Publications by authors named "Zhe Yang"

552 Publications

Application of Smart Healthcare in LTCI, Outpatient Mutual-Aid Guarantee Mechanism, and Sustainability of Medical Insurance Fund for Urban Employees.

Authors:
Yating Ren Zhe Yang

J Healthc Eng 2022 7;2022:3406977. Epub 2022 Jan 7.

Tianjin University of Finance and Economics, Tianjin, China.

With the aggravation of population aging and the increase of life expectancy, long-term care insurance (LTCI) system has been established to meet the medical and long-term care needs of the increasing elderly population. In China, LTCI system is currently not a stand-alone insurance, but it is attached to the national basic medical insurance fund for urban employees (MIUE). As a result, the expenditure of LTCI is a part of the expenditure of the MIUE, which has an impact on the sustainability of the MIUE. By modeling the income and expenditure of MIUE, especially including the expenditure of LTCI, this study optimized an LTCI system with a higher individual out-of-pocket payment ratio of LTCI and implementation of the outpatient mutual-aid guarantee mechanism (OMAGM), which could improve the sustainability of the MIUE. The study also reveals the following: (i) solely increasing individual out-of-pocket payment ratio of LTCI to 20%-50% can only postpone the deficit on Social Pooling Accounts (SPAs) by 1 or 2 years, and the effect is very limited. (ii) Besides a higher individual out-of-pocket payment ratio, further implementation of a partial OMAGM from 2022 will postpone the deficit on SPAs by 7-9 years, and the implementation of a complete OMAGM from 2022 will postpone the deficit by 14-18 years. Accordingly, China should implement OMAGM as soon as possible to enhance the solvency of MIUE fund, and, in the long run, an independent LTCI scheme should be established to ensure the stability and sustainability of the LTCI fund and the MIUE fund.
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http://dx.doi.org/10.1155/2022/3406977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759885PMC
January 2022

Designing Conductive-Bridge Phase-Change Memory to Enable Ultralow Programming Power.

Adv Sci (Weinh) 2022 Jan 14:e2103478. Epub 2022 Jan 14.

Center for Alloy Innovation and Design (CAID), State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.

Phase-change material (PCM) devices are one of the most mature nonvolatile memories. However, their high power consumption remains a bottleneck problem limiting the data storage density. One may drastically reduce the programming power by patterning the PCM volume down to nanometer scale, but that route incurs a stiff penalty from the tremendous cost associated with the complex nanofabrication protocols required. Instead, here a materials solution to resolve this dilemma is offered. The authors work with memory cells of conventional dimensions, but design/exploit a PCM alloy that decomposes into a heterogeneous network of nanoscale crystalline domains intermixed with amorphous ones. The idea is to confine the subsequent phase-change switching in the interface region of the crystalline nanodomain with its amorphous surrounding, forming/breaking "nano-bridges" that link up the crystalline domains into a conductive path. This conductive-bridge switching mechanism thus only involves nanometer-scale volume in programming, despite of the large areas in contact with the electrodes. The pore-like devices based on spontaneously phase-separated Ge Sb O alloy enable a record-low programming energy, down to a few tens of femtojoule. The new PCM/fabrication is fully compatible with the current 3D integration technology, adding no expenses or difficulty in processing.
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http://dx.doi.org/10.1002/advs.202103478DOI Listing
January 2022

Tumor acidity-activatable photothermal/Fenton nanoagent for synergistic therapy.

J Colloid Interface Sci 2021 Dec 25;612:355-366. Epub 2021 Dec 25.

Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR; State Key Laboratory of Terahertz and Millimeter Waves, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR. Electronic address:

Intracellular formation of therapeutic agents has become one of the effective ways for cancer-specific treatment. Herein, a tumor acidity-activatable photothermal/Fenton nanoagent (denoted as CoPy) was constructed based on oxidized zeolitic imidazolate framework-67 (oxZIF-67) nanosheet and pyrrole (Py) monomer for synergistic therapy. The CoPy showed negligible toxicity to normal cell models RAW264.7 and 3T3 cell lines, and could be degraded by ascorbic acid in normal physiological conditions. However, once uptaken by 4T1 cells, the acidic pH led to the release of Co, which served as a strong oxidant to induce the polymerization of Py to form polypyrrole (PPy) for site-specific photothermal therapy (PTT). Most appealingly, the PPy could chelate the generated Co in the polymerization process to initiate the Fenton-like reaction, which was more capable to produce highly toxic hydroxyl radical (•OH) for chemodynamic therapy (CDT) compared to the free Co ones. In vitro and in vivo experiments demonstrated that all functionalities on CoPy worked collaboratively, and 78% of tumors were inhibited through cooperative PTT/CDT. Such a novel therapeutic nanoagent with tumor selectivity opens new opportunities for combinational treatment paradigms.
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http://dx.doi.org/10.1016/j.jcis.2021.12.134DOI Listing
December 2021

Supplementation of amino acids and organic acids prevents the increase in blood pressure induced by high salt in Dahl salt-sensitive rats.

Food Funct 2022 Jan 7. Epub 2022 Jan 7.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.

A high-salt (HS) diet leads to metabolic disorders in Dahl salt-sensitive (SS) rats, and promotes the development of hypertension. According to the changes in the metabolites of SS rats, a set of combined dietary supplements containing amino acids and organic acids (AO) were designed. The purpose of the present study was to evaluate the effect of AO supplementation on the blood pressure of SS rats after the HS diet and clarify the mechanism of AO by metabolomics and biochemical analyses. The results showed that AO supplementation avoided the elevation of blood pressure induced by the HS diet in SS rats, increased the renal antioxidant enzyme activities (catalase, superoxide dismutase, glutathione reductase, and glutathione S-transferase), reduced the HO and MDA levels, and restored the normal antioxidant status of the serum and kidneys. AO also reversed the decrease in the nitric oxide (NO) levels and NO synthase activity induced by the HS feed, which involved the L-arginine/NO pathway. Metabolomics analysis showed that AO administration increased the levels of amino acids such as cysteine, glycine, hypotaurine, and lysine in the renal medulla and the levels of leucine, isoleucine, and serine in the renal cortex. Of note, lysine, hypotaurine and glycine had higher metabolic centrality in the metabolic correlation network of the renal medulla after AO administration. In conclusion, AO intervention could prevent HS diet-induced hypertension in SS rats by restoring the metabolic homeostasis of the kidneys. Hence, AO has the potential to become a functional food additive to improve salt-sensitive hypertension.
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http://dx.doi.org/10.1039/d1fo03577kDOI Listing
January 2022

G6PD upregulates Cyclin E1 and MMP9 to promote clear cell renal cell carcinoma progression.

Int J Med Sci 2022 1;19(1):47-64. Epub 2022 Jan 1.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Kunming Medical University, Yunnan, Kunming 650500, P.R. China.

Clear cell renal cell carcinoma (ccRCC) is a cell metabolic disease with high metastasis rate and poor prognosis. Our previous studies demonstrate that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in ccRCC and predicts poor outcomes of ccRCC patients. The aims of this study were to confirm the oncogenic role of G6PD in ccRCC and unravels novel mechanisms involving Cyclin E1 and MMP9 in G6PD-mediated ccRCC progression. Real-time RT-PCR, Western blot and immunohistochemistry were used to determine the expression patterns of G6PD, Cyclin E1 and MMP9 in ccRCC. TCGA dataset mining was used to identify Cyclin E1 and MMP9 correlations with G6PD expression, relationships between clinicopathological characteristics of ccRCC and the genes of interest, as well as the prognosis of ccRCC patients. The role of G6PD in ccRCC progression and the regulatory effect of G6PD on Cyclin E1 and MMP9 expression were investigated by using a series of cytological function assays . To verify this mechanism , xenografted mice models were established. G6PD, Cyclin E1 and MMP9 were overexpressed and positively correlated in ccRCC, and they were associated with poor prognosis of ccRCC patients. Moreover, G6PD changed cell cycle dynamics, facilitated cells proliferation, promoted migration , and enhanced ccRCC development , more likely through enhancing Cyclin E1 and MMP9 expression. These findings present G6PD, Cyclin E1 and MMP9, which contribute to ccRCC progression, as novel biomarkers and potential therapeutic targets for ccRCC treatment.
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http://dx.doi.org/10.7150/ijms.58902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692124PMC
January 2022

ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.

Front Mol Biosci 2021 13;8:764900. Epub 2021 Dec 13.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.

Pancreatic cancer is one of the most lethal cancers and its prognosis is extremely poor. Clarification of molecular mechanisms and identification of prognostic biomarkers are urgently needed. Though we previously found that LGMN was involved in pancreatic carcinoma progression, the upstream regulation of LGMN remains unknown. We used reliable software to search for the potential transcription factors that may be related with LGMN transcription, we found that ELK1 could be a new regulator of LGMN transcription that binded directly to the LGMN promoter. Moreover, knocking down of ELK1 reduced pancreatic cancer cells proliferation, invasion and survival, while LGMN restored the malignancy of pancreatic cancer and . Overexpression of ELK1 further increased cancer cells proliferation, invasion and survival. Clinically, ELK1 and LGMN were positively correlated with clinical stage, degree of differentiation and Lymph node infiltration. ELK1 and LGMN were identified as independent prognostic factors for overall survival. The patients with low expression of ELK1/LGMN survived an average of 29.65 months, whereas those with high expression of ELK1/LGMN survived an average of 16.67 months. In conclusive, our results revealed a new mechanism by which ELK1 promoted the progression of pancreatic cancer LGMN and conferred poor prognosis.
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http://dx.doi.org/10.3389/fmolb.2021.764900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8711721PMC
December 2021

Comprehensive next-generation sequencing reveals novel predictive biomarkers of recurrence and thoracic toxicity risks following chemoradiotherapy in limited stage small-cell lung cancer.

Int J Radiat Oncol Biol Phys 2021 Dec 20. Epub 2021 Dec 20.

Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong, Jinan, Shandong, China; Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China. Electronic address:

Purpose: While definitive chemoradiotherapy (dCRT) remains the most effective treatment modality in limited stage small-cell lung cancer (SCLC), some progress quickly or develop serious radiation-induced thoracic toxicity (RITT). Molecular correlates of response to dCRT remain to be explored.

Methods And Materials: Genomic profiling was performed retrospectively on 231 limited-stage SCLC patients treated with dCRT between 2015 and 2019 using a customized panel covering cancer- and radiotherapy response-related genes. Exploratory associations of progression-free survival (PFS), overall survival (OS) and RITT with clinical features, tumor genetic, genomic and molecular pathway alterations and single nucleotide polymorphisms (SNPs) were conducted.

Results: In addition to the common SCLC genes, such as TP53, RB1, and NOTCH1/2, potentially actionable mutations in EGFR, KRAS and BRCA1/2 were among the top alterations in the cohort. At the single-gene level, CDK4 and GATA6 alterations were independent predictors of poor survival by multivariate analysis. At the genomic level, high tumor mutational burden (TMB) was strongly associated with favorable survival outcome. Pathway-level analysis showed that activating mutations in the MAPK/ERK pathway genes, particularly those in EGFR/ERBB2, correlated with poor survival. Combined analysis enabled optimized risk stratification of post-dCRT survival. On the other hand, our study also confirmed that SNPs in MTHFR, CYP2B6, NQO1, and LIG4 were risk alleles of high-grade RITT. Remarkably, somatic loss-of-function mutations in the DNA damage repair pathway genes were associated increased risk of high-grade RITT, particularly pneumonitis, which likely reflect a complex interplay between the tumor and its immune microenvironment.

Conclusions: Taken together, by examining the mutational landscape of a large cohort of limited-stage SCLC, we identified novel molecular predictors of survival and RITT. Our findings also implicate several key molecular pathways, including the MAPK/ERK and DDR pathways, in the regulation of dCRT response.
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http://dx.doi.org/10.1016/j.ijrobp.2021.12.009DOI Listing
December 2021

Unraveling the Kinetics and Mechanism of Surfactant-Induced Wetting in Membrane Distillation: An In Situ Observation with Optical Coherence Tomography.

Environ Sci Technol 2022 Jan 20;56(1):556-563. Epub 2021 Dec 20.

Department of Civil Engineering, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

In this study, we performed a direct contact membrane distillation and successfully demonstrated the non-invasive imaging of surfactant-induced wetting using optical coherence tomography. This method enabled us to investigate the wetting kinetics, which was found to follow a "three-region" relationship between the wetting rate and surfactant concentration: the (i) nonwetted region, (ii) concentration-dependent region, and (iii) concentration-independent region at low, intermediate, and high surfactant concentrations, respectively. This wetting behavior was explained by the "autophilic effect", i.e., the wetting was caused by the transfer of surfactants from the water-vapor interface to the unwetted membrane and rendered this membrane hydrophilic, and then the wetting frontier moved forward under capillary forces. At region-(i), the surfactant concentration in the water-vapor interface () was too low to make the unwetted membrane sufficiently hydrophilic; thereby, the membrane could not be wetted. At region-(ii), due to the fast adsorption of the surfactant on the newly wetted membrane, the wetting rate was determined by the advection/diffusion of surfactants from the feed stream. Consequently, the wetting rate increased with the increases in the water flux and surfactant concentration. At region-(iii), the advection/diffusion provided excess surfactants for adsorption, and thus reached its upper limit (maximum surface excess) and the wetting rate leveled off.
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http://dx.doi.org/10.1021/acs.est.1c05090DOI Listing
January 2022

Corrigendum: Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model.

Front Immunol 2021 18;12:808329. Epub 2021 Nov 18.

Department of Kidney Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

[This corrects the article DOI: 10.3389/fimmu.2021.778359.].
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http://dx.doi.org/10.3389/fimmu.2021.808329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637963PMC
November 2021

NIR/MRI-Guided Oxygen-Independent Carrier-Free Anti-Tumor Nano-Theranostics.

Small 2021 Dec 2:e2106000. Epub 2021 Dec 2.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, P. R. China.

Imaging-guided photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer treatment are beneficial for precise localization of the malignant lesions and combination of multiple cell killing mechanisms in eradicating stubborn thermal-resistant cancer cells. However, overcoming the adverse impact of tumor hypoxia on PDT efficacy remains a challenge. Here, carrier-free nano-theranostic agents are developed ([email protected] NPs) for magnetic resonance imaging (MRI)-guided synergistic PTT/thermodynamic therapy (TDT). Two IR780 derivatives are synthesized as the subject of nanomedicine to confer the advantages for the nanomedicine, which are by feat of amphiphilic IR780-PEG to enhance the sterical stability and reduce the risk from reticuloendothelial system uptake, and IR780-ATU to chelate Mn for T -weighted MRI. Dimethyl 2,2'-azobis(2-methylpropionate) (AIBME), acting as thermally decomposable radical initiators, are further introduced into nanosystems with the purpose of generating highly cytotoxic alkyl radicals upon PTT launched by IR780 under 808 nm laser irradiation. Therefore, the sequentially generated heat and alkyl radicals synergistically induce cell death via synergistic PTT/TDT, ignoring tumor hypoxia. Moreover, these carrier-free nano-theranostic agents present satisfactory biocompatibility, which could be employed as a powerful weapon to hit hypoxic tumors via MRI-guided oxygen-independent PTT and photonic TDT.
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http://dx.doi.org/10.1002/smll.202106000DOI Listing
December 2021

Nanofiltration for drinking water treatment: a review.

Front Chem Sci Eng 2021 Nov 26:1-18. Epub 2021 Nov 26.

Membrane-based Environmental & Sustainable Technology (MembEST) Group, Department of Civil Engineering, The University of Hong Kong, Hong Kong, China.

In recent decades, nanofiltration (NF) is considered as a promising separation technique to produce drinking water from different types of water source. In this paper, we comprehensively reviewed the progress of NF-based drinking water treatment, through summarizing the development of materials/fabrication and applications of NF membranes in various scenarios including surface water treatment, groundwater treatment, water reuse, brackish water treatment, and point of use applications. We not only summarized the removal of target major pollutants (e.g., hardness, pathogen, and natural organic matter), but also paid attention to the removal of micropollutants of major concern (e.g., disinfection byproducts, per- and polyfluoroalkyl substances, and arsenic). We highlighted that, for different applications, fit-for-purpose design is needed to improve the separation capability for target compounds of NF membranes in addition to their removal of salts. Outlook and perspectives on membrane fouling control, chlorine resistance, integrity, and selectivity are also discussed to provide potential insights for future development of high-efficiency NF membranes for stable and reliable drinking water treatment.
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http://dx.doi.org/10.1007/s11705-021-2103-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617557PMC
November 2021

Lenvatinib and CuS nanocrystals co-encapsulated in poly(D,L-lactide--glycolide) for synergistic chemo-photothermal therapy against advanced hepatocellular carcinoma.

J Mater Chem B 2021 12 15;9(48):9908-9922. Epub 2021 Dec 15.

Cancer Center, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, 430022, China.

Lenvatinib (LT) is gradually replacing sorafenib as an alternative targeted drug against advanced hepatocellular carcinoma (HCC). However, the anticancer effects of LT are still limited because of its low cytotoxicity, multidrug resistance (MDR), and tumor relapse. Herein, we constructed a smart biophotonic nanoplatform to overcome the barriers preventing high performance. LT and copper sulfide nanocrystals (CuS NCs) with excellent photothermal properties in the near-infrared-II (NIR-II) zone were co-encapsulated in poly(D,L-lactide--glycolide) (PLGA) through nanoprecipitation. Both and evaluations demonstrated that CuS NCs enhanced the anticancer efficacy of LT, without recurrence. In addition, the presence of copper ions could allow glutathione (GHS) to be consumed and oxygen to be produced, likely suppressing the expression of P-glycoprotein (P-gp) and overcoming the issue of MDR relating to LT. More importantly, synergistic chemo-photothermal therapy with LT and CuS NCs was more effective than any single therapy or theoretical combination. This nanoplatform is promising for advancing future LT-based treatment strategies for HCC therapy.
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http://dx.doi.org/10.1039/d1tb01808fDOI Listing
December 2021

β-Aminoisobutyric acid supplementation attenuated salt-sensitive hypertension in Dahl salt-sensitive rats through prevention of insufficient fumarase.

Amino Acids 2021 Nov 27. Epub 2021 Nov 27.

The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, 710049, China.

The human Dietary Approaches to Stop Hypertension-Sodium Trial has shown that β-aminoisobutyric acid (BAIBA) may prevent the development of salt-sensitive hypertension (SSHT). However, the specific antihypertensive mechanism remains unclear in the renal tissues of salt-sensitive (SS) rats. In this study, BAIBA (100 mg/kg/day) significantly attenuated SSHT via increased nitric oxide (NO) content in the renal medulla, and it induced a significant increase in NO synthesis substrates (L-arginine and malic acid) in the renal medulla. BAIBA enhanced the activity levels of total NO synthase (NOS), inducible NOS, and constitutive NOS. BAIBA resulted in increased fumarase activity and decreased fumaric acid content in the renal medulla. The high-salt diet (HSD) decreased fumarase expression in the renal cortex, and BAIBA increased fumarase expression in the renal medulla and renal cortex. Furthermore, in the renal medulla, BAIBA increased the levels of ATP, ADP, AMP, and ADP/ATP ratio, thus further activating AMPK phosphorylation. BAIBA prevented the decrease in renal medullary antioxidative defenses induced by the HSD. In conclusion, BAIBA's antihypertensive effect was underlined by the phosphorylation of AMPK, the prevention of fumarase's activity reduction caused by the HSD, and the enhancement of NO content, which in concert attenuated SSHT in SS rats.
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http://dx.doi.org/10.1007/s00726-021-03092-7DOI Listing
November 2021

Novel organoselenides (NSAIDs-Se derivatives) protect against LPS-induced inflammation in microglia by targeting the NOX2/NLRP3 signaling pathway.

Int Immunopharmacol 2021 Dec 23;101(Pt B):108377. Epub 2021 Nov 23.

College of Life Science, Liaoning University, Shenyang 110036, China. Electronic address:

Neuro-inflammation is an immune response of the central nervous system (CNS) to pathogens, and it is associated with a variety of neurodegenerative diseases. Microglial cells are the main category of macrophages in the CNS parenchyma, and they represent one of the most important cellular drivers and regulators of neuroinflammation. In this study, nine new organoselenium compounds based on the hybridization of nonsteroidal anti-inflammatory drugs (NSAIDs) skeleton and organoselenium motif (-SeCN and -SeCF3) were synthesized and their potential anti-neuroinflammatory effects were evaluated using LPS-induced BV2 mouse microglia. The cells were first treated with the organoselenium compounds and the extent of oxidative stress and inflammatory response of the cells was determined by measuring the levels of NO, ROS, IL-1β, and IL-18. Among the nine compounds, 1-39 and 1A-38 exhibited the most significant effect on oxidative stress and inflammatory response. Subsequent studies carried out with 1-39 and 1A-38 showed that both compounds could reduce the production of ROS in the cells, probably through down-regulating NOX2 and its downstream targets, including TXNIP (thioredoxin-interacting protein) and NLRP3 (NOD-like receptor protein 3). In addition, 1-39 and 1A-38 also suppressed the ability of the cells to secret IL-18 and IL-1β, which greatly dampened the response of the cells to LPS-induced inflammation. Our finding demonstrated that organoselenium compounds derived from NSAID might play an important role in the protection of brain microglia against inflammation-related neurodegenerative disease by potentially down-regulating the NOX2/NLRP3 signaling axis.
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http://dx.doi.org/10.1016/j.intimp.2021.108377DOI Listing
December 2021

YTHDF1 promotes mRNA degradation via YTHDF1-AGO2 interaction and phase separation.

Cell Prolif 2021 Nov 25:e13157. Epub 2021 Nov 25.

School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Objectives: YTHDF1 is known as a m A reader protein, and many researches of YTHDF1 focused on the regulation of mRNA translation efficiency. However, YTHDF1 is also related to RNA degradation, but how YTHDF1 regulates mRNA degradation is indefinite. Liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in mammal cells, and there are few reports focused on the correlation of RNA degradation with LLPS. In this research, we focused on the mechanism of YTHDF1 degraded mRNA through LLPS.

Materials And Methods: The CRISPR/Cas9 knock out system was used to establish the YTHDF1 knock out (YTHDF1-KO) cell lines (HEK293 and HeLa) and METTL14 knock out (METTL14-KO) cell line (HEK293). 4SU-TT-seq was used to check the half-life changes of mRNAs. Actinomycin D and qPCR were used to test the half-life changes of individual mRNA. RNA was stained with SYTO RNA-select dye in wild type (WT) and YTHDF1-KO HeLa cell lines. Co-localization of YTHDF1 and AGO2 was identified by immunofluorescence. The interaction domain of YTHDF1 and AGO2 was identified by western blot. Phase separation of YTHDF1 was performed in vitro and in vivo. Fluorescence recovery after photobleaching (FRAP) was performed on droplets as an assessment of their liquidity.

Results: In this research, we found that deletion of YTHDF1 led to massive RNA patches deposited in cytoplasm. The results of 4SU-TT-seq showed that deletion of YTHDF1 would prolong the half-life of mRNAs. Immunofluorescence data showed that YTHDF1 and AGO2 could co-localize in P-body, and Co-IP results showed that YTHDF1 could interact with AGO2 through YT521-B homology (YTH) domain. We confirmed that YTHDF1 could undergo phase separation in vitro and in vivo, and compared with AGO2, YTHDF1 was more important in P-body formation. The FRAP results showed that liquid AGO2 droplets would convert to gel/solid when YTHDF1 was deleted. As AGO2 plays important roles in miRISCs, we also found that miRNA-mediate mRNA degradation is related to YTHDF1.

Conclusions: YTHDF1 recruits AGO2 through the YTH domain. YTHDF1 degrades targeting mRNAs by promoting P-body formation through LLPS. The deletion of YTHDF1 causes the P-body to change from liquid droplets to gel/solid droplets, and form AGO2/RNA patches, resulting in a degradation delay of mRNAs. These findings reveal a previously unrecognized crosstalk between YTHDF1 and AGO2, raising a new sight of mRNA post-transcriptional regulation by YTHDF1.
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http://dx.doi.org/10.1111/cpr.13157DOI Listing
November 2021

Overlap phenotypes of the left ventricular noncompaction and hypertrophic cardiomyopathy with complex arrhythmias and heart failure induced by the novel truncated DSC2 mutation.

Orphanet J Rare Dis 2021 Nov 24;16(1):496. Epub 2021 Nov 24.

Department of Physiology, The School of Medicine of Jinan University, Guangzhou, 510000, China.

Background: The left ventricular noncompaction cardiomyopathy (LVNC) is a rare subtype of cardiomyopathy associated with a high risk of heart failure (HF), thromboembolism, arrhythmia, and sudden cardiac death.

Methods: The proband with overlap phenotypes of LVNC and hypertrophic cardiomyopathy (HCM) complicates atrial fibrillation (AF), ventricular tachycardia (VT), and HF due to the diffuse myocardial lesion, which were diagnosed by electrocardiogram, echocardiogram and cardiac magnetic resonance imaging. Peripheral blood was collected from the proband and his relatives. DNA was extracted from the peripheral blood of proband for high-throughput target capture sequencing. The Sanger sequence verified the variants. The protein was extracted from the skin of the proband and healthy volunteer. The expression difference of desmocollin2 was detected by Western blot.

Results: The novel heterozygous truncated mutation (p.K47Rfs*2) of the DSC2 gene encoding an important component of desmosomes was detected by targeted capture sequencing. The western blots showed that the expressing level of functional desmocollin2 protein (~ 94kd) was lower in the proband than that in the healthy volunteer, indicating that DSC2 p.K47Rfs*2 obviously reduced the functional desmocollin2 protein expression in the proband.

Conclusion: The heterozygous DSC2 p.K47Rfs*2 remarkably and abnormally reduced the functional desmocollin2 expression, which may potentially induce the overlap phenotypes of LVNC and HCM, complicating AF, VT, and HF.
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http://dx.doi.org/10.1186/s13023-021-02112-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8611834PMC
November 2021

A randomized, split-face controlled trial on the safety and effects of microneedle fractional radiofrequency and fractional erbium-doped glass 1,565-nm laser therapies for baggy lower eyelids.

J Cosmet Laser Ther 2021 Nov 23:1-8. Epub 2021 Nov 23.

Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, SN, China.

The non-ablative fractional erbium-doped glass 1,565-nm laser (NAFL) and the microneedle fractional radiofrequency (MFR) procedures are effective treatments that enable periorbital skin rejuvenation. To compare the clinical effectiveness and side effects of MFR and the NAFL for baggy lower eyelids (BLEs) in the Chinese population. Fifteen Chinese subjects with BLEs received three split-face treatments on a monthly basis randomly. Objective and subjective assessments were performed at baseline, as well as 1 month and 3 months after the third treatment. The results were evaluated using Antera-3D and CineScan systems. Blinded investigator assessments were performed by two plastic surgeons using a 0 to 4 score in six anatomic categories of BLEs. The patients also reported their level of satisfaction based on a four-point score. Most of the patients reported a greater than 47% satisfaction rate with both treatments. The cumulative contribution scores of prolapse of orbital fat, hollow tear trough, and skin laxity for each category variable declined with time. Using Antera 3D, the volume of elevation (mm) decreased from 0.6 ± 0.4 to 0.4 ± 0.3 and from 0.6 ± 0.3 to 0.3 ± 0.3, the elevation area (mm) decreased from 17.0 ± 8.4 to 13.0 ± 7.1 and from 17.0 ± 7.8 to 10.0 ± 5.6, and the maximum peak height (mm) also decreased from 0.10 ± 0.04 to 0.06 ± 0.04 and from 0.10 ± 0.03 to 0.06 ± 0.02 in the MFR and NAFL groups, respectively. Using CineScan, the depth of middle orbital fat (mm) decreased significantly from 10.2 ± 2.2 to 8.0 ± 0.7 and from 9.8 ± 1.1 to 8.0 ± 0.9 and the length of orbital fat significantly decreased from 9.2 ± 1.2 to 7.7 ± 0.7 and from 9.7 ± 1.4 to 7.8 ± 0.6 in the MFR and NAFL groups, respectively. MFR and NAFL therapies were effective for the treatment of BLEs, especially in BLE patients with skin elasticity in addition to tear trough deformity and orbital fat prolapse. Trial registration number: NCT04237324. Trial register: ClinicalTrials.gov. Level of Evidence: Level I, therapeutic study.
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http://dx.doi.org/10.1080/14764172.2021.2001532DOI Listing
November 2021

Predicting changes in osmolality.

Elife 2021 11 18;10. Epub 2021 Nov 18.

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States.

Two neural circuits control the release of vasopressin in response to eating and drinking before there are any detectable changes in blood water levels.
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http://dx.doi.org/10.7554/eLife.74551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601660PMC
November 2021

The abnormal level of HSP70 is related to Treg/Th17 imbalance in PCOS patients.

J Ovarian Res 2021 Nov 15;14(1):155. Epub 2021 Nov 15.

Reproductive Medical Centre, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China.

Background: Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio and to provide evidence for the role of HSP70 in the immunological etiology of PCOS.

Results: There was no significant difference in age and body mass index (BMI) between the two groups. The concentrations of basal estradiol (E), basal follicle-stimulating hormone (FSH) did not show a significant difference between the two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.01), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in the control group. The protein levels of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.01), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in the PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17, and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-β (TGF-β) were significantly lower in the PCOS group (P < 0.001). Spearman rank correlation analysis showed a strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10, and TGF-β levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, insulin, and glucose levels.

Conclusion: The abnormal level of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.
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http://dx.doi.org/10.1186/s13048-021-00867-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8591891PMC
November 2021

Reconstruction of Soft Tissue Defects on the Face, Neck, and Chest by Expanded Cervico-Acromial Flap.

J Craniofac Surg 2021 May;32(3):974-977

The 2nd Department of Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shijinshan District, Beijing, China.

Background: Repairing the defects of face and neck remains a big challenge for plastic surgeons. Here we present a case series of pre-expanded cervico-acromial flaps in the repair of soft tissue defects.

Method: This is a retrospective study that a total of 126 patients between 2001 and 2019 were included. One patient was excluded since he did not complete the treatment. All patients were followed for at least 0.5 years (range: 0.5-4 years, mean 2.50 years) after surgery.

Results: All patients are satisfied with the appearance. The color and texture of expanded flaps were similar to surroundings. One patient (0.8%) had complete necrosis and received skin grafts. The size of cervico-acromial was 26-10 × 14-6 cm (mean, 15.389 ± 2.701× 8.341 ± 1.075 cm). The time of operation during stage 1 was 59.254 ± 9.895 minutes, 96.912 ± 18.936 minutes during stage 2, and 38.146 ± 9.478 minutes during stage 3. Surgical complication rate was 14.3%, given that 18 patients had complications following the surgery.

Conclusions: The cercico-acromial flap is a reliable and multifunctional method for face, neck, and chest reconstruction.
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http://dx.doi.org/10.1097/SCS.0000000000007371DOI Listing
May 2021

Blockade of IL-6/IL-6R Signaling Attenuates Acute Antibody-Mediated Rejection in a Mouse Cardiac Transplantation Model.

Front Immunol 2021 28;12:778359. Epub 2021 Oct 28.

Department of Kidney Transplantation, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.

Acute antibody-mediated rejection (AAMR) is an important cause of cardiac allograft dysfunction, and more effective strategies need to be explored to improve allograft prognosis. Interleukin (IL)-6/IL-6R signaling plays a key role in the activation of immune cells including B cells, T cells and macrophages, which participate in the progression of AAMR. In this study, we investigated the effect of IL-6/IL-6R signaling blockade on the prevention of AAMR in a mouse model. We established a mouse model of AAMR for cardiac transplantation presensitization of skin grafts and addition of cyclosporin A, and sequentially analyzed its features. Tocilizumab, anti-IL-6R antibody, and recipient IL-6 knockout were used to block IL-6/IL-6R signaling. We demonstrated that blockade of IL-6/IL-6R signaling significantly attenuated allograft injury and improved survival. Further mechanistic research revealed that signaling blockade decreased B cells in circulation, spleens, and allografts, thus inhibiting donor-specific antibody production and complement activation. Moreover, macrophage, T cell, and pro-inflammatory cytokine infiltration in allografts was also reduced. Collectively, we provided a highly practical mouse model of AAMR and demonstrated that blockade of IL-6/IL-6R signaling markedly alleviated AAMR, which is expected to provide a superior option for the treatment of AAMR in clinic.
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http://dx.doi.org/10.3389/fimmu.2021.778359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581398PMC
October 2021

Bioconversion of Apple Pomace into Microbial Protein Feed Based on Extrusion Pretreatment.

Appl Biochem Biotechnol 2021 Nov 11. Epub 2021 Nov 11.

School of Agricultural Engineering and Food Science, Shandong University of Technology, Zibo, 255049, Shandong, China.

Apple pomace (AP) is often used directly as animal feed, while the value of feeding is limited by its low protein content. In this study, extrusion pretreatment was performed for AP, and further fermentation was carried out to improve its nutrition value. Strains suitable for extruded apple pomace (EAP) to produce high-quality microbial protein (MP) feed were screened from 12 different strains. Results showed that Aspergillus niger 3.324 (Asn), Candida utilis1314 (Cau), Geotrichum candidum 1315 (Gec), Bacillus subtilis A308 (Bas1), and Lactic acid bacteria (Lac) were screened as the dominant strains, which exhibited higher feeding value. Strong symbiotic effect was observed in fermentation with mixed strains of Asn, Cau, Gec, and Lac at the ratio of 1:1:1:1. Compared with AP, the pure protein content in the optimized fermented EAP (FEAP) was increased by 138% accompanying with a pleasant flavor and taste. And its pure protein content was increased by 19.20% in comparison to that of the fermented apple pomace. The nutrition value of FEAP was characterized by amino acid profiles; it found that FEAP was comparable to other commercial proteins with higher contents of histidine, phenylalanine, threonine, and valine. Combination of fermentation and extrusion technology significantly enhanced pure protein content and nutritional composition of apple pomace, which was revalorized as a nutritive animal feed rich in microbial protein.
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http://dx.doi.org/10.1007/s12010-021-03727-1DOI Listing
November 2021

In Situ Preparation of MXenes in Ambient-Temperature Organic Ionic Liquid Aluminum Batteries with Ultrastable Cycle Performance.

ACS Appl Mater Interfaces 2021 Nov 11;13(46):55112-55122. Epub 2021 Nov 11.

Laboratory of Advanced Materials, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.

A fluorine-free and water-free electrochemical preparation of MXenes is achieved in Lewis acidic molten salts at ambient temperature. In addition, the anode reaction of the MAX phase VAlC is studied in the organic ionic liquid aluminum battery and the extraction voltages of the metal atoms Al and V in the MAX phase VAlC are determined. This points out the direction for the constant-voltage electrochemical preparation of MXenes. Furthermore, the electrochemical performance of the etched VAlC (E-VAlC) in an aluminum battery is studied. The one-stop preparation-application process prevents the MXenes from contacting water and air, and the MXenes etched in the aluminum battery are more conducive to the intercalation/deintercalation of Al. Therefore, E-VAlC exhibits excellent electrochemical performance in an aluminum battery. Under the conditions of a voltage window of 0.01-2.3 V (V Al/Al) and a current density of 500 mA g, the specific discharge capacity is about 100 mAh g after 6500 cycles. In addition, the energy storage mechanism and Faraday energy storage method of E-VAlC in an aluminum battery are studied. The diffusion coefficient of Al is determined by a galvanostatic intermittent titration technique. The reasons for its excellent electrochemical performance are clarified from the perspective of kinetics.
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http://dx.doi.org/10.1021/acsami.1c16706DOI Listing
November 2021

Digenic heterozygous mutations of KCNH2 and SCN5A induced young and early-onset long QT syndrome and sinoatrial node dysfunction.

Ann Noninvasive Electrocardiol 2022 Jan 9;27(1):e12889. Epub 2021 Nov 9.

The Cardiovascular Center, Department of Cardiology, Interventional Medical Center, Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.

Introduction: Long QT syndrome (LQTS) is a life-threatening inherited channelopathy, and prolonged QT intervals easily trigger malignant arrhythmias, especially torsades de pointes and ventricular fibrillation.

Materials And Methods: The proband with overlapped phenotypes of LQTS and sinoatrial node dysfunction underwent some necessary examinations, including echocardiography, electrocardiogram (ECG), and Holter monitoring. Next, whole-exome sequencing was performed, and candidate genes were validated by Sanger sequencing. RNA secondary structure and protein physical-chemical parameter analyses were used to predict the possible structural change of the proteins induced by the mutations.

Results: We identified the digenic heterozygous mutations of KCNH2 p.307_308del (NM_001204798, c.921_923del) and SCN5A p.R1865H (NM_001160160, c.G5594A) in the female and young proband (II: 1) of LQTS and ventricular fibrillation with repeat syncope at rest. Subsequently, she occurred with obvious sinus arrest with persistent ventricular pacing of implantable cardioverter-defibrillator. The heterozygous SCN5Ap.R1865H was carried by her father and sister but not carried by I:2. II:1 carried with KCNH2 p.307_308del as a de novo mutation, but not existed in other family members. RNA secondary structure of KCNH2 p.307_308del showed a false regional double helix, and its amino acids' hydrophobicity was significantly weakened. For the Na 1.5 protein property, SCN5A p.R1865H slightly increased the molecular weight and aliphatic index but reduced the instability index.

Conclusions: The digenic heterozygous KCNH2 and SCN5A mutations were associated with young early-onset long QT syndrome and sinoatrial node dysfunction.
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http://dx.doi.org/10.1111/anec.12889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739608PMC
January 2022

Effect of Bloodletting at Shaoshang and Shangyang Acupuncture Points on Outcome and Prognosis of Severe Community-Acquired Pneumonia in the Elderly.

Dis Markers 2021 26;2021:3295021. Epub 2021 Oct 26.

Department of Intensive Care Unit, Tongzhou District Branch, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 101100, China.

Objectives: The aim of this study was to explore, whether treatment with bloodletting at Shaoshang and Shangyang acupuncture points would affect therapy outcome and prognosis for severe community-acquired pneumonia (SCAP) in the elderly.

Methods: A total of 62 patients, who met the diagnostic criteria for SCAP, were enrolled in the study and randomly divided into two groups, i.e., treatment group ( = 31) and control group ( = 31). All patients received a therapy according to the Chinese Clinical Practice and Expert Consensus of Emergency Severe Pneumonia from 2016. In addition to that, a bloodletting at Shaoshang (LU11) and Shangyang (LI1) acupuncture points was applied for the treatment group. This intervention was repeated for three times (ones daily), bloodletting a volume of 2-3 ml at each time point. Differences in a main index of clinical efficacy, body temperature (T), respiratory rate (RR), heart rate (Hr), white blood cell count (WBC), neutrophil percentage (N%), and C-reactive protein level (CRP) as well as different scores (CURB-65 score, SOFA score, and Apache II score) were compared between groups. Moreover, the 28-day mortality was compared between treatment and control group. The statistical methods involved in carrying out the current study include -test, Wilcoxon test, and chi-square test.

Results: The clinical effective rate of the treatment group was 82.9%, which was significantly higher than the 17.1% in the control group ( < 0.05). After finishing the intervention, the treatment group showed significantly lower T (37.28 ± 0.54 vs. 37.82 ± 0.81), RR (20.06 ± 2.67 vs. 23.71 ± 6.85), Hr (81.71 ± 10.38 vs. 93.84 ± 15.39), CUBR-65 score (2.16 ± 0.74 vs. 3.03 ± 0.98), and SOFA score (5.84 ± 3.83 vs. 8.16 ± 4.2) compared to the control group ( < 0.05). The 28-day mortality rate of the treatment group was significantly lower than in the control group (12.9% vs. 45.2%, = 0.05).

Conclusions: Bloodletting at Shaoshang and Shangyang acupuncture points can support improving the clinical treatment efficacy for SCAP and reduce the 28-day mortality rate in the elderly.
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http://dx.doi.org/10.1155/2021/3295021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563111PMC
October 2021

Significance and Surgical Options for Nontranssexual Phalloplasty: A Retrospective Single-Center Analysis of 166 Patients.

Ann Plast Surg 2021 Oct 26. Epub 2021 Oct 26.

From the 2nd Department, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: This study aimed to evaluate the long-term outcomes of phalloplasty and explore the clinical significance and selection of methods for penile reconstruction.

Methods: The same surgical team performed primary phalloplasty in 166 nontranssexual patients using different surgical approaches between September 2000 and September 2020. All patients had at least 6 months of follow-up. Surgical techniques, complications, and outcomes were retrospectively recorded.

Results: A total of 166 patients with indications such as penile trauma (n = 68 [41%]), amputation injury (n = 15 [9%]), iatrogenic (n = 13 [8%]), penile aplasia (n = 54 [32%]), genital ambiguity (n = 15 [9%]), and Peyronie disease (n = 1 [0.6%]) underwent different techniques of phalloplasty. Four patients (2.4%) had total flap necrosis, and 17 (10%) had partial flap necrosis. The total urethral complications rate was 32.5% (54 of 166); however, all the patients were able to void while standing after successful corrective surgery.

Conclusions: Individualized selection of appropriate penile reconstruction methods tailored to the cause of penile defect, patients' personal needs, thickness of donor site, and the blood supply of the flap are conducive to achieving satisfactory treatment results, reducing complications, and improving patient satisfaction. We believe that a scapular flap has certain advantages in nontranssexual patients, whereas other flaps also have their own indications.
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http://dx.doi.org/10.1097/SAP.0000000000003031DOI Listing
October 2021

Response to pretransplant downstaging therapy predicts patient outcome after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombus.

Hepatobiliary Pancreat Dis Int 2021 Oct 14. Epub 2021 Oct 14.

Department of Hepatobiliary and Pancreatic Surgery, Department of Liver Transplantation, Shulan (Hangzhou) Hospital, Zhejiang Shuren University School of Medicine, Hangzhou 310022, China; Division of Hepatobiliary Pancreatic Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. Electronic address:

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http://dx.doi.org/10.1016/j.hbpd.2021.09.012DOI Listing
October 2021

Removal of Antimony(V) from Drinking Water Using nZVI/AC: Optimization of Batch and Fix Bed Conditions.

Toxics 2021 Oct 14;9(10). Epub 2021 Oct 14.

Henan International Joint Laboratory of New Civil Engineering Structure, College of Civil Engineering, Luoyang Institute of Science and Technology, Luoyang 471023, China.

Antimony (Sb) traces in water pose a serious threat to human health due to their negative effects. In this work, nanoscale zero-valent iron (Fe) supported on activated carbon (nZVI) was employed for eliminating Sb(V) from the drinking water. To better understand the overall process, the effects of several experimental variables, including pH, dissolved oxygen (DO), coexisting ions, and adsorption kinetics on the removal of Sb(V) from the SW were investigated by employing fixed-bed column runs or batch-adsorption methods. A pH of 4.5 and 72 h of equilibrium time were found to be the ideal conditions for drinking water. The presence of phosphate (PO43-), silicate (SiO42-), chromate (CrO42-) and arsenate (AsO43-) significantly decreased the rate of Sb(V) removal, while humic acid and other anions exhibited a negligible effect. The capacity for Sb(V) uptake decreased from 6.665 to 2.433 mg when the flow rate was increased from 5 to 10 mL·min. The dynamic adsorption penetration curves of Sb(V) were 116.4% and 144.1% with the weak magnetic field (WMF) in fixed-bed column runs. Considering the removal rate of Sb(V), reusability, operability, no release of Sb(V) after being incorporated into the iron (hydr)oxides structure, it can be concluded that WMF coupled with ZVI would be an effective Sb(V) immobilization technology for drinking water.
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http://dx.doi.org/10.3390/toxics9100266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540850PMC
October 2021

Activity of chlorhexidine acetate in combination with fluconazole against suspensions and biofilms of Candida auris.

J Infect Chemother 2022 Jan 19;28(1):29-34. Epub 2021 Oct 19.

Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, China. Electronic address:

Objectives: As a newly emerging pathogen, Candida auris has spread rapidly and caused a serious invasive infection. Candida auris often appeared high resistance to classical antifungal drugs. Drug combination therapy is emerging as an effective and well-established strategy to relieve drug resistance problems. The objective of present work was to examine the activity of fluconazole in combination with chlorhexidine acetate against Candida auris isolates.

Methods: Antiplanktonic activity was studied using the EUCAST methodology and growth curve assay. Antibiofilm effectiveness was determined by the crystal violet method, checkerboard microdilution assay, scanning electron microscopy, and confocal laser scanning microscopy.

Results: The results indicated that the 80% minimal inhibitory concentrations for fluconazole alone against Candida auris were 2-32 mg/L and for chlorhexidine acetate were 2-8 mg/L. The combination of fluconazole with chlorhexidine acetate exhibited synergism with the growth curve assay. In addition, the checkerboard microdilution assay presented that fluconazole was strongly synergistic with chlorhexidine acetate (sFICI <0.1875) in inhibiting the growth of Candida auris biofilms. The scanning electron microscopy and confocal laser scanning microscopy further exhibited the alteration of morphology of the cells and architecture of the biofilms.

Conclusion: The combination therapy of fluconazole and chlorhexidine acetate provides a new potential strategy for the treatment of clinical Candida auris infection.
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http://dx.doi.org/10.1016/j.jiac.2021.09.018DOI Listing
January 2022
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