charge transfer (MLCT) in combination with ligand-to-ligand charge transfer (LLCT). In complexes 1-3, the characteristic peak at 1.4 THz is mainly related to the C-Hπ interaction formed by the H atom on the 4#/5# position of 2,3-f and the benzene ring from the bdppmapy on the adjacent asymmetric unit. The common C-Hπ interaction enhances the rigidity of the structure and has non-negligible influence on the photoluminescence quantum yields (PLQYs): the stronger the C-Hπ interaction is, the higher the quantum yield (QY) is. In complexes 4-6, similar absorption peaks (1.10-1.30 THz) are mainly related to the C-Hπ interactions, and strong absorption peaks (1.50-1.90 THz) are affected by the typical hydrogen bonds N-HF/O and O-HO. These results show that some weak interactions can be characterized by THz time-domain spectroscopy (THz-TDS). So, the THz spectroscopy method would make it possible to tune some of the weak interactions in complex structures to regulate the luminescence of materials.
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http://dx.doi.org/10.1039/d1dt01023aDOI Listing
July 2021

Controllable synthesis of ZIF-derived NiCoO nanotube array hierarchical structures based on self-assembly for high-performance hybrid alkaline batteries.

Dalton Trans 2021 Jul;50(26):9088-9102

Shaanxi Key Laboratory of Fiber Reinforced Light Composite Materials, Northwestern Polytechnical University, Xi'an 710072, China.

In this study, a novel NixCo3-xO4 nanotube array hierarchical structure derived from zeolitic imidazolate frameworks (ZIFs) is grown on Ni foam (NixCo3-xO4 NAHS/Ni foam) using the template-assisted and self-assembly approach for a high-performance hybrid energy storage device in alkaline solution. The material characteristics of the resultant samples were characterized by XPS, XRD, ICP, SEM, TEM and BET. Due to the unique hollow structure with a large specific surface area and the exposure of large active sites originating from ZIFs, the optimal NixCo3-xO4 NAHS/Ni foam exhibits substantially enhanced electrochemical properties. The NixCo3-xO4 NAHS/Ni foam directly acts as an electrode, which provides an excellent specific capacity of 290.48 mA h g-1 at 1 A g-1. Subsequently, the corresponding hybrid alkaline batteries that consist of NixCo3-xO4 NAHS/Ni foam and carbon materials display a highly satisfactory specific capacity of 54.94 mA h g-1 at 1 A g-1, a satisfactory long-term stability of 85.47% after 2000 cycles, a maximum energy density of 43.95 W h kg-1 and a power density of 8000 W kg-1. This work combines the design of the electronic structure with the optimization of composition, and provides a reference for the application of hybrid rechargeable alkaline batteries (RABs).
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http://dx.doi.org/10.1039/d1dt01419fDOI Listing
July 2021

High Mountain Asian glacier response to climate revealed by multi-temporal satellite observations since the 1960s.

Nat Commun 2021 07 5;12(1):4133. Epub 2021 Jul 5.

Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing, China.

Knowledge about the long-term response of High Mountain Asian glaciers to climatic variations is paramount because of their important role in sustaining Asian river flow. Here, a satellite-based time series of glacier mass balance for seven climatically different regions across High Mountain Asia since the 1960s shows that glacier mass loss rates have persistently increased at most sites. Regional glacier mass budgets ranged from -0.40 ± 0.07 m w.e.a in Central and Northern Tien Shan to -0.06 ± 0.07 m w.e.a in Eastern Pamir, with considerable temporal and spatial variability. Highest rates of mass loss occurred in Central Himalaya and Northern Tien Shan after 2015 and even in regions where glaciers were previously in balance with climate, such as Eastern Pamir, mass losses prevailed in recent years. An increase in summer temperature explains the long-term trend in mass loss and now appears to drive mass loss even in regions formerly sensitive to both temperature and precipitation.
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http://dx.doi.org/10.1038/s41467-021-24180-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257854PMC
July 2021

Biochemical and functional characterization of two microbial type terpene synthases from moss Stereodon subimponens.

Plant Physiol Biochem 2021 Jun 25;166:750-760. Epub 2021 Jun 25.

National Engineering Laboratory for Resource Development of Endangered Crude Drugs in Northwest China, The Key Laboratory of Medicinal Resources and Natural Pharmaceutical Chemistry, The Ministry of Education, College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710119, The People's Republic of China. Electronic address:

Terpenes constitute a large class of plant secondary metabolites. Usually, there is only one type of terpene synthase in seed plants, which is called typical plant terpene synthase. Currently, as a new family of plant terpene synthases, microbial terpene synthase-like (MTPSL) is identificated in nonseed plants. However, our knowledge about the biological function of most MTPSLs in nonseed plants is very limited. Here, we investigated the biochemical and functional characterization of the enzymes encoded by two MTPSLs from moss Stereodon subimponens, SsMTPSL1 and SsMTPSL2. A phylogenetic tree analysis showed that SsMTPSL1 and SsMTPSL2 are homologous to AaMTPSL1, AaMTPSL3, ApMTPSL1, and ApMTPSL3 from hornworts. The enzyme activity experiment demonstrated that SsMTPSL1 has monoterpene synthase and sesquiterpene synthase activity, and SsMTPSL2 has monoterpene synthase activity. Next, we selected SsMTPSL1 to study its biochemical functions. Anti-bacterial activity test in vitro showed that the products of SsMTPSL1 have an anti-bacterial effect on Escherichia coli, Pseudomonas syringae pv. Tomato DC3000 (Pst DC3000), and Staphylococcus aureus. To further understand the function of SsMTPSL1, the transgenic Arabidopsis thaliana plant of SsMTPSL1 is inoculated by Pst DC3000, and the result showed that SsMTPSL1 enhances the resistance of A. thaliana to Pst DC3000. All in all, this study provides new information about the functions of moss MTPSLs.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.047DOI Listing
June 2021
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