Publications by authors named "Jiang Wu"

1,116 Publications

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Comparison of Dosimetric Benefits of Three Precise Radiotherapy Techniques in Nasopharyngeal Carcinoma Patients Using a Priority-Classified Plan Optimization Model.

Front Oncol 2021 27;11:646584. Epub 2021 Sep 27.

Department of Radiotherapy, Yunnan Cancer Hospital, the Third Affiliated Hospital of Kunming Medical University, Kunming, China.

Introduction: Although intensity-modulated radiotherapy (IMRT), volumetric-modulated arc therapy (VMAT) and tomotherapy (TOMO) are broadly applied for nasopharyngeal carcinoma (NPC), the best technique remains unclear. Therefore, this study was conducted to address this issue.

Methods: The priority-classified plan optimization model was applied to IMRT, VMAT and TOMO plans in forty NPC patients according to the latest international guidelines. And the dosimetric parameters of planning target volumes (PTVs) and organs at risk (OARs) were compared among these three techniques. The Friedman M test in SPSS software was applied to assess significant differences.

Results: The median PGTVnx coverage of IMRT was the lowest (93.5%, P < 0.001) for all T categories. VMAT was comparable to TOMO in OARs clarified as priority I and II, and both satisfied the prescribed requirement. IMRT resulted in a relatively high dose for V25 and V30. Interestingly, subgroup analysis showed that the median PTV coverage of the three techniques was no less than 95% in the early T stage. The heterogeneity index (HI) of PGTVnx in VMAT was better than that in IMRT (P = 0.028). Compared to TOMO, VMAT showed a strong ability to protect eyesight and decrease low-dose radiation volumes. In the advanced T stage subgroup, TOMO numerically achieved the highest median PGTVnx coverage volume compared with VMAT and IMRT (93.61%, 91% and 90%, respectively). The best CI and HI of PCTV-1 were observed in TOMO. Furthermore, TOMO was better than VMAT for sparing the brain stem, spinal cord and temporal lobes (all P < 0.05). However, the median V5, V10, V15, V20 and V25 were significantly higher with TOMO than with VMAT (all P < 0.05).

Conclusion: In the early T stage, VMAT provides a similar dose coverage and protection of OARs to IMRT, and there are no obvious advantages to choosing TOMO for NPC patients in the early T stage. TOMO may be recommended for patients in the advanced T stage due as it provides the largest dose coverage of PGTVnx and the best protection of the brain stem, spinal cord and temporal lobes. Additionally, more randomized clinical trials are needed for further clarification.
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http://dx.doi.org/10.3389/fonc.2021.646584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504456PMC
September 2021

Global syndromes induced by changes in solutes of the world's large rivers.

Nat Commun 2021 Oct 12;12(1):5940. Epub 2021 Oct 12.

State Environmental Protection Key Laboratory of All Materials Fluxes in River Ecosystems, Peking University, 100871, Beijing, P. R. China.

Solute-induced river syndromes have grown in intensity in recent years. Here we investigate seven such river syndromes (salinization, mineralization, desalinization, acidification, alkalization, hardening, and softening) associated with global trends in major solutes (Ca, Mg, Na, K, SO, Cl, HCO) and dissolved silica in the world's large rivers (basin areas ≥ 1000 km). A comprehensive dataset from 600 gauge stations in 149 large rivers reveals nine binary patterns of co-varying trends in runoff and solute concentration. Solute-induced river syndromes are associated with remarkable increases in total dissolved solids (68%), chloride (81%), sodium (86%) and sulfate (142%) fluxes from rivers to oceans worldwide. The syndromes are most prevalent in temperate regions (30~50°N and 30~40°S based on the available data) where severe rock weathering and active human interferences such as urbanization and agricultural irrigation are concentrated. This study highlights the urgency to protect river health from extreme changes in solute contents.
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http://dx.doi.org/10.1038/s41467-021-26231-wDOI Listing
October 2021

Biofabrication of cell-free dual drug-releasing biomimetic scaffolds for meniscal regeneration.

Biofabrication 2021 Oct 18;14(1). Epub 2021 Oct 18.

School of Medicine, Nankai University, Tianjin 300071, People's Republic of China.

Regenerating the meniscus remains challenging because of its avascular, aneural, and alymphatic nature. Three-dimensional (3D) printing technology provides a promising strategy to fabricate biomimetic meniscal scaffolds with an anisotropic architecture, a proper biomechanical microenvironment, and bioactive components. Herein, 3D printing technology is adopted by coencapsulating chemokines (platelet-derived growth factor-BB, PDGF-BB) and small chondroinductive molecules (kartogenin, KGN) within biomimetic polycaprolactone/hydrogel composite scaffolds. The incorporated PDGF-BB is expected to promote endogenous stem cell homing, and KGN in poly(lactic-co-glycolic) acid microspheres is employed to target the chondrogenesis of resident mesenchymal stem cells (MSCs). First, we chose basic bioinks composed of gelatin methacrylamide and hyaluronic acid methacrylate and then incorporated four concentrations (0%, 0.5%, 1.0%, and 2.0%) of meniscal extracellular matrix into the bioink to systematically study the superiority of these combinations and identify the optimally printable bioink. Next, we investigated the scaffold morphology and drug release profile. The effects of releasing the drugs in a sequentially controlled manner from the composite scaffolds on the fate of MSCs were also evaluated. The biofabricated scaffolds, with and without dual drug loading, were further studied in a rabbit model established with a critical-size medial meniscectomy. We found that meniscal scaffolds containing both drugs had combinational advantages in enhancing cell migration and synergistically promoted MSC chondrogenic differentiation. The dual drug-loaded scaffolds also significantly promotedneomeniscal regeneration three and six months after implantation in terms of histological and immunological phenotypes. The results presented herein reveal that this 3D-printed dual drug-releasing meniscal scaffold possesses the potential to act as an off-the-shelf product for the clinical treatment of meniscal injury and related joint degenerative diseases.
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http://dx.doi.org/10.1088/1758-5090/ac2cd7DOI Listing
October 2021

Whole Transcriptome Analysis Revealed a Stress Response to Deep Underground Environment Conditions in Chinese Hamster V79 Lung Fibroblast Cells.

Front Genet 2021 16;12:698046. Epub 2021 Sep 16.

Deep Underground Space Medical Center, West China Hospital, Sichuan University, Chengdu, China.

Prior studies have shown that the proliferation of V79 lung fibroblast cells could be inhibited by low background radiation (LBR) in deep underground laboratory (DUGL). In the current study, we revealed further molecular changes by performing whole transcriptome analysis on the expression profiles of long non-coding RNA (lncRNA), messenger RNA (mRNA), circular RNA (circRNA) and microRNA (miRNA) in V79 cells cultured for two days in a DUGL. Whole transcriptome analysis including lncRNA, mRNAs, circ RNA and miRNA was performed in V79 cells cultured for two days in DUGL and above ground laboratory (AGL), respectively. The differentially expressed (DE) lncRNA, mRNA, circRNA, and miRNA in V79 cells were identified by the comparison between DUGL and AGL groups. Quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to verify the selected RNA sequencings. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed for the DE mRNAs which enabled to predict target genes of lncRNA and host genes of circRNA. With |log(Fold-change)| ≥ 1.0 and < 0.05, a total of 1257 mRNAs (353 mRNAs up-regulated, 904 mRNAs down-regulated), 866 lncRNAs (145 lncRNAs up-regulated, 721 lncRNAs down-regulated), and 474 circRNAs (247 circRNAs up-regulated, 227 circRNAs down-regulated) were significantly altered between the two groups. There was no significant difference in miRNA between the two groups. The altered RNA profiles were mainly discovered in lncRNAs, mRNAs and circRNAs. DE RNAs were involved in many pathways including ECM-RI, PI3K-Akt signaling, RNA transport and the cell cycle under the LBR stress of the deep underground environment. Taken together, these results suggest that the LBR in the DUGL could induce transcriptional repression, thus reducing metabolic process and reprogramming the overall gene expression profile in V79 cells.
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http://dx.doi.org/10.3389/fgene.2021.698046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481809PMC
September 2021

Heterologous prime-boost regimens with HAdV-5 and NDV vectors elicit stronger immune responses to Ebola virus than homologous regimens in mice.

Arch Virol 2021 Sep 30. Epub 2021 Sep 30.

Institute for Immunization and Prevention, Beijing Center for Disease Prevention and Control, Beijing Research Center for Preventive Medicine, No. 16, Hepingli Middle Street, Dongcheng District, Beijing, 100013, China.

The 2014 Ebola outbreak in West Africa resulted in more than 11,000 deaths, highlighting the need for a vaccine. A phase I clinical trial of a human adenovirus type 5 vector-based Ebola virus (EBOV) vaccine (HAdV-5-MakGP) showed that a homologous prime-boost regimen with HAdV-5 vaccine elicited a robust humoral response but a weak cellular immune response. Due to pre-existing anti-vector immunity, boosting with the same vaccine did not increase the magnitude of the cellular immune response, which contributes significantly to protection against EBOV infection. Here, we generated a recombinant Newcastle disease virus (NDV), based on the LaSota vaccine strain, expressing the GP protein of the EBOV variant Makona (rLS/EB-GP) using reverse genetics technology. The humoral and cellular immune responses to this vaccine candidate in mice immunized using a homologous prime-boost regimen or a heterologous prime-boost regimen with the HAdV-5-vectored Ebola vaccine were assessed using ELISA and ELISPOT assays. The ELISA and ELISPOT results showed that mice primed with rLS/EB-GP and boosted with HAdV-5-MakGP (NDV+HAdV-5) or, reversed, primed with HAdV-5-MakGP and boosted with rLS/EB-GP (HAdV-5+NDV) exhibited more-potent EBOV GP-specific antibody and cellular immune responses than those receiving the same vaccine twice. The most robust EBOV GP-specific antibody and T-cell responses were detected in the HAdV-5-MakGP-primed and rLS/EB-GP-boosted (HAdV-5+NDV) mice. These results suggest that the HAdV-5 prime-NDV boost regimen is more effective in stimulating EBOV-specific immunity than homologous regimens alone, indicating the potential boosting ability of the NDV vector in human vaccine use.
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http://dx.doi.org/10.1007/s00705-021-05234-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482741PMC
September 2021

Piezoelectric polarization modulated novel BiWO/g-CN/ZnO Z-scheme heterojunctions with g-CN intermediate layer for efficient piezo-photocatalytic decomposition of harmful organic pollutants.

J Colloid Interface Sci 2021 Sep 11;607(Pt 2):1589-1602. Epub 2021 Sep 11.

State Key Laboratory of Optoelectronic Materials and Technologies, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address:

It is of great significance to understand the role of carrier in piezocatalysis of composites by studying the separation mode of carriers under dynamic polarization field. Herein, the separation and migration pathways of carriers under piezoelectric field are investigated by synthesizing heterojunctions with BiWO (BWO) nanosheets grown vertically on g-CN (CN) coated ZnO nanorods and directly on ZnO. Compared with the photocatalysis, the piezocatalytic efficiency of Rhodamine B (RhB) by BWO/ZnO is significantly increased to 0.121 min, which indicated the polarization field promotes band tilt and Z-scheme formation. After introducing the CN interlayer, the piezocatalytic efficiency of BWO/CN/ZnO is further improved (0.217 min), which can be attributed to the unique core-shell structure with Z-scheme heterojunctions. This unique structure provides more active sites and excited carrier concentration, the intermediate layer CN also reduces the direct contact and recombination of electrons and holes controlled by polarization potential at the interface between BWO and ZnO. This work deeply analyzes the influence of carrier concentration, separation efficiency and transport process on piezocatalysis, which provides a reference for the design of efficient catalysts.
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http://dx.doi.org/10.1016/j.jcis.2021.09.007DOI Listing
September 2021

TacticFlow: Visual Analytics of Ever-Changing Tactics in Racket Sports.

IEEE Trans Vis Comput Graph 2021 Sep 29;PP. Epub 2021 Sep 29.

Event sequence mining is often used to summarize patterns from hundreds of sequences but faces special challenges when handling racket sports data. In racket sports (e.g., tennis and badminton), a player hitting the ball is considered a multivariate event consisting of multiple attributes (e.g., hit technique and ball position). A rally (i.e., a series of consecutive hits beginning with one player serving the ball and ending with one player winning a point) thereby can be viewed as a multivariate event sequence. Mining frequent patterns and depicting how patterns change over time is instructive and meaningful to players who want to learn more short-term competitive strategies (i.e., tactics) that encompass multiple hits. However, players in racket sports usually change their tactics rapidly according to the opponent's reaction, resulting in ever-changing tactic progression. In this work, we introduce a tailored visualization system built on a novel multivariate sequence pattern mining algorithm to facilitate explorative identification and analysis of various tactics and tactic progression. The algorithm can mine multiple non-overlapping multivariate patterns from hundreds of sequences effectively. Based on the mined results, we propose a glyph-based Sankey diagram to visualize the ever-changing tactic progression and support interactive data exploration. Through two case studies with four domain experts in tennis and badminton, we demonstrate that our system can effectively obtain insights about tactic progression in most racket sports. We further discuss the strengths and the limitations of our system based on domain experts' feedback.
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http://dx.doi.org/10.1109/TVCG.2021.3114832DOI Listing
September 2021

Contralateral risk-reducing local therapy in breast cancer patients with BRCA1/2 mutations: systemic review and meta-analysis.

Cancer Cell Int 2021 Sep 25;21(1):512. Epub 2021 Sep 25.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.

Background: Unilateral breast cancer (UBC) patients with germline pathogenic BRCA1/2 variants have a higher risk of developing contralateral breast cancer (CBC) and need contralateral risk-reducing local treatments, including contralateral risk-reducing mastectomy (CRRM) and prophylactic irradiation (CPI). The aim of our study was to systematically explore the efficacy of CRRM and CPI in reducing CBC risk and increasing survival.

Methods: A search was done, and eligible randomized trials and cohort studies should include and compare UBC patients with germline pathogenic BRCA1/2 variants who have and have not received contralateral risk-reducing local treatment. Random-effects meta-analysis was used in this study. Primary outcomes of the studies included overall survival (OS) and the incidence of contralateral breast cancer (CBC), and secondary outcomes included breast cancer-specific survival (BCSS).

Results: A total of five studies with 1769 UBC patients with germline pathogenic BRCA1/2 variants were enrolled in our meta-analysis. CRRM was correlated with a lower risk of CBC in UBC patients with germline pathogenic BRCA1/2 variants (summary RR = 0.07; 95%CI 0.03-0.13, I = 3%), a significantly increased OS (summary RR, 1.15; 95%CI 1.04-1.26, I = 26%) and a significantly increased BCSS (summary RR, 1.18; 95%CI 1.07-1.31, I = 64%) compared with surveillance. CPI also decreased the risk of CBC (RR 0.02; 95%CI 0.05-0.88) but did not significantly improve OS (RR 0.97; 95%CI 0.90-1.05) and BCSS (RR 0.97; 95%CI 0.90-1.05) compared with surveillance.

Conclusions: CRRM reduces CBC risk and increases OS and BCSS in UBC patients with germline pathogenic BRCA1/2 variants, and could be offered as a risk-reducing local treatment. For those who oppose CRRM, CPI could be offered for CBC-risk reduction, while its survival benefit is still uncertain.
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http://dx.doi.org/10.1186/s12935-021-02194-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466340PMC
September 2021

Epidemiological characteristics and clinical manifestations of pediatric patients with COVID-19 in China: A multicenter retrospective study.

Pediatr Investig 2021 Aug 12:e12282. Epub 2021 Aug 12.

Chinese University of Hong Kong Shatin Hong Kong China.

Importance: The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians.

Objective: This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China.

Methods: This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed.

Results: In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died.

Interpretation: Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.
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http://dx.doi.org/10.1002/ped4.12282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441896PMC
August 2021

Cationic peptide-based salt-responsive antibacterial hydrogel dressings for wound healing.

Int J Biol Macromol 2021 Nov 10;190:754-762. Epub 2021 Sep 10.

College of Materials Science& Engineering, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address:

Development of biological dressings has received widespread attentions due to their good breathability, biocompatibility, wettability, and the ability to absorb wound exudate without sticking to the wound. However, current proposed antibacterial hydrogels are limited antibacterial ability, short service life and insufficient biocompatibility, which are still challenging to address intricate practical applications. Here we develop a cationic peptide-based, salt-responsive hydrogel dressing with triple functions of antifouling, bactericidal, and bacterial release by combining ε-poly-l-lysine, poly(ethylene glycol) diglycidyl ether, and poly(DVBAPS-co-GMA) via a one-pot method. These designed hydrogels enabled to further quaternize to enhance antibacterial property due to the presence of amine residues. The resultant hydrogels present good antibacterial activity (>90%), biocompatibility, cell proliferation efficacy (~400%) and adhesiveness. Through in vivo and in vitro antibacterial capability tests, it is also found that hydrogels have good antifouling and sterilization capabilities, and the sterilization rate could reach up to ~96%. In addition, ~94% of the attached bacterial can be released after saline/water switching for several cycles. Taken together, the designed multiple antibacterial dressing prolongs the lifespan relying on reversible salt-responsive release and meet special requirements for wound healing. This work not only provides a platform to highlight its promising potentials in wound management but also gives a custom strategy to biomedical applications.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.09.019DOI Listing
November 2021

Gadolinium chloride pre-treatment reduces the inflammatory response and preserves intestinal barrier function in a rat model of sepsis.

Exp Ther Med 2021 Oct 9;22(4):1143. Epub 2021 Aug 9.

Department of Pathophysiology, Shihezi University School of Medicine, The Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi, Xinjiang 832002, P.R. China.

The inflammatory response is closely associated with sepsis occurrence and progression. Damage to the function of the intestinal mucosal barrier is considered to be the ῾initiation factor᾿ for the development of multiple organ dysfunction syndrome, which is the most severe progression of sepsis. The aim of the present study was to investigate whether gadolinium chloride (GdCl) could alleviate the systemic inflammatory response and protect the function of the intestinal mucosal barrier in a rat model of sepsis. The mechanism underlying this protective effect was also explored. Sprague-Dawley rats were divided into four groups: Sham, sham + GdCl, cecal ligation and puncture (CLP; a model of sepsis) and CLP + GdCl. In each group, blood was collected from the abdominal aorta, and intestinal tissue was collected after 6, 12 and 24 h of successful modeling. Levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were determined using ELISA. Western blot analysis was used to determine levels of occludin, tight junction protein ZO-1 (ZO-1), myosin light chain kinase 3 (MLCK), NF-κB and caspase-3 in intestinal tissues. Hematoxylin-eosin staining was used to observe the degree of damage to intestinal tissue. The results indicated that in CLP sepsis model rats treated with GdCl, the release of systemic and intestinal pro-inflammatory factors was reduced and tissue damage was alleviated when compared with untreated CLP rats. Additionally, the expression of occludin and ZO-1 was increased, while that of NF-κB, MLCK, and caspase-3 was reduced in the CLP + GdCl rats compared with the CLP rats. GdCl may alleviate systemic and intestinal inflammatory responses and reduce the expression of MLCK through inhibition of the activation of NF-kB. The results of the present study also indicated that GdCl promoted the expression of occludin and ZO-1. GdCl was also demonstrated to reduce cell apoptosis through the inhibition of caspase-3 expression.
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http://dx.doi.org/10.3892/etm.2021.10577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393272PMC
October 2021

Impact of alanyl-tRNA synthetase editing deficiency in yeast.

Nucleic Acids Res 2021 Sep;49(17):9953-9964

Department of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD 20742, USA.

Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes that provide the ribosome with aminoacyl-tRNA substrates for protein synthesis. Mutations in aaRSs lead to various neurological disorders in humans. Many aaRSs utilize editing to prevent error propagation during translation. Editing defects in alanyl-tRNA synthetase (AlaRS) cause neurodegeneration and cardioproteinopathy in mice and are associated with microcephaly in human patients. The cellular impact of AlaRS editing deficiency in eukaryotes remains unclear. Here we use yeast as a model organism to systematically investigate the physiological role of AlaRS editing. Our RNA sequencing and quantitative proteomics results reveal that AlaRS editing defects surprisingly activate the general amino acid control pathway and attenuate the heatshock response. We have confirmed these results with reporter and growth assays. In addition, AlaRS editing defects downregulate carbon metabolism and attenuate protein synthesis. Supplying yeast cells with extra carbon source partially rescues the heat sensitivity caused by AlaRS editing deficiency. These findings are in stark contrast with the cellular effects caused by editing deficiency in other aaRSs. Our study therefore highlights the idiosyncratic role of AlaRS editing compared with other aaRSs and provides a model for the physiological impact caused by the lack of AlaRS editing.
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http://dx.doi.org/10.1093/nar/gkab766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464055PMC
September 2021

Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re-establishing autophagic flux via promoting leptin signalling in a 6-hydroxydopamine rat model of Parkinson's disease.

Clin Exp Pharmacol Physiol 2021 Sep 8. Epub 2021 Sep 8.

The First Affiliated Hospital, Institute of Neurology, Hengyang Medical School, University of South China, Hengyang, Hunan, China.

Previous studies reveal that hydrogen sulphide (H S) exerts neuroprotection against neurotoxin-induced Parkinson's disease (PD), but the underlying mechanism remains elusive. The present study was aimed to investigate whether H S inhibits neuronal apoptosis of substantia nigra with the involvement of autophagy via promoting leptin signalling in 6-hydroxydopamine (6-OHDA)-induced PD rats. In this study, neuronal apoptosis was analysed by TUNEL staining, the activity of caspase-3 was measured by Caspase-3 fluorometric assay kit, the expressions of Bax, Bcl-2, Beclin-1, LC3II, P62 and leptin were determined by Western blot analysis, and the numbers of autophagosomes and autolysosomes were assessed by transmission electron microscopy. Results showed that NaHS, a donor of exogenous H S, mitigates 6-OHDA-induced the increases in the numbers of TUNEL-positive cells, the activity of caspase-3 and the expression of Bax, and attenuates 6-OHDA-induced a decrease in the expression of Bcl-2 in substantia nigra of rats. In addition, 6-OHDA enhanced the expressions of Beclin-1, LC3-II and P62, increased the number of autophagosomes, and decreased the number of autolysosomes in the substantia nigra, which were also blocked by administration of NaHS. Furthermore, NaHS reversed 6-OHDA-induced the down-regulation of leptin expression in the substantia nigra, and treatment with leptin-OBR, a blocking antibody of leptin receptor, attenuated the inhibition of NaHS on neuronal apoptosis and the improvement of NaHS on the blocked autophagic flux in substantia nigra of 6-OHDA-treated rats. Taken together, these results demonstrated that H S attenuates neuronal apoptosis of substantia nigra depending on restoring impaired autophagic flux through up-regulating leptin signalling in PD.
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http://dx.doi.org/10.1111/1440-1681.13587DOI Listing
September 2021

MXene-GaN van der Waals metal-semiconductor junctions for high performance multiple quantum well photodetectors.

Light Sci Appl 2021 Sep 2;10(1):177. Epub 2021 Sep 2.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, 610054, Chengdu, China.

A MXene-GaN-MXene based multiple quantum well photodetector was prepared on patterned sapphire substrate by facile drop casting. The use of MXene electrodes improves the responsivity and reduces dark current, compared with traditional Metal-Semiconductor-Metal (MSM) photodetectors using Cr/Au electrodes. Dark current of the device using MXene-GaN van der Waals junctions is reduced by three orders of magnitude and its noise spectral intensity shows distinct improvement compared with the traditional Cr/Au-GaN-Cr/Au MSM photodetector. The improved device performance is attributed to low-defect MXene-GaN van der Waals interfaces. Thanks to the high quality MXene-GaN interfaces, it is possible to verify that the patterned substrate can locally improve both light extraction and photocurrent collection. The measured responsivity and specific detectivity reach as high as 64.6 A/W and 1.93 × 10 Jones, respectively, making it a potential candidate for underwater optical detection and communication. The simple fabrication of MXene-GaN-MXene photodetectors spearheaded the way to high performance photodetection by combining the advantages of emerging 2D MXene materials with the conventional III-V materials.
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http://dx.doi.org/10.1038/s41377-021-00619-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410839PMC
September 2021

Chemical oxygen demand and nitrogen transformation in a large pilot-scale plant with a combined submerged anaerobic membrane bioreactor and one-stage partial nitritation-anammox for treating mainstream wastewater at 25 °C.

Bioresour Technol 2021 Dec 26;341:125840. Epub 2021 Aug 26.

Graduate School of Environmental Studies, Tohoku University, 6-6-06 Aza-Aoba, Aramaki, Aoba Ward, Sendai, Miyagi 980-8579, Japan; Laboratory of Environmental Protection Engineering, Department of Civil and Environmental Engineering, Graduate School of Engineering, Tohoku University, 6-6-06 Aza-Aoba, Aramaki, Aoba Ward, Sendai, Miyagi 980-8579, Japan. Electronic address:

A novel municipal wastewater treatment process towards energy neutrality and reduced carbon emissions was established by combining a submerged anaerobic membrane bioreactor (SAnMBR) with a one-stage partial nitritation-anammox (PN/A), and was demonstrated at pilot-scale at 25 °C. The overall COD and BOD removal efficiencies were 95.1% and 96.4%, respectively, with 20.3 mg L COD and 5.2 mg L BOD remaining in the final effluent. The total nitrogen (TN) removal efficiency was 81.7%, resulting 7.3 mg L TN was discharged from the system. The biogas yield was 0.222 NL g COD with a methane content range of 78-81%. Approximately 90% of influent COD was removed in the SAnMBR, and 70% of influent nitrogen was removed in the PN/A. The denitrification which occurred in the PN/A enhanced overall COD and nitrogen removal. The successful operation of this pilot-scale plant indicates the SAnMBR-PN/A process is suitable for treating real municipal wastewater.
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http://dx.doi.org/10.1016/j.biortech.2021.125840DOI Listing
December 2021

Physiological characteristics and miRNA sequencing of two root zones with contrasting ammonium assimilation patterns in Populus.

Genes Genomics 2021 Aug 29. Epub 2021 Aug 29.

State Key Laboratory of Tree Genetics and Breeding, Key Laboratory of Silviculture of the National Forestry and Grassland Administration, Research Institute of Forestry, Chinese Academy of Forestry, Beijing, 100091, China.

Background: The net ammonium fluxes differ among the different root zones of Populus, but the physiological and microRNA regulatory mechanisms are unclear.

Objective: To elucidate the physiological and miRNA regulatory mechanisms, we investigated the two root zones displaying significant differences in net NH effluxes of P. × canescens.

Methods: Populus plantlets were cultivated with 500 μM NHCl for 10 days. Six plants were randomly selected to determine the net NH fluxes using a noninvasive microtest technique. High-throughput sequencing were used to determine the dynamic expression profile of miRNA among the different root zones of Populus.

Results: Net NH efflux in zone I (from 0 to 40 mm from the root apex) was - 19.64 pmol cm s and in zone II (from 40 to 80 mm) it was - 43.96 pmol cm s. The expression of eleven miRNAs was significantly upregulated, whereas fifteen miRNAs were downregulated. Moreover, eighty-eight target genes of the significantly differentially expressed miRNAs were identified in root zone II compared with zone I. Particularly, ptc-miR171a/b/e and their target, SCL6, were found to be important for the difference in net NH effluxes in the two root zones. Moreover, the expression of the target of ptc-miR169d, NFYA3 was upregulated in root zone II compared with root zone I, contributing to increased NH efflux and decreased NH assimilation in root zone II.

Conclusion: These results indicate that miRNAs regulate the expression levels of their target genes and thus play key roles in net NH fluxes and NH assimilation in different poplar root zones.
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http://dx.doi.org/10.1007/s13258-021-01156-2DOI Listing
August 2021

Pregnancy outcomes in women affected by fetal alpha-thalassemia: a case control study.

Sci Rep 2021 08 27;11(1):17305. Epub 2021 Aug 27.

Department of Maternity-Child Health and Family Planning Services, Affiliated Nanning Maternal and Child Health Hospital of Guangxi Medical University, No. 20 Liwan Road, Qingxiu District, Nanning City, 530022, Guangxi Province, China.

To evaluate the possible associations between fetal α-thalassemia and risk of adverse pregnancy outcomes using a provincial woman-child health service information database in China. This was a case control study (N = 438,747) in which we compared all singleton pregnancies of women with or without the α-thalassemia trait from May 2016 to May 2020, and where women with the trait were further allocated to a normal fetal group, a group of fetuses with the α-thalassemia trait, and a fetal group with hemoglobin H (HbH) disease according to the results of fetal DNA analysis. With thalassemic women whose fetuses were normal as the reference, fetuses in the HbH disease group showed a higher increase in the odds of Apgar scores being < 7 at 1 min (adjusted odds ratio [aOR], 2.79; 1.03-7.59) and 5 min (aOR, 4.56; 1.07-19.40). With non-thalassemic women as the reference, these trends were more obvious (aOR, 4.83; 2.55-9.16; aOR, 6.24; 2.75-14.18, respectively); whereas the normal fetal group was more likely to be diagnosed with postpartum hemorrhage (aOR, 1.66; 1.10-2.50). In addition, fetal HbH disease and gestational age were two independent factors influencing low Apgar scores, and their combination reflected medium accuracy in Apgar predictions.
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http://dx.doi.org/10.1038/s41598-021-95998-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397743PMC
August 2021

Emerging Topochemical Strategies for Designing Two-Dimensional Energy Materials.

Micromachines (Basel) 2021 Jul 23;12(8). Epub 2021 Jul 23.

Yangtze Delta Region Institute (Huzhou), University of Electronic Science and Technology of China, Huzhou 313001, China.

The unique properties of two-dimensional (2D) materials make them increasingly attractive in various fields, especially for energy harvesting, conversion, or storage. Simultaneously, numerous synthetic methods have been rapidly developed. Recently, topochemical strategies were demonstrated, and they show tremendous promising potential for synthesizing 2D materials due to their simplicity, scalability, and high efficiency. Considering the suitability of material structures and their synthesis methods, as well as the relationship between material properties and applications, it is necessary for researchers to comprehensively review and determine the prospects of 2D materials based on topological chemical synthesis methods and their related applications. Therefore, in this review, we systematically summarize and analyze the representative topochemical strategies for synthesizing 2D materials, including salt-templating methods for non-layered 2D materials, molten Lewis acid etching strategy for novel MXenes, and the chalcogen vapors etching and substituting strategy for phase-controlled 2D materials and so on, with the application of these 2D materials in energy-related fields including batteries, supercapacitors, and electrocatalysis. At the end of the paper, the corresponding perspective was also illustrated, and we expect that this could provide a reference for the future research in the field.
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http://dx.doi.org/10.3390/mi12080867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398671PMC
July 2021

Elevated serum triglyceride levels at first prenatal visit is associated with the development of gestational diabetes mellitus.

Diabetes Metab Res Rev 2021 Aug 18:e3491. Epub 2021 Aug 18.

Department of Clinical Nutrition, Huadong Hospital, Fudan University, Shanghai, China.

Aims: While several studies have indicated that maternal serum lipid profiles are associated with the development of gestational diabetes mellitus (GDM), the results have been inconsistent. This study aimed to explore the relationship between maternal lipids profiles at first prenatal visit and GDM and determine the optimal cut-off values of possible trimester-specific variables in predicting GDM.

Materials And Methods: Clinical data of women with singleton pregnancies who delivered in Xinhua Hospital between January 2016 and January 2017 were collected from electronic databases. Multivariate logistic regression was used to determine the potential risk factors of GDM (specific to the trimester at first prenatal visit), including age, body mass index (BMI), and serum lipid profile and fasting plasma glucose (FPG) levels. The receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of significant variables.

Results: Among the 2191 pregnant women included, 315 (14.38%) were diagnosed with GDM. Of these, 880 (40.16%) had their first prenatal visit before 14 gestational weeks. Univariate and multivariate analyses showed that both FPG and triglyceride (TG) levels in the first and second trimesters were associated with a high risk of GDM (p < 0.05). The ROC curve showed that serum TG levels >1.235 mmol/L and >1.525 mmol/L in the first and second trimesters, respectively, were significantly associated with the development of GDM (p < 0.05).

Conclusions: TG levels at first prenatal visit is associated with GDM risk. Different TG cut-off values should be applied in the different trimesters of pregnancy for GDM screening.
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http://dx.doi.org/10.1002/dmrr.3491DOI Listing
August 2021

Immunogenicity of inactivated COVID-19 vaccines at different vaccination intervals.

Hum Vaccin Immunother 2021 10 4;17(10):3310-3313. Epub 2021 Aug 4.

Beijing Center for Disease Prevention and Control, Beijing Center for Preventive Medicine Research, Beijing, China.

To evaluate the immunogenicity of inactivated COVID-19 vaccines administered at different intervals. Subjects who had received two doses of inactivated COVID-19 vaccines at an interval of 21 days or 1-7 months were selected to collect 5 ml of venous blood after the second dose for the detection of specific IgG antibody against SARS-CoV-2 using the chemiluminescent immunoassay. Blood samples were collected from 348 and 174 individuals vaccinated at an interval of 21 days or 1-7 months, respectively. Seropositive rate 2 weeks after two doses of vaccination at 21-days and 1-7 months interval was 95.7% and 97.1%, respectively, with no statistically significant difference. The post-vaccination antibody level was 23.7 with 21-days interval, higher than 14.2 with 1-7 months interval. Among the individuals vaccinated with two doses more than 1-month apart, seropositive rate was 98.5%, 90.0%, 91.7%, and 100% with 1- month (1-2 months, 2 months was not included, the same below), 2- month, 3- month, and 4-7 months of interval, respectively, and no statistically significant difference was observed. Appropriate extension of the vaccination interval between two doses of inactivated COVID-19 vaccine does not affect the production of specific IgG antibodies. The inactivated COVID-19 vaccine should be administered in accordance with the recommended vaccination schedule, and the vaccination interval can be extended appropriately under special circumstances.
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http://dx.doi.org/10.1080/21645515.2021.1945902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425430PMC
October 2021

The Distinct Performances of Ultrasound, Mammograms, and MRI in Detecting Breast Cancer in Patients With Germline Pathogenic Variants in Cancer Predisposition Genes.

Front Oncol 2021 13;11:710156. Epub 2021 Jul 13.

Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

A proportion of up to 10% of breast cancer resulted from hereditary germline pathogenic variants (GPVs) in cancer predisposition genes (CPGs), which been demonstrated distinct clinical features and imaging manifestations. However, the performance of imaging modalities for breast cancer surveillance in CPG mutation-carriers is still unclear, especially in Asian women. A population of 3002 breast cancer patients who received germline genetic testing of CPGs was enrolled from three hospitals in China. In total, 343 (11.6%) patients were found to harbor GPVs in CPGs, including 137 (4.6%) in and 135 (4.6%) in . We compared the performances of ultrasound, mammograms, MRI, and the combining strategies in CPG mutation carriers and non-carriers. As a result, the ultrasound showed a higher detection rate compared with mammograms regardless of the mutation status. However, its detection rate was lower in CPG mutation carriers than in non-carriers (93.2% 98.0%, =2.1×10), especially in the mutation carriers (90.9% 98.0%, =2.0×10). MRI presented the highest sensitivity (98.5%) and the lowest underestimation rate (14.5%) in CPG mutation carriers among ultrasound, mammograms, and their combination. Supplemental ultrasound or mammograms would add no significant value to MRI for detecting breast cancer (>0.05). In multivariate logistic regression analysis, the family or personal cancer history could not replace the mutation status as the impact factor for the false-negative result and underestimation. In summary, clinicians and radiologists should be aware of the atypical imaging presentation of breast cancer in patients with GPVs in CPGs.
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http://dx.doi.org/10.3389/fonc.2021.710156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316045PMC
July 2021

Evaluation of bio-energy recovery from the anaerobic treatment of municipal wastewater by a pilot-scale submerged anaerobic membrane bioreactor (AnMBR) at ambient temperature.

Bioresour Technol 2021 Nov 13;339:125551. Epub 2021 Jul 13.

Laboratory of Environmental Protection Engineering, Department of Civil and Environmental Engineering, Graduate School of Engineering, Tohoku University, 6-6-06 Aza-Aoba, Aramaki, Aoba Ward, Sendai, Miyagi 980-8579, Japan. Electronic address:

The potential of bio-energy recovery from real municipal wastewater was investigated using a one-stage pilot-scale submerged anaerobic membrane bioreactor (AnMBR) for a range of HRTs from 24 h to 6 h at ambient temperature around 25 °C. This pilot-scale AnMBR demonstrated a high COD removal efficiency of over 90% during an operation of 217 days for municipal wastewater treatment. The energy balance of the AnMBR was calculated from both theoretical and practical aspects. The theoretical net energy potential was calculated as 0.174 kWh/m by applying operational data to empirical equations, obtaining a bio-energy recovery efficiency of 69.4%. The practical net energy potential was estimated as -0.014 kWh/m using the powers of engines applied in a full-scale wastewater treatment plant. This is considerably lower than that of the conventional activated sludge process. These results are evidence of the potential of the AnMBR and feasibility in the treatment of municipal wastewater treatment.
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http://dx.doi.org/10.1016/j.biortech.2021.125551DOI Listing
November 2021

Facile Fabrication of Ultrasensitive Honeycomb Nano-Mesh Ultraviolet Photodetectors Based on Self-Assembled Plasmonic Architectures.

ACS Appl Mater Interfaces 2021 Aug 21;13(30):35972-35980. Epub 2021 Jul 21.

Institute of Fundamental and Frontier Sciences, University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, China.

The dilemma of harvesting fugacious photons by photoactive nanomaterials of limited absorption volume fundamentally hinders the photodetection at relatively lower light intensities. To address the insufficient light utilization efficiency, spatial light confinement becomes an effective and promising approach. High-performance ultraviolet (UV) photodetectors based on the self-assembled Au nanoparticle/ZnO honeycomb nano-mesh (Au NP/ZnO HN) are demonstrated through a facile solution-processed method on anodized aluminum oxide (AAO) membranes. The congregated geometry of the self-assembled ZnO HNs is well-defined by the AAO matrixes, which also effectively collects the transmitted light beams back to the photoactive layers. Benefiting from surface plasmon resonance, the enhanced absorption of the ZnO HNs is eventually obtained via the recursive light utilization between Au NPs and AAO matrixes as a function of AAO pore diameters (). With a systematic control of the photodetector configurations, an optimal performance is obtained with growth duration of the ZnO HNs for 40 min on the AAO substrates ( = 100 nm), and an excellent responsivity of 23.4 A/W is witnessed even under a relatively low light intensity of 0.4 mW/cm, providing a novel route to realize high-performance UV photodetection under low-power illumination.
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http://dx.doi.org/10.1021/acsami.1c08739DOI Listing
August 2021

Environmentally relevant perinatal exposure to DBP disturbs testicular development and puberty onset in male mice.

Toxicology 2021 07 16;459:152860. Epub 2021 Jul 16.

Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address:

Di-n-butyl phthalate (DBP) is considered as a potential modifier of puberty. However, different results indicate that DBP plays an accelerated, delayed, or neutral role in the initiation of puberty. Furthermore, whether the effect of DBP on puberty will disrupt the function of reproductive system in the adults is still ambiguous. Therefore, we aimed to investigate the effect of maternal exposure to DBP on the onset of puberty in male offspring mice and the subsequent changes in the development of reproductive system. Here, pregnant mice were treated with 0 (control), 50, 250, or 500 mg/kg/day DBP in 1 mL/kg corn oil administered daily by oral gavage from gestation day (GD) 12.5 to parturition. Compared with the control group, the 50 mg/kg/day DBP group accelerated puberty onset and testicular development were quite remarkable in male offspring mice during early puberty. Furthermore, in 22-day male offspring mice, 50 mg/kg/day DBP induced increased levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone in serum, and promoted the expression of steroidogenesis-related genes in the testes. Testicular Leydig cells (LCs) were isolated from the testes of 3-week-old mice and treated with 0 (control), 0.1, 1 mM monobutyl phthalate (MBP, the active metabolite of DBP) for 24 h. Consistent with the in vivo results, the expression of steroidogenesis-related genes and testosterone production were increased in LCs following exposure to 0.1 mM MBP. In adulthood, testes of the male offspring mice exposed to all doses of DBP exhibited adverse morphology compared with the control group. These results demonstrated that maternal exposure to 50 mg/kg/day DBP induced earlier puberty and precocious development of the testis, and eventually damaged the reproductive system in the later life.
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http://dx.doi.org/10.1016/j.tox.2021.152860DOI Listing
July 2021

Peptide 11R‑VIVIT promotes fracture healing in osteoporotic rats.

Int J Mol Med 2021 Aug 19;48(2). Epub 2021 Jul 19.

Department of Orthopedics, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China.

Osteoporotic fracture healing is a complex clinical issue. The present study was conducted to investigate the repair properties of 11R‑VIVIT on osteoporotic fractures and to examine the potential effects of 11R‑VIVIT on osteoporotic bone marrow‑derived mesenchymal stem cells (BMSCs), A rat model of osteoporotic femoral fracture was established, and the effects of the daily local injection of 11R‑VIVIT or saline on fracture repairing were evaluated by micro‑CT scans and H&E staining. Moreover, BMSCs from osteoporotic rats were treated with 11R‑VIVIT, and the osteogenic and adipogenic differentiation of BMSCs was evaluated. The results revealed that 11R‑VIVIT promoted bone formation and increased fracture healing. In addition, 11R‑VIVIT promoted the differentiation of osteoporotic BMSCs into osteoblasts rather than adipocytes. Furthermore, mechanistic analysis revealed that 11R‑VIVIT promoted autophagy by blocking the protein kinase B (AKT)/nuclear factor of activated T‑cells (NFATc1) signaling pathway. Consistently, the activation and inhibition of autophagy using rapamycin and LY294002 confirmed the regulatory effects of 11R‑VIVIT on autophagy. On the whole, the findings of the present study demonstrate that 11R‑VIVIT promotes fracture healing in osteoporotic rats and enhances the osteogenic differentiation of osteoporotic BMSCs by dysregulating the AKT/NFATc1 signaling pathway.
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http://dx.doi.org/10.3892/ijmm.2021.4995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262658PMC
August 2021

Comparison of Clinical Characteristics Among COVID-19 and Non-COVID-19 Pediatric Pneumonias: A Multicenter Cross-Sectional Study.

Front Cell Infect Microbiol 2021 1;11:663884. Epub 2021 Jul 1.

Department of Pediatrics, Yichang Central People's Hospital, Yichang, China.

Background: The pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias.

Methods: We conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test.

Results: A total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups.

Conclusion: Majority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.
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http://dx.doi.org/10.3389/fcimb.2021.663884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281119PMC
July 2021

Antimicrobial α-defensins as multi-target inhibitors against amyloid formation and microbial infection.

Chem Sci 2021 Jul 28;12(26):9124-9139. Epub 2021 May 28.

Department of Chemical, Biomolecular, and Corrosion Engineering, The University of Akron Ohio USA

Amyloid aggregation and microbial infection are considered as pathological risk factors for developing amyloid diseases, including Alzheimer's disease (AD), type II diabetes (T2D), Parkinson's disease (PD), and medullary thyroid carcinoma (MTC). Due to the multifactorial nature of amyloid diseases, single-target drugs and treatments have mostly failed to inhibit amyloid aggregation and microbial infection simultaneously, thus leading to marginal benefits for amyloid inhibition and medical treatments. Herein, we proposed and demonstrated a new "anti-amyloid and antimicrobial hypothesis" to discover two host-defense antimicrobial peptides of α-defensins containing β-rich structures (human neutrophil peptide of HNP-1 and rabbit neutrophil peptide of NP-3A), which have demonstrated multi-target, sequence-independent functions to (i) prevent the aggregation and misfolding of different amyloid proteins of amyloid-β (Aβ, associated with AD), human islet amyloid polypeptide (hIAPP, associated with T2D), and human calcitonin (hCT, associated with MTC) at sub-stoichiometric concentrations, (ii) reduce amyloid-induced cell toxicity, and (iii) retain their original antimicrobial activity upon the formation of complexes with amyloid peptides. Further structural analysis showed that the sequence-independent amyloid inhibition function of α-defensins mainly stems from their cross-interactions with amyloid proteins β-structure interactions. The discovery of antimicrobial peptides containing β-structures to inhibit both microbial infection and amyloid aggregation greatly expands the new therapeutic potential of antimicrobial peptides as multi-target amyloid inhibitors for better understanding pathological causes and treatments of amyloid diseases.
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http://dx.doi.org/10.1039/d1sc01133bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261786PMC
July 2021

Genetically encoded FRET fluorescent sensor designed for detecting MOF histone acetyltransferase activity in vitro and in living cells.

Anal Bioanal Chem 2021 Sep 16;413(21):5453-5461. Epub 2021 Jul 16.

Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China.

Acetylation of lysine in the histone H4 N-terminal is one of the most significant epigenetic modifications in cells. Aberrant changes involving lysine acetylation modification are commonly reported in multiple types of cancers. Currently, whether it is for in vivo or in vitro, there are limited approaches for the detection of H4 lysine acetylation levels. In particular, the main problems are the high cost and the cumbersome detection process, such as for radioactive C isotope detection. Therefore, there is an important need to develop a simple, fast, and low-cost means of detection. In this study, we reported the development of a gene-coding protein sensor. This protein sensor was designed based on the mechanism of fluorescence resonance energy transfer (FRET). The four kinds of sensors, varying from substrate and linker length, were evaluated, with ~20% increases in response efficiency. Next, sensors with different lysine mutation sites in the substrate sequence or mutation of key amino acids in the binding domain were also analyzed to determine site specificity. We found single-site lysine mutant could not cause a significant decrease in response efficiency. Furthermore, addition of MG149, a histone acetyltransferase inhibitor, resulted in a decrease in the ratio change value. Moreover, histone deacetylase1 HDAC1 was also found to reduce the ratio change values when added to reaction system. Finally, the optimized sensor was applied to living cells and established to provide a sensitive response with overexpression and knockdown of MOF (males absent on the first). These results indicated that the sensor can be used for screening chemical drugs regulating H4 N-terminal lysine acetylation level in vitro, as well as monitoring dynamic changes of lysine acetylation levels in living cells.
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http://dx.doi.org/10.1007/s00216-021-03528-9DOI Listing
September 2021

Neuronal activity-induced BRG1 phosphorylation regulates enhancer activation.

Cell Rep 2021 Jul;36(2):109357

Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Neuronal activity-induced enhancers drive gene activation. We demonstrate that BRG1, the core subunit of SWI/SNF-like BAF ATP-dependent chromatin remodeling complexes, regulates neuronal activity-induced enhancers. Upon stimulation, BRG1 is recruited to enhancers in an H3K27Ac-dependent manner. BRG1 regulates enhancer basal activities and inducibility by affecting cohesin binding, enhancer-promoter looping, RNA polymerase II recruitment, and enhancer RNA expression. We identify a serine phosphorylation site in BRG1 that is induced by neuronal stimulations and is sensitive to CaMKII inhibition. BRG1 phosphorylation affects its interaction with several transcription co-factors, including the NuRD repressor complex and cohesin, possibly modulating BRG1-mediated transcription outcomes. Using mice with knockin mutations, we show that non-phosphorylatable BRG1 fails to efficiently induce activity-dependent genes, whereas phosphomimic BRG1 increases enhancer activity and inducibility. These mutant mice display anxiety-like phenotypes and altered responses to stress. Therefore, we reveal a mechanism connecting neuronal signaling to enhancer activities through BRG1 phosphorylation.
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http://dx.doi.org/10.1016/j.celrep.2021.109357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315893PMC
July 2021
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