Publications by authors named "Ying Zheng"

1,037 Publications

  • Page 1 of 1

Oxidosqualene Cyclases Involved in the Biosynthesis of Diverse Triterpenes in .

J Agric Food Chem 2022 Jun 21. Epub 2022 Jun 21.

Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.

is an important economic plant that is rich in lipophilic triterpenols with pharmacological activities including antiallergic, anti-inflammatory, and anticancer activities. However, the key enzymes related to triterpene biosynthesis have seldom been studied in . Oxidosqualene cyclases (OSCs) are the rate-limiting enzymes related to triterpene biosynthesis. In this study, seven putative genes () were mined from the transcriptome. Six CsOSCs were characterized for the biosynthesis of diverse triterpene skeletons, including α-amyrin, β-amyrin, δ-amyrin, dammarenediol-II, ψ-taraxasterol, taraxasterol, and cycloartenol by the heterologous expression system. CsOSC3 was a multiple functional α-amyrin synthase. Three key residues, Trp260, Tyr262, and Phe415, are critical to the catalytic performance of CsOSC3 judging from the results of molecular docking and site-directed mutagenesis. These findings provide important insights into the biosynthesis pathway of triterpenes in .
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http://dx.doi.org/10.1021/acs.jafc.2c03011DOI Listing
June 2022

Fatty acid composition of macroinvertebrate scrapers in relation to environmental conditions in subtropical mountain streams.

Environ Sci Pollut Res Int 2022 Jun 21. Epub 2022 Jun 21.

Zhejiang Provincial Key Laboratory of Aquatic Resources Conservation and Development, College of Life Sciences, Huzhou University, Huzhou, 313000, People's Republic of China.

Biochemical fatty acids (FAs) in vivo are essential to the growth and reproduction of animals including macroinvertebrates in streams and are subject to ambient abiotic variables. However, the main abiotic drivers of FA composition in macroinvertebrate scrapers are varying and uncertain. The aim of this research was to quantify the contributions of abiotic variables, including stream physical, chemical, and climatic variables, to the variation of FAs of macroinvertebrate functional feeding group-scrapers (e.g., Bellamya aeruginosa, Radix swinhoe, Heptagenia sp., and Stenelmis sp.). Stream physical, chemical, and climatic variables and the FAs of scrapers were measured in six subtropical streams during spring. The principal component analysis (PCA) indicated the parameters responsible for FA variation were mainly related to polyunsaturated fatty acids (PUFAs), saturated fatty acids (SAFAs), ω3 PUFA, and ω6 PUFA. Multiple factor analysis (MFA) showed that the FA profiles of scrapers strongly correlated with the physical variables. Specifically, the correlation analysis showed that PUFA and terrestrial FA were significantly positively associated with canopy cover, and in contrast that SAFA was negatively correlated with canopy cover. Although water quality and climate variables did not have a good relationship with FAs, they had a strong correlation with physical variables. This research suggested that the influence of environmental variables (e.g., stream physical, chemical, and climatic variables) on FAs of macroinvertebrate scrapers has complex paths. This study provides a theoretical basis for stream management and an empirical framework for the construction of an interactive network beyond food webs that includes environmental variables.
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http://dx.doi.org/10.1007/s11356-022-21265-zDOI Listing
June 2022

Osteocalcin association with vascular function in chronic kidney disease.

J Clin Hypertens (Greenwich) 2022 Jun 10. Epub 2022 Jun 10.

Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, China.

Osteocalcin (OCN) is a bone-derived and vitamin K dependent hormone that affects energy metabolism and vascular calcification. The relationship between serum OCN and vascular function in patients with chronic kidney disease (CKD) is uncertain. This study investigated the association between serum OCN and vascular function as expressed with reactive hyperemia index (RHI) and augmentation index (AIx) measured by Endo-PAT 2000 device. This cross-sectional analysis was based on 256 pre-dialysis CKD patients who had completed the Endo-PAT 2000 test and serum OCN at the First Center of Chinese PLA Hospital from November 2017 to December 2019. Based on whether the RHI was less than 1.67, the patients were divided into endothelial dysfunction and normal endothelial function groups. Multiple logistic and linear regression were used to analyze the association between OCN and vascular function. Subgroup analyses were performed to examine the effects of OCN on vascular function in different CKD populations. After multivariate adjustment, CKD with low OCN were more likely to have endothelial dysfunction (OR: 0.794; 95%CI: 0.674-0.934; P = .006); on the contrary, patients with high OCN had a higher degree of arterial stiffness (standardized β: 0.174; P = .003). Subgroup analyses showed that higher OCN was associated with severe arterial stiffness but a better endothelial function in young (age < 65 years, P /P = .027/.011), male (P /P = .040/.016), patients with a history of hypertension (P /P = .004/.009) or diabetes (P /P = .005/.005), and in early CKD (P /P = .014/.015). In conclusion, serum OCN correlates with vascular function in CKD patients: beneficial for endothelial function but detrimental to arterial stiffness.
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http://dx.doi.org/10.1111/jch.14523DOI Listing
June 2022

Engineering the multiscale complexity of vascular networks.

Nat Rev Mater 2022 May 31:1-15. Epub 2022 May 31.

Department of Bioengineering, University of Washington, Seattle, WA USA.

The survival of vertebrate organisms depends on highly regulated delivery of oxygen and nutrients through vascular networks that pervade nearly all tissues in the body. Dysregulation of these vascular networks is implicated in many common human diseases such as hypertension, coronary artery disease, diabetes and cancer. Therefore, engineers have sought to create vascular networks within engineered tissues for applications such as regenerative therapies, human disease modelling and pharmacological testing. Yet engineering vascular networks has historically remained difficult, owing to both incomplete understanding of vascular structure and technical limitations for vascular fabrication. This Review highlights the materials advances that have enabled transformative progress in vascular engineering by ushering in new tools for both visualizing and building vasculature. New methods such as bioprinting, organoids and microfluidic systems are discussed, which have enabled the fabrication of 3D vascular topologies at a cellular scale with lumen perfusion. These approaches to vascular engineering are categorized into technology-driven and nature-driven approaches. Finally, the remaining knowledge gaps, emerging frontiers and opportunities for this field are highlighted, including the steps required to replicate the multiscale complexity of vascular networks found in nature.
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http://dx.doi.org/10.1038/s41578-022-00447-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154041PMC
May 2022

SQLE facilitates the pancreatic cancer progression via the lncRNA-TTN-AS1/miR-133b/SQLE axis.

J Cell Mol Med 2022 May 31. Epub 2022 May 31.

Department of Digestive Disease and Gastrointestinal Motility Research Room, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Studies have shown that SQLE is highly expressed in a variety of tumours and promotes tumour progression. However, the role of SQLE in pancreatic cancer (PC) has not been reported. Here, we aim to study the role and molecular mechanism of SQLE in PC. Immunohistochemistry and functional experiments showed that SQLE was highly expressed in PC tissues and promoted the proliferation and invasion of PC cells. Terbinafine, an inhibitor of SQLE, inhibited this effect. In order to further study the upstream mechanism that regulates SQLE, we used bioinformatics technology to lock miR-133b and lncRNA-TTN-AS. In situ hybridization was used to detect the expression of miR-133b and lncRNA-TTN-AS1 in PC tissues. The luciferase reporter gene experiment was used to confirm the binding of miR-133b and lncRNA-TTN-AS1. The results showed that miR-133b was down-regulated in PC tissues and negatively correlated with the expression of SQLE. LncRNA-TTN-AS1 was upregulated in pancreatic cancer tissues and positively correlated with the expression of SQLE. Luciferase gene reporter gene analysis confirmed lncRNA-TTN-AS1 directly binded to miR-133b. Therefore, we propose that targeting the lncRNA-TTN-AS1/miR-133b/SQLE axis is expected to provide new ideas for the clinical treatment of PC patients.
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http://dx.doi.org/10.1111/jcmm.17347DOI Listing
May 2022

NIR-II Responsive Molybdenum Dioxide Nanosystem Manipulating Cellular Immunogenicity for Enhanced Tumor Photoimmunotherapy.

Nano Lett 2022 Jun 27;22(12):4741-4749. Epub 2022 May 27.

MOE Key Laboratory of Laser Life Science and Guangdong Provincial Key Laboratory of Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.

Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has emerged as a better candidate for deep-tissue tumor elimination. More interestingly, the photothermal ablated tumor cells also manifest somewhat immunostimulation potency to elicit antitumor immunity, although most dying cells are undergoing apoptosis that is commonly considered as immunologically silent. Here, a NIR-II responsive nanosystem is established for tumor photoimmunotherapy using molybdenum dioxide (MoO) nanodumbbells as the nanoconverter. Meanwhile, an apoptosis-blocking strategy is proposed to regulate the cell death pattern under NIR-II laser irradiation in order to improve the immunogenic cell death. The nanoformulation can efficiently block caspase 8-dependent apoptotic pathway in photothermal ablated tumor cells and transform into more immunogenic death patterns, thereby activating systemic immunity to inhibit tumor growth and metastasis. In addition, this strategy also helps enhance the body's responses to α-PD-1 immune checkpoint inhibitor, which implies a potential optimal combination for cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.nanolett.2c00899DOI Listing
June 2022

Surpassing the Background Barrier for Multidimensional Single-Molecule Localization Super-Resolution Imaging: A Case of Lysosome-Exclusively Turn-on Probe.

Anal Chem 2022 Jun 25;94(22):7990-7995. Epub 2022 May 25.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, China.

The background barrier restricts the dimensionality of live-cell single-molecule localization super-resolution imaging. Ideally, a probe exclusively turned on by its target, without any nonspecific fluorescence signals from off-target molecules, constitutes a practical solution to surpass this barrier. Yet, few such fluorophores have been developed. A lysosome with a unique acidic lumen was chosen as the target for demonstrating the concept advantage. A representative lyso-tracker (piperazine rhodamine) with high brightness has been spirocyclized with -phenylenediamine to form . This probe shifted its bright-dark spirocyclization balance to a strong acidity domain (p = -0.18). Consequently, under no-wash conditions, showed almost undetectable background photons (only one-sixtieth of that of ) in a neutral cellular environment, and it formed sparsely brightened molecules at a low ratio (∼1 × 10%) in lysosomes. This background-free probe enabled super-resolution imaging and modeling of live-cell lysosomes in four dimensions at 2 s resolution, with quantitative determination of lysosomal volume expansion and deformation at starvation. Our molecular approach sheds new light on surpassing the background barrier for multidimensional super-resolution imaging.
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http://dx.doi.org/10.1021/acs.analchem.2c00987DOI Listing
June 2022

[Preparation and application of rabbit polyclonal antibody against mouse Tubby-like protein 2 (TULP2)].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2022 May;38(5):452-459

Institute of Obstetrics, Gynecology and Reproduction, Department of Histology and Embryology, School of Medicine; Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Yangzhou University, Yangzhou 225001, China. *Corresponding author, E-mail:

Objective To generate rabbit polyclonal antibody against mouse Tubby(Tub)-like protein 2 (TULP2) and detect the expression of TULP2 in mouse testis. Methods pET30a (+)-TULP2 and pET30(+)-TULP2-C recombinant plasmids were constructed by inserting TULP2 full-length gene fragment and TULP2-C gene fragment containing Tub domain into pET30a (+). pET30a (+)-TULP2 and pET30(+)-TULP2-C were transformed into E. coli BL21, and the prokaryotic protein expressions were induced with the supplementation of IPTG. The prokaryotic recombinant proteins were purified with His-Binding-resin, and denaturation was performed by adding urea with gradient concentration. Adult male New Zealand white rabbits were inoculated with recombinant TULP2 and TULP2-C proteins as immunogens to generate two kinds of TULP2 polyclonal antibodies. Titers of antibodies were detected by ELISA. The efficiency and specificity of antibodies were determined by Western blot and immunofluorescence (IF) staining. Results pET30a (+)-TULP2 and pET30a (+)-TULP2-C recombinant plasmids were constructed successfully, and the protein expressions of TULP2 and TULP2-C could be induced by adding IPTG. The titers of polyclonal antibodies were 1:1 000 000. Western blot and IF staining showed poor specificity of TULP2-C antibody. TULP2 antibody could specifically recognize the endogenous TULP2 protein in the testes of adult wild-type mice, and IF staining showed that TULP2 was expressed specifically in the round spermatids and elongating spermatids of mice. Conclusion A rabbit anti-mouse TULP2 polyclonal antibody is generated successfully using TULP2 full-length protein, which can be used for detecting TULP2 expression by Western blot and IF staining.
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May 2022

Light-Induced Crystalline Size Heterogeneity of Polymers Enables Programmable Writing, Morphing, and Mechanical Performance Designing.

ACS Macro Lett 2022 06 19;11(6):739-746. Epub 2022 May 19.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China.

Constructing the spatio-selective crystalline structures has been an effective strategy to diversify the functions and applications of polymers. However, it is still challenging to program the crystalline heterogeneity into commercialized polymers and realize associate functions by a simple yet generalizable method. Herein, we propose a facile approach to fabricate multifunctional materials by programming the spatial distribution of crystal size in semicrystalline polymers. Various crystal size patterns in both plane and depth directions are introduced by the photothermal effect of printed ink and subsequent crystallization at different temperatures, which can be reprogrammed by repeated melting and crystallization. These obtained materials with well-defined crystal size heterogeneities exhibit diverse and regulable optics, mechanical and swelling properties, as manifested in applications including rewritable polymer paper, programmed mechanics, and advanced morphing devices. The light-induced crystal size heterogeneity of polymers has provided insights into developing advanced multifunctional materials.
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http://dx.doi.org/10.1021/acsmacrolett.2c00237DOI Listing
June 2022

Landslide Susceptibility Mapping Using Machine Learning Algorithm Validated by Persistent Scatterer In-SAR Technique.

Sensors (Basel) 2022 Apr 19;22(9). Epub 2022 Apr 19.

Key State Laboratory of Information Engineering in Surveying, Mapping and Remote Sensing (LIESMARS), Wuhan University, Wuhan 430079, China.

Landslides are the most catastrophic geological hazard in hilly areas. The present work intends to identify landslide susceptibility along Karakorum Highway (KKH) in Northern Pakistan, using landslide susceptibility mapping (LSM). To compare and predict the connection between causative factors and landslides, the random forest (RF), extreme gradient boosting (XGBoost), k nearest neighbor (KNN) and naive Bayes (NB) models were used in this research. Interferometric synthetic aperture radar persistent scatterer interferometry (PS-InSAR) technology was used to explore the displacement movement of retrieved models. Initially, 332 landslide areas alongside the Karakorum Highway were found to generate the landslide inventory map using various data. The landslides were categorized into two sections for validation and training, of 30% and 70%. For susceptibility mapping, thirteen landslide-condition factors were created. The area under curve (AUC) of the receiver operating characteristic (ROC) curve technique was utilized for accuracy comparison, yielding 83.08, 82.15, 80.31, and 72.92% accuracy for RF, XGBoost, KNN, and NB, respectively. The PS-InSAR technique demonstrated a high deformation velocity along the line of sight (LOS) in model-sensitive areas. The PS-InSAR technique was used to evaluate the slope deformation velocity, which can be used to improve the LSM for the research region. The RF technique yielded superior findings, integrating with the PS-InSAR outcomes to provide the region with a new landslide susceptibility map. The enhanced model will help mitigate landslide catastrophes, and the outcomes may help ensure the roadway's safe functioning in the study region.
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http://dx.doi.org/10.3390/s22093119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102666PMC
April 2022

Polymer Chains Fold Prior to Crystallization.

ACS Macro Lett 2022 03 8;11(3):284-288. Epub 2022 Feb 8.

School of Polymer Science and Polymer Engineering, The University of Akron, Akron, Ohio 44325-3909, United States.

There are long-standing debates in crystallization mechanism of polymer chains at the molecular levels: Which comes first, chain folding or lamellae formation during crystallization? In this study, we report the local chain trajectory of C-labeled semicrystalline polymer in an extreme case of rapidly quenched glassy state as well as thermodynamically stable crystals formed via different pathways from glass and melt. Magnetically dipole interactions do not require a long-range order of molecular objects and thus enable us to trace the local chain trajectory of polymer chains even in a glassy state. To accurately characterize the local chain trajectory of polymer glass, the natural abundance effect on C-C double-quantum (DQ) nuclear magnetic resonance (NMR) signal is re-examined using extended chain conformation. As results, it is found that glassy chains adopt the same adjacent re-entry structure (adjacent re-entry number, = 1) with the melt- and cold-grown crystals. From these results, it is concluded that (i) folding occurs prior to crystallization and (ii) melt and cold crystallization do not induce additional folding but proceed with rearrangements of polymer chains in the existing templates.
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http://dx.doi.org/10.1021/acsmacrolett.1c00789DOI Listing
March 2022

Retarded Crystallization and Promoted Phase Transition of Freeze-Dried Polybutene-1: Direct Evidence for the Critical Role of Chain Entanglement.

ACS Macro Lett 2022 Feb 24;11(2):257-263. Epub 2022 Jan 24.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China.

Polymorphism and crystal transition are common phenomena of semicrystalline polymers. These two behaviors are known to be controlled by the nucleation and chain mobility of polymers, both of which are constrained by the chain entanglement at the molecular level. However, the role of chain entanglement in polymorphic crystallization and crystal phase transition of polymers has not been well understood. Herein, we use isotactic polybutene-1 (PB-1) as a model polymorphic polymer and present the crucial role of chain entanglement in the polymorphic crystallization kinetics and solid-solid phase transition. A series of less-entangled PB-1 with different entanglement degrees were successfully prepared by freeze-drying the polymer dilute solution. Compared to the bulk sample and re-entangled one, chain disentangling of PB-1 suppressed the crystallization kinetics of form II but significantly increased the phase transition rate and final transition degree from form II to form I. The disentangling-promoted II-I phase transition originated from the reduced nucleation barrier and enhanced chain mobility. This work would advance the in-depth understanding on the formation and transition mechanisms of polymorphic polymer crystals at the molecular level.
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http://dx.doi.org/10.1021/acsmacrolett.1c00794DOI Listing
February 2022

Asymmetric Molecular Dynamics and Anisotropic Phase Separation in the Cocrystal of the Crystalline/Crystalline Polymer Blend.

ACS Macro Lett 2022 Feb 14;11(2):193-198. Epub 2022 Jan 14.

School of Polymer Science and Polymer Engineering, The University of Akron, Akron, Ohio 44325-3909, United States.

Semicrystalline polymers are categorized as either mobile or fixed crystals, depending on chain mobility in the crystalline region. In this work, we investigate molecular dynamics and phase structure in the cocrystal consisting of fixed and mobile polymer crystals by solid-state (ss) nuclear magnetic resonance (NMR) spectroscopy. It is demonstrated that (i) the mobile component begins large amplitude motions associated with crystal-crystal transition, while fixed ones keep their rigidity in the cocrystal, and (ii) asymmetric molecular dynamics leads to nanosegregations into mobile- and fixed-rich domains in the cocrystal below the melting temperature (). The observed phase separation induced by asymmetric molecular dynamics is similar to the phase separation of the miscible amorphous polymer blend; however, it is limited to two dimensions due to the parallel packing of the stems inside the cocrystal, as well as chain connectivity at the crystalline-amorphous boundary.
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http://dx.doi.org/10.1021/acsmacrolett.1c00745DOI Listing
February 2022

Role of Chain Entanglements in the Stereocomplex Crystallization between Poly(lactic acid) Enantiomers.

ACS Macro Lett 2021 08 21;10(8):1023-1028. Epub 2021 Jul 21.

State Key Laboratory of Chemical Engineering, College of Chemical and Biological Engineering, Zhejiang University, 38 Zheda Road, Hangzhou 310027, China.

Stereocomplex (SC) crystallization between polymer enantiomers has opened a promising avenue for preparing high-performance materials. However, high-crystallinity SCs are difficult to achieve for high-molecular-weight (HMW) enantiomeric blends of chiral polymers [e.g., poly(lactic acid)]. Despite extensive studies, why HMW enantiomeric blends have difficulty in SC crystallization has not been clarified. Herein, we chose the HMW poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) 1/1 blend as the model system and demonstrated the crucial role of chain entanglement in regulating SC crystallization. PLLA/PDLA blends with various entanglement degrees were prepared by freeze-drying. We observed that disentangling promoted not only the crystallization rate but also the crystallinity of SCs in both the nonisothermal and isothermal processes. The less-entangled samples crystallized exclusively as the high-crystallinity SCs at different temperatures, in contrast to the predominant homocrystallization that occurred in the common entangled samples. This study provides deep insight into the SC crystallization mechanism of polymers and paves the way for future research attempting to prepare SC materials.
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http://dx.doi.org/10.1021/acsmacrolett.1c00394DOI Listing
August 2021

The Transumbilical Laparoendoscopic Single-Site Extraperitoneal Approach for Pelvic and Para-Aortic Lymphadenectomy: A Technique Note and Feasibility Study.

Front Surg 2022 15;9:863078. Epub 2022 Apr 15.

Department of Obstetrics and Gynecology, Shanxi Bethune Hospital, Taiyuan, China.

Background: Nowadays, lymphadenectomy could be performed by the transperitoneal or extraperitoneal approach. Nevertheless, each approach has its own advantages and disadvantages. Under these circumstances, we developed a transumbilical laparoendoscopic single-site (TU-LESS) extraperitoneal approach for lymphadenectomy. In this research, the primary goal is to demonstrate the feasibility of the novel approach in systematic lymphadenectomy and present the surgical process step-by-step.

Methods: Between May 2020 and June 2021, patients who had the indications of systematic lymphadenectomy underwent lymphadenectomy via the TU-LESS extraperitoneal approach. This new approach was described in detail, and the clinical characteristics and surgical outcomes were collected and analyzed.

Results: Eight patients with gynecological carcinoma were included in the research, including four with high-risk endometrial cancer and four with early-stage ovarian cancer. The TU-LESS extraperitoneal approach for pelvic and para-aortic lymphadenectomy was successfully performed in all patients without conversion. In all, a median of 26.5 pelvic lymph nodes (range 18-35) and 18.0 para-aortic lymph nodes (range 7-43) were retrieved. There was a median of 166.5 min of surgical time (range 123-205). Patients had speedy recoveries without complications. All patients had positive pain responses after surgery, as well as satisfactory cosmetic and body image outcomes.

Conclusion: Our initial experience showed that it is feasible to perform systematic lymphadenectomy with the TU-LESS extraperitoneal approach. And this new approach may provide a new measure or a beneficial supplement for lymphadenectomy in gynecologic cancer.
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http://dx.doi.org/10.3389/fsurg.2022.863078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053588PMC
April 2022

Identification of Neutrophil-Related Factor LCN2 for Predicting Severity of Patients With Influenza A Virus and SARS-CoV-2 Infection.

Front Microbiol 2022 12;13:854172. Epub 2022 Apr 12.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Background: Influenza and COVID-19 are respiratory infectious diseases that are characterized by high contagiousness and high mutation and pose a serious threat to global health. After Influenza A virus (IAV) and SARS-CoV-2 infection, severe cases may develop into acute lung injury. Immune factors act as an important role during infection and inflammation. However, the molecular immune mechanisms still remain unclear. We aimed to explore immune-related host factors and core biomarker for severe infection, to provide a new therapeutic target of host factor in patients.

Methods: Gene expression profiles were obtained from Gene Expression Omnibus and the Seurat R package was used for data process of single-cell transcriptome. Differentially expressed gene analysis and cell cluster were used to explore core host genes and source cells of genes. We performed Gene Ontology enrichment, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis to explore potential biological functions of genes. Gene set variation analysis was used to evaluate the important gene set variation score for different samples. We conduct Enzyme-linked immunosorbent assay (ELISA) to test plasma concentrations of Lipocalin 2 (LCN2).

Results: Multiple virus-related, cytokine-related, and chemokine-related pathways involved in process of IAV infection and inflammatory response mainly derive from macrophages and neutrophils. LCN2 mainly in neutrophils was significantly upregulated after either IAV or SARS-CoV-2 infection and positively correlated with disease severity. The plasma LCN2 of influenza patients were elevated significantly compared with healthy controls by ELISA and positively correlated with disease severity of influenza patients. Further bioinformatics analysis revealed that LCN2 involved in functions of neutrophils, including neutrophil degranulation, neutrophil activation involved in immune response, and neutrophil extracellular trap formation.

Conclusion: The neutrophil-related LCN2 could be a promising biomarker for predicting severity of patients with IAV and SARS-CoV-2 infection and may as a new treatment target in severe patients.
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http://dx.doi.org/10.3389/fmicb.2022.854172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039618PMC
April 2022

Challenges and opportunities of hydrothermal carbonisation in the UK; case study in Chirnside.

RSC Adv 2021 Oct 27;11(55):34870-34897. Epub 2021 Oct 27.

Institute for Materials and Processes, School of Engineering, The University of Edinburgh Edinburgh EH9 3FB UK

The latest research and development in hydrothermal carbonisation (HTC) processes are reviewed and the feasibility of application to small towns in the UK is assessed. The HTC process designed in this report is theoretically evaluated for the biodegradable municipal waste and sewage waste produced by the small town of Chirnside, in the Scottish Borders. Calculation of mass and energy balances of the process are carried out alongside the evaluation of challenges and environmental, social and economic opportunities presented. The hypothetical HTC plant is capable of processing 267.14 t per year of food waste and 105.12 t per year of faecal sludge produced by Chirnsides estimated 2250 residents in 2041. The plant would be capable of producing 99.08 t per year of hydrochar with an estimated total energy content of 540.26 MWh per year. When used in a Biomass Combined Heat and Power Plant, the hydrochar would be capable of supplying Chirnsides residents with 0.71% and 3.43% of its domestic thermal energy demand and domestic electrical energy demand in 2041, respectively. Both the expected opportunities and challenges for the application of HTC are discussed, shedding light on the associated research in regards to this sustainable technology.
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http://dx.doi.org/10.1039/d1ra06736bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9042953PMC
October 2021

Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage.

Autophagy 2022 Apr 26:1-17. Epub 2022 Apr 26.

State Key Laboratory of Bioelectronics, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, Jiangsu, China.

Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss.
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http://dx.doi.org/10.1080/15548627.2022.2062872DOI Listing
April 2022

Topical Application of Tetrandrine Nanoemulsion Promotes the Expansion of CD4Foxp3 Regulatory T Cells and Alleviates Imiquimod-Induced Psoriasis in Mice.

Front Immunol 2022 6;13:800283. Epub 2022 Apr 6.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, Macau SAR, China.

There is compelling evidence that CD4Foxp3 regulatory T cells (Tregs) are indispensable in the inhibition of autoimmune inflammatory responses, including psoriasis. Recently, we showed that systemically treatment with tetrandrine (TET), a two-pore channel inhibitor identified from the Chinese herb . Moor, could promote the proliferative expansion of Tregs in mice through stimulation of TNF-TNFR2 interaction. We thus hypothesized that topical administration of TET might also expand Tregs and consequently inhibit psoriasis. To this end, we developed a TET nanoemulsion and examined its effect on the expansion of Tregs after topical administration on mouse psoriasis induced by imiquimod. The result of our experiment showed that topical treatment with TET nanoemulsion markedly increased the proportion and number of Tregs in the spleen, as well as TNFR2 and Ki-67 expression by Tregs, in WT and TNFR1 KO mice, but not in TNFR2 KO mice. Consequently, TET nanoemulsion potently inhibited IL-17-expressing cells in the spleen and lymph nodes of imiquimod-treated WT mice, accompanied by decreased serum levels of IL-17A, INF-γ, and TNF and their mRNA levels in the flamed lesion. Importantly, TET nanoemulsion treatment markedly inhibited the development of psoriasis-like disease in WT and TNFR1 KO mice but not in TNFR2 KO mice. Therefore, our study indicates that the topical administration of TET could also stimulate the expansion of Tregs through the TNF-TNFR2 pathway. This effect of TET and its analogs may be useful in the treatment of inflammatory skin diseases such as psoriasis.
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http://dx.doi.org/10.3389/fimmu.2022.800283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020220PMC
April 2022

SLC1A1-mediated cellular and mitochondrial influx of R-2-hydroxyglutarate in vascular endothelial cells promotes tumor angiogenesis in IDH1-mutant solid tumors.

Cell Res 2022 Apr 22. Epub 2022 Apr 22.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Mutant isocitrate dehydrogenase 1 (mIDH1) drives tumorigenesis via producing oncometabolite R-2-hydroxyglutarate (R-2-HG) across various tumor types. However, mIDH1 inhibitors appear only effective in hematological tumors. The therapeutic benefit in solid tumors remains elusive, likely due to the complex tumor microenvironment. In this study, we discover that R-2-HG produced by IDH1-mutant tumor cells is preferentially imported into vascular endothelial cells and remodels mitochondrial respiration to promote tumor angiogenesis, conferring a therapeutic vulnerability in IDH1-mutant solid tumors. Mechanistically, SLC1A1, a Na-dependent glutamate transporter that is preferentially expressed in endothelial cells, facilitates the influx of R-2-HG from the tumor microenvironment into the endothelial cells as well as the intracellular trafficking of R-2-HG from cytoplasm to mitochondria. R-2-HG hijacks SLC1A1 to promote mitochondrial Na/Ca exchange, which activates the mitochondrial respiratory chain and fuels vascular endothelial cell migration in tumor angiogenesis. SLC1A1 deficiency in mice abolishes mIDH1-promoted tumor angiogenesis as well as the therapeutic benefit of mIDH1 inhibitor in solid tumors. Moreover, we report that HH2301, a newly discovered mIDH1 inhibitor, shows promising efficacy in treating IDH1-mutant cholangiocarcinoma in preclinical models. Together, we identify a new role of SLC1A1 as a gatekeeper of R-2-HG-mediated crosstalk between IDH1-mutant tumor cells and vascular endothelial cells, and demonstrate the therapeutic potential of mIDH1 inhibitors in treating IDH1-mutant solid tumors via disrupting R-2-HG-promoted tumor angiogenesis.
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http://dx.doi.org/10.1038/s41422-022-00650-wDOI Listing
April 2022

Cyclodextrin-Derived ROS-Generating Nanomedicine with pH-Modulated Degradability to Enhance Tumor Ferroptosis Therapy and Chemotherapy.

Small 2022 May 22;18(20):e2200330. Epub 2022 Apr 22.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macau, 999078, China.

Nowadays, destruction of redox homeostasis to induce cancer cell death is an emerging anti-cancer strategy. Here, the authors utilized pH-sensitive acetalated β-cyclodextrin (Ac-β-CD) to efficiently deliver dihydroartemisinin (DHA) for tumor ferroptosis therapy and chemodynamic therapy in a synergistic manner. The Ac-β-CD-DHA based nanoparticles are coated by an iron-containing polyphenol network. In response to the tumor microenvironment, Fe /Fe can consume glutathione (GSH) and trigger the Fenton reaction in the presence of hydrogen peroxide (H O ), leading to the generation of lethal reactive oxygen species (ROS). Meanwhile, the OO bridge bonds of DHA are also disintegrated to enable ferroptosis of cancer cells. Their results demonstrate that these nanoparticles acted as a ROS generator to break the redox balance of cancer cells, showing an effective anticancer efficacy, which is different from traditional approaches.
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http://dx.doi.org/10.1002/smll.202200330DOI Listing
May 2022

Exploring Potential Regulatory Anesthetic Drugs Based on RNA Binding Protein and Constructing CESC Prognosis Model: A Study Based on TCGA Database.

Front Surg 2022 5;9:823566. Epub 2022 Apr 5.

Department of Anesthesiology, First Affiliated Hospital of Soochow University, Suzhou, China.

Objective: To investigate the differential expression of RBPs in cervical squamous cell carcinoma (CESC), analyze the regulatory effect of narcotic drugs on RBPs, and establish the prognostic risk model of CESC patients.

Methods: RNA-SEQ data and clinical case data of cancer and normal samples from CESC patients were obtained from the Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) database. Differentially expressed RBPs were screened by R language and enriched. The CMAP database is used to predict the anesthetic drugs that regulate the differential expression of RBPs. The prognostic risk score model was constructed by COX regression analysis. Risk score of each CESC patient was calculated and divided into high-risk group and low-risk group according to the median risk score. The prediction efficiency of prognostic risk model was evaluated by Kaplan-Meier (KM) analysis and receiver operating characteristic (ROC) curve, and the correlation between prognostic risk model and clinical characteristics was analyzed. Immunohistochemistry was used to detect the expression of RNASEH2A and HENMT1 in tissues.

Results: There were 65 differentially expressed RBPs in CESC. Five anesthetics, including benzocaine, procaine, pentoxyverine, and tetracaine were obtained to regulate RBPs. Survival analysis showed that seven genes were related to the prognosis of patients, and the CESC risk score model was constructed by COX regression. The risk score can be used as an independent prognostic factor. RNASEH2A and HENMT1 are up-regulated in tumors, which can effectively distinguish normal tissues from tumor tissues.

Conclusion: It is found that different anesthetic drugs have different regulatory effects on the differential expression of RBPs. Based on the differentially expressed RBPs, the prognostic risk score model of CESC patients was constructed. To provide ideas for the formulation of individualized precise anesthesia scheme and cancer pain analgesia scheme, which is helpful to improve the perioperative survival rate of cancer patients.
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http://dx.doi.org/10.3389/fsurg.2022.823566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018109PMC
April 2022

Accelerating Decreases in the Incidences of Hepatocellular Carcinoma at a Younger Age in Shanghai Are Associated With Hepatitis B Virus Vaccination.

Front Oncol 2022 4;12:855945. Epub 2022 Apr 4.

School of Public Health, Fudan University, Shanghai, China.

Background: Routine vaccination of infants for protecting against hepatitis B virus (HBV) infection and its serious consequences, including hepatocellular cancer (HCC), has been carried out in Shanghai, China, since 1986. We therefore have examined the trend of HBV infection and HCC incidences before and after HBV vaccination over decades to assess the potential influences of the Shanghai HBV vaccination program.

Methods: Data on incidences of HBV infection and HCC were collected from the Shanghai Cancer Registry and the Shanghai HBV vaccination follow-up study. Joint-point regression and the Bayesian age-period-cohort statistical analysis methods were used.

Results: The incidences of HBV infection dramatically declined from 23.09 and 1.13 per 100,000 for males and females in 2000 to 3.24 (-85.97%) and 0.22 (-80.53%) per 100,000 in 2014, respectively. Sero-epidemiological data from the sampling surveys during 20 years of follow-up showed that less than 1% of people undergoing HBV vaccination have a positive serum HBsAg. Consistently, the annual adjusted standardization rates (ASR) of HCC steadily fell from 33.38 and 11.65 per 100,000 for males and females in 1973 to 17.34 (-49.2%) and 5.60 (-51.9%) per 100,000 in 2014, respectively. The annual percentage change in overall HCC incidences is about -2%. HCC incidences in males at younger age groups (age <50 years old), particularly in those with age <34 groups, showed an accelerating decrease over time, whereas HCC incidences significantly declined in the female population across all age groups except for those under 19 years of age. The results supported that the universal HBV vaccination in newborns is easy to implement with high coverages and is effective for preventing both HBV infection and HCC in populations.
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http://dx.doi.org/10.3389/fonc.2022.855945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9014260PMC
April 2022

Activation of YAP1 by STK25 contributes to the progression of hepatocellular carcinoma.

Tissue Cell 2022 Jun 6;76:101797. Epub 2022 Apr 6.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157 Xi Wu Road, Xi'an, Shaanxi 710004, China.

A pathogenic role of serine/threonine protein kinase 25 (STK25) has been observed in several chronic liver diseases. However, whether STK25 participates in hepatocellular carcinoma (HCC) remains unexplored. The current work aimed to explore the role and mechanism of STK25 in HCC. A high STK25 level was found in HCC tissue, which was associated with reduced overall survival. HCC cells with STK25 silencing displayed a marked decrease in proliferative and invasive ability, but were highly sensitive to apoptosis induced by the chemotherapy drug sorafenib. Reciprocally, HCC cells with forced expression of STK25 displayed the opposite effects. Further data unveiled that STK25 silencing restrained the activation of Yes-associated protein 1 (YAP1) associated with regulation of mammalian STE20-like protein kinase 1/2 (MST1/2). Forced expression of constitutively active YAP1 abolished STK25 silencing-induced antitumor effects, while repression of YAP1 reversed STK25 upregulation-induced protumor effects. Additionally, HCC cells with STK25 silencing exhibited reduced tumorigenic potential in vivo. Collectively, the results show that STK25 exerts a protumor function in HCC by enhancing YAP1 activation via regulation of MST1/2. These findings propose STK25 as a viable target for the development of anti-HCC therapy.
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http://dx.doi.org/10.1016/j.tice.2022.101797DOI Listing
June 2022

Switching Diagram of Core-Shell FePt/Fe Nanocomposites for Bit Patterned Media.

Materials (Basel) 2022 Mar 31;15(7). Epub 2022 Mar 31.

Department of Materials Science and Engineering, Xiamen Institute of Technology, Xiamen 361021, Fujian Province, China.

In the current work, a core-shell type exchange coupled composite structure was constructed by micromagnetic simulation with a phase FePt core and an iron shell. Four types of switching loops with magnetic domain structure evolution were demonstrated. Based on the simulation results, a switching type diagram was constructed, which displays various hysteresis loops as a function of core radius and shell thickness. Furthermore, the effects of switching type and composite structure on the coercivity and remanent magnetization were predicted and discussed. This finding indicates that core-shell type FePt/Fe composite structure film has a large advantage in designing exchange-coupled bit patterned media to realize high-density storage devices at the nanoscale.
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http://dx.doi.org/10.3390/ma15072581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000370PMC
March 2022

Effect of light quality on the growth and main chemical composition of Bletilla striata.

J Plant Physiol 2022 May 1;272:153690. Epub 2022 Apr 1.

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University, Hangzhou, 311300, China; Zhejiang Provincial Key Laboratory of Resources Protection and Innovation of Traditional Chinese Medicine, Zhejiang A&F University, Hangzhou, 311300, China. Electronic address:

This study aimed to investigate the effects of light quality on the morphological traits, photosynthetic pigment content, protective enzyme (superoxide dismutase, peroxidase, and catalase) activity, and bioactive compound (BSP, total phenol, and militarine) content in Bletilla striata. Plants of B. striata were grown under light filtered through three differently colored films. The treatments were red film (RF), yellow film (YF), and blue film (BF), and an uncovered treatment was included as a control (CK). Compared with the B. striata plants in the RF, YF, and CK treatment groups, those receiving BF treatment showed significantly promoted growth of the aerial parts. Meanwhile, the total phenol and militarine contents in B. striata tubers were increased without affecting the accumulation of B. striata polysaccharides. These results show that growing B. striata plants under blue film could be a useful technique to improve quality and production. This technique is conducive to achieving large-scale sustainable production of high-quality plant materials.
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http://dx.doi.org/10.1016/j.jplph.2022.153690DOI Listing
May 2022

Treatment of refractory acne using selective sebaceous gland electro-thermolysis combined with non-thermal plasma.

J Cosmet Laser Ther 2022 Apr 7:1-7. Epub 2022 Apr 7.

Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Acne is one of the most common skin diseases whose disfiguring results may cause psychological problems. Despite of the various choices in the treatment of acne, new therapy with fewer complications and lower relapse rate is still in need. In this study, we aim to evaluate the clinical efficacy of a new therapy using selective sebaceous gland electro-thermolysis and non-thermal plasma (NTP) in refractory acne patients. Treatments were given at a monthly interval for three times. The last visit was set at 3 months after the third treatment. Thirty-six moderate to very severe acne patients were enrolled. All the patients got more than 50% clearance after the third treatment. The excellent response rate was 44% at 1 month after the third treatment and 50% at 3 months after the third treatment. Porphyrin and erythema values were significantly reduced after the third treatment. No irreversible complication was reported. Selective sebaceous gland electro-thermolysis combined with NTP can be a safe and effective new option in the treatment of acne.
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http://dx.doi.org/10.1080/14764172.2022.2050760DOI Listing
April 2022

Application Value of Predictive Model Based on Maternal Coagulation Function and Glycolipid Metabolism Indicators in Early Diagnosis of Gestational Diabetes Mellitus.

Front Public Health 2022 21;10:850191. Epub 2022 Mar 21.

Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Objective: To investigate whether first-trimester fasting plasma glucose (FPG), blood coagulation function and lipid metabolism could predict gestational diabetes mellitus (GDM) risk.

Methods: From October 2020 to May 2021, a total of 584 pregnant women who took prenatal care in Shanghai Jiaotong University Affiliated Sixth People's Hospital were chosen as the observation subjects. The clinical information and serum samples of all pregnant women were collected at 10-13 weeks of gestation and the blood coagulation function, fasting blood glucose and lipid profiles of the pregnant women were detected. A 75 g oral glucose tolerance test was performed up to 24-28 weeks of gestation. One hundred forty-two pregnant women with GDM and 442 pregnant women without GDM were detected. Data were expressed by x ± s or median (interquartile range) and were analyzed using student's -test, Wilcoxon rank sum test and Logistic regression analysis. The area under the curve (AUC) was calculated by receiver operating characteristic curve (ROC) to analyze the predictive values.

Results: Compared with non-GDM group, age, pre-pregnancy BMI, FPG, FIB, D-Dimer, FDP, FPG, TC, TG, LDL-C, sdLDL-C, APOB and APOE in GDM group were significantly higher than those in non-GDM group, while PT, INR, APTT and TT were significantly lower than those in non-GDM group. Univariate logistic regression analysis was used to explore the risk factors of GDM. Gestational age, pre-pregnancy BMI, FPG, PT, INR, APTT, FIB, TT, D-Dimer, TC, TG, LDL-C, sdLDL-C, APOB and APOE were all independent predictors of GDM. Multivariatelogistic regression showed that pre-pregnancy BMI, FPG, APTT, TT, TG, LDL-C, sdLDL-C and APOB were risk factors for GDM. The AUC of the established GDM risk prediction model was 0.892 (0.858-0.927), and the sensitivity and specificity were 80.71 and 86.85%, respectively; which were greater than that of pre-pregnancy BMI, FPG, APTT, TT,TG, LDL-C, sdLDL-C, APOB alone, and the difffference was statistically signifificant ( < 0.05).

Conclusions: FPG, APTT, TT, TG, LDL-C, sdLDL-C, APOB and pre-pregnancy BMI in early pregnancy has important clinical value for the prediction of GDM, We combined these laboratory indicators and established a GDM risk prediction model, which is conducive to the early identification, intervention and treatment of GDM, so as to reduce the morbidity of maternal and infant complications.
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http://dx.doi.org/10.3389/fpubh.2022.850191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8978602PMC
April 2022

Breast cancer screening and early diagnosis in Chinese women.

Cancer Biol Med 2022 Apr 5. Epub 2022 Apr 5.

Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Breast cancer is the most common malignant tumor in Chinese women, and its incidence is increasing. Regular screening is an effective method for early tumor detection and improving patient prognosis. In this review, we analyze the epidemiological changes and risk factors associated with breast cancer in China and describe the establishment of a screening strategy suitable for Chinese women. Chinese patients with breast cancer tend to be younger than Western patients and to have denser breasts. Therefore, the age of initial screening in Chinese women should be earlier, and the importance of screening with a combination of ultrasound and mammography is stressed. Moreover, Chinese patients with breast cancers have several ancestry-specific genetic features, and aiding in the determination of genetic screening strategies for identifying high-risk populations. On the basis of current studies, we summarize the development of risk-stratified breast cancer screening guidelines for Chinese women and describe the significant improvement in the prognosis of patients with breast cancer in China.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2021.0676DOI Listing
April 2022

Atypical deletion of Williams-Beuren syndrome reveals the mechanism of neurodevelopmental disorders.

BMC Med Genomics 2022 04 4;15(1):79. Epub 2022 Apr 4.

Department of Cardiovascular Surgery of Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Genes associated with specific neurocognitive phenotypes in Williams-Beuren syndrome are still controversially discussed. This study identified nine patients with atypical deletions out of 111 patients with Williams-Beuren syndrome; these deletions included seven smaller deletions and two larger deletions. One patient had normal neurodevelopment with a deletion of genes on the distal side of the Williams-Beuren syndrome chromosomal region, including GTF2I and GTF2IRD1. However, another patient retained these genes but showed neurodevelopmental abnormalities. By comparing the genotypes and phenotypes of patients with typical and atypical deletions and previous reports in the literature, we hypothesize that the BAZ1B, FZD9, and STX1A genes may play an important role in the neurodevelopment of patients with WBS.
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http://dx.doi.org/10.1186/s12920-022-01227-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981662PMC
April 2022
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