Publications by authors named "Han Wu"

494 Publications

Exosome-derived miR-let-7c promotes angiogenesis in multiple myeloma by polarizing M2 macrophages in the bone marrow microenvironment.

Leuk Res 2021 Mar 31;105:106566. Epub 2021 Mar 31.

School of Basic Medical Sciences, Zhengzhou University, No. 100 Ke Xue Avenue, Zhengzhou, 450000, China; Henan Key Laboratory of Tumor Pathology, Zhengzhou University, No. 40 Da Xue Avenue, Zhengzhou, 450000, China; Department of Pathology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian She Dong Avenue, Zhengzhou, 450000, China. Electronic address:

Angiogenesis is an integral part of the multiple myeloma (MM) microenvironment, and affects tumorigenesis, progression, invasion, and metastasis. Exosomes are essential for cell-cell communication and help in regulating the bone marrow microenvironment. Herein, we investigated macrophage polarization and angiogenesis in MM in vitro via exosome-derived miR-let-7c. We observed that exosomal miR-let-7c secreted by mesenchymal stem cells promoted M2 macrophage polarization, thereby enhancing angiogenesis in the bone marrow microenvironment. Suppressing miR-let-7c expression significantly inhibited vascular endothelial cell function in myeloma. Thus, exosomal miR-let-7c may be a reliable biomarker for early prediction of tumor progression and a promising therapeutic target for MM.
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http://dx.doi.org/10.1016/j.leukres.2021.106566DOI Listing
March 2021

In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers.

Genome Med 2021 Apr 12;13(1):57. Epub 2021 Apr 12.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

Background: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD.

Methods: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors.

Results: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan.

Conclusions: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.
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http://dx.doi.org/10.1186/s13073-021-00876-0DOI Listing
April 2021

In-situ responses of phytoplankton to graphene photocatalysis in the eutrophic lake Xingyun, southwestern China.

Chemosphere 2021 Apr 5;278:130489. Epub 2021 Apr 5.

Jiangsu Shuangliang Graphene Photocatalytic Technology Co. LTD., Jiangyin, 214444, China.

Graphene photocatalysis is receiving increased attention for its potential to be used as a novel green technology for mitigating harmful algae in highly eutrophic waters. However, graphene is seldom applied to in situ aquatic ecosystems for environmental applications. Here, the impacts of graphene photocatalysis on phytoplankton and environmental conditions were evaluated through an in situ macrocosm experiment in the eutrophic Lake Xingyun, southwestern China. The graphene photocatalysis treated area had significantly reduced conductivity, total nitrogen (TN), total phosphorus (TP) and dissolved phosphorus concentrations, as well as increased dissolved oxygen (DO) concentrations. The abundances of all species of the genus Microcystis were significantly reduced in the graphene photocatalysis-treated area; in contrast, the abundances of all species of the diazotrophic genera, including Anabaena and Aphanizomenon, greatly increased after treatment with graphene photocatalysis. Eukaryotic algae, especially Chlorophyta, Euglenophyta and Pyrrophyta, as well as Cryptophyta, had significantly higher abundances in the graphene photocatalysis-treated area, whereas most of the eutrophic diatom species had lower abundances in the treated area. These observed differences in eukaryotic algae between the two groups might be related to their sensitivity to graphene photocatalysis and their tolerance of nutrients. Generally, graphene photocatalysis can make a great contribution to the improvement of eutrophic water, as evidenced by the reduction in cyanobacteria abundance and phosphorus concentration, as well as the increase in species richness and the dissolved oxygen concentration in the treated area. However, the mechanisms underlying these differences in phytoplankton community structure and environmental conditions require further study.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130489DOI Listing
April 2021

Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior.

Nano Lett 2021 Apr 8. Epub 2021 Apr 8.

Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.

The genetic heterogeneities in cancer cells pose challenges to achieving precise drug treatment in a widely applicable manner. Most single-cell gene analysis methods rely on cell lysis for gene extraction and identification, showing limited capacity to provide the correlation of genetic properties and real-time cellular behaviors. Here, we report a single living cell analysis nanoplatform that enables interrogating gene properties and drug resistance in millions of single cells. We designed a Domino-probe to identify intracellular target RNAs while releasing 10-fold amplified fluorescence signals. An on-chip addressable microwell-nanopore array was developed for enhanced electro-delivery of the Domino-probe and in situ observation of cell behaviors. The proof-of-concept of the system was validated in primary lung cancer cell samples, revealing the positive-correlation of the ratio of EGFR mutant cells with their drug susceptibilities. This platform provides a high-throughput yet precise tool for exploring the relationship between intracellular genes and cell behaviors at the single-cell level.
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http://dx.doi.org/10.1021/acs.nanolett.1c00199DOI Listing
April 2021

Cyr61 promotes Schwann cell proliferation and migration via αvβ3 integrin.

BMC Mol Cell Biol 2021 Apr 7;22(1):21. Epub 2021 Apr 7.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Nantong University, Nantong, 226001, People's Republic of China.

Background: Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs.

Results: We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs.

Conclusions: In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC's function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.
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http://dx.doi.org/10.1186/s12860-021-00360-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028786PMC
April 2021

Mumps Orchitis: Clinical Aspects and Mechanisms.

Front Immunol 2021 18;12:582946. Epub 2021 Mar 18.

Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

The causative agent of mumps is a single-stranded, non-segmented, negative sense RNA virus belonging to the family. Besides the classic symptom of painfully swollen parotid salivary glands (parotitis) in mumps virus (MuV)-infected men, orchitis is the most common form of extra-salivary gland inflammation. Mumps orchitis frequently occurs in young adult men, and leads to pain and swelling of the testis. The administration of MuV vaccines in children has been proven highly effective in reducing the incidence of mumps. However, a recent global outbreak of mumps and the high rate of orchitis have recently been considered as threats to male fertility. The pathogenesis of mumps orchitis remains largely unclear due to lack of systematic clinical data analysis and animal models studies. The alarming increase in the incidence of mumps orchitis and the high risk of the male fertility have thus become a major health concern. Recent studies have revealed the mechanisms by which MuV-host cells interact and MuV infection induces inflammatory responses in testicular cells. In this mini-review, we highlight advances in our knowledge of the clinical aspects and possible mechanisms of mumps orchitis.
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http://dx.doi.org/10.3389/fimmu.2021.582946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013702PMC
March 2021

Ubiquitin-specific peptidase 39 promotes human glioma cells migration and invasion by facilitating ADAM9 mRNA maturation.

Mol Oncol 2021 Apr 2. Epub 2021 Apr 2.

Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Department of Immunology, School of Medicine, Shenzhen University, Shenzhen, 518055, China.

Glioma cells are characterized by high migration and invasion ability, however the molecular mechanism behind both processes still remain to be investigated. Several studies have demonstrated that ubiquitin specific protease 39 (USP39) plays an oncogenic role in various cancer types. Here, we investigated the expression and function of USP39 in patients with glioma. Oncomine database analysis revealed that high USP39 expression significantly correlated with poor overall survival in patients with glioma. Knockdown of USP39 in U251 and U87 cell lines significantly inhibited their migration and invasion in vitro. Gene expression profiling of glioma cells transduced with shRNA against USP39 revealed that ADAM9, a molecule previously related to tumor cell migration and invasion, was significantly downregulated. Further on, USP39 induced ADAM9 mRNA maturation and decreased the expression of integrin β1. Additionally, overexpression of ADAM9 inhibited the migration and invasion of glioma cells caused by USP39 depletion in vitro. USP39 promoted the invasion of glioma cells in vivo and reduced the overall survival of the mice. Altogether, our data shows that USP39 induces mRNA maturation and elevates the expression of ADAM9 in glioma cells and may thus be considered as potential target for treating patients with glioma.
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http://dx.doi.org/10.1002/1878-0261.12958DOI Listing
April 2021

RNA interference-mediated functional characterization of Group I chitin deacetylases in Holotrichia parallela Motschulsky.

Pestic Biochem Physiol 2021 Mar 8;173:104770. Epub 2021 Jan 8.

College of Plant Protection, Hebei Agricultural University, Baoding, China; Graduate School of Chinese Academy of Agricultural Sciences, Beijing, China. Electronic address:

Chitin deacetylases (CDAs, EC 3.5.1.41) catalyze the N-deacetylation of chitin to produce chitosan, which is essential for insect survival. Hence, CDAs are promising targets for the development of novel insecticidal drugs. In this study, the putative Group I chitin deacetylase genes HpCDA1, HpCDA2-1 and HpCDA2-2 were identified from Holotrichia parallela. Conserved domain database search identified a chitin-binding peritrophin-A domain (ChBD), a low-density lipoprotein receptor class A domain (LDLa), and a putative CDA-like catalytic domain. RT-qPCR analysis showed that the Group I HpCDAs were expressed in various tissues and predominant in the integument. The developmental expression patterns from the first-instar to third-instar larvae showed that HpCDAs were highly expressed on the first day and gradually declined after molting. The functional characteristics of the Group I CDAs in cuticle organization were examined using RNA interference (RNAi) and transmission electron microscopy (TEM) methods. Administration of double-stranded HpCDA (dsHpCDA) through larval injection could suppress the expression levels of HpCDA1 and HpCDA2, thus resulting in abnormal or lethal phenotypes. TEM analysis revealed that RNAi of either HpCDA1 or HpCDA2 remarkably affected the cuticle integrity, as evidenced by cuticle disorganization and chitin laminae disruption, suggesting the crucial role of CDAs in chitin modification. These experimental results demonstrate the important contribution of putative key genes involved in chitin metabolism, and provide a foundation for developing new strategies to control H. parallela.
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http://dx.doi.org/10.1016/j.pestbp.2021.104770DOI Listing
March 2021

Transcriptome Characterization and Expression Analysis of Chemosensory Genes in (Lepidoptera Crambidae), a Key Pest of Sugarcane.

Front Physiol 2021 5;12:636353. Epub 2021 Mar 5.

Guangdong Engineering Research Center for Pesticide and Fertilizer, Institute of Bioengineering, Guangdong Academy of Sciences, Guangzhou, China.

Insect chemoreception involves many families of genes, including odourant/pheromone binding proteins (), chemosensory proteins (), odourant receptors (), ionotropic receptors (), and sensory neuron membrane proteins (), which play irreplaceable roles in mediating insect behaviors such as host location, foraging, mating, oviposition, and avoidance of danger. However, little is known about the molecular mechanism of olfactory reception in , which is a major pest of sugarcane. A set of 72 candidate chemosensory genes, including 31 , 15 , 11 , 13 , and two , were identified in four transcriptomes from different tissues and genders of . Phylogenetic analysis was conducted on gene families and paralogs from other model insect species. Quantitative real-time PCR (qRT-PCR) showed that most of these chemosensory genes exhibited antennae-biased expression, but some had high expression in bodies. Most of the identified chemosensory genes were likely involved in chemoreception. This study provides a molecular foundation for the function of chemosensory proteins, and an opportunity for understanding how behaviors are mediated via chemical cues. This research might facilitate the discovery of novel strategies for pest management in agricultural ecosystems.
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http://dx.doi.org/10.3389/fphys.2021.636353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982955PMC
March 2021

Development and validation of a RNA binding protein-associated prognostic model for head and neck squamous cell carcinoma.

Aging (Albany NY) 2021 Mar 24;13(6):7975-7997. Epub 2021 Mar 24.

Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Evidence shows that defects in RNA-binding proteins (RBPs) are closely related to the occurrence and development of HNSCC. We obtained 502 tumors and 44 normal samples from the TCGA database, among which 190 differentially expressed RBPs were screened. Finally, a prognostic model containing nine RBPs ( and ) was produced. Further analysis showed that the overall survival rate in the high-risk group was lower than that in the low-risk group. The area under the ROC curve (AUC) in the training and testing groups was significant (3-year AUC, 0.735 vs 0.796; 5-year AUC, 0.821 vs 0.804). In addition, a comprehensive analysis of nine identified RBPs showed that most of them were related to the OS of HNSCC patients, and three of them ( and ) were differentially expressed in HNSCC and control tissues at the protein level. In addition, our data revealed that the identified RBPs are highly interconnected, with high frequency copy number changes in HNSCC samples. GSEA indicated that the abnormal biological processes related to RNA and the activation of some classical tumor signaling pathways were important driving forces for the development of HNSCC. Our results provide novel insights into the pathogenesis of HNSCC, among which nine RBP markers have potential application value in clinical decision-making and individualized treatment of HNSCC.
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http://dx.doi.org/10.18632/aging.202848DOI Listing
March 2021

ZMK1 Is Involved in K Uptake and Regulated by Protein Kinase ZmCIPK23 in .

Front Plant Sci 2021 3;12:517742. Epub 2021 Mar 3.

State Key Laboratory of Plant Physiology and Biochemistry (SKLPPB), College of Biological Sciences, China Agricultural University, Beijing, China.

Potassium (K) is one of essential mineral elements for plant growth and development. K channels, especially AKT1-like channels, play crucial roles in K uptake in plant roots. Maize is one of important crops; however, the K uptake mechanism in maize is little known. Here, we report the physiological functions of K channel ZMK1 in K uptake and homeostasis in maize. is a homolog of channel in maize, and mainly expressed in maize root. Yeast complementation experiments and electrophysiological characterization in oocytes indicated that ZMK1 could mediate K uptake. rescued the low-K-sensitive phenotype of mutant and enhanced K uptake in . Overexpression of also significantly increased K uptake activity in maize, but led to an oversensitive phenotype. Similar to AKT1 regulation, the protein kinase ZmCIPK23 interacted with ZMK1 and phosphorylated the cytosolic region of ZMK1, activating ZMK1-mediated K uptake. could also complement the low-K-sensitive phenotype of / mutant. These findings demonstrate that ZMK1 together with ZmCIPK23 plays important roles in K uptake and homeostasis in maize.
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http://dx.doi.org/10.3389/fpls.2021.517742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966722PMC
March 2021

Long-term oncologic outcomes of liver resection for hepatocellular carcinoma in adolescents and young adults: A multicenter study from A hepatitis B virus-endemic area.

Am J Surg 2021 Mar 10. Epub 2021 Mar 10.

Department of Hepatobiliary Pancreatic and Minimal Invasive Surgery, Zhejiang Provincial People's Hospital (People's Hospital of Hangzhou Medical College), Hangzhou, Zhejiang, China; School of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China; Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection.

Methods: From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR.

Results: Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR.

Conclusions: Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.
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http://dx.doi.org/10.1016/j.amjsurg.2021.03.009DOI Listing
March 2021

Clinical characteristics of endocrinopathies in Chinese patients with hereditary haemochromatosis.

Diabetes Metab Res Rev 2021 Mar 18. Epub 2021 Mar 18.

Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Aims: Hereditary haemochromatosis (HH) is a genetic disorder characterised by systemic iron overload and can lead to end-organ failure. However, very few data on this disorder, especially those on endocrine gland involvement in Chinese populations, are currently available. This study aimed to analyse the clinical features of endocrinopathies in patients with HH to generate concern among endocrinologists and improve the management of this disorder.

Materials And Methods: Chinese patients with HH-related endocrine dysfunction were enrolled at Peking Union Medical College Hospital from January 2010 to December 2018. All clinical data were analysed and summarised.

Results: A total of six patients were enrolled in this study, comprising five men and one woman; the average age was 36.5 ± 13.3 years. Mean serum ferritin concentration was 4508.8 ± 1074.3 ng/ml, and median transferrin saturation was 97.9% (96.6%-110.0%). Endocrine gland involvement associated with HH included the pancreas (5/6 patients), the adenohypophysis (5/6 patients) and the bones (1/6 patients); secondary endocrinopathies consisted of diabetes mellitus, hypogonadism, adrenal insufficiency and osteoporosis. Based on phlebotomy and iron chelation therapy, five patients were treated with exogenous insulin preparations, and three patients were treated with exogenous sex hormone replacement therapy. The clinical symptoms of five patients improved, although one patient died of hepatic encephalopathy and multiple organ failure.

Conclusions: HH can cause multiple endocrinopathies. The possibility of HH should be carefully considered in patients with endocrine gland dysfunctions and concomitant elevated serum ferritin levels. Endocrine gland function should also be assessed and followed up in patients with a clear diagnosis of HH.
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http://dx.doi.org/10.1002/dmrr.3448DOI Listing
March 2021

Morbidity and Mortality of Patients Who Underwent Minimally Invasive Esophagectomy After Neoadjuvant Chemoradiotherapy vs Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial.

JAMA Surg 2021 Mar 17. Epub 2021 Mar 17.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), The First Department of Thoracic Surgery, Peking University Cancer Hospital and Institute, Peking University School of Oncology, Beijing, China.

Importance: Safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) vs neoadjuvant chemotherapy (nCT) for treatment of locally advanced esophageal squamous cell carcinoma (ESCC) remain uncertain given lack of high-level clinical evidence.

Objective: To compare safety and long-term survival of nCRT followed by minimally invasive esophagectomy (MIE) with that of nCT followed by MIE for patients with locally advanced ESCC.

Design, Setting, And Participants: A prospective, multicenter, open-label, randomized clinical trial that compared safety and efficacy of nCRT vs nCT followed by MIE for patients with locally advanced ESCC. From January 1, 2017, to December 31, 2018, 264 patients with ESCC of clinical stages from cT3 to T4aN0 to 1M0 were enrolled. Analysis was performed on an intention-to-treat basis from January 1, 2017, to August 30, 2020.

Interventions: Eligible patients were randomized to the nCRT group (n = 132) or the nCT group (n = 132) by a computer-generated random system. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while 40 Gy of concurrent radiotherapy was added for the nCRT group. At about 6 weeks after neoadjuvant therapy, MIE via thoracoscopy and laparoscopy was performed for the patients in both groups.

Main Outcomes And Measures: The primary outcome was 3-year overall survival. Secondary outcomes included postoperative complications, mortality, postoperative pathologic outcome, recurrence-free survival time, and quality of life.

Results: Among 264 patients (226 men [85.6%]; mean [SD] age, 61.4 [6.8] years), postoperative morbidity was 47.4% in the nCRT group (54 of 114) and 42.6% in the nCT group (46 of 108), with no significant difference between groups (difference, 4.8%; 95% CI, -8.2% to 17.5%; P = .48). Distribution of the severity of complications was similar between the 2 groups based on Clavien-Dindo classification. The 90-day perioperative mortality rate was 3.5% for the nCRT group (4 of 114) and 2.8% for the nCT group (3 of 108) (P = .94). The R0 resection rates were similar between groups (109 of 112 [97.3%] vs 100 of 104 [96.2%]; P = .92). However, patients in the nCRT group had a higher pathologic complete response (residual tumor, 0%) rate (40 of 112 [35.7%] vs 4 of 104 [3.8%]; P < .001) and a higher rate of negative lymph nodes (ypN0, 74 of 112 [66.1%] vs 48 of 104 [46.2%]; P = .03) than those in the nCT group. One-year overall survival using intention-to-treat analysis was 87.1% in the nCRT group (115 of 132) and 82.6% in the nCT group (109 of 132) (P = .30). Furthermore, deaths caused by tumor progression or recurrence were significantly less in the nCRT group than in the nCT group (9 of 132 [6.8%] vs 19 of 132 [14.4%]; P = .046); however, deaths from nontumor causes were similar (8 of 132 [6.1%] vs 4 of 132 [3.0%]; P = .24).

Conclusions And Relevance: Initial results of the trial showed that nCRT followed by MIE has similar safety to and better histopathologic outcome than nCT followed by MIE for treatment of locally advanced ESCC.

Trial Registration: ClinicalTrials.gov Identifier: NCT03001596.
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http://dx.doi.org/10.1001/jamasurg.2021.0133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970392PMC
March 2021

High-mobility group box-1 promotes vascular calcification in diabetic mice via endoplasmic reticulum stress.

J Cell Mol Med 2021 Mar 16. Epub 2021 Mar 16.

Department of Cardiology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Several studies reported the role of endoplasmic reticulum stress (ERS) in vascular calcification. High-mobility group box-1 (HMGB-1) plays a substantial role in diabetes and its complications. However, relatively little information is available regarding the association between HMGB-1 and calcification, and the underlying mechanism has still remained elusive. Therefore, in the present study, we attempted to indicate whether HMGB-1 could promote vascular calcification via ERS in diabetes. After induction of diabetes by Streptozotocin (STZ), mice were treated with glycyrrhizin (Gly) or 4-phenylbutyrate (4-PBA). Mineral deposition was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and calcium assay. In cell experiments, calcification of vascular smooth muscle cells (VSMCs) was performed with Alizarin Red staining, alkaline phosphatase (ALP) activity and RT-PCR. Expression and location of HMGB-1 in aortic tissue were detected by Western blotting, immunocytochemistry (ICC) and immunohistochemistry (IHC). Diabetic mice demonstrated increased HMGB-1 expression, ERS and vascular calcification. However, inhibition of HMGB-1 with Gly or inhibition of ERS with 4-PBA ameliorated the enhanced vascular calcification and ERS in diabetic mice. In vitro experiments unveiled that inhibition of HMGB-1 attenuated advanced glycation end products (AGEs)-induced ERS in VSMCs. In addition, AGEs promoted translocation and secretion of HMGB-1 in VSMCs, which was reversed by 4-PBA. Moreover, VSMCs exhibited increased mineralization and osteogenic gene expressions in response to HMGB-1 and AGEs. However, inhibition of ERS with 4-PBA partially, although noticeably, attenuated VSMC calcification induced by HMGB-1. Thus, diabetes induced translocation and secretion of HMGB-1 via ERS, which resulted in calcification in diabetic mice and in AGEs-treated VSMCs.
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http://dx.doi.org/10.1111/jcmm.16075DOI Listing
March 2021

Characterization of an Antiviral Component in Human Seminal Plasma.

Front Immunol 2021 19;12:580454. Epub 2021 Feb 19.

Institute of Basic Medical Sciences, School of Basic Medicine, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Numerous types of viruses have been found in human semen, which raises concerns about the sexual transmission of these viruses. The overall effect of semen on viral infection and transmission have yet to be fully investigated. In the present study, we aimed at the effect of seminal plasma (SP) on viral infection by focusing on the mumps viral (MuV) infection of HeLa cells. MuV efficiently infected HeLa cells . MuV infection was strongly inhibited by the pre-treatment of viruses with SP. SP inhibited MuV infection through the impairment of the virus's attachment to cells. The antiviral activity of SP was resistant to the treatment of SP with boiling water, Proteinase K, RNase A, and DNase I, suggesting that the antiviral factor would not be proteins and nucleic acids. PNGase or PLA2 treatments did not abrogate the antiviral effect of SP against MuV. Further, we showed that the prostatic fluid (PF) showed similar inhibition as SP, whereas the epididymal fluid and seminal vesicle extract did not inhibit MuV infection. Both SP and PF also inhibited MuV infection of other cell types, including another human cervical carcinoma cell line C33a, mouse primary epididymal epithelial cells, and Sertoli cell line 15P1. Moreover, this inhibitory effect was not specific to MuV, as the herpes simplex virus 1, dengue virus 2, and adenovirus 5 infections were also inhibited by SP and PF. Our findings suggest that SP contains a prostate-derived pan-antiviral factor that may limit the sexual transmission of various viruses.
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http://dx.doi.org/10.3389/fimmu.2021.580454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933687PMC
February 2021

Mapping the Worldwide Trends on Energy Poverty Research: A Bibliometric Analysis (1999-2019).

Int J Environ Res Public Health 2021 Feb 11;18(4). Epub 2021 Feb 11.

College of Public Administration, Huazhong University of Science and Technology, Wuhan 430074, China.

Energy poverty is one of the main challenges facing humanity in the 21st century. Research on energy poverty is becoming a common focus of scholars in many areas. Bibliometrics can help researchers dig deep into the information of specific research fields from a quantitative perspective. In this study, we collected 1018 research papers in the field of energy poverty published in the period 1999-2019 from the Web of Science databases and conducted a bibliometric analysis on them. Cleaning and screening of sample papers, matrix construction, and visualization were performed using Bibliometrix, VOSviewer, and HistCite, summarizing the internal and external characteristics of the papers. With regard to external characteristics, a total of 982 research institutions in 80 regions conducted research in this field. There is extensive cooperation between the countries, and the UK, the USA, Australia, and Italy play the most active role in the cooperation network. With regard to internal characteristics, we found the two most representative citation paths: one path starts from the concerns of energy-poor groups and stops at an ethical discussion on energy poverty; the second path is based on the existing technological path, continuously developing coping policies, evaluation methods, and a conceptual framework for dealing with energy poverty. Furthermore, through coupling analysis, we discovered four focuses of energy poverty research: improvement of definition, improvement of evaluation methods, effects of coping policy, and energy justice. Through a comprehensive analysis of existing papers, this paper reveals some limitations of previous studies and recommends some promising directions for future research on energy poverty.
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http://dx.doi.org/10.3390/ijerph18041764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918555PMC
February 2021

Tectorigenin alleviates intrahepatic cholestasis by inhibiting hepatic inflammation and bile accumulation via activation of PPARγ.

Br J Pharmacol 2021 Mar 4. Epub 2021 Mar 4.

Department of Endocrinology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China.

Background And Purpose: Increasing evidence suggests that human cholestasis is closely associated with the accumulation and activation of hepatic macrophages. Research indicates that activation of peroxisome proliferator-activated receptor-γ (PPARγ) exerts liver protective effects in cholestatic liver disease (CLD), particularly by ameliorating inflammation and fibrosis, thus limiting disease progression. However, the existing PPARγ agonists, such as troglitazone and rosiglitazone, have significant side effects that impede their clinical application in the treatment of CLD. In this study, we found that tectorigenin (TEC) alleviates intrahepatic cholestasis in mice by activating PPARγ.

Experimental Approach: Wild-type mice were intragastrically administered α-naphthylisothiocyanate (ANIT) or fed a diet containing 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) to simultaneously establish an experimental model of intrahepatic cholestasis and TEC intervention, followed by determination of intrahepatic cholestasis and the mechanisms involved. In addition, PPARγ-deficient mice were administered ANIT and/or TEC to determine whether TEC exerts its liver protective effect by activating PPARγ.

Key Results: We demonstrated that TEC intervention alleviated intrahepatic cholestasis by inhibiting the recruitment and activation of hepatic macrophages as well as by promoting the expression of bile transporters via activation of PPARγ. Furthermore, our results show that TEC increased bile salt export pump (BSEP) expression through enhanced PPARγ binding to the BSEP promoter. We also demonstrated that PPARγ deficiency blocked the hepatoprotective effect of TEC during cholestasis.

Conclusions And Implications: In conclusion, TEC reduced the recruitment and activation of hepatic macrophages, and enhanced the export of bile acids by activating PPARγ. Taken together, our results suggest that TEC is a candidate compound for cholestasis treatment.
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http://dx.doi.org/10.1111/bph.15429DOI Listing
March 2021

Evolution and roles of cytokinin genes in angiosperms 2: Do ancient CKXs play housekeeping roles while non-ancient CKXs play regulatory roles?

Hortic Res 2020 Mar 1;7(1):29. Epub 2020 Mar 1.

State Key Laboratory of Crop Genetics and Germplasm Enhancement and College of Horticulture, Nanjing Agricultural University, Nanjing, P. R. China.

Cytokinin oxidase/dehydrogenase (CKX) is a key enzyme responsible for the degradation of endogenous cytokinins. However, the origins and roles of CKX genes in angiosperm evolution remain unclear. Based on comprehensive bioinformatic and transgenic plant analyses, we demonstrate that the CKXs of land plants most likely originated from an ancient chlamydial endosymbiont during primary endosymbiosis. We refer to the CKXs retaining evolutionarily ancient characteristics as "ancient CKXs" and those that have expanded and functionally diverged in angiosperms as "non-ancient CKXs". We show that the expression of some non-ancient CKXs is rapidly inducible within 15 min upon the dehydration of Arabidopsis, while the ancient CKX (AtCKX7) is not drought responsive. Tobacco plants overexpressing a non-ancient CKX display improved oxidative and drought tolerance and root growth. Previous mutant studies have shown that non-ancient CKXs regulate organ development, particularly that of flowers. Furthermore, ancient CKXs preferentially degrade cis-zeatin (cZ)-type cytokinins, while non-ancient CKXs preferentially target N-(Δ-isopentenyl) adenines (iPs) and trans-zeatins (tZs). Based on the results of this work, an accompanying study (Wang et al. https://doi.org/10.1038/s41438-019-0211-x) and previous studies, we hypothesize that non-ancient CKXs and their preferred substrates of iP/tZ-type cytokinins regulate angiosperm organ development and environmental stress responses, while ancient CKXs and their preferred substrates of cZs play a housekeeping role, which echoes the conclusions and hypothesis described in the accompanying report (Wang, X. et al. Evolution and roles of cytokinin genes in angiosperms 1: Doancient IPTs play housekeeping while non-ancient IPTs play regulatory roles? Hortic Res 7, (2020). https://doi.org/10.1038/s41438-019-0211-x).
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http://dx.doi.org/10.1038/s41438-020-0246-zDOI Listing
March 2020

Volume reduction for ≥2 cm benign breast lesions after ultrasound-guided microwave ablation with a minimum 12-month follow-up.

Int J Hyperthermia 2021 ;38(1):341-348

Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China.

Objective: To prospectively evaluate the efficacy of microwave ablation (MWA) for benign breast lesions (BBLs) ≥2 cm and explore the possible factors associated with the volume reduction rate (VRR) of ablated lesions.

Materials And Methods: From November 2013 to December 2017, a total of 80 patients with 104 biopsy-proved BBLs larger than 2 cm in size underwent MWA. After the procedure, patients were followed up physical and imaging examination consisting of contrast-enhanced ultrasound (CEUS) and magnetic resonance imaging (MRI). Possible factors associated with 12-month VRR were assessed, including basic patient characteristics, index lesions and parameters of ablation technique.

Results: The mean tumor size was 2.6 ± 0.6 cm (ranging 2.0-6.3 cm). Of the 104 lesions, 70 were fibroadenomas, 27 adenosis and 7 fibrocystic changes. Post-procedure CEUS or contrast-enhanced MRI showed that all lesions were completely ablated. No immediate or delayed complications were observed. All patients were followed up for more than 12 months (median follow-up 12.5 months). After MWA, the ablated lesion volume decreased significantly by 12 months ( < 0.001), with a mean volume reduction of 80.2 ± 13.1%. Multiple linear regression analysis showed that location adjacent to areola ( = 7.5, 95%CI: 1.0-13.9,  = 0.025) and location adjacent to skin ( = -7.4, 95%CI: -12.7 to -13.9,  = 0.007) were independent factors respectively associated with the increased and decreased 12-month VRR.

Conclusion: For BBLs larger than 2 cm, US-guided MWA is a favorable treatment modality, with BBLs adjacent to the areola being associated with more significant 12-month VRR after MWA.
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http://dx.doi.org/10.1080/02656736.2020.1845401DOI Listing
January 2021

CRISPR/Cas9 mediated β-globin gene knockout in rabbits recapitulates human β-thalassemia.

J Biol Chem 2021 Feb 24:100464. Epub 2021 Feb 24.

Key Lab for Major Obstetric Diseases of Guangdong Province, Experimental Department of Institute of Gynecology and Obstetrics, the Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China. Electronic address:

β-thalassemia, autosomal recessive blood disorders that reduce the production of hemoglobin, are majorly caused by the point mutation of the HBB gene resulting in reduced or absent β-globin chains of the hemoglobin tetramer. Animal models recapitulating both the phenotype and genotype of human disease are valuable in the exploration of pathophysiology and for in vivo evaluation of novel therapeutic treatments. The docile temperament, short vital cycles and low cost of rabbits make them an attractive animal model. However, β-thalassemia rabbit models are currently unavailable. Here, using CRISPR/Cas9-mediated genome editing, we point mutated the rabbit β-globin gene HBB2 with high efficiency and generated a β-thalassemia rabbit model. Hematological and histological analyses demonstrated that the genotypic mosaic F0 displayed a mild phenotype of anemia, and the heterozygous F1 exhibited typical characteristics of β-thalassemia. Whole blood transcriptome analysis revealed that the gene expression was altered in HBB2-targeted when compared to WT rabbits. And the highly expressed genes in HBB2-targeted rabbits were enriched in lipid and iron metabolism, innate immunity and hematopoietic processes. In conclusion, using CRISPR-mediated HBB2 knockout, we have created a β-thalassemia rabbit model the accurately recapitulates the human disease phenotype. We believe this tool will be valuable in advancing the investigation of pathogenesis and novel therapeutic targets of β-thalassemia and associated complications.
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http://dx.doi.org/10.1016/j.jbc.2021.100464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024976PMC
February 2021

The complete plastid genome sequence of (H. Lév.) Loes, the most abundant medicinal holly in Mount Huangshan.

Mitochondrial DNA B Resour 2021 Feb 9;6(2):468-469. Epub 2021 Feb 9.

Co-Innovation Center for Sustainable Forestry in Southern China, College of Biology and the Environment, Nanjing Forestry University, Nanjing, China.

Holly ( L.) is a woody dioecious genus cultivated as pharmaceutical, ornamentals, and industrial materials. (H. Lév.) Loes is an endemic medicinal holly with a predominant distribution in Mount Huangshan, China. In the present work, the complete plastid genome of was sequenced by high-throughput sequencing technology. The newly-assembled plastid genome holds 37.6% of the overall GC content and a length of 157,857 bp, comprising a large single-copy (LSC, 87,255 bp), a small single-copy (SSC, 18,398 bp), and a pair of inverted repeat (IRs, 26,102 bp) regions. The plastid genome annotation suggested the presence of a total of 89 protein-encoding genes, 37 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The plastome-mediated phylogenetic topology revealed that clustered together with and in the same clade, and a strong relationship between clades and biogeography was found. These data contribute to the understanding of genetic diversity and conservation study of in Mount Huangshan.
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http://dx.doi.org/10.1080/23802359.2021.1872428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889211PMC
February 2021

Histone demethylase KDM4A overexpression improved the efficiency of corrected human tripronuclear zygote development.

Mol Hum Reprod 2021 Feb;27(3)

Department of Gynecology and Obstetrics, Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510150, China.

Human zygotes are difficult to obtain for research because of limited resources and ethical debates. Corrected human tripronuclear (ch3PN) zygotes obtained by removal of the extra pronucleus from abnormally fertilized tripronuclear (3PN) zygotes are considered an alternative resource for basic scientific research. In the present study, eight-cell and blastocyst formation efficiency were significantly lower in both 3PN and ch3PN embryos than in normal fertilized (2PN) embryos, while histone H3 lysine 9 trimethylation (H3K9me3) levels were much higher. It was speculated that the aberrant H3K9me3 level detected in ch3PN embryos may be related to low developmental competence. Microinjection of 1000 ng/µl lysine-specific demethylase 4A (KDM4A) mRNA effectively reduced the H3K9me3 level and significantly increased the developmental competence of ch3PN embryos. The quality of ch3PN zygotes improved as the grading criteria, cell number and pluripotent expression significantly increased in response to KDM4A mRNA injection. Developmental genes related to zygotic genome activation (ZGA) were also upregulated. These results indicate that KDM4A activates the transcription of the ZGA program by enhancing the expression of related genes, promoting epigenetic modifications and regulating the developmental potential of ch3PN embryos. The present study will facilitate future studies of ch3PN embryos and could provide additional options for infertile couples.
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http://dx.doi.org/10.1093/molehr/gaab012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939728PMC
February 2021

High throughput error correction in information reconciliation for semiconductor superlattice secure key distribution.

Sci Rep 2021 Feb 16;11(1):3909. Epub 2021 Feb 16.

Beijing Electronic Science and Technology Institute, Beijing, 100070, China.

Semiconductor superlattice secure key distribution (SSL-SKD) has been experimentally demonstrated to be a novel scheme to generate and agree on the identical key in unconditional security just by public channel. The error correction in the information reconciliation procedure is introduced to eliminate the inevitable differences of analog systems in SSL-SKD. Nevertheless, the error correction has been proved to be the performance bottleneck of information reconciliation for high computational complexity. Hence, it determines the final secure key throughput of SSL-SKD. In this paper, different frequently-used error correction codes, including BCH codes, LDPC codes, and Polar codes, are optimized separately to raise the performance, making them usable in practice. Firstly, we perform multi-threading to support multi-codeword decoding for BCH codes and Polar codes and updated value calculation for LDPC codes. Additionally, we construct lookup tables to reduce redundant calculations, such as logarithmic table and antilogarithmic table for finite field computation. Our experimental results reveal that our proposed optimization methods can significantly promote the efficiency of SSL-SKD, and three error correction codes can reach the throughput of Mbps and provide a minimum secure key rate of 99%.
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http://dx.doi.org/10.1038/s41598-021-82684-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886916PMC
February 2021

Circular suture of the uterine serosa and myometrium layer around placental attachment site for refractory postpartum hemorrhage.

J Obstet Gynaecol Res 2021 Feb 15. Epub 2021 Feb 15.

Department of Obstetrics and Gynecology, Jianhu Hospital Affiliated to Nantong University, Jiangsu, P. R. China.

Objective: The aim of the study was to analyze the clinical outcomes of circular suture at placental attachment site for refractory postpartum hemorrhage (PPH), which could block blood supply of the serosa and myometrium layer.

Methods: Eighty cases of refractory PPH were enrolled and retrospective analyzed in this study for further analysis from a consecutive single center database between 2010 and 2018. After undergoing circular suture of the uterine serosa and myometrium layer around placental attachment site, surgical and perioperative outcomes were recorded and analyzed.

Results: Among all the patients enrolled, 28 cases (35.0%) of refractory PPH were mainly caused by uterine inertia, 36 cases (45.0%) caused by ectopic placenta, and 2 cases (2.5%) caused by coagulation disorders. After circular suture of the uterine serosa and myometrium layer at placental attachment site, all the uterine active bleeding was controlled below 40 ml without recurrence. The perioperative results were similar between the vaginal and cesarean sections groups.

Conclusions: Circular suture of the uterine serosa and myometrium at the placental attachment site could control refractory PPH with few postoperative complications. Circular suture around placenta site could be applied in time to protect the endometrium even in primary hospital.
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http://dx.doi.org/10.1111/jog.14695DOI Listing
February 2021

Transcriptomic analysis of endometrial receptivity for a genomic diagnostics model of Chinese women.

Fertil Steril 2021 Feb 12. Epub 2021 Feb 12.

Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China; Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China. Electronic address:

Objective: To define the transcriptomic signature with respect to human endometrial receptivity in Chinese women by next-generation sequencing and to develop a more refined and customized bioinformatic predictive method for endometrial dating in Chinese women.

Design: Randomized.

Setting: A tertiary hospital-based reproductive medicine center.

Patient(s): Ninety healthy, fertile Chinese women.

Intervention(s): Human endometrial biopsies.

Main Outcome Measure(s): Gene expression of endometrial biopsies.

Result(s): Ninety endometrial samples from healthy Chinese women during their menstrual cycles-including prereceptive (luteinizing hormone [LH] + 3 days/LH + 5 days), receptive (LH + 7 days), and post-receptive (LH + 9 days) phases-were subjected to transcriptomic analysis using messenger RNA (mRNA)-enriched RNA-Seq. Feature genes were obtained and used to train the predictor for endometrial dating, with 63 samples for the training set and 27 samples for the validation set. Differentially expressed genes (DEGs) were identified by comparing samples from different phases of the menstrual cycle. Based on the transcriptomic feature genes, we constructed a bioinformatic predictor for endometrial dating. The accuracy on assessment of the endometrium on days LH + 3, LH + 5, LH + 7, and LH + 9 was 100% in the training set and 85.19% in the validation set.

Conclusion(s): Our transcriptomic profiling method can be used to monitor the window of implantation with regard to the endometrium in the Chinese population. This method potentially provides an evaluation of endometrial status, and can be used to predict a personal window of implantation by reproductive medicine clinicians.
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http://dx.doi.org/10.1016/j.fertnstert.2020.11.010DOI Listing
February 2021

Danthron ameliorates obesity and MAFLD through activating the interplay between PPARα/RXRα heterodimer and adiponectin receptor 2.

Biomed Pharmacother 2021 May 12;137:111344. Epub 2021 Feb 12.

Department of Endocrinology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China. Electronic address:

Obesity and associated metabolic associated fatty liver diseases (MAFLD) are strongly associated with dysfunction of glucose and lipid metabolism. AMPKα and PPARα are key regulators in the lipid and glucose homeostasis, indicating that novel agents to activate them are promising therapeutic approaches for metabolic syndrome. Noticeably, as a natural anthraquinone derivative extracted from rhubarb, danthron can activate AMPKα in vitro. However, the protective effect of danthron on obesity and associated MAFLD in vivo, as well as the underlying mechanism remains unknown. In this study, obesity and associated MAFLD was induced in C57BL/6J mice by high fat diet (HFD), which were subjected to evaluations on the parameters of systematic metabolism. Simultaneously, the molecular mechanism of danthron on lipid metabolism was investigated in 3T3-L1-derived adipocytes and HepG2 cells in vitro. In vivo, danthron significantly attenuated the obesity and MAFLD by enhancing hepatic fatty acid oxidation, decreasing lipid synthesis, and promoting mitochondrial homeostasis. Mechanistically, danthron significantly promoted combination of RXRα and PPARα, enhanced the binding of RXRα/PPARα heterodimer to the promoter of adiponectin receptor 2 (AdipoR2), by which activating the AMPKα and PPARα pathway. Moreover, PPARα and AdipoR2 can interplay in a loop style. Collectively, this study demonstrates that danthron can substantially ameliorate obesity and associated hepatic steatosis via AdipoR2-mediated dual PPARα/AMPKα activation, which suggests that danthron might be a novel therapeutic approach for inhibition of obesity and hepatic steatosis.
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http://dx.doi.org/10.1016/j.biopha.2021.111344DOI Listing
May 2021

MicroRNA-200a and microRNA-141 have a synergetic effect on the suppression of epithelial-mesenchymal transition in liver cancer by targeting STAT4.

Oncol Lett 2021 Feb 20;21(2):137. Epub 2020 Dec 20.

Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

MicroRNAs (miRNAs or miRs) are non-coding small RNAs that target specific messenger RNAs to inhibit protein translation. miR-200a and miR-141 function as tumor suppressors by targeting STAT4. These two miRNAs belong to the same family, and their expression is often decreased in various cancer types, but are located on different chromosomes of the human genome. The present study showed that the expression levels of miR-141 and miR-200a in serum and cells of liver cancer are significantly downregulated. The expression levels of miR-141 and miR-200a are closely associated with clinicopathological features of liver cancer, especially metastasis and invasion. It is first reported that STAT4 is the new common target gene of miR-141 and miR-200a. In the present study, miR-141 and miR-200a were confirmed to inhibit the expression of E-cadherin and vimentin synergistically during epithelial-mesenchymal transition to regulate the proliferation, migration and invasion of liver cancer cells by targeting STAT4. Simultaneous overexpression of miR-200a and miR-141 resulted in stronger effects compared with each miRNA alone. In addition, overexpression of STAT4 significantly reversed the tumor suppressive roles of miR-200a and miR-141 in liver cancer cells. These findings enrich the tumor suppressor mechanisms of the miR-200 family, and may also provide new experimental and theoretical basis for the use of miRNAs for early diagnosis, prognosis and thorough treatment of liver cancer.
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http://dx.doi.org/10.3892/ol.2020.12398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798046PMC
February 2021

Prevalence and trends in tobacco use among adolescents aged 13-15 years in 143 countries, 1999-2018: findings from the Global Youth Tobacco Surveys.

Lancet Child Adolesc Health 2021 04 2;5(4):245-255. Epub 2021 Feb 2.

Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Background: Tobacco use is a leading preventable cause of morbidity and mortality worldwide. Little is known about recent prevalence and trends in tobacco use among adolescents globally. We aimed to assess the recent global prevalence of tobacco use in young adolescents and the secular trends in prevalence between 1999 and 2018.

Methods: We used the most recent Global Youth Tobacco Surveys data on adolescents aged 13-15 years from 143 countries or territories that had done at least one survey between Jan 1, 2010, and Dec 31, 2018, to assess the recent prevalence of tobacco use; and data from 140 countries that had done two or more surveys between Jan 1, 1999, and Dec 31, 2018, to assess the trends in the prevalence of tobacco use.

Findings: 530 234 adolescents were included from the 143 countries that had done at least one survey between 2010 and 2018. 1 192 312 adolescents were included from the 140 countries that had done two or more surveys between 1999 and 2018. The most recent global prevalence of cigarette smoking was 11·3% (95% CI 10·3-12·3) in boys and 6·1% (5·6-6·6) in girls, based on cigarette smoking on at least 1 day during the past 30 days, 6·0% (5·5-6·6) and 2·6% (2·4-2·9) based on smoking on at least 3 days, and 4·2% (3·8-4·6) and 1·6% (1·4-1·8) based on smoking on at least 6 days. The most recent prevalence of the use of tobacco products other than cigarettes (eg, chewing tobacco, snuff, dip, cigars, cigarillos, pipe, electronic cigarettes) on at least 1 day during the past 30 days was 11·2% (9·9-12·6) in boys and 7·0% (6·4-7·7) in girls. The most recent prevalence of any tobacco use on at least 1 day during the past 30 days was 17·9% (16·1-19·6) in boys and 11·5% (10·5-12·4) in girls. The prevalence of cigarette smoking on at least 1 day during the past 30 days decreased between the first and last surveys in 80 (57·1%) of 140 countries, was unchanged in 39 countries (27·9%), and increased in 21 countries (15·0%). However, the prevalence of the use of tobacco products other than cigarettes was unchanged or increased in 81 (59·1%) of 137 countries.

Interpretation: The global prevalence of tobacco use among adolescents aged 13-15 years was substantial. Although the prevalence of cigarette smoking decreased over time in the majority of countries, the prevalence of the use of other tobacco products increased or did not change in the majority of countries during the past two decades. These findings re-emphasise the need to strengthen tobacco control efforts among young adolescents globally.

Funding: Shandong University.
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http://dx.doi.org/10.1016/S2352-4642(20)30390-4DOI Listing
April 2021

Characterization and Genomic Analysis of ɸSHP3, a New Transposable Bacteriophage Infecting Stenotrophomonas maltophilia.

J Virol 2021 Apr 12;95(9). Epub 2021 Apr 12.

College of Life Sciences, Wuhan University, Wuhan, China

This study describes a novel transposable bacteriophage, ɸSHP3, continuously released by strain c31. Morphological observation and genomic analysis revealed that ɸSHP3 is a siphovirus with a 37,611-bp genome that encodes 51 putative proteins. Genomic comparisons indicated that ɸSHP3 is a B3-like transposable phage. Its genome configuration is similar to that of phage B3, except for the DNA modification module. Similar to B3-like phages, the putative transposase B of ɸSHP3 is a homolog of the type two secretion component ExeA, which is proposed to serve as a potential virulence factor. Moreover, most proteins of ɸSHP3 have homologs in transposable phages, but only ɸSHP3 carries an RdgC-like protein encoded by gene 3, which exhibits exonuclease activity Two genes and their promoters coding for ɸSHP3 regulatory proteins were identified and appear to control the lytic-lysogenic switch. One of the proteins represses one promoter activity and confers immunity to ɸSHP3 superinfection The short regulatory region, in addition to the canonical bacterial promoter sequences, displays one LexA and two CpxR recognition sequences. This suggests that LexA and the CpxR/CpxA two-component system might be involved in the control of the ɸSHP3 genetic switch. is an emerging global pathogenic bacterium that displays genetic diversity in both environmental and clinical strains. Transposable phages have long been known to improve the genetic diversity of bacterial strains by transposition. More than a dozen phages of have been characterized. However, no transposable phage infecting has been reported to date. Characterization of the first transposable phage, ɸSHP3, from will contribute to our understanding of host-phage interactions and genetic diversity, especially the interchange of genetic materials among .
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http://dx.doi.org/10.1128/JVI.00019-21DOI Listing
April 2021