Publications by authors named "Jia Zhou"

708 Publications

Differential Modulation of the Voltage-Gated Na Channel 1.6 by Peptides Derived From Fibroblast Growth Factor 14.

Front Mol Biosci 2021 7;8:742903. Epub 2021 Sep 7.

Department of Pharmacology and Toxicology, Galveston, TX, United States.

The voltage-gated Na (Nav) channel is a primary molecular determinant of the initiation and propagation of the action potential. Despite the central role of the pore-forming α subunit in conferring this functionality, protein:protein interactions (PPI) between the α subunit and auxiliary proteins are necessary for the full physiological activity of Nav channels. In the central nervous system (CNS), one such PPI occurs between the C-terminal domain of the Nav1.6 channel and fibroblast growth factor 14 (FGF14). Given the primacy of this PPI in regulating the excitability of neurons in clinically relevant brain regions, peptides targeting the FGF14:Nav1.6 PPI interface could be of pre-clinical value. In this work, we pharmacologically evaluated peptides derived from FGF14 that correspond to residues that are at FGF14's PPI interface with the CTD of Nav1.6. These peptides, Pro-Leu-Glu-Val (PLEV) and Glu-Tyr-Tyr-Val (EYYV), which correspond to residues of the β12 sheet and β8-β9 loop of FGF14, respectively, were shown to inhibit FGF14:Nav1.6 complex assembly. In functional studies using whole-cell patch-clamp electrophysiology, PLEV and EYYV were shown to confer differential modulation of Nav1.6-mediated currents through mechanisms dependent upon the presence of FGF14. Crucially, these FGF14-dependent effects of PLEV and EYYV on Nav1.6-mediated currents were further shown to be dependent on the N-terminal domain of FGF14. Overall, these data suggest that the PLEV and EYYV peptides represent scaffolds to interrogate the Nav1.6 channel macromolecular complex in an effort to develop targeted pharmacological modulators.
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http://dx.doi.org/10.3389/fmolb.2021.742903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452925PMC
September 2021

Discovery of Novel Viruses Associated With the Invasive Cane Toad () in Its Native and Introduced Ranges.

Front Microbiol 2021 6;12:733631. Epub 2021 Sep 6.

School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

Cane toads () are notoriously successful invaders: from 101 individuals brought to Australia in 1935, poisonous toads now cover an area >1.2 million km with adverse effects on native fauna. Despite extensive research on the role of macroparasites in cane toad invasion, viral research is lagging. We compared viral prevalence and diversity between toads in their native range (French Guiana, =25) and two introduced ranges: Australia (=151) and Hawai'i (=10) with a metatranscriptomic and metagenomic approach combined with PCR screening. Australian toads almost exclusively harbor one of seven viruses detected globally. Rhimavirus-A () exhibited low genetic diversity and likely actively infected 9% of sampled Australian toads extending across ~2,000km of Northern Australia and up to the current invasion front. In native range cane toads, we identified multiple phylogenetically distinct viruses (, , , and Nackedna-like virus). None of the same viruses was detected in both ranges, suggesting that Australian cane toads have largely escaped the viral infection experienced by their native range counterparts. The novel native range viruses described here are potential biocontrol agents, as Australian toads likely lack prior immunological exposure to these viruses. Overall, our evidence suggests that there may be differences between viruses infecting cane toads in their native vs. introduced ranges, which lays the groundwork for further studies on how these viruses have influenced the toads' invasion history.
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http://dx.doi.org/10.3389/fmicb.2021.733631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450580PMC
September 2021

Cx32 inhibits the autophagic effect of Nur77 in SH-SY5Y cells and rat brain with ischemic stroke.

Aging (Albany NY) 2021 Sep 22;13(undefined). Epub 2021 Sep 22.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.

The pathogenesis of cerebral ischemia-reperfusion (I/R) is complex. Cx32 expression has been reported to be up-regulated in ischemic lesions of aged human brain. Nevertheless, the function of Cx32 during cerebral I/R is poorly understood. Autophagy is of vital importance in the pathogenesis of cerebral I/R. In the current study, we found that oxygen-glucose deprivation/reoxygenation (OGD/R) or I/R insult significantly induced the up-regulation of Cx32 and activation of autophagy. Inhibition of Cx32 alleviated OGD/R or I/R injury, and further activated autophagy. In addition, Nur77 expression was found to be up-regulated after OGD/R or I/R. After inhibiting Cx32, the expression of Nur77 was further increased and Nur77 was translocated from nucleus to mitochondrial. Inhibition of Cx32 also activated mitophagy by promoting autophagosome formation and up-regulating the expression of mitochondrial autophagy marker molecules. Of note, in the siNur77-transfected cells, the number of dysfunctional mitochondrial was increased, and mitophagy was suppressed, which aggravated OGD/R-induced neuronal injury. In conclusion, Cx32 might act as a regulatory factor of Nur77 controlling neuronal autophagy in the brains. Understanding the mechanism of this regulatory pathway will provide new insight into the role Cx32 and Nur77 in cerebral ischemia, offering new opportunities for therapeutics.
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http://dx.doi.org/10.18632/aging.203526DOI Listing
September 2021

Embryonic Ectoderm Development (EED) as a Novel Target for Cancer Treatment.

Curr Top Med Chem 2021 Sep 20. Epub 2021 Sep 20.

Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314. United States.

The polycomb repressive complex 2 (PRC2) can methylate at lysine 27 of histone H3 at the trimethylation level (H3K27me3). This leads to gene silencing and is known to be dysregulated in many cancers. PRC2 is made up of three core subunits: EZH2, SUZ12, and EED. EED is essential for the regulation of PRC2 function by the binding to H3K27me3. Targeting the allosteric site within EED offers new strategies to disrupt the PRC2 activity. In this mini review, we summarize some of the recent developments in small molecules that target EED and its interaction with other core proteins in the PRC2 complex.
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http://dx.doi.org/10.2174/1568026621666210920154942DOI Listing
September 2021

Modeling Riverine NO Sources, Fates, and Emission Factors in a Typical River Network of Eastern China.

Environ Sci Technol 2021 Sep 14. Epub 2021 Sep 14.

College of Environmental & Resource Sciences, Zhejiang University, Hangzhou, Zhejiang Province 310058, China.

Estimates of riverine NO emission contain great uncertainty because of the lack of quantitative knowledge concerning riverine NO sources and fates. Using a 3.5-year record of monthly NO measurements from the Yongan River network of eastern China, we developed a mass-balance model to address the riverine NO source and sink processes. We achieved reasonable model efficacies ( = 0.44-0.84, Nash-Sutcliffe coefficients = 0.40-0.80) across three tributaries and the entire river system. Estimated riverine NO loads originated from groundwater (38-88%), surface runoff (3-26%), and in-stream production (4-48%). Estimated in-stream losses via atmospheric release + complete denitrification accounted for 76, 95, 25, and 89% of riverine NO fate for the agricultural, residential, forest, and entire river system, respectively. Considering limited complete denitrification, the model estimated an upper-bound riverine NO emission rate of 2.65 ton NO-N km year for the entire river system. Riverine NO emission estimates were of comparable magnitude to those estimated with a power-law scaling model. Riverine NO emissions using the IPCC default emission factor (0.26%) overestimated emissions by 3-15 times, whereas the dissolved NO concentration-based emission factor overestimated or underestimated emissions. This study highlights the importance of combining comprehensive information on NO sources and fates to achieve accurate riverine NO emission estimates.
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http://dx.doi.org/10.1021/acs.est.1c01301DOI Listing
September 2021

The role of antifungal activity of ethyl acetate extract from Artemisia argyi on Verticillium dahliae.

J Appl Microbiol 2021 Sep 8. Epub 2021 Sep 8.

Hubei Provincial Key Laboratory of Resource Science and Chemistry in Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei, China.

Aims: This study investigated the antifungal activity and mechanisms of ethyl acetate extract of Artemisia argyi (EAAA) against Verticillium dahliae.

Methods And Results: Optical and scanning electron microscopy observation showed that 2.0 mg ml EAAA treatment reduced spore germination rate to 4.56%. Histochemical staining showed that 2.0 mg ml EAAA treatment increased reactive oxygen species (ROS) by more than two times. Physiological test showed that EAAA treatment decreased the contents of soluble proteins and sugars, and reduced the activities of malate dehydrogenase and succinate dehydrogenase by nearly half. Transcriptome analysis showed that EAAA treatment down-regulated the expression of genes involved in primary metabolic pathways of V. dahliae.

Conclusions: Our results revealed that EAAA inhibited the growth and development of V. dahliae from multiple levels and multiple targets, including inhibiting the germination and development of V. dahliae spores, destroying the structure of cell membranes, inducing ROS burst, reducing the activities of respiratory-related enzymes and down-regulating the expression of genes in primary metabolic pathways.

Significance And Impact Of The Study: The mechanism of the multitarget effects of EAAA against V. dahliae may limit the potential of fungus developing resistance and provide the efficient methods to control verticillium wilt disease in the future.
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http://dx.doi.org/10.1111/jam.15298DOI Listing
September 2021

Transcriptome and metabolome analyses revealed the response mechanism of apple to different phosphorus stresses.

Plant Physiol Biochem 2021 Aug 30;167:639-650. Epub 2021 Aug 30.

Beijing Academy of Agriculture and Forestry Sciences, Institute of Forestry and Pomology, Beijing Academy of Forestry and Pomology Sciences, Beijing Engineering Research Center for Deciduous Fruit Trees, Key Laboratory of Biology and Genetic Improvement of Horticultural Crops, Ministry of Agriculture and Rural Affairs, Beijing, 100093, China. Electronic address:

Phosphorus (P) is an important element in numerous metabolic reactions and signalling pathways, but the molecular details of these pathways remain largely unknown. In this study, physiological, transcriptome and metabolite analyses of apple leaves and roots were compared under different P conditions. The results showed that different P stresses influenced phenotypic characteristics, soil plant analytical development (SPAD) values and the contents of flavonoids and anthocyanins in apple seedlings. The contents of hydrogen peroxide (HO) and malondialdehyde (MDA) and the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), acid phosphatase (ACP) and purple acid phosphatase (PAP) were also affected by different P stresses. In addition, RNA sequencing (RNA-seq) was used to characterize the influence of different P stresses on apple seedlings. Compared with control apple plants, there were 1246 and 1183 differentially expressed genes (DEGs) in leaves and roots under the low-P treatment and 60 and 1030 DEGs in leaves and roots under the high-P treatment, respectively. Gene Ontology (GO) analysis indicated that apple trees might change their responses to metabolic processes, cell proliferation, regulation of biological processes, reactive oxygen species metabolic processes and flavonoid metabolic processes under P stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis further indicated that DEGs act on the mitogen-activated protein kinase (MAPK) signalling pathway, flavonoid biosynthesis, phenylpropanoid biosynthesis, and ATP-binding cassette (ABC) transporters. The metabolome analysis revealed that the levels of most amino acids and their derivatives, organic acids and flavonoids in roots treated with low-P stress were higher than those in roots of apple seedlings under control growth conditions. Apple seedlings regulate the flavonoid pathway to respond to different phosphorus environments. The results provide a framework for understanding the metabolic processes underlying different P responses and provide a foundation for improving the utilization efficiency of P in apple trees.
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http://dx.doi.org/10.1016/j.plaphy.2021.08.040DOI Listing
August 2021

Efficacy of Novel Aminooxyacetic Acid Prodrugs in Colon Cancer Models: Towards Clinical Translation of the Cystathionine β-Synthase Inhibition Concept.

Biomolecules 2021 07 21;11(8). Epub 2021 Jul 21.

Department of Anesthesiology, University of Texas, Medical Branch, Galveston, TX 77555, USA.

Upregulation of hydrogen sulfide (HS) biosynthesis, at least in part related to the upregulation of cystathionine β-synthetase (CBS) in cancer cells, serves as a tumor-promoting factor and has emerged as a possible molecular target for antitumor drug development. To facilitate future clinical translation, we have synthesized a variety of novel CBS-targeting, esterase-cleavable prodrugs based on the structure of the prototypical CBS inhibitor aminooxyacetic acid (AOAA). The pharmacological properties of these compounds were evaluated in cell-free assays with recombinant human CBS protein, the human colon cancer cell line HCT116, and in vivo using various tumor-bearing mice models. The prodrug YD0251 (the isopropyl ester derivative of AOAA) was selected for detailed characterization. YD0251 exhibits improved antiproliferative efficacy in cell culture models when compared to AOAA. It is up to 18 times more potent than AOAA at suppressing HCT116 tumor growth in vivo and is effective when administered to tumor-bearing mice either via subcutaneous injection or oral gavage. Patient-derived xenografts (PDTXs) with higher levels of CBS protein grew significantly larger than tumors with lower levels, and YD0251 treatment inhibited the growth of PDTXs with elevated CBS, whereas it had no significant effect on PDTXs with low CBS protein levels. The toxicity of YD0251 was assessed in mice subjected to subchronic administration of supratherapeutic doses the inhibitor; no significant alteration in circulating markers of organ injury or histopathological alterations were noted, up to 60 mg/kg/day × 5 days. In preparation to a future theranostic concept (to match CBS inhibitor therapy to high-CBS expressors), we identified a potential plasma marker of CBS-expressing tumors. Colon cancer cells produced significant levels of lanthionine, a rare metabolic intermediate of CBS-mediated HS biosynthesis; forced expression of CBS into non-transformed epithelial cells increased lanthionine biogenesis in vitro and in vivo (measured in the urine of tumor-bearing mice). These current results may be useful to facilitate the translation of a CBS inhibition-based antitumor concept into the clinical space.
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http://dx.doi.org/10.3390/biom11081073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394431PMC
July 2021

Case Report: A Novel Variant c.2262+3A>T of the Gene Results in Intron Retention Associated With Incessant Ventricular Tachycardias.

Front Med (Lausanne) 2021 4;8:659119. Epub 2021 Aug 4.

Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Nanjing, China.

Voltage-gated sodium channel Na1.5 encoded by the gene plays crucial roles in cardiac electrophysiology. Previous genetic studies have shown that mutations in are associated with multiple inherited cardiac arrhythmias. Here, we investigated the molecular defect in a Chinese boy with clinical manifestations of arrhythmias. Gene variations were screened using whole-exome sequencing and validated by direct Sanger sequencing. A minigene assay and reverse transcription PCR (RT-PCR) were performed to confirm the effects of splice variants . Western blot analysis was carried out to determine whether the c.2262+3A>T variant produced a truncated protein. By genetic analysis, we identified a novel splice variant c.2262+3A>T in gene in a Chinese boy with incessant ventricular tachycardias (VT). This variant was predicted to activate a new cryptic splice donor site and was identified by analysis. The variant retained 79 bp at the 5' end of intron 14 in the mature mRNA. Furthermore, the mutant transcript that created a premature stop codon at 818 amino acids [p.(R818)] could be produced as a truncated protein. We verified the pathogenic effect of splicing variant c.2262+3A>T, which disturbed the normal mRNA splicing and caused a truncated protein, suggesting that splice variants play an important role in the molecular basis of early onset incessant ventricular tachycardias, and careful molecular profiling of these patients will be essential for future effective personalized treatment options.
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http://dx.doi.org/10.3389/fmed.2021.659119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371685PMC
August 2021

Artificial intelligence in echocardiography: detection, functional evaluation, and disease diagnosis.

Cardiovasc Ultrasound 2021 Aug 20;19(1):29. Epub 2021 Aug 20.

The First Affiliated Hospital, Medical Imaging Centre, Hengyang Medical School, University of South China, 69 Chuanshan Road, Hengyang, 421001, China.

Ultrasound is one of the most important examinations for clinical diagnosis of cardiovascular diseases. The speed of image movements driven by the frequency of the beating heart is faster than that of other organs. This particularity of echocardiography poses a challenge for sonographers to diagnose accurately. However, artificial intelligence for detection, functional evaluation, and disease diagnosis has gradually become an alternative for accurate diagnosis and treatment using echocardiography. This work discusses the current application of artificial intelligence in echocardiography technology, its limitations, and future development directions.
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http://dx.doi.org/10.1186/s12947-021-00261-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379752PMC
August 2021

Omega‑3 polyunsaturated fatty acids inhibit IL‑11/STAT3 signaling in hepatocytes during acetaminophen hepatotoxicity.

Int J Mol Med 2021 Oct 20;48(4). Epub 2021 Aug 20.

Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Omega‑3 polyunsaturated fatty acids (n‑3 PUFAs) exert a negative effect on IL‑6 production in several liver disorders, including cirrhosis, acute liver failure and fatty liver disease. However, its effect on the production of IL‑11, another important IL‑6 family cytokine, remains unclear. IL‑11 was found to be significantly elevated in acetaminophen (APAP)‑induced liver damage. The aim of the present study was to investigate whether and how n‑3 PUFAs modulate IL‑11 production during APAP‑induced liver injury. For that purpose, wild‑type (WT) and ‑1 transgenic mice were intraperitoneally injected with APAP to induce liver injury. Serum was collected for ELISA and alanine aminotransferase assay. The hepatocytes of APAP‑injected mice were isolated for reverse transcription‑quantitative PCR and western blot analyses. For the study, primary hepatocytes isolated from WT or ‑1 mice were stimulated with APAP. The results revealed that both endogenous and exogenous n‑3 PUFAs significantly aggravated APAP‑induced liver damage via the downregulation of STAT3 signaling. Notably, n‑3 PUFAs inhibited IL‑11 expression, but not IL‑6 expression in hepatocytes during the APAP challenge. Furthermore, it was demonstrated that limited phosphorylation of ERK1/2 and Fos‑​like‑1 (Fra‑1) expression are responsible for the n‑3 PUFA‑mediated inhibitory effect on IL‑11 production in APAP‑treated hepatocytes. It was concluded that n‑3 PUFAs inhibit IL‑11 production and further STAT3 activation in hepatocytes during APAP‑induced liver injury. Therefore, ERK1/2‑mediated Fra‑1 expression is responsible for the effect of n‑3 PUFAs on IL‑11 expression.
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http://dx.doi.org/10.3892/ijmm.2021.5023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416141PMC
October 2021

Improving the ameliorative effects of berberine and curcumin combination via dextran-coated bilosomes on non-alcohol fatty liver disease in mice.

J Nanobiotechnology 2021 Aug 4;19(1):230. Epub 2021 Aug 4.

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, China.

Background: The combination of berberine (BER) and curcumin (CUR) has been verified with ameliorative effects on non-alcohol fatty liver disease (NAFLD). However, discrepant bioavailability and biodistribution of BER and CUR remained an obstacle to achieve synergistic effects. Multilayer nanovesicles have great potential for the protection and oral delivery of drug combinations. Therein lies bile salts inserted liposomes, named as bilosomes, that possesses long residence time in the gastrointestinal tract (GIT) and permeability across the small intestine. Diethylaminoethyl dextran (DEAE-DEX) is generally used as an outside layer on the nanovesicles to increase the mucinous stability and promote oral absorption. Herein, we developed a DEAE-DEX-coated bilosome with BER and CUR encapsulated ([email protected]) for the treatment of NAFLD.

Results: [email protected] with 150 nm size exhibited enhanced permeation across mucus and Caco-2 monolayer. In vivo pharmacokinetics study demonstrated that [email protected] profoundly prolonged the circulation time and improved the oral absorption of both BER and CUR. Intriguingly, synchronized biodistribution of BER and CUR and highest biodistribution at liver was achieved by [email protected], which contributed to the optimal ameliorative effects on NAFLD. It was further verified to be mainly mediated by anti-oxidation and anti-inflammation related pathways CONCLUSION: DEAE-DEX coated bilosome displayed promoted oral absorption, prolonged circulation and synchronized biodistribution of BER and CUR, leading to improved ameliorative effects on NAFLD in mice, which provided a promising strategy for oral administration of drug combinations.
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http://dx.doi.org/10.1186/s12951-021-00979-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336351PMC
August 2021

Hyaluronic acid-modified manganese dioxide-enveloped hollow copper sulfide nanoparticles as a multifunctional system for the co-delivery of chemotherapeutic drugs and photosensitizers for efficient synergistic antitumor treatments.

J Colloid Interface Sci 2021 Jul 23;605:296-310. Epub 2021 Jul 23.

Department of Pharmaceutics, School of Pharmacy, Xuzhou Medical University, Xuzhou 221004, China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China. Electronic address:

This paper presents the design of a new type of intelligent and versatile all-in-one therapeutic nanoplatform for the co-delivery of chemotherapeutic drugs and photosensitizers to facilitate multimodal antitumor treatment; the system is based on hyaluronic acid (HA)-modified manganese dioxide (MnO)-enveloped hollow porous copper sulfide (CuS) nanoparticles ([email protected]/HA NPs). In this system, a CuS inner shell allows for the co-loading of doxorubicin (DOX) and indocyanine green (ICG) and induces photothermal effects, and a biodegradable MnO external shell affords on-demand tumor microenvironment (TME)-triggered release and catalase- andFenton-like activities. Moreover, the HA modification endows the system with a CD44 receptor-mediated tumor-targeting property. The formulated DOX and ICG co-loaded [email protected]/HA (DOX/[email protected]/HA) NPs were found to exhibit excellent photothermal performance both in vitro and in vivo. In addition, DOX/[email protected]/HA NPs were found to display both TME and near-infrared (NIR)-responsive controlled release properties. The NPs also have a superior reactive oxygen species (ROS) generation capacity due to the combination of enhanced ICG-induced singlet oxygen and [email protected] hydroxyl radicals. The cellular uptake, fluorescence imaging property, cytotoxicity, and thermal imaging of these NPs were also evaluated. In tumor-bearing mice, the DOX/[email protected]/HA NPs displayeda superior antitumor efficacy (2.57-fold) as compared with free DOX. Therefore, the developed DOX/[email protected]/HA NPs have a great potential for use as an all-in-one nanotherapeutic agent for the efficient and precise induction of chemo/photothermal/photodynamic/chemodynamic therapy with superior antitumor efficacy and fewer side effects.
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http://dx.doi.org/10.1016/j.jcis.2021.07.092DOI Listing
July 2021

Study on environmental behaviour of fluopyram in different banana planting soil.

Sci Rep 2021 Jul 28;11(1):15346. Epub 2021 Jul 28.

Analysis and Testing Center, Chinese Academy of Tropical Agricultural Sciences, No. 4 Xueyuan Road, Haikou, 571101, China.

Fluopyram is commonly used to control banana leaf spot, anthracnose, and scab in tropical agricultural areas. To explore its behaviour in tropical agricultural environments, dissipation, adsorption, and leaching behaviours of fluopyram in three typical banana planting soils were studied. Also, its dissipation and migration capabilities in different regions and different soil types were evaluated. The results showed that the dissipation of fluopyram was in accordance with the first-order kinetic equation in the three banana soils, but the degradation rates were quite different. The degradation half-lives in the Hainan latosol, Yunnan sandy soil, and Fujian Plain alluvial soil were 46.21 days, 36.48 days and 57.76 days, respectively. Fluopyram also exhibited high adsorption and low leachability in the three soils. The Fujian Plain alluvial soil had the highest adsorption capacity for fluopyram, while fluopyram had the low leachability in the Yunnan sandy soil.
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http://dx.doi.org/10.1038/s41598-021-91460-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319309PMC
July 2021

UTMD promoted local delivery of miR-34a-mimic for ovarian cancer therapy.

Drug Deliv 2021 Dec;28(1):1616-1625

The First Affiliated Hospital, Medical Imaging Centre, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

MicroRNA-mediated gene therapy is emerging as a promising method for the treatment of ovarian cancer, but the development of miRNA mimic delivery vectors is still in its infancy, where the safety and efficacy of miR-34a-mimic remain unknown. Ultrasound-targeted microbubble destruction (UTMD) can be an effective and minimally invasive tool for the delivery of miR-34a-mimic and . Here, we describe a high-efficiency gene delivery strategy by using miR-34a-mimic loaded folate modified microbubbles (miR-34a-FM) with a portable ultrasonic irradiation system. Ultrasonic parameters, including acoustic intensity (AI), exposure time (ET) and duty cycle (DC), were optimized and the optimal acoustic condition (1.0 W/cm, 20 s, and 15% DC) was used to deliver miRNA-34a into cells MiR-34a mimic was successfully introduced into the cytoplasm and was found to inhibit proliferation and induce apoptosis of SK-OV-3 cells. Next, miR-34a-mimic was delivered to tumor tissue via UTMD, inhibiting tumor growth and prolonging the survival time of mice. In summary, UTMD-mediated miR-34a-mimic delivery has potential application in the clinical treatment of ovarian cancer.
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http://dx.doi.org/10.1080/10717544.2021.1955041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330777PMC
December 2021

Using a sulfur autotrophic fluidized bed reactor for simultaneous perchlorate and nitrate removal from water: S disproportionation prediction and system optimization.

Biodegradation 2021 Jul 27. Epub 2021 Jul 27.

College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, Henan, China.

The sulfur autotrophic reduction (SAR) process is promising in co-reduction of perchlorate and nitrate from aqueous solution. To further understand the reaction process, we developed a sulfur autotrophic fluidized bed reactor where the proceeding extent of sulfur (S) disproportionation was predicted by Response surface methodology (RSM) for the first time. Three fundamental reaction parameters including the hydraulic retention time (HRT), co-existing nitrate concentration ([Formula: see text]) and recirculation ratio (R) were considered for reactor optimization. The results demonstrated that S disproportionation was promoted by long HRT and high R, whereas was inhibited by high [Formula: see text]. Also, the optimal HRT, [Formula: see text] and R were 0.50 h, 10.00 mg/L and 14, respectively, the bioreactor can achieve high reduction efficiency of perchlorate and nitrate (> 98.45%), and generate less sulfate (236.07 mg/L). High-throughput sequencing showed that Chlorobaculum was related to S disproportionation, and Sulfurovum was associated with nitrate/perchlorate reducing. All results indicate that the sulfur autotrophic fluidized bed reactor is a promising candidate for the treatment of perchlorate and nitrate wastewater in future practical applications.
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http://dx.doi.org/10.1007/s10532-021-09957-8DOI Listing
July 2021

Discovery of a novel plant-derived agent against Ralstonia solanacearum by targeting the bacterial division protein FtsZ.

Pestic Biochem Physiol 2021 Aug 5;177:104892. Epub 2021 Jun 5.

Laboratory of Natural Products Pesticides, College of Plant Protection, Southwest University, Chongqing 400715, China. Electronic address:

Ralstonia solanacearum (R. solanacearum) is one of the most devastating bacterial pathogens and leads to serious economic losses in crops worldwide. In this study, the antibacterial activities of novel plant-derived coumarins against R. solanacearum and their underlying mechanisms were initially investigated. The bioactivity assay results showed that certain coumarins had significant in vitro inhibitory effects against R. solanacearum. Notably, 6-methylcoumarin showed the best in vitro antibacterial activity with 76.79%. Interestingly, 6-methylcoumarin was found to cause cell elongation, disrupt cell division, and suppress the expression of the bacterial division protein coding genes ftsZ. Compared with the control treatment, the ∆ftsZ mutant inhibited bacterial growth and caused the bacteria to be more sensitive to 6-methylcoumarin. The application of 6-methylcoumarin effectively suppressed the development of tobacco bacterial wilt in pot and field experiments, and significantly reduced the bacterial population in tobacco stems. The control efficiency of 6-methylcoumarin treatment was 35.76%, 40.51%, 38.99% at 10, 11, and 12 weeks after tobacco transplantation in field condition. All of these results demonstrate that 6-methylcoumarin has potential as an eco-friendly and target specificity agent for controlling tobacco bacterial wilt.
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http://dx.doi.org/10.1016/j.pestbp.2021.104892DOI Listing
August 2021

Evaluation of artemisinin derivative artemether as a fluconazole potentiator through inhibition of Pdr5.

Bioorg Med Chem 2021 Aug 25;44:116293. Epub 2021 Jun 25.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

Antifungal development has gained increasing attention due to its limited armamentarium and drug resistance. Drug repurposing holds great potential in antifungal discovery. In this study, we explored the antifungal activity of artemisinin and its derivatives, dihydroartemisinin, artesunate and artemether. We identified that artemisinins can inhibit the growth of Candida albicans, and can enhance the activity of three commonly used antifungals, amphotericin B, micafungin and fluconazole (FLC), on Candida albicans growth and filamentation. Artemisinins possess stronger antifungal effect with FLC than with other antifungals. Among artemisinins, artemether exhibits the most potent antifungal activity with FLC and can recover the susceptibility of FLC-resistant clinical isolates to FLC treatment. The combinatorial antifungal activity of artemether and FLC is broad-spectrum, as it can inhibit the growth of Candida auris, Candida tropicalis, Candida parapsilosis, Saccharomyces cerevisiae and Cryptococcus neoformans. Mechanistic investigation revealed that artemether might enhance azole efficacy through disrupting the function of Pdr5, leading to intracellular accumulation of FLC. This study identified artemether as a novel FLC potentiator, providing potential therapeutic insights against fungal infection and antifungal resistance.
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http://dx.doi.org/10.1016/j.bmc.2021.116293DOI Listing
August 2021

[Minute Pulmonary Meningothelial-like Nodule:A Case Report and Literature Review].

Zhongguo Yi Xue Ke Xue Yuan Xue Bao 2021 Jun;43(3):494-500

Department of Respiratory and Critical Care Medicine,the First Affiliated Hospital of CQMU,Chongqing 400016,China.

Minute pulmonary meningothelial-like nodule(MPMN)is a rare respiratory disease with no specific clinical manifestations and requires bronchial or percutaneous lung biopsy for diagnosis.Here we report a case of an old male patient with recurrent cough and sputum as the main manifestations,which failed to be cured by antibiotic.His chest computed tomography showed a mass-like tumorous lesion located in the posterior segment of the right upper lobe,and the pathological diagnosis by percutaneous lung biopsy confirmed MPMN with lung infection.At the same time,we reviewed 34 cases to summarize the clinical data,pathological manifestation,diagnosis,treatment,and prognosis of MPMN.
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http://dx.doi.org/10.3881/j.issn.1000-503X.12811DOI Listing
June 2021

Relationship between Plasma Trimethylamine N-Oxide Levels and Renal Dysfunction in Patients with Hypertension.

Kidney Blood Press Res 2021 7;46(4):421-432. Epub 2021 Jul 7.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Introduction: Trimethylamine N-oxide (TMAO) is a metabolite produced by gut bacteria. Although increased TMAO levels have been linked to hypertension (HTN) and chronic kidney disease (CKD) with poor prognosis, no clinical studies have directly addressed the relationship between them. In this study, we investigated the relationship between TMAO and renal dysfunction in hypertensive patients.

Methods: We included healthy controls (n = 50), hypertensive patients (n = 46), and hypertensive patients with renal dysfunction (n = 143). Their blood pressure values were taken as the highest measured blood pressure. Renal function was evaluated using the estimated glomerular filtration rate. Plasma TMAO levels were measured using high-performance liquid chromatography tandem mass spectrometry.

Results: We found significant differences in plasma TMAO levels among the 3 groups (p < 0.01). The plasma TMAO of patients with HTN was significantly higher than that of healthy people, and the plasma TMAO of patients with HTN complicated by renal dysfunction was significantly higher than either of the other groups. Patients in the highest TMAO quartile were at a higher risk of developing CKD stage 5 than those in the lowest quartile. In the receiver operating characteristic curve, the area under the curve of TMAO combined with β 2-macroglobulin for predicting renal dysfunction in patients with HTN was 0.85 (95% confidence interval 0.80-0.90).

Conclusion: An elevated TMAO level reflects higher levels of HTN and more severe renal dysfunction. TMAO, combined with β 2-macroglobulin levels, may assist in diagnosing CKD in hypertensive patients. Plasma TMAO has predictive value for early kidney disease in hypertensive patients.
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http://dx.doi.org/10.1159/000513033DOI Listing
July 2021

SARS-CoV-2 infection in the mouse olfactory system.

Cell Discov 2021 Jul 6;7(1):49. Epub 2021 Jul 6.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.

SARS-CoV-2 infection causes a wide spectrum of clinical manifestations in humans, and olfactory dysfunction is one of the most predictive and common symptoms in COVID-19 patients. However, the underlying mechanism by which SARS-CoV-2 infection leads to olfactory disorders remains elusive. Herein, we demonstrate that intranasal inoculation with SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), not the olfactory bulb (OB), resulting in transient olfactory dysfunction in humanized ACE2 (hACE2) mice. The sustentacular cells and Bowman's gland cells in the OE were identified as the major target cells of SARS-CoV-2 before invasion into olfactory sensory neurons (OSNs). Remarkably, SARS-CoV-2 infection triggers massive cell death and immune cell infiltration and directly impairs the uniformity of the OE structure. Combined transcriptomic and quantitative proteomic analyses revealed the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptor (OR) genes in the OE from the infected animals. Overall, our mouse model recapitulates olfactory dysfunction in COVID-19 patients and provides critical clues for understanding the physiological basis for extrapulmonary manifestations of COVID-19.
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http://dx.doi.org/10.1038/s41421-021-00290-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260584PMC
July 2021

[Simultaneous determination of 18 chlorinated hydrocarbon organic solvents in cosmetics by gas chromatography-mass spectrometry].

Se Pu 2021 Mar;39(3):324-330

Industrial Products Testing Center, Nanjing Customs, Nanjing 210019, China.

Organic solvents can be used to dissolve and disperse flavors, bactericides, preservatives, surfactants, oils, and coloring agents during the production of cosmetics. However, harmful chlorinated hydrocarbon organic solvents are found in cosmetics such as manicure products, anti-acne products, and perfumes. Long-term contact with such cosmetics will have an adverse effect on the consumers' health. Past research has focused on very few chlorinated hydrocarbon organic solvents in cosmetics. Most organic solvents with low boiling points are typically determined by headspace-gas chromatography-mass spectrometry. In this study, a high-boiling-point solvent was used as the injection solvent, and the solvent delay time was cancelled. The compounds that could only peak during the solvent delay time were effectively separated. A method coupling sample pretreatment with gas chromatography-mass spectrometry (GC-MS) was developed for the simultaneous determination of 18 chlorinated hydrocarbon organic solvents in cosmetics: vinylidene chloride, dichloromethane, -1,2-dichloroethylene, 1,1-dichloroethane, -1,2-dichloroethylene, chloroform, 1,1,1-trichloroethane, carbon tetrachloride, 1,2-dichloroethane, trichloroethylene, 1,1,2-trichloroethane, tetrachloroethylene, 1,1,1,2-tetrachloroethane, 1,1,2,2-tetrachloroethane, 1,2,3-trichloropropane, pentachloroethane, hexachloroethane, and hexachloro-1,3-butadiene. These 18 solvents have a wide range of polarities and a notable difference in volatilities, in addition to many isomers and structural analogs, which renders their separation difficult. Therefore, the separation effect of three kinds of GC columns with different polarities was compared. -Tetradecane, an injection solvent with good solubility, was selected as the extraction solvent. An organic solvent with high polarity has low extraction rate because of its weak polarity. Adding sodium chloride solution to the sample to induce the "salting out" effect could change the partition coefficient of the components, thereby improving the extraction rate. Therefore, the concentration of the sodium chloride solution added to the sample was optimized. In this work, liquid-liquid extraction was the main extraction process, so the effects of different shaking times, temperatures, and frequencies on the extraction rate were discussed. The optimized results are as follows: at normal temperature, the sample dispersed or dissolved in saturated sodium chloride solution was extracted by -tetradecane at an oscillating speed of 100 r/min for 20 min. Separation was performed on an Agilent J&W DB-624 column (30 m×0.25 mm×1.4 μm) by GC-MS with an electrospray ionization (EI) source in the selected ion monitoring (SIM) mode. The external standard method was used for quantitative determination. The 18 compounds could be analyzed within 19 min. The linear equations, linear correlation coefficients, and linear ranges were obtained by analyzing a series of mixed standard working solutions. The limits of detection (LODs, =3) and limits of quantification (LOQs, =10) of the 18 components were determined. The negative lipstick (solid) and mouthwash (liquid) samples were used as the spiked sample matrix at three levels, and the recoveries and precisions were calculated. The calibration curves showed good linearities for the 18 chlorinated hydrocarbon organic solvents in range of 0.2-100 mg/L, with correlation coefficients () not less than 0.9992. The LODs and LOQs were in the range of 0.033-0.049 mg/L and 0.10-0.15 mg/L, respectively. The average recoveries of the 18 chlorinated hydrocarbon organic solvents in lipstick (solid) and mouthwash (liquid) were 92.4%-103.1% and 93.3%-102.4% respectively; the corresponding relative standard deviations (RSDs) were 3.1%-5.3% and 2.8%-5.4% (=6). This method was used to determine 115 different types of cosmetics, and tetrachloroethylene was detected in three nail polishes. With its advantages of high sensitivity, good precision, and accuracy, the developed method is suitable for the quantitative analysis of the aforesaid 18 compounds in all kinds of cosmetics. The study findings would serve as a reference for the quality and safety monitoring of cosmetics.
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http://dx.doi.org/10.3724/SP.J.1123.2020.05010DOI Listing
March 2021

Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.

Viruses 2021 06 21;13(6). Epub 2021 Jun 21.

Department of Pediatrics, The University of Texas Medical Branch, Galveston, TX 77555-0372, USA.

The recently discovered exchange protein directly activated by cAMP (EPAC), compared with protein kinase A (PKA), is a fairly new family of cAMP effectors. Soon after the discovery, EPAC has shown its significance in many diseases including its emerging role in infectious diseases. In a recent study, we demonstrated that EPAC, but not PKA, is a promising therapeutic target to regulate respiratory syncytial virus (RSV) replication and its associated inflammation. In mammals, there are two isoforms of EPAC-EPAC1 and EPAC2. Unlike other viruses, including Middle East respiratory syndrome coronavirus (MERS-CoV) and Ebola virus, which use EPAC1 to regulate viral replication, RSV uses EPAC2 to control its replication and associated cytokine/chemokine responses. To determine whether EPAC2 protein has a broad impact on other respiratory viral infections, we used an EPAC2-specific inhibitor, MAY0132, to examine the functions of EPAC2 in human metapneumovirus (HMPV) and adenovirus (AdV) infections. HMPV is a negative-sense single-stranded RNA virus belonging to the family Pneumoviridae, which also includes RSV, while AdV is a double-stranded DNA virus. Treatment with an EPAC1-specific inhibitor was also included to investigate the impact of EPAC1 on these two viruses. We found that the replication of HMPV, AdV, and RSV and the viral-induced immune mediators are significantly impaired by MAY0132, while an EPAC1-specific inhibitor, CE3F4, does not impact or slightly impacts, demonstrating that EPAC2 could serve as a novel common therapeutic target to control these viruses, all of which do not have effective treatment and prevention strategies.
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http://dx.doi.org/10.3390/v13061179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233786PMC
June 2021

A first-in-class Polymerase Theta Inhibitor selectively targets Homologous-Recombination-Deficient Tumors.

Nat Cancer 2021 Jun 17;2(6):598-610. Epub 2021 Jun 17.

Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.

DNA polymerase theta (POLθ) is synthetic lethal with Homologous Recombination (HR) deficiency and thus a candidate target for HR-deficient cancers. Through high-throughput small molecule screens we identified the antibiotic Novobiocin (NVB) as a specific POLθ inhibitor that selectively kills HR-deficient tumor cells and . NVB directly binds to the POLθ ATPase domain, inhibits its ATPase activity, and phenocopies POLθ depletion. NVB kills HR-deficient breast and ovarian tumors in GEMM, xenograft and PDX models. Increased POLθ levels predict NVB sensitivity, and BRCA-deficient tumor cells with acquired resistance to PARP inhibitors (PARPi) are sensitive to NVB and Mechanistically, NVB-mediated cell death in PARPi-resistant cells arises from increased double-strand break end resection, leading to accumulation of single-strand DNA intermediates and non-functional RAD51 foci. Our results demonstrate that NVB may be useful alone or in combination with PARPi in treating HR-deficient tumors, including those with acquired PARPi resistance. (151/150).
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http://dx.doi.org/10.1038/s43018-021-00203-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224818PMC
June 2021

Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance.

Genes Dis 2021 Jul 5;8(4):448-462. Epub 2020 Jul 5.

Department of Genetics, Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.

Cancer is one of the diseases with high morbidity and mortality on a global scale. Chemotherapy remains the primary treatment option for most cancer patients, including patients with progressive, metastatic, and recurrent diseases. To date, hundreds of chemotherapy drugs are used to treat various cancers, however, the anti-cancer efficacy and outcomes are largely hampered by chemotherapy-associated toxicity and acquired therapeutic resistance. The natural product (NP) oridonin has been extensively studied for its anti-cancer efficacy. More recently, oridonin has been shown to overcome drug resistance through multiple mechanisms, with yet-to-be-defined targets. Hundreds of oridonin derivative analogs (oridonalogs) have been synthesized and screened for improved potency, bioavailability, and other drug properties. Particularly, many of these oridonalogs have been tested against oridonin for tumor growth inhibition, potential for overcoming therapeutic resistance, and immunity modulation. This concise review seeks to summarize the advances in this field in light of identifying clinical-trial level drug candidates with the promise for treating progressive cancers and reversing chemoresistance.
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http://dx.doi.org/10.1016/j.gendis.2020.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209342PMC
July 2021

Metal-free N and O Co-doped carbon directly derived from bicrystal Zn-based zeolite-like metal-organic frameworks as durable high-performance pH-universal oxygen reduction reaction catalyst.

Nanotechnology 2021 Jul 12;32(40). Epub 2021 Jul 12.

Key Laboratory of Applied Surface and Colloid Chemistry (Shaanxi Normal University), Ministry of Education, Xi'an 710119, People's Republic of China.

A simple and green approach is studied for the preparation of a high-activity metal-free N,O-codoped porous carbon (NOPC) electrocatalyst by one-step pyrolysis of pristine zinc-based zeolite-like metal-organic framework (Zn-ZMOF) synthesized by hydrothermal method from Znand 4,5-imidazoledicarboxylic acid (HIDC) in HO solvent. It is found that the structure and electroactivity of Zn-ZMOF and NOPC vary with the molar ratio of HIDC to zinc acetate. NOPC shows pH-universal electrocatalytic property for oxygen reduction reaction and its electrocatalytic performance is similar to that of Pt/C in alkaline and neutral electrolytes, and is close to that of Pt/C in acidic electrolyte, which is a relatively rare case for metal-free porous carbon derived from pristine MOF. Meanwhile, NOPC displays higher long-term stability and better tolerance to methanol and carbon monoxide poisoning than that of commercial Pt/C. The excellent performance of NOPC is mainly due to the special structure of the precursor Zn-ZMOF, and the synergism of abundant active sites, micro/mesoporous structure, large specific surface area, and high degree of graphitization.
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http://dx.doi.org/10.1088/1361-6528/ac0e6aDOI Listing
July 2021

Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in schizophrenia.

Australas Psychiatry 2021 Jun 16:10398562211022753. Epub 2021 Jun 16.

Peking University HuiLongGuan Clinical Medical School, Beijing HuiLongGuan Hospital, Beijing, P. R. China.

Objective: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have been used as markers of inflammation in mental illness. However, these indices have not been widely used in schizophrenia research in Chinese participants. Our aim was to use these ratios to explore the relationship between schizophrenia and inflammation.

Methods: In this retrospective cross-sectional study, we collected total blood cell counts of 549 patients with schizophrenia and 930 healthy controls at Beijing Huilongguan Hospital in October 2019. We analyzed the subjects' platelet, lymphocyte, monocyte, and neutrophil counts; compared the calculated NLR, MLR, and PLR between patients and healthy controls; and evaluated the correlations with age and gender.

Results: Platelet and lymphocyte counts were significantly lower, while NLR and MLR were significantly higher, in patients with schizophrenia compared to healthy controls. Additionally, monocyte count, lymphocyte count, MLR, and NLR were different between male and female subjects.

Conclusion: This study supports the inflammatory hypothesis of schizophrenia in the Chinese population.
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http://dx.doi.org/10.1177/10398562211022753DOI Listing
June 2021

Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway.

Front Cardiovasc Med 2021 28;8:659643. Epub 2021 May 28.

School of Pharmaceutical, Changchun University of Chinese Medicine, Changchun, China.

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.
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http://dx.doi.org/10.3389/fcvm.2021.659643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194399PMC
May 2021

MMP-7 affects peritoneal ultrafiltration associated with elevated aquaporin-1 expression via MAPK/ERK pathway in peritoneal mesothelial cells.

J Cell Mol Med 2021 Jul 11;25(14):6887-6898. Epub 2021 Jun 11.

Division of Nephrology, State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangdong Provincial Key Laboratory of Renal Failure Research, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long-term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP-7 levels markedly increased in the patients with PD, and the elevated MMP-7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP-7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP-7 activated mitogen-activated protein kinases (MAPKs)-extracellular signal-regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin-1 (AQP-1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP-7-mediating AQP-1 up-regulation and cellular homeostasis. In summary, all the findings indicate that MMP-7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP-7 might be a non-invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.
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http://dx.doi.org/10.1111/jcmm.16697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278116PMC
July 2021

Utilization of Echocardiography After Acute Kidney Injury Was Associated with Improved Outcomes in Patients in Intensive Care Unit.

Int J Gen Med 2021 1;14:2205-2213. Epub 2021 Jun 1.

Department of Ultrasound Imaging, Renmin Hospital of Wuhan University, Wuhan, 430061, People's Republic of China.

Background: We aimed to investigate the association between usage of transthoracic echocardiography (TTE) within 24 hours after acute kidney injury (AKI) and the prognosis of patients in intensive care unit (ICU).

Methods: The Medical Information Mart for Intensive Care III (MIMIC-III) database was used to identify AKI patients with and without TTE administration. The primary outcome was 28-day mortality. Multivariable regression was used to clarify the association between TTE and clinical outcomes and propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to validate our findings.

Results: Among 23,945 eligible AKI patients, 3361 patients who received TTE and 3361 who did not conduct TTE had similar propensity scores which were included in this study. After matching, the TTE group had a significantly lower 28-day mortality (OR 0.80, 95% CI 0.72-0.88, P<0.001). Patients in the TTE group received more fluid on day 1 and day 2 and had a more urine volume on day 1 and day 3, and the reduction in serum creatinine was greater than that in the no TTE group. The mediating effect of creatinine reduction was remarkable for the whole cohort (P=0.02 for the average causal mediation effect).

Conclusion: TTE utilization was associated with decreased risk-adjusted 28-day mortality for AKI patients in ICU and was proportionally mediated through creatinine reduction.
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http://dx.doi.org/10.2147/IJGM.S310445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183456PMC
June 2021
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