Publications by authors named "Jingjing Wang"

1,298 Publications

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The landscape in the gut microbiome of long-lived families reveals new insights on longevity and aging - relevant neural and immune function.

Gut Microbes 2022 Jan-Dec;14(1):2107288

Department of Gastroenterology, Key Laboratory of Holistic Integrative Enterology, The Second Affiliated Hospital of Nanjing Medical University, Jiangsu, China.

Human longevity has a strong familial and genetic component. Dynamic characteristics of the gut microbiome during aging associated with longevity, neural, and immune function remained unknown. Here, we aim to reveal the synergistic changes in gut microbiome associated with decline in neural and immune system with aging and further obtain insights into the establishment of microbiome homeostasis that can benefit human longevity. Based on 16S rRNA and metagenomics sequencing data for 32 longevity families including three generations, centenarians, elderly, and young groups, we found centenarians showed increased diversity of gut microbiota, severely damaged connection among bacteria, depleted in microbial-associated essential amino acid function, and increased abundance of anti-inflammatory bacteria in comparison to young and elderly groups. Some potential probiotic species, such as were enriched with aging, which might possibly support health maintenance. The level of Amyloid-β (Aβ) and brain-derived neurotrophic factor (BDNF) related to neural function showed increased and decreased with aging, respectively. The elevated level of inflammatory factors was observed in centenarians compared with young and elderly groups. The enriched in centenarians might promote longevity through up-regulating anti-inflammatory factor IL-10 expression to mediate the critical balance between health and disease. Impressively, the associated analysis for gut microbiota with the level of Aβ, BDNF, and inflammatory factors suggests could be a particularly beneficial bacteria in the improvement of impaired neural and immune function. Our results provide a rationale for targeting the gut microbiome in future clinical applications of aging-related diseases and extending life span.: : 16S ribosomal RNA; : Metagenome-assembled genomes; : Amplicon sequence variants; : Deoxyribonucleic acid; : False discovery rate: : Kyoto Encyclopedia of Genes and Genomes; : Principal coordinates analysis; : Polymerase chain reaction; : Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; : Amyloid-β (Aβ); : Brain-derived neurotrophic factor.
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http://dx.doi.org/10.1080/19490976.2022.2107288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361766PMC
August 2022

The Plasmodium falciparum Nuclear Protein Phosphatase NIF4 Is Required for Efficient Merozoite Invasion and Regulates Artemisinin Sensitivity.

mBio 2022 Aug 8:e0189722. Epub 2022 Aug 8.

Department of Immunology, College of Basic Medical Science, China Medical Universitygrid.254145.3, Shenyang, Liaoning, China.

Artemisinin resistance in Plasmodium falciparum has been associated with a mutation in the NLI-interacting factor-like phosphatase PfNIF4, in addition to the mutations in the Kelch13 protein as the major determinant. We found that PfNIF4 was predominantly expressed at the schizont stage and localized in the nuclei of the parasite. To elucidate the functions of PfNIF4 in P. falciparum, we performed PfNIF4 knockdown (KD) using the inducible ribozyme system. PfNIF4 KD attenuated merozoite invasion and affected gametocytogenesis. PfNIF4 KD parasites also showed significantly increased susceptibility to artemisinins. Transcriptomic and proteomic analysis revealed that PfNIF4 KD led to the downregulation of gene categories involved in invasion and artemisinin resistance (e.g., mitochondrial function, membrane, and Kelch13 interactome) at the trophozoite and/or schizont stage. Consistent with PfNIF4 being a protein phosphatase, PfNIF4 KD resulted in an overall upregulation of the phosphoproteome of infected erythrocytes. Quantitative phosphoproteomic profiling identified a set of PfNIF4-regulated phosphoproteins with functional similarity to FCP1 substrates, particularly proteins involved in chromatin organization and transcriptional regulation. Specifically, we observed increased phosphorylation of Ser2/5 of the tandem repeats in the C-terminal domain (CTD) of RNA polymerase II (RNAPII) upon PfNIF4 KD. Furthermore, using the TurboID-based proteomic approach, we identified that PfNIF4 interacted with the RNAPII components, AP2-domain transcription factors, and chromatin-modifiers and binders. These findings suggest that PfNIF4 may act as the RNAPII CTD phosphatase, regulating the expression of general and parasite-specific cellular pathways during the blood-stage development. Protein phosphorylation regulates a multitude of cellular processes. The eukaryotic FCP1 phosphatase acts as a CTD-phosphatase to critically balance the phosphorylation status of the CTD of the RNAPII, controlling the accurate execution of the transcription process. Here, we identified PfNIF4 as the FCP1-like phosphatase in P. falciparum. PfNIF4 KD specifically downregulated genes involved in merozoite invasion, resulting in the attenuation of this process. Consistent with the earlier finding of the association of PfNIF4 mutations with artemisinin resistance in Southeast Asian parasite populations, PfNIF4 KD significantly increased susceptibility to artemisinins. The regulation of these cellular processes in P. falciparum by PfNIF4 is likely realized through RNAPII-mediated transcription, because PfNIF4 was found to interact with RNAPII subunits and KD of PfNIF4 caused CTD hyperphosphorylation. Our results reveal the functions of the PfNIF4 phosphatase in controlling the transcription of invasion- and resistance-related genes in the malaria parasite.
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http://dx.doi.org/10.1128/mbio.01897-22DOI Listing
August 2022

Construction of a cross-species cell landscape at single-cell level.

Nucleic Acids Res 2022 Aug 5. Epub 2022 Aug 5.

Women's Hospital, and Institute of Genetics, Zhejiang University School of Medicine, Hangzhou 310058, China.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging.
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http://dx.doi.org/10.1093/nar/gkac633DOI Listing
August 2022

EML4-ALK fusion gene in non-small cell lung cancer.

Oncol Lett 2022 Aug 24;24(2):277. Epub 2022 Jun 24.

Department of Pathology, Qianjiang Central Hospital, Qianjiang, Hubei 433100, P.R. China.

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate that is a threat to human health. With the development of molecular targeted research, breakthroughs have been made on the molecular mechanism of lung cancer. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is one of the most important pathogenic driver genes of NSCLC discovered thus far. Four generations of targeted drugs for EML4-ALK have been developed, with patients benefiting significantly from these drugs. Therefore, EML4-ALK has become a research hotspot in NSCLC. The aim of the present study is to introduce the current research progress of EML4-ALK and its association with NSCLC.
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http://dx.doi.org/10.3892/ol.2022.13397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344266PMC
August 2022

Rap2A/p-ERK1/2 is involved in glioma proliferation and migration.

Curr Mol Med 2022 Aug 4. Epub 2022 Aug 4.

Department of Neurosurgery , Second Affiliated Hospital, University of South China, Hengyang, Hunan Province, China.

Background: Gliomas, the most common and malignant primary tumors, relate to the highest mortality rate of all central nervous system cancers. Previously, it has been demonstrated that Rap2A plays an essential role in tumor growth in human cancer cell lines. However, it remains largely unclear as to whether and how Rap2A is involved in the development of gliomas. In the current study, the role of Rap2A in glioma and its specific molecular mechanism are investigated by our group.

Methods: Expression of Rap2A was examined in glioma cell lines and human normal astrocyte cells using Western blot analysis. Using the CCK-8 cell proliferation assay, wound healing assay, and transwell migration assay, we elucidated the role of Rap2A in glioma cell proliferation and migration. Levels of E-cadherin, vimentin and phosphorylation of ERK1/2 were also determined using Western blot.

Results: The results suggested that Rap2A expression was remarkably decreased in glioma cells compared to the normal astrocyte cells. Overexpression of Rap2A prominently suppressed cell proliferation and migration as well as enhanced E-cadherin expression and reduced vimentin level in both U87 and U251 cells. In vivo assay proved that Rap2A overexpression slowed tumor growth of glioma. In particular, Rap2A overexpression remarkably inhibited ERK1/2 phosphorylation.

Conclusions: Therefore, our findings demonstrated that Rap2A functioned as a tumor suppressor via modulating the ERK1/2 signaling pathway, which may be a potential therapeutic candidate for treating glioma.
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http://dx.doi.org/10.2174/1566524022666220804152049DOI Listing
August 2022

Vitrification of bovine germinal vesicle oocytes significantly decreased the methylation level of their in vitro derived MII oocytes.

Reprod Fertil Dev 2022 Aug 5. Epub 2022 Aug 5.

Context: The vitrification of oocytes is important for the conservation of animals, and the effect of vitrification on methylation patterns of bovine oocytes remains unclear.

Aims: This article aims to investigate the effect of vitrification on the DNA methylation patterns on vitrified GV oocytes and their in vitro derived MII oocytes.

Methods: 5-MeC staining and single-cell whole genome bisulphite sequencing (SC-WGBS) were utilised to analyse fresh GV oocytes (F_GV group), MII oocytes (F_MII group), vitrified GV oocytes (V_GV group) and their in vitro derived MII oocytes (V_MII group).

Key Results: Results of both 5-MeC staining and SC-WGBS showed that no significant difference was found between the F_GV group and the V_GV group, while the methylation level of the V_MII group was significantly lower than that of the F_MII group. Moreover, supplementation of 2μM resveratrol (Res) in IVM medium significantly improved maturation and development ability of vitrified GV oocytes by restoring their DNA methylation levels.

Conclusion: In conclusion, vitrification of bovine GV oocytes significantly decreased the DNA methylation level of their in vitro derived MII oocytes, and 2μM Res improved their development ability by restoring DNA methylation level.

Implications: Our results provide an efficient approach to improve the maturation and fertilisation ability of vitrified GV oocytes.
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http://dx.doi.org/10.1071/RD22130DOI Listing
August 2022

Biodegradable MnO-Based Nanoparticles with Engineering Surface for Tumor Therapy: Simultaneous Fenton-Like Ion Delivery and Immune Activation.

ACS Nano 2022 Aug 4. Epub 2022 Aug 4.

Beijing Key Laboratory for Magnetoelectric Materials and Devices, School of Materials Science and Engineering, Peking University, Beijing 100871, China.

Immune checkpoint inhibitors have achieved significant clinical success but are still suffering from inadequate immune activation. It is worth noting that manganese as a nutritional inorganic trace element is closely associated with immune activation to fight against tumor growth and metastasis the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. Herein, we designed hollow mesoporous silica-coated MnO nanoparticles (NPs), followed by conjugation of tumor homing peptide iRGD (CRGDKGPD). The obtained NPs ([email protected] NPs) were applied to magnetic resonance imaging (MRI)-guided tumor immune-chemodynamic combination therapy, in which MnO NPs can be harnessed for cGAS-STING pathway-activated immunotherapy, Fenton-like reaction-induced reactive oxygen species upregulation, and T-weighted MRI. The rough surface and large cavities of the mSiO shell promote cellular uptake and MnO NPs delivery. Meanwhile, it was found that [email protected] NPs would dissociate under an acid environment, resulting in tumor specificity of MRI and exogenous Mn release. Our results revealed that these pH-responsive biodegradable [email protected] NPs synergized with α-PD-1 (PD-1 = programmed cell death-1) blocking antibody to highly elicit cytotoxic T lymphocyte infiltration and restrict melanoma progression and metastasis, which were envisioned as a promising candidate for tumor theranostics.
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http://dx.doi.org/10.1021/acsnano.2c00969DOI Listing
August 2022

The impact of inflammation-induced tumor plasticity during myeloid transformation.

Cancer Discov 2022 Aug 4. Epub 2022 Aug 4.

New York University Langone Medical Center, United States.

Clonal hematopoiesis (CH) is an aging-associated condition characterized by the clonal outgrowth of mutated pre-leukemic cells. Individuals with CH are at an increased risk of developing hematopoietic malignancies. Here, we describe a novel animal model carrying a recurrent TET2 missense mutation, frequently found in CH and leukemic patients. In a fashion similar to CH, animals show signs of disease late in life when they develop a wide range of myeloid neoplasms, including acute myeloid leukemia (AML). Using single cell transcriptomic profiling of the bone marrow, we show that disease progression in aged animals correlates with an enhanced inflammatory response and the emergence of an aberrant inflammatory monocytic cell population. The gene signature characteristic of this inflammatory population is associated to poor prognosis in AML patients. Our study illustrates an example of collaboration between a genetic lesion found in CH and inflammation, leading to transformation and the establishment of blood neoplasms.
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http://dx.doi.org/10.1158/2159-8290.CD-21-1146DOI Listing
August 2022

[Analysis of clinical characteristics of patients with different vaccines and underlying diseases infected with novel coronavirus Omicron variant].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2022 Jun;34(6):571-575

Department of Critical Care Medicine, Key Laboratory for Critical Care Medicine of the Ministry of Health, Emergency Medicine Research Institute, Tianjin First Center Hospital, Tianjin 300192, China. Corresponding author: Wang Yongqiang, Email:

Objective: To analyze the clinical characteristics of patients inoculated with different vaccines and underlying diseases, infected with the novel coronavirus Omicron variant.

Methods: The data of 430 patients infected with the novel coronavirus Omicron variant who were admitted to Tianjin First Center Hospital from January 21, 2022 to March 7, 2022 were collected. A total of 108 patients with Omicron variant infection with underlying diseases were selected and enrolled. The gender, age, body mass index (BMI), history of underlying diseases, vaccination status (vaccination times, vaccination type), clinical symptoms, laboratory test indicators, imaging data, hospitalization time, nucleic acid negative conversion time, re-positivity and antibody titer from the two groups of the patients were collected and analyzed.

Results: In the 108 patients, 93 cases received inactivated vaccine and 15 cases received adenovirus vaccine. There was no statistically significant difference between the two groups in terms of gender, age, BMI, disease types, whether completed the fully vaccinated, whether had prime boost and underlying diseases. Both groups had fever, dry cough, sore throat, runny nose and other clinical symptoms, but there were no statistical difference between the two groups. There were no statistically significant differences in laboratory blood routine tests, biochemical indexes, C-reactive protein (CRP) level and the results of chest computed tomography (CT) imaging between the two groups. There were no statistically significant differences in hospitalization days, nucleic acid negative conversion time, whether admission to intensive care unit (ICU), turn re-positive on nucleic acid tests and immunoglobulin M (IgM) antibody titer expression between the two groups, but immunoglobulin G (IgG) antibody titer in adenovirus group was higher than that in inactivated group (g/L: 229.67±26.13 vs. 194.33±61.56, P = 0.020). There were also no significant differences in laboratory examinations, hospitalization days, nucleic acid negative conversion time, turn re-positive on nucleic acid tests and Novel coronavirus antibody titers expression of the patients with booster shots between the inactivated vaccine group and the adenovirus vaccine group.

Conclusions: The protection of inactivated virus vaccine is equivalent to adenovirus vaccine in patients with underlying disease Omicron variant infection, and the titer of IgG antibody in patients with adenovirus vaccine is higher than that in patients with inactivated virus vaccine after one week of recovery.
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http://dx.doi.org/10.3760/cma.j.cn121430-20220415-00378DOI Listing
June 2022

Author Correction: Systematic identification of cell-fate regulatory programs using a single-cell atlas of mouse development.

Nat Genet 2022 Aug 3. Epub 2022 Aug 3.

Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

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http://dx.doi.org/10.1038/s41588-022-01176-yDOI Listing
August 2022

Organohalide Respiration with Diclofenac by .

Environ Sci Technol 2022 Aug 3. Epub 2022 Aug 3.

Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied Ecology, Chinese Academy of Sciences, Room 512 South Building, 72 Wenhua Road, Shenyang, Liaoning 110016, China.

Diclofenac (DCF) is a pharmaceutically active contaminant frequently found in aquatic ecosystems. The transformation pathways and microbiology involved in the biodegradation of DCF, particularly under anoxic conditions, remain poorly understood. Here, we demonstrated microbially mediated reductive dechlorination of DCF in anaerobic enrichment culture derived from contaminated river sediment. Over 90% of the initial 76.7 ± 3.6 μM DCF was dechlorinated at a maximum rate of 1.8 ± 0.3 μM day during a 160 days' incubation. Mass spectrometric analysis confirmed that 2-(2-((2-chlorophenyl)amino)phenyl)acetic acid (2-CPA) and 2-anilinophenylacetic acid (2-APA) were formed as the monochlorinated and nonchlorinated DCF transformation products, respectively. A survey of microbial composition and Sanger sequencing revealed the enrichment and dominance of a new population, designated as sp. strain DCF, in the DCF-dechlorinating community. Following the stoichiometric conversion of DCF to 2-CPA (76.0 ± 2.1 μM) and 2-APA (3.7 ± 0.8 μM), strain DCF cell densities increased by 24.4 ± 4.4-fold with a growth yield of 9.0 ± 0.1 × 10 cells per μmol chloride released. Our findings expand the metabolic capability in the genus and highlight the relevant roles of organohalide-respiring bacteria for the natural attenuation of halogenated contaminants of emerging concerns (e.g., DCF).
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http://dx.doi.org/10.1021/acs.est.1c08824DOI Listing
August 2022

Genotype-Phenotype Correlation Reanalysis in 83 Chinese Cases with Mutations.

Genet Res (Camb) 2022 19;2022:1473260. Epub 2022 Jul 19.

Department of Nephrology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: Both Lowe syndrome and Dent-2 disease are caused by variants in the gene. However, the reason why patients with similar gene mutations presented with different phenotypes remains uncertain.

Methods: Children with hemizygous pathogenic or likely pathogenic variants in were compiled from published and unpublished consecutive cases from China. Furthermore, a Chi-square test was employed to analyze the correlation of the location and types of mutations on the phenotype of children with Lowe syndrome or Dent-2 disease.

Results: Among the total 83 patients, 70.8% (34/48) cases of Lowe syndrome presented with truncating mutations, while only 31.4% (11/35) cases of Dent-2 disease presented with truncating mutation (Χ = 12.662; < 0.001). Meanwhile, the majority of mutations in Dent-2 disease are located in Exon 2-12 (21/35, 60.0%), while the majority of mutations in Lowe syndrome are located in Exon 13-23 (39/48, 81.3%; Χ = 14.922; < 0.001).

Conclusions: Truncating mutations of the gene were more common in patients with Lowe syndrome than in Dent-2 disease, while mutation is more likely located at exon 2-12 in Dent-2 disease than that in Lowe syndrome. The type and location of mutation are important indicators for the phenotypes in patients with mutation. This is a large cohort study analyzing the genotype-phenotype correlation in patients with Lowe syndrome and Dent-2 disease in China. Our data may improve the interpretation of new variants and genetic counseling. Furthermore, a large international study would be necessary to illustrate the genotype-phenotype correlation in patients with mutations.
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http://dx.doi.org/10.1155/2022/1473260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325342PMC
August 2022

The Spectrum of Vestibular Disorders Presenting With Acute Continuous Vertigo.

Front Neurosci 2022 13;16:933520. Epub 2022 Jul 13.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Objective: To explore the composition of vestibular disorders presenting with the acute vestibular syndrome (AVS).

Methods: We performed a case analysis of 209 AVS patients between January 2016 and December 2020. These patients were grouped into different disorder categories according to the relevant diagnostic criteria.

Results: We classified the 209 patients into 14 disorder categories, including 110 cases of vestibular neuritis, 30 of idiopathic sudden sensorineural hearing loss with vertigo, 17 of the first attack of continuous vertigo with migraine, 15 of Ramsay Hunt syndrome, 11 of acute labyrinthitis secondary to chronic otitis media, 8 of vestibular schwannoma, 6 of posterior circulation infarction and/or ischemia, 3 of cerebellar abscess secondary to chronic otitis media, 3 of AVS caused by trauma or surgery, 2 of AVS with down-beating nystagmus, 1 of multiple sclerosis of the medulla oblongata, 1 of epidermoid cyst of the posterior cranial fossa, 1 of a probable acute otolithic lesion, and 1 of AVS without measurable vestibular dysfunction.

Conclusion: When a group of disorders present with AVS, characteristic clinical manifestations and imaging help with an accurate diagnosis.
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http://dx.doi.org/10.3389/fnins.2022.933520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326068PMC
July 2022

CFO Gender, Corporate Risk-Taking, and Information Disclosure Violations.

Front Psychol 2022 13;13:902472. Epub 2022 Jul 13.

School of Finance, Jiangxi University of Finance and Economics, Nanchang, China.

The sex ratio at birth in China exhibits a major occurrence of "missing women" due to the high son preference in Chinese culture. Clearly, the large gender discrepancy in China can be explained not only by ethical, moral, or social fairness theories but also by the economic benefits of women's particular abilities, experiences, and talents. This article examines the influence of female chief financial officers (CFOs) on information disclosure violations in order to highlight women's positive contributions. Our data imply that having a female CFO can dramatically lower the number of companies that fail to disclose information. The results are strong after controlling endogeneity with propensity score matching, Heckman's two-stage self-selection model, and CFO change, as well as controlling the gender of the chairman and chief executive officer, utilizing different study periods, and using exogenous shock. We further examined the moderate effects of CFO power and external monitoring, and we found that CFO power magnifies the negative effect of female CFO on violations; the more the power, the more the negative effect of female CFO on violations. We also found that when the firm has effective external monitoring, there are fewer future infractions of information disclosure.
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http://dx.doi.org/10.3389/fpsyg.2022.902472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326254PMC
July 2022

Engineered disulfide reveals structural dynamics of locked SARS-CoV-2 spike.

PLoS Pathog 2022 Jul 29;18(7):e1010583. Epub 2022 Jul 29.

Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.

The spike (S) protein of SARS-CoV-2 has been observed in three distinct pre-fusion conformations: locked, closed and open. Of these, the function of the locked conformation remains poorly understood. Here we engineered a SARS-CoV-2 S protein construct "S-R/x3" to arrest SARS-CoV-2 spikes in the locked conformation by a disulfide bond. Using this construct we determined high-resolution structures confirming that the x3 disulfide bond has the ability to stabilize the otherwise transient locked conformations. Structural analyses reveal that wild-type SARS-CoV-2 spike can adopt two distinct locked-1 and locked-2 conformations. For the D614G spike, based on which all variants of concern were evolved, only the locked-2 conformation was observed. Analysis of the structures suggests that rigidified domain D in the locked conformations interacts with the hinge to domain C and thereby restrains RBD movement. Structural change in domain D correlates with spike conformational change. We propose that the locked-1 and locked-2 conformations of S are present in the acidic high-lipid cellular compartments during virus assembly and egress. In this model, release of the virion into the neutral pH extracellular space would favour transition to the closed or open conformations. The dynamics of this transition can be altered by mutations that modulate domain D structure, as is the case for the D614G mutation, leading to changes in viral fitness. The S-R/x3 construct provides a tool for the further structural and functional characterization of the locked conformations of S, as well as how sequence changes might alter S assembly and regulation of receptor binding domain dynamics.
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http://dx.doi.org/10.1371/journal.ppat.1010583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365160PMC
July 2022

Retrospective analysis of 2054 cases from 24 hospitals underwent ultrasonic consultation in a tertiary prenatal diagnosis center in Beijing, China.

J Clin Ultrasound 2022 Jul 29. Epub 2022 Jul 29.

Department of Ultrasound, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Objectives: To investigate the practices of prenatal ultrasound consultation in a region of the China and to describe the rate of concordance between the suspected anomaly and the final diagnosis of the referral examination.

Methods: Retrospective study with all cases referred from 24 hospitals (Beijing, China) to a tertiary prenatal diagnosis center for ultrasonic consultation in 2018. The concordance between the suspected ultrasonic signs of fetal abnormalities of the referrer and the ultrasonic consultation results were evaluated and divided into full concordance, partial concordance, and discordance.

Results: From 1938 patients with suspected ultrasonic signs, 2054 ultrasound consultation records were obtained. The most frequent anomalies for consultation in the first trimester (348, 91.3%) were cystic hygroma (CH), nuchal translucency (NT), or nuchal fold (NF) thickening, followed by signs of brain abnormalities in the second (173, 22.4%) and the third (182, 34.1%) trimester. The discordant rates of the first single signs were 19.8% for the first trimester, 41.6% for the second trimester, and 37.4% for the third trimester, respectively.

Conclusions: Our study demonstrated that the discordance of the first single signs was relatively low in the first trimester and higher in the second and third trimesters. The number of sonographers could be increased to ensure timeliness, strengthen training for those with poor concordance rates by referring to appropriate guidelines, and reduce ultrasonic consultation for those with high consistency after further research to save medical resources.
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http://dx.doi.org/10.1002/jcu.23282DOI Listing
July 2022

Case Report: Lung Adenocarcinoma Initially Presenting With Cutaneous and Subcutaneous Metastases.

Front Oncol 2022 12;12:925382. Epub 2022 Jul 12.

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

Cutaneous and subcutaneous soft tissue metastases are rare in lung adenocarcinoma and suggest poor prognosis. We report a patient with lung adenocarcinoma who initially presented with cutaneous and subcutaneous metastases to the abdomen that were initially presumed to be herpes zoster and an occult subcutaneous soft tissue mass. Because the lesions progressed over 3 weeks despite routine herpes zoster treatment, magnetic resonance imaging was performed and showed a presumed sarcoma; however, F-fluourodeoxyglucose positron emission tomography/computed tomography demonstrated pulmonary lesions. Biopsy of the abdominal lesion confirmed poorly differentiated lung adenocarcinoma. Early diagnosis of soft tissue metastasis can be difficult. Clinicians should suspect internal organ malignancy when a progressive cutaneous or subcutaneous soft tissue lesion is encountered.
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http://dx.doi.org/10.3389/fonc.2022.925382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316617PMC
July 2022

[Analysis of the Effcacy and Safety of Amivantamab in Non-small Cell Lung Cancer 
Patients with EGFR/MET Gene Abnormalities: A Single Center's Experience].

Zhongguo Fei Ai Za Zhi 2022 Jul;25(7):493-500

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), 
Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.

Background: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital.

Methods: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events.

Results: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%).

Conclusions: Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2022.102.26DOI Listing
July 2022

Glomerular IgA Deposition and Serum Antineutrophil Cytoplasmic Antibody Positivity in a Child With Dystrophic Epidermolysis Bullosa: Case Report and Literature Review.

Front Pediatr 2022 11;10:939069. Epub 2022 Jul 11.

Department of Nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Patients with epidermolysis bullosa (EB) could develop significant urological complications, such as hydroureteronephrosis, renal amyloidosis and IgA nephropathy (IgAN). Here, we presented a 12-year-old boy carrying pathogenic COL7A1 mutation with diagnosis of dystrophic epidermolysis bullosa (DEB). The patient had concomitant gross hematuria and proteinuria. Pathological examinations and immunostaining of renal biopsy showed glomeruli with mesangial hypercellularity and deposition of IgA, which were indicative of IgAN. Interestingly, serological evaluation showed antineutrophil cytoplasmic antibody (ANCA) directed against myeloperoxidase and proteinase 3. Treatment with glucocorticoid, immunosuppressants, angiotensin-converting enzyme inhibitor and antibiotics efficiently improved hemato-proteinuria, and ANCAs became negative as well. This case of DEB presented a unique collection of clinical manifestations and pathological alterations. IgAN and serum positive ANCA were possibly associated with sustained infection secondary to DEB, and can be managed by empirical treatment for primary IgAN.
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http://dx.doi.org/10.3389/fped.2022.939069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309483PMC
July 2022

Tracing the Status of Silica Fume in Cementitious Materials Subjected to Deterioration Mechanisms with Raman Microscope.

Materials (Basel) 2022 Jul 27;15(15). Epub 2022 Jul 27.

Department of Civil, Environmental and Geomatic Engineering, University College London, Gower Street, London WC1E 6BT, UK.

The status and stability of the unreacted silica fume (SF) agglomerates existing in concrete structures subjected to various deterioration environments is largely unknown, but is a critical issue which could cause public concern. This work employed a Raman microscope, which combines the Raman spectroscopy with a light optical microscope, to characterize the phase assemblage in 6-month-old SF blended Portland cement (PC) pastes after 3-month exposure to simulated deterioration mechanisms (viz. carbonation, chloride attack, or sulfate attack), in order to illustrate the status of SF. Unhydrated SF phases, in terms of amorphous silica (Raman shift at about 350-540 cm), were identified in the SF blended paste samples after being exposed to carbonation and sulfate attack, indicating that there is a potential hazard to the living system, especially the structures undergoing long-term 'interactions' with a contiguous environment.
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http://dx.doi.org/10.3390/ma15155195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332786PMC
July 2022

Deformed Mediated Larval Incisor Lobe Development Causes Differing Feeding Behavior between Oriental Armyworm and Fall Armyworm.

Insects 2022 Jun 29;13(7). Epub 2022 Jun 29.

Anhui Province Key Laboratory of Crop Integrated Pest Management, College of Plant Protection, Anhui Agricultural University, Hefei 230036, China.

Mandibular incisor lobes are important for insect feeding behavior, living habits and niche. However, the molecular regulation of insect incisor lobe development remains unknown. In this study, we found that two maize pests, oriental armyworm and fall armyworm , have different feeding patterns in maize, which are closely associated with the different development patterns of their incisor lobes. Different from first to sixth instar , which feed on leaf tissues and whorls with sharp incisor lobes, older instars of feed from leaf margins with no incisor lobes. Hox gene () is important for head appendages, but its function in incisor lobe development is not clear. Here, were identified from two armyworm species, and both were expressed highly in heads and eggs. Interestingly, the expression levels of were relatively high in larval mandibles and decreased dramatically from fourth-instar mandibles in . Knockdown of resulted in malformed mandibles with no incisor lobe in , making the larvae unable to perform window-feeding. However, RNAi of did not affect the mandibles and window-feeding pattern of , indicating the different roles of in these two species. Moreover, the mortality of new first instar increased after feeding ds but did not for feeding ds. These findings revealed that mediated the larval mandibular incisor lobe morphology, affecting its feeding pattern in , broadening the knowledge of functions in insect mandibles and feeding behavior.
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http://dx.doi.org/10.3390/insects13070594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320430PMC
June 2022

Taurine Alleviates LPS-Induced Acute Lung Injury by Suppressing TLR-4/NF-κB Pathway.

Adv Exp Med Biol 2022 ;1370:63-72

Liaoning Provincial Key Laboratory of Zoonosis, College of Animal Science & Veterinary Medicine, Shenyang Agricultural University, Shenyang, Liaoning, People's Republic of China.

Taurine has the function of immune regulation, relieving acute and chronic inflammation caused by various agents, and maintaining cell homeostasis. This investigation focused on the protective functions of taurine targeting acute lung injury (ALI) induced by LPS. Sixty male SD rats aged 6-7 weeks were segregated at random: blank control group (C group), taurine control group (T group), ALI model group (LPS group), and taurine prevention groups (LPST1, LPST, LPST3 Groups). C group and LPS group were given normal drinking water, while T group and LPST group were given 2% taurine in drinking water. LPST1 group was given 1% taurine in drinking water while. LPST3 group was given 3% taurine in drinking water. On the 14th and 28th day, LPS group and LPST1, LPST, and LPST3 groups were subjected to injection of LPS (25 mg/kg) into the trachea of rats. Serum, peripheral blood, lung tissue, and bronchoalveolar lavage fluid (BALF) were collected at 6 h post-LPS injection. The wet/dry ratio (W/D) of lung was measured by hot drying method. The population of white blood cells and the abundance of inflammatory-related cells within peripheral blood were counted by an automatic blood cell analyzer. The population of white blood cells within BALF was counted by a white blood cell counting plate combined with Swiss Giemsa staining, while the proportion of related white blood cells was calculated. BCA reagent was used to determine the protein concentration in BALF. The levels of pro-inflammatory factors (IL-1 β, IL-6, IL-18, TNF - α), anti-inflammation factors (IL-10, IL-4), and taurine within serum and lung tissue were detected by ELISA. Lung structural tissue alterations were observed through HE staining techniques. Myeloperoxidase (MPO) activities within lung tissue were detected through colorimetry. Protein expression levels of TLR4, MyD88, NF-κ Bp65, NF-κ Bp-p65, MCP-1, together with CD68 within lung tissue, were analyzed by Western blot (WB) and immunohistochemistry (IHC). The taurine pretreatment group contained significantly reduced W/D, MPO activity, and the number of inflammatory cells in BALF induced by LPS. In addition, compared with ALI model group, the taurine pretreatment group contained significantly reduced levels of pro-inflammatory factors in lung tissue, increased levels of anti-inflammatory factors, and decreased expression levels of key proteins in TLR-4/NF-κ B pathway. Taurine can protect rats from ALI by inhibiting the activation of neutrophils, macrophages, and TLR-4/NF-κ B signaling pathway.
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http://dx.doi.org/10.1007/978-3-030-93337-1_6DOI Listing
July 2022

Role of corneal radius of curvature in early identification of fundus tessellation in children with low myopia.

Br J Ophthalmol 2022 Jul 26. Epub 2022 Jul 26.

Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Eye Diseases, Center of Eye Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, People's Republic of China

Aim: To assess the role of the corneal radius of curvature (CR) in the identification of fundus tessellation in children with low myopia.

Methods: In the cross-sectional study, students aged 9-12 years from 24 primary schools in Shanghai were enrolled by cluster sampling. Participants underwent measurements including cycloplegic refraction and axial length. Fundus images and choroidal thickness were obtained by swept-source optical coherence tomography. Fundus tessellation was classified into four grades according to fundus photographs.

Results: A total of 1127 children with low myopia (spherical equivalence (SE) >-3.00 dioptre (D) but ≤-0.50 D) were included, with a mean age of 10.29±0.60 years and a mean SE of -1.44±0.69 D. Fundus tessellation was found in 591 (52.4%) cases (grade 1: 428, 38.0%; grade 2: 128, 11.4%; grade 3: 35, 3.1%). Choroidal thickness decreased as fundus tessellation grade increased (p trend <0.001). According to regression analysis, higher fundus tessellation grade was independently associated with larger CR (OR, 7.499; 95% CI 2.279 to 24.675, p=0.001). For those with CR >7.9 mm, along with CR, degree and proportion of fundus tessellation increased sharply.

Conclusion: Fundus tessellation existed in more than half of children with low myopia. Preliminary fundus photography conducted in children with low myopia with large CR would be necessary and beneficial to the early management of myopic fundus changes. NCT02980445.
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http://dx.doi.org/10.1136/bjo-2022-321295DOI Listing
July 2022

Cell landscape of larval and adult Xenopus laevis at single-cell resolution.

Nat Commun 2022 Jul 25;13(1):4306. Epub 2022 Jul 25.

Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.

The rapid development of high-throughput single-cell RNA sequencing technology offers a good opportunity to dissect cell heterogeneity of animals. A large number of organism-wide single-cell atlases have been constructed for vertebrates such as Homo sapiens, Macaca fascicularis, Mus musculus and Danio rerio. However, an intermediate taxon that links mammals to vertebrates of more ancient origin is still lacking. Here, we construct the first Xenopus cell landscape to date, including larval and adult organs. Common cell lineage-specific transcription factors have been identified in vertebrates, including fish, amphibians and mammals. The comparison of larval and adult erythrocytes identifies stage-specific hemoglobin subtypes, as well as a common type of cluster containing both larval and adult hemoglobin, mainly at NF59. In addition, cell lineages originating from all three layers exhibits both antigen processing and presentation during metamorphosis, indicating a common regulatory mechanism during metamorphosis. Overall, our study provides a large-scale resource for research on Xenopus metamorphosis and adult organs.
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http://dx.doi.org/10.1038/s41467-022-31949-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314398PMC
July 2022

Pipeline embolization of complex, wide-necked middle cerebral artery bifurcation aneurysms: A single-center experience.

Interv Neuroradiol 2022 Jul 25:15910199221115924. Epub 2022 Jul 25.

Department of Neuro-interventional Radiology, 12636The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Purpose: To evaluate the performance of Pipeline Embolization Device (PED) in complex, wide-necked middle cerebral artery (MCA) bifurcation aneurysms.

Methods: We performed a retrospective review of patients treated with PED for complex, wide-necked MCA bifurcation aneurysms between August 2016 and March 2021. In addition to demographic data, we collected aneurysmal neck width, dome-to-neck ratio, complications, and clinical and angiographic follow-up. The embolization degree of aneurysms was evaluated by O'Kelly-Marotta (OKM) grading scale, and the prognosis was assessed with the modified Rankin Scale (mRS).

Results: From August 2016 to March 2021, a total of 46 patients with 49 MCA bifurcation aneurysms in our center were enrolled, of whom all received PEDs successfully. The O'Kelly-Marotta (OKM) grading showed that post-procedure 15 patients (32.6%) were grade C, another 8 patients (17.4%) were grade D. Aneurysms with small remnant or complete occlusion were 50%, symptomatic ischemic events occurred in 3 (6.5%), and bleeding events in 1 (2.2%). 41 patients underwent a 6-month angiography follow-up, in which 7 patients (17.1%) remained OKM grade C and 30 patients (73.2%) achieved OKM grade D. Complete occlusion and small remnant aneurysms were up to 90.3%. 40 (97.6%) patients' mRS scores were 0, and 1 (2.4%) patient was 2. No new bleeding and ischemic events occurred during the 6-month.

Conclusions: The Pipeline Embolization Device provides a safe and effective treatment alternative for complex, wide-necked MCA aneurysms. A larger number with longer-term follow-up data is needed for further verification.
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http://dx.doi.org/10.1177/15910199221115924DOI Listing
July 2022

Relationship Between Serum Complement C3 Levels and Outcomes Among Patients With Anti-GBM Disease.

Front Immunol 2022 8;13:929155. Epub 2022 Jul 8.

National Clinical Research Center of Kidney Diseases, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background: IgG and complement 3 (C3) are generally found to be deposited along the glomerular basement membrane (GBM) in human anti-GBM disease. The pathogenic role of complement activation in kidney damage of anti-GBM disease has been explored in recent years. Therefore, we investigated the relationship between serum C3 and outcomes among patients with anti-GBM disease in this study.

Methods: Ninety-four anti-GBM disease patients between January 2004 and December 2020 at the National Clinical Research Center of Kidney Diseases Jinling Hospital were retrospectively analyzed, and were divided into the low C3 group and the normal C3 group according to serum C3 levels at diagnosis. Fifty-six patients had undergone renal biopsy. We analyzed the clinical manifestations, laboratory tests, kidney pathology, treatment, and outcomes between the two groups. The primary endpoint was kidney failure. Cox regression and smooth curve fitting of generalized additive mixed model analysis were used to explore the correlation between serum C3 and kidney failure. The outcomes of the two groups were compared by the Kaplan-Meier curve.

Results: A total of 94 patients (aged 43.6 ± 16.2; male patients, 46%) with anti-GBM disease were enrolled. There were 26 patients with low C3 levels and 68 patients with normal C3 levels. Compared with the normal C3 group, patients in the low C3 group have a higher proportion of glomerular sclerosis progressing to kidney failure. Multivariate Cox regression analysis suggested that C3 is associated with kidney outcomes in patients with anti-GBM disease (HR = 0.782, 95% CI = 0.673-0.907, = 0.001). Smooth curve fitting of generalized additive mixed model analysis indicated that the level of C3 had a linear relationship with the changing trend of kidney failure. The Kaplan-Meier curve showed that there was a statistical difference between the two groups in terms of kidney failure ( = 0.033).

Conclusion: The kidney outcomes of anti-GBM disease in the low C3 group were poorer than those in the normal C3 group. The influence of C3 on the kidney outcomes of patients with anti-GBM disease may be of clinical relevance.
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http://dx.doi.org/10.3389/fimmu.2022.929155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305472PMC
July 2022

Construction of the axolotl cell landscape using combinatorial hybridization sequencing at single-cell resolution.

Nat Commun 2022 Jul 22;13(1):4228. Epub 2022 Jul 22.

Center for Stem Cell and Regenerative Medicine, and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.

The Mexican axolotl (Ambystoma mexicanum) is a well-established tetrapod model for regeneration and developmental studies. Remarkably, neotenic axolotls may undergo metamorphosis, a process that triggers many dramatic changes in diverse organs, accompanied by gradually decline of their regeneration capacity and lifespan. However, the molecular regulation and cellular changes in neotenic and metamorphosed axolotls are still poorly investigated. Here, we develop a single-cell sequencing method based on combinatorial hybridization to generate a tissue-based transcriptomic landscape of the neotenic and metamorphosed axolotls. We perform gene expression profiling of over 1 million single cells across 19 tissues to construct the first adult axolotl cell landscape. Comparison of single-cell transcriptomes between the tissues of neotenic and metamorphosed axolotls reveal the heterogeneity of non-immune parenchymal cells in different tissues and established their regulatory network. Furthermore, we describe dynamic gene expression patterns during limb development in neotenic axolotls. This system-level single-cell analysis of molecular characteristics in neotenic and metamorphosed axolotls, serves as a resource to explore the molecular identity of the axolotl and facilitates better understanding of metamorphosis.
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http://dx.doi.org/10.1038/s41467-022-31879-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307617PMC
July 2022

VEGF promotes tendon regeneration of aged rats by inhibiting adipogenic differentiation of tendon stem/progenitor cells and promoting vascularization.

FASEB J 2022 Aug;36(8):e22433

Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, China.

Studies have shown that the stem cell microenvironment is a key factor for stem cell maintenance or differentiation. In this study, we compared the expression of 23 cytokines such as IL-6, IL-10, and TNFα between young and aged rats during patellar tendon repair by cytokine microarray, and found that significant difference between IL-10, G-CSF, and VEGF at 3, 7, or 14 days post-operatively. The effects of these factors on adipogenic differentiation of TPSCs were examined through western blot and oil red O experiments. It was shown that VEGF had an inhibitive effect on the adipogenic differentiation of TPSCs. SPP-1 was figured out as our target by RNA sequencing and confirmed by western blot in vitro. Further in vivo studies showed that adipocyte accumulation was also decreased in the tendons of aged rats after injection of VEGF and the histological score and biomechanical property were also improved via targeting SPP-1. Furthermore, histochemical results showed that vascularization of the injury sites was significantly elevated. In conclusion, VEGF not only plays an important role in decreasing adipocyte accumulation but also improves vascularization of the tendon during aged tendon healing. We believe active regulation of VEGF may improve the treatment of age-related tendon diseases and tendon injuries.
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http://dx.doi.org/10.1096/fj.202200213RDOI Listing
August 2022

Hepatitis B Virus Reactivation and Mycobacterial Infections Associated With Ustekinumab: A Retrospective Study of an International Pharmacovigilance Database.

Front Pharmacol 2022 4;13:921084. Epub 2022 Jul 4.

Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Reports were recently published on hepatitis B virus reactivation (HBVr), tuberculosis (TB), and atypical mycobacterial infection (AMI) in patients with ustekinumab treatment. However, the literature is limited to case reports and series. The study was aimed to investigate their relationships by using an extensive population-based database. Using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database, we collected all cases of HBVr, TB, and AMI between 1 January 2009 and 30 September 2021, for ustekinumab and other drugs. Disproportionality was analyzed using the reporting odds ratio (ROR), which was considered significant when the lower limit of the 95% confidence interval (95% CI) was >1. Of the 18,760,438 adverse cases reported to FAERS for all drugs, 56,581 cases had been exposed to ustekinumab. Adverse events of HBVr, TB, and AMI were reported in 21, 210, and 20 cases, respectively. The ROR for HBVr with ustekinumab was 2.33 (95% CI, 1.52-3.58), for TB was 5.09 (95% CI, 4.44-5.84), and for AMI was 2.09 (95% CI, 1.35-3.24). In the ustekinumab exposure group, no death occurred in patients with HBVr, but one patient experienced life-threatening liver failure. For those with TB, 24 cases experienced hospitalization and 2 deaths occurred. No death occurred in patients with AMI but eight experienced hospitalization. We identified positive signals between ustekinumab exposure and HBVr, TB, and AMI in FAERS. Although these complications are rare, clinicians using ustekinumab should be aware of the risks.
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http://dx.doi.org/10.3389/fphar.2022.921084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9289361PMC
July 2022

A hybrid hydrogel encapsulating human umbilical cord mesenchymal stem cells enhances diabetic wound healing.

J Mater Sci Mater Med 2022 Jul 18;33(8):60. Epub 2022 Jul 18.

Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, 510663, China.

Background: Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy, but the development of hydrogel with suitable properties remains a great challenge. Thus, our study was conducted to combine an optimized hydrogel with stem cell to improve complex diabetic wound treatment.

Methods: This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound.

Results: We explored the relationship between mechanical stiffness and cell proliferation and differentiation potency, and found 10% GelMA hydrogel with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1β, promoted vascular regeneration and collagen deposition after treatment of hUMSCs.

Conclusions: The optimized hydrogel encapsulating hUMSCs improved diabetic wound healing, and has a broad implication for the treatment of diabetic complication. Diabetic wound is a severe complication of diabetes. Stem cell is considered as a promising therapy for diabetic skin wounds. Hydrogel can supply niche for cells adhesion and survival to improve the efficacy of stem cell therapy. This study constructed a hydrogel with low toxicity and adjustable mechanical properties from gelatin methacrylate (GelMA) and chitosan-catechol (Chi-C), and encapsulated human umbilical cord-mesenchymal stem cells (hUMSCs) to repair full-thickness diabetic wound. Hydrogel of 10% GelMA with an optimal stiffness improved hUMSCs adhesion, proliferation, and differentiation potency maintenance in vitro. Assistant with optimized hydrogel encapsulating hUMSCs, diabetic wound healing process was greatly accelerated, including accelerated wound closure, inhibited secretion of inflammatory factors TNF-α and IL-1β, promoted vascular regeneration and collagen deposition after treatment of hUMSCs. The study supplies an alternative treatment for diabetic complication. Hydrogel-hUMSCs combined treatment accelerates wound closure in diabetic mice. A. Representative images of wounds during 21-day in vivo experiments. B. Quantification of wound closure rate (%) over 21-day period. C. HE staining of wounds at days 7, 14 and 21. The bar corresponds to 200 μm.
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http://dx.doi.org/10.1007/s10856-022-06681-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9293866PMC
July 2022
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