Publications by authors named "Lei Han"

1,054 Publications

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The Application of Artificial Neural Network Combined with Virtual Reality Technology in Environment Art Design.

Authors:
Lei Han Li Gan

Comput Intell Neurosci 2022 14;2022:7562167. Epub 2022 May 14.

School of Design, NingboTech University, Ningbo 315100, Zhejiang, China.

Virtual reality is a computer technology that produces a simulated environment. It is completely immersive and gives users the viewpoint that they are somewhere else. In recent times, it has become a highly interactive and visualization tool that has gained interest among educators and scholars. Art learning is a teaching-learning approach that is dependent on learning "" and ";" it can be a procedure in which art develops the medium of teaching-learning and an important model in some subjects of the curriculum. In this work, we develop a grey wolf optimization with the residual network form of virtual reality application for environmental art learning (GWORN-EAL) technique. It aims to provide metacognitive actions to improve environmental art learning for young children or adults. The GWORN-EAL technique is mainly based on the stimulation of particular features of the target painting over a default image. The color palette of the recognized image of the Fauve painter was mapped to the target image using the Fauve vision of the painter and represented by vivid colors. For optimal hyperparameter tuning of the ResNet model, the GWO algorithm is employed. The experimental results indicated that the GWORN-EAL technique has accomplished effectual outcomes in several aspects. A brief experimental study highlighted the improvement of the GWORN-EAL technique compared to existing models.
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http://dx.doi.org/10.1155/2022/7562167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9124091PMC
May 2022

Practice guidance for the use of terlipressin for liver cirrhosis-related complications.

Therap Adv Gastroenterol 2022 18;15:17562848221098253. Epub 2022 May 18.

Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China.

Background: Liver cirrhosis is a major global health burden worldwide due to its high risk of morbidity and mortality. Role of terlipressin for the management of liver cirrhosis-related complications has been recognized during recent years. This article aims to develop evidence-based clinical practice guidance on the use of terlipressin for liver cirrhosis-related complications.

Methods: Hepatobiliary Study Group of the Chinese Society of Gastroenterology of the Chinese Medical Association and Hepatology Committee of the Chinese Research Hospital Association have invited gastroenterologists, hepatologists, infectious disease specialists, surgeons, and clinical pharmacists to formulate the clinical practice guidance based on comprehensive literature review and experts' clinical experiences.

Results: Overall, 10 major guidance statements regarding efficacy and safety of terlipressin in liver cirrhosis were proposed. Terlipressin can be beneficial for the management of cirrhotic patients with acute variceal bleeding and hepatorenal syndrome (HRS). However, the evidence regarding the use of terlipressin in cirrhotic patients with ascites, post-paracentesis circulatory dysfunction, and bacterial infections and in those undergoing hepatic resection and liver transplantation remains insufficient. Terlipressin-related adverse events, mainly including gastrointestinal symptoms, electrolyte disturbance, and cardiovascular and respiratory adverse events, should be closely monitored.

Conclusion: The current clinical practice guidance supports the use of terlipressin for gastroesophageal variceal bleeding and HRS in liver cirrhosis. High-quality studies are needed to further clarify its potential effects in other liver cirrhosis-related complications.
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http://dx.doi.org/10.1177/17562848221098253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121451PMC
May 2022

A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease.

J Nanobiotechnology 2022 May 19;20(1):237. Epub 2022 May 19.

School of Pharmacy & Minhang Hospital, Shanghai Engineering Research Center of Immunotherapeutic, Fudan University, Shanghai, 201203, China.

Background: Nonalcoholic fatty liver disease (NAFLD) is a metabolic disease mainly on account of hypercholesterolemia and may progress to cirrhosis and hepatocellular carcinoma. The discovery of effective therapy for NAFLD is an essential unmet need. Angiopoietin-like protein 3 (ANGPTL3), a critical lipid metabolism regulator, resulted in increased blood lipids and was elevated in NAFLD. Here, we developed a nanobody-heavy chain antibody (VHH-Fc) to inhibit ANGPTL3 for NAFLD treatment.

Results: In this study, we retrieved an anti-ANGPTL3 VHH and Fc fusion protein, C44-Fc, which exhibited high affinities to ANGPTL3 proteins and rescued ANGPLT3-mediated inhibition of lipoprotein lipase (LPL) activity. The C44-Fc bound a distinctive epitope within ANGPTL3 when compared with the approved evinacumab, and showed higher expression yield. Meanwhile, C44-Fc had significant reduction of the triglyceride (~ 44.2%), total cholesterol (~ 36.6%) and LDL-cholesterol (~ 54.4%) in hypercholesterolemic mice and ameliorated hepatic lipid accumulation and liver injury in NAFLD mice model.

Conclusions: We discovered a VHH-Fc fusion protein with high affinity to ANGPTL3, strong stability and also alleviated the progression of NAFLD, which might offer a promising therapy for NAFLD.
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http://dx.doi.org/10.1186/s12951-022-01456-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118633PMC
May 2022

Piezoelectric Strain-Controlled Magnon Spin Current Transport in an Antiferromagnet.

Nano Lett 2022 May 18. Epub 2022 May 18.

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

As the core of spintronics, the transport of spin aims at a low-dissipation data process. The pure spin current transmission carried by magnons in antiferromagnetic insulators is natively endowed with superiority such as long-distance propagation and ultrafast speed. However, the traditional control of magnon transport in an antiferromagnet via a magnetic field or temperature variation adds critical inconvenience to practical applications. Controlling magnon transport by electric methods is a promising way to overcome such embarrassment and to promote the development of energy-efficient antiferromagnetic logic. Here, the experimental realization of an electric field-induced piezoelectric strain-controlled magnon spin current transmission through the antiferromagnetic insulator in the YFeO/CrO/Pt trilayer is reported. An efficient and nonvolatile manipulation of magnon propagation/blocking is achieved by changing the relative direction between the Néel vector and spin polarization, which is tuned by ferroelastic strain from the piezoelectric substrate. The piezoelectric strain-controlled antiferromagnetic magnon transport opens an avenue for the exploitation of antiferromagnet-based spin/magnon transistors with ultrahigh energy efficiency.
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http://dx.doi.org/10.1021/acs.nanolett.2c00405DOI Listing
May 2022

Prevalence and management of pain in lung cancer patients in northern China: A multicenter cross-sectional study.

Thorac Cancer 2022 May 17. Epub 2022 May 17.

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing, China.

Background: Pain is a fearful yet common symptom among lung cancer patients. This multicenter, cross-sectional study was conducted to examine the current status of pain prevalence and management in lung cancer patients in northern China.

Methods: A total of 18 hospitals across northern China were selected. Patients with primary lung cancer who visited the outpatient clinic or were admitted in the wards on a preplanned day were invited to complete a questionnaire. Meanwhile, physicians who had experience of treating primary lung cancer patients were also surveyed.

Results: A total of 533 patients and 197 physicians provided valid responses to the survey, of which 45.4% (242/533) of patients reported pain during the course of disease and 24.2% (129/533) of patients had experienced pain within the past 24 h. The mean average pain intensity by the brief pain inventory was 3.47 ± 1.55. The binary logistic regression analysis showed female gender and stage IV disease were significantly associated with the presence of pain. A total of 74.4% (96/129) of patients reporting pain within 24 h were taking analgesics. The most common reason for patients not using analgesics was that the pain was tolerable (48.2%), while the most common barriers to prescribing opioids as reported by physicians were fear of adverse reactions (43.7%) and fear of addiction (43.1%).

Conclusion: Despite recognition of the importance of pain control by most physicians and an improvement in cancer pain management, inadequate treatment of cancer pain still exists in lung cancer patients in northern China. High-quality pain education for both patients and physicians is needed in the future.
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http://dx.doi.org/10.1111/1759-7714.14444DOI Listing
May 2022

Industry Distribution Characteristics of Benzene-Induced Leukemia - 7 PLADs, China, 2005-2019.

China CDC Wkly 2022 Apr;4(17):358-363

Key Laboratory of Chemical Safety and Health, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.

What Is Already Known About This Topic?: In the 1980s. benzene-induced leukemia (BIL) mainly occurred in shoemaking and painting industries. Now the industry distribution of benzene-induced leukemia may have changed over time.

What Is Added By This Report?: BlL cases mainly occurred in the manufacturing industry from 2005-2019, especially in private enterprises and small/medium-sized enterprises. The industry with the largest number of new cases of BIL was the general and special equipment manufacturing. The number of leukemia cases in emerging industries such as computer/electronic product manufacturing was found to be increasing.

What Are The Implications For Public Health Practice?: Strengthening supervision and regulation of manufacturing, especially of small/medium-sized enterprises and emerging manufacturing industry, may be effective in reducing BIL.
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http://dx.doi.org/10.46234/ccdcw2022.084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081900PMC
April 2022

LAMC1-mediated preadipocytes differentiation promoted peritoneum pre-metastatic niche formation and gastric cancer metastasis.

Int J Biol Sci 2022 24;18(7):3082-3101. Epub 2022 Apr 24.

Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, China.

Gastric cancer is anatomically proximal to peritoneum. Gastric cancer peritoneal metastasis is a complex biological process which is corresponded with disharmony within dysfunctional adipose tissue and metabolism reprogramming. Laminin gamma 1 (LAMC1) is highly expressed in cancer cells of peritoneal metastatic sites, however, the mechanism of LAMC1-metiated gastric cancer metastases to adipose tissue-rich peritoneum remains unclear. In our study, immunohistochemical staining, single cell sequencing, a co-culture model, luciferase reporter, RNA immunoprecipitation (RIP), Chromatin immunoprecipitation (CHIP) and single-molecular magnetic tweezers assays were conducted, and our results showed that LAMC1 related to Perilipin-1 content was highly expressed in peritoneal metastatic sites and mainly secreted by tumor cells. Gastric cancer cells secreted LAMC1 in an autocrine manner to detached from the primary site and promoted preadipocytes mature, rupture and release of free fatty acids (FFAs) in the peritoneal microenvironment to form pre-metastatic niche by the paracrine pathway. Reversely, differentiated preadipocyte-derived conditioned medium inhibited glycolysis and enhanced fatty acid oxidation (FAO) rate to promote cell proliferation, mesenchymal-epithelial transformation which led to tumor peritoneal colonization. In terms of biological mechanisms, one of differentiated preadipocyte-derived FFAs, palmitic acid-activated STAT3 inhibited miR-193a-3p by binding to its promoter directly; Using single-molecular magnetic tweezers, this binding manner was proved to be stable, reversable and ATP-dependent. Moreover, miR-193a-3p regulated LAMC1 in a post-translational manner. Furthermore, high LAMC1 expression in serum predicted a higher risk of peritoneal metastasis. In conclusion, our results illustrated that palmitic acid/p-STAT3/miR-193a-3p/LAMC1 pathway promotes preadipocyte differentiation, pre-metastatic niche formation and gastric cancer cell colonization to peritoneum.
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http://dx.doi.org/10.7150/ijbs.70524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9066104PMC
May 2022

A robust air superhydrophilic/superoleophobic diatomite porous ceramic for high-performance continuous separation of oil-in-water emulsion.

Chemosphere 2022 May 6;303(Pt 1):134756. Epub 2022 May 6.

College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, EX4 4QF, UK.

Three-dimensional (3D) porous architecture has attracted considerable attention in remediation of oil/water emulsion. In present work, an air superhydrophilic/superoleophobic diatomite porous ceramic (AS-DC) was prepared, using SiO whiskers modified diatomite ceramic as the substrate and FS-50 as the modifier. The interconnected SiO whiskers intertwined on the skeleton of ceramic block forming a 3D network structure, which not only improved the wettability of AS-DC, but also reinforced its mechanical property (about 2.5 MPa of compressive strength). The as-prepared AS-DC with intrinsically superoleophobicity (154°) and superhydrophilicity (0°) exhibited an underwater oil contact angle of 161°, suggesting a multifunctional separation capability. By simply assembling AS-DC with pipes and a pump, it could not only separate the surfactant-stabilized oil-in-water emulsion in a permeation flux as high as 107.8 kg min m with a selectivity of >95%, but also collect the clean water from the floating oil/water mixture in a flux of 197.4 kg min m and a selectivity of ∼99%. In addition, the AS-DC was resistant to the salt/acid/alkaline corrosion and temperature fluctuation. The mechanical/chemical firmness of AS-DC renders it tremendous potential as a robust 3D architecture in real application for purification of oil/water mixture.
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http://dx.doi.org/10.1016/j.chemosphere.2022.134756DOI Listing
May 2022

Spatiotemporal transcriptomic atlas of mouse organogenesis using DNA nanoball-patterned arrays.

Cell 2022 May 4;185(10):1777-1792.e21. Epub 2022 May 4.

BGI-Shenzhen, Shenzhen 518103, China.

Spatially resolved transcriptomic technologies are promising tools to study complex biological processes such as mammalian embryogenesis. However, the imbalance between resolution, gene capture, and field of view of current methodologies precludes their systematic application to analyze relatively large and three-dimensional mid- and late-gestation embryos. Here, we combined DNA nanoball (DNB)-patterned arrays and in situ RNA capture to create spatial enhanced resolution omics-sequencing (Stereo-seq). We applied Stereo-seq to generate the mouse organogenesis spatiotemporal transcriptomic atlas (MOSTA), which maps with single-cell resolution and high sensitivity the kinetics and directionality of transcriptional variation during mouse organogenesis. We used this information to gain insight into the molecular basis of spatial cell heterogeneity and cell fate specification in developing tissues such as the dorsal midbrain. Our panoramic atlas will facilitate in-depth investigation of longstanding questions concerning normal and abnormal mammalian development.
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http://dx.doi.org/10.1016/j.cell.2022.04.003DOI Listing
May 2022

Boosting the energy storage performance of MOF-derived CoS nanoarrays sulfur vacancy and surface engineering.

Chem Commun (Camb) 2022 May 24;58(42):6243-6246. Epub 2022 May 24.

School of Materials Science & Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China.

Hierarchical CoS hollow nanosheet arrays are prepared through a MOF-engaged strategy, followed by room-temperature NaBH treatment, resulting in simultaneous regulation of sulfur vacancies and surface morphology. The obtained electrode exhibits excellent electrochemical properties due to large active sites, fast charge diffusion and high electronic conductivity resulting from the hierarchical hollow structure and rich sulfur vacancies.
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http://dx.doi.org/10.1039/d2cc01274jDOI Listing
May 2022

[Analysis of risk factors of healthy side fracture after hip fracture surgery in the elderly].

Zhongguo Gu Shang 2022 Apr;35(4):353-6

Department of Orthopaedics, the Second Affiliated Hospital Zhejiang University School of Medicine International Medical Center, Hangzhou 311201, Zhejiang, China.

Objective: To investigate the incidence and related risk factors of healthy side fracture after hip fracture surgery in the elderly, so as to provide basis for the prevention of re-fracture.

Methods: The data of 452 patients over 65 years old with femoral neck fracture or intertrochanteric fracture treated with hip arthroplasty or proximal femoral intramedullary nailing from June 2012 to June 2017 were analyzed, including 168 males and 284 females, the age ranged from 65 to 97(75.5±7.5) years. There were 191 cases of femoral neck fracture and 261 cases of femoral intertrochanteric fracture. According to whether there was a fracture in the healthy hip after operation, the patients were divided into fracture group and no fracture group. The gender, age, body mass index, fracture type, initial treatment method, bone mineral density, bed time, medical compliance, postoperative short-term delirium, whether there were medical diseases before injury and Harris score of hip joint in the final follow-up were recorded. Univariate Logistic regression analysis was used to screen out the risk factors of healthy side fracture after operation, and then statistically significant risk factors were included in multi factor Logistic regression analysis to screen out the independent risk factors of healthy side fracture after operation of hip fracture in the elderly.

Results: Among them, 42 of the 452 patients had hip fractures on the healthy side with an incidence of 9.3%. The average interval between the two fractures was (2.9±2.1) years. Univariate Logistic regression analysis showed that there were significant differences in age, bone mineral density, medical compliance, short-term postoperative deliriun, pre-injury complicated with medical diseases and Harris score of hip joint in the final follow-up (<0.05). Multivariate Logistic analysis showed that age(=4.227), bone mineral density(=4.313), combined with medical diseases (=5.616) and low hip Harris score at the final follow-up (=3.891) were independent risk factors for healthy side fractures after hip fracture surgery in elderly(<0.05).

Conclusion: The age, bone mineral density, combined with medical diseases and low Harris score of hip joint in the final follow-up are the main risk factors of healthy side fracture after hip fracture in the elderly. It is necessary to strengthen the treatment of medical diseases, anti osteoporosis and improve hip joint function within 3 years after operation, so as to prevent the occurrence of healthy side hip fracture.
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http://dx.doi.org/10.12200/j.issn.1003-0034.2022.04.011DOI Listing
April 2022

A New Fusion Fault Diagnosis Method for Fiber Optic Gyroscopes.

Sensors (Basel) 2022 Apr 8;22(8). Epub 2022 Apr 8.

School of Mechanical Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China.

The fiber optic gyroscope (FOG) is a high precision inertial navigation device, and it is necessary to ensure its reliability for effective use. However, the extracted fault features are easily distorted due to the interference of vibrations when the FOG is in operation. In order to minimize the influence of vibrations to the greatest extent, a fusion diagnosis method was proposed in this paper. It extracted features from fault data with Fast Fourier Transform (FFT) and wavelet packet decomposition (WPD), and built a strong diagnostic classifier with a sparse auto encoder (SAE) and a neural network (NN). Then, a fusion neural network model was established based on the diagnostic output probabilities of the two primary classifiers, which improved the diagnostic accuracy and the anti-vibration capability. Then, five fault types of the FOG under random vibration conditions were established. Fault data sets were collected and generated for experimental comparison with other methods. The results showed that the proposed fusion fault diagnosis method could perform effective and robust fault diagnosis for the FOG under vibration conditions with a high diagnostic accuracy.
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http://dx.doi.org/10.3390/s22082877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027276PMC
April 2022

Tracking the response to Pseudomonas aeruginosa infection in ozone-induced chronic obstructive pulmonary disease mouse models.

Biomed Pharmacother 2022 Apr 19;150:112980. Epub 2022 Apr 19.

Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. Electronic address:

Pseudomonas aeruginosa (P. aeruginosa) is commonly isolated from the sputum of COPD patients. However, the precise role of P. aeruginosa infection in the progression of COPD, especially its role in altering inflammation remains unclear. Here, we designed mice models of COPD infected with P. aeruginosa (PA) and observed dynamic changes of lung structure, lung inflammatory microenvironment, lung function. After infection, the level of mucus secretion peaked on day 3 and remained higher throughout the study period, and the airway remodeling and emphysema was starkly apparent on day 14 and 21. On day 3, interferon-γ and interleukin (IL)- 5 levels increased rapidly, accompanied by elevated T-bet mRNA expression and CD4T-bet cells; at the late stage of infection (days 14 and 21), consistent with increased GATA3 mRNA expression and CD4GATA3 cells, IL-4 and IL-13 levels significantly increased; IL-17A level, Foxp3 mRNA expression, CD4ROR-γt cells and CD4FOXP3 cells remained at higher levels throughout the course of the infection. Small-airway function showed a decline from day 3 to day 21; large airway function showed a decline on day 14 and 21. Overall, P. aeruginosa infection contributed to the progression of COPD. During the infection, an early Th1-related inflammation gradually shifted to a later Th2-related inflammation, and small-airway function decline occurred earlier than that of large-airway function. On the basis of infection control, the appropriate use of glucocorticoid might slow disease progression by mitigating the enhanced Th2-related inflammation, and small airways could be also an important treatment target in P. aeruginosa -infected COPD patients.
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http://dx.doi.org/10.1016/j.biopha.2022.112980DOI Listing
April 2022

Hotair promotes the migration and proliferation in ovarian cancer by miR-222-3p/CDK19 axis.

Cell Mol Life Sci 2022 Apr 22;79(5):254. Epub 2022 Apr 22.

Department of Pathology, School of Basic Medical Sciences, Xiangya HospitalCentral South UniversityHunan Province, Changsha, 410000, China.

Previous studies in our laboratory have reported that miR-222-3p was a tumor-suppressive miRNA in OC. This study aims to further understand the regulatory role of miR-222-3p in OC and provide a new mechanism for its prevention and treatment. We first found that miR-222-3p inhibited the migration and proliferation of OC cells. Then, we observed CDK19 was highly expressed in OC and inversely correlated with miR-222-3p. Besides, we observed that miR-222-3p directly binds to the 3'-UTR of CDK19 and inhibits CDK19 translation, thus inhibiting OC cell migration and proliferation in vitro and repressed tumor growth in vivo. We also observed the inhibitory effect of Hotair on miR-222-3p in OC. In addition, Hotair could promote the proliferation and migration of OC cells in vitro and facilitate the growth and metastasis of tumors in vivo. Moreover, Hotair was positively correlated with CDK19 expression. These results suggest Hotair indirectly up-regulates CDK19 through sponging miR-222-3p, which enhances the malignant behavior of OC. This provides a further understanding of the mechanism of the occurrence and development of OC.
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http://dx.doi.org/10.1007/s00018-022-04250-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033702PMC
April 2022

Hypoxia-induced HIF-1α/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer.

Redox Biol 2022 06 9;52:102312. Epub 2022 Apr 9.

Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China; Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China; Wuhan Peritoneal Cancer Clinical Medical Center, No.169 Donghu Road, Wuchang District, Wuhan, 430071, China. Electronic address:

Peritoneal metastasis (PM) is the main site of gastric cancer (GC) distant metastasis and indicates an extremely poor prognosis and survival. Hypoxia is a common feature of peritoneal metastases and up-regulation of hypoxia inducible factor 1 alpha (HIF-1α) may be a potential driver in the occurrence of PM. Ferroptosis is a recently discovered form of regulated cell death and closely related to the occurrence and development of tumors. However, the underlying mechanism link HIF-1α to ferroptosis in PM of GC remains unknown. Here, lncRNA-microarrays and RNA library construction/lncRNA-seq results shown that lncRNA-PMAN was highly expressed in PM and significantly modulated by HIF-1α. Upregulation of PMAN is associated with poor prognosis and PM in patients with GC. PMAN was up-regulated by HIF-1α and improved the stability of SLC7A11 mRNA by promoting the cytoplasmic distribution of ELAVL1, which was identified in RNA-pulldown/mass spectrometry results. Accumulation of SLC7A11 increases the level of l-Glutathione (GSH) and inhibits the accumulation of reactive oxygen species (ROS) and irons in the GC cells. Finally protect GC cells against ferroptosis induced by Erastin and RSL3. Our findings have elucidated the effect of HIF-1α/PMAN/ELAVL1 in GC cells ferroptosis and provides theoretical support for the potential diagnostic biomarkers and therapeutic targets for PM in GC.
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http://dx.doi.org/10.1016/j.redox.2022.102312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043498PMC
June 2022

Pan-Cancer Analysis Shows That ALKBH5 Is a Potential Prognostic and Immunotherapeutic Biomarker for Multiple Cancer Types Including Gliomas.

Front Immunol 2022 4;13:849592. Epub 2022 Apr 4.

Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin, China.

Background: AlkB homolog 5 (ALKBH5) is a N-methyladenosine (mA) demethylase associated with the development, growth, and progression of multiple cancer types. However, the biological role of ALKBH5 has not been investigated in pan-cancer datasets. Therefore, in this study, comprehensive bioinformatics analysis of pan-cancer datasets was performed to determine the mechanisms through which ALKBH5 regulates tumorigenesis.

Methods: Online websites and databases such as NCBI, UCSC, CCLE, HPA, TIMER2, GEPIA2, cBioPortal, UALCAN, STRING, SangerBox, ImmuCellAl, xCell, and GenePattern were used to extract data of ALKBH5 in multiple cancers. The pan-cancer patient datasets were analyzed to determine the relationship between ALKBH5 expression, genetic alterations, methylation status, and tumor immunity. Targetscan, miRWalk, miRDB, miRabel, LncBase databases and Cytoscape tool were used to identify microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate expression of ALKBH5 and construct the lncRNA-miRNA-ALKBH5 network. CCK-8, wound healing, Transwell and M2 macrophage infiltration assays as well as xenograft animal experiments were performed to determine the biological functions of ALKBH5 in glioma cells.

Results: The pan-cancer analysis showed that ALKBH5 was upregulated in several solid tumors. ALKBH5 expression significantly correlated with the prognosis of cancer patients. Genetic alterations including duplications and deep mutations of the gene were identified in several cancer types. Alterations in the gene correlated with tumor prognosis. GO and KEGG enrichment analyses showed that ALKBH5-related genes were enriched in the inflammatory, metabolic, and immune signaling pathways in glioma. ALKBH5 expression correlated with the expression of immune checkpoint (ICP) genes, and influenced sensitivity to immunotherapy. We constructed a lncRNA-miRNA network that regulates ALKBH5 expression in tumor development and progression.  and experiments showed that ALKBH5 promoted proliferation, migration, and invasion of glioma cells and recruited the M2 macrophage to glioma cells.

Conclusions: ALKBH5 was overexpressed in multiple cancer types and promoted the development and progression of cancers through several mechanisms including regulation of the tumor-infiltration of immune cells. Our study shows that ALKBH5 is a promising prognostic and immunotherapeutic biomarker in some malignant tumors.
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http://dx.doi.org/10.3389/fimmu.2022.849592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9013910PMC
April 2022

Rescue of mis-splicing of a common mutant associated with sensorineural hearing loss by antisense oligonucleotides.

Mol Ther Nucleic Acids 2022 Jun 19;28:280-292. Epub 2022 Mar 19.

Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China.

A wide spectrum of mutations causes Pendred syndrome and enlarged vestibular aqueduct, both associated with sensorineural hearing loss (SNHL). A splice-site mutation, c.919-2A>G (A-2G), which is common in Asian populations, impairs the 3' splice site of intron 7, resulting in exon 8 skipping during pre-mRNA splicing and a subsequent frameshift that creates a premature termination codon in the following exon. Currently, there is no effective drug treatment for SHNL. For A-2G-triggered SNHL, molecules that correct mis-splicing of the mutant hold promise to treat the disease. Antisense oligonucleotides (ASOs) can promote exon inclusion when targeting specific splicing silencers. Here, we systematically screened a large number of ASOs in a minigene system and identified a few that markedly repressed exon 8 skipping. A lead ASO, which targets a heterogeneous nuclear ribonucleoprotein (hnRNP) A1/A2 intronic splicing silencer (ISS) in intron 8, promoted efficient exon 8 inclusion in cultured peripheral blood mononuclear cells derived from two homozygous patients. In a partially humanized A-2G mouse model, two subcutaneous injections of the ASO at 160 mg/kg significantly rescued exon 8 splicing in the liver. Our results demonstrate that the ISS-targeting ASO has therapeutic potential to treat genetic hearing loss caused by the A-2G mutation in .
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http://dx.doi.org/10.1016/j.omtn.2022.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8987850PMC
June 2022

Cell transcriptomic atlas of the non-human primate Macaca fascicularis.

Nature 2022 04 13;604(7907):723-731. Epub 2022 Apr 13.

BGI-Shenzhen, Shenzhen, China.

Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.
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http://dx.doi.org/10.1038/s41586-022-04587-3DOI Listing
April 2022

Survival analysis of 15,402 pneumoconiosis cases in Jiangsu Province of China from 1961 to 2019.

Ann Palliat Med 2022 Apr 6. Epub 2022 Apr 6.

Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.

Background: Pneumoconiosis has been reported as one of the major global burdens of occupational health-related diseases. The global prevalence had increased since 1990. Prevention and treatment of pneumoconiosis in the project of occupational health have been a priority of the action plan of Healthy China 2030.

Methods: A life table was used to explore the survival and fatality rate of pneumoconiosis. Using Cox proportional hazards regression model, the factors of survival time were investigated.

Results: A total of 15,402 cases had several species of pneumoconiosis, including silicosis, coal worker pneumoconiosis and welder pneumoconiosis that accounted for 68.49%, 19.41% and 3.84% of total pneumoconiosis, respectively. Eighty percent of cases were initially diagnosed at stage I, 15.5% at stage II, and 4.5% at stage III. The overall average survival time was determined as 14.74±9.57 years, the life expectancy reached 34.324 years in total, and the total mortality of patients suffering from pneumoconiosis was 19.89%. The average dust exposure period, average survival time and life expectancy progressively decreased with the stage upgrade, whereas the age of onset and mortality rate tended to increase. Dust exposure years, initially diagnosed at stage II or stage III, stage I upgrade to stage II, stage I upgrade to stage III and low economic level were found as important risk factors for the survival of patients suffering from pneumoconiosis.

Conclusions: Stage II and stage III of pneumoconiosis may have a direct effect on the survival time of patients suffering from pneumoconiosis. The prevention and delay of the progression of pneumoconiosis are critical to prolonging the survival time of cases.
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http://dx.doi.org/10.21037/apm-21-2824DOI Listing
April 2022

Application Value of Contrast-Enhanced Ultrasound Combined with Enhanced MR Scanning in Patients with Intrahepatic Cholangiocarcinoma.

J Healthc Eng 2022 31;2022:6402646. Epub 2022 Mar 31.

Department of Hepatobiliary Surgery, Ganyu District People's Hospital of Lianyungang City, Lianyungang 222100, China.

Objective: To explore the clinical application effect of contrast-enhanced ultrasound (CEUS) combined with enhanced MR scanning in patients with intrahepatic cholangiocarcinoma (ICC).

Methods: 90 patients with ICC admitted to Ganyu District People's Hospital of Lianyungang City from June 2017 to June 2018 were selected as the research objects and randomly divided into control group and experimental group, with 45 cases in each group. The control group was tested by CEUS, and the experimental group was tested by CEUS combined with enhanced MR scanning. The test results of the two groups were compared, and the benign and malignant indicators of the two groups were detected.

Results: The rate of lesion detection, accuracy of localization qualitative accuracy, and diagnosis coincidence rate of the experimental group were significantly better than those of the control group ( < 0.05). The lesion length, tube wall thickness, and enhancement ratio of triple-phase multislice CT scan of the experimental group were lower than the control group (<0.05).

Conclusions: CEUS combined with enhanced MR scanning has high sensitivity and specificity and can significantly improve the accuracy of the detection results. It provides scientific and accurate scientific basis for clinical treatment and diagnosis of ICC, which is worthy of popularization and application.
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http://dx.doi.org/10.1155/2022/6402646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989578PMC
March 2022

Linking natural resources, innovations, and environment in the Belt and Road Initiative countries using dynamic panel techniques: the role of innovations and renewable energy consumption.

Environ Sci Pollut Res Int 2022 Apr 8. Epub 2022 Apr 8.

China Center for Special Economic Zone Research, Shenzhen University, Shenzhen, China.

The issue of natural resources and environment are a matter of clashing argument in recent studies. An increase in natural resources raises economic growth which in turn increases carbon emission, that is a challenge for environmental sustainability. There is a lack of research on weather innovations playing any important role by acquiring renewable energy sources, enhancing energy efficiency, and boosting economic growth by lowering the use of natural resources to raise environmental quality. Consequently, this study investigates the effect of natural resources, innovations, economic growth, and renewable energy consumption on carbon dioxide emission in 39 Belt and Road Initiative countries from 1981 to 2019. OLS, fixed effect, and generalized method of moments models were used for analysis, where the results indicate that natural resources, innovations, and economic growth significantly increase carbon dioxide emission, while renewable energy reduces emission and raises environmental quality. The square term of natural resources is negative; thus, it indicates that natural resource use reduces emission when it reaches a certain level. Likewise, our results validate the Environmental Kuznets Curve hypothesis in the Belt and Road initiative countries. The findings have considerable policy implications for the Belt and Road countries regarding natural resource use, innovations, and renewable energy consumption.
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http://dx.doi.org/10.1007/s11356-022-20093-5DOI Listing
April 2022

An Outer Membrane Protein YiaD Contributes to Adaptive Resistance of Meropenem in Acinetobacter baumannii.

Microbiol Spectr 2022 Apr 4;10(2):e0017322. Epub 2022 Apr 4.

Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Acinetobacter baumannii is an important nosocomial pathogen that can develop various resistance mechanisms to many antibiotics. However, little is known about how it evolves from an antibiotic sensitive to a resistant phenotype. In this study, we investigated the transition of outer membrane proteins (OMPs) under antibiotic stress and identified YiaD as an OMP marker involved in the development of adaptive resistance to meropenem (MEM) in A. baumannii. Following stimulation of a carbapenem-sensitive strain AB5116 with sub-MIC of MEM, showed significantly decreased expression, and this decrease continued with prolonged stimulation for 8 h. The downregulation of was not only observed in clinically sensitive strains but also in 45 carbapenem-resistant isolates that produced the β-lactamases TEM and OXA-23. However, the extent of the reduction of expression in resistant strains was less than that in sensitive strains. Lack of resulted in a 4-fold increase in the MIC of AB5116 to MEM. The same level of depressed susceptibility induced by deletion was observed in both a growth curve test and a survival rate assay. Moreover, the colony shape became enlarged and irregular after loss of , and the biofilm formation ability of A. baumannii was influenced by YiaD. These results suggest that YiaD could respond to the stimulus of MEM in A. baumannii with a downregulation trend that kept pace with the prolonged stimulation time, indicating that it participates in various routes to benefit MEM resistance evolution in both carbapenem-sensitive and -resistant A. baumannii strains. Acinetobacter baumannii can develop various resistance mechanisms to carbapenems. However, the factors involved in the evolutionary process that leads from transition to the sensitive to resistant phenotype are not clear. The outer membrane protein YiaD of A. baumannii was downregulated under the stress of meropenem (MEM), and its expression level was continuously reduced with prolonged stimulation time. The downregulation of was not only observed in sensitive strains but also in carbapenem-resistant isolates producing the β-lactamases TEM and OXA-23. However, the extent of reduction was less in resistant strains than in sensitive strains. Lack of resulted in an increased MEM MIC, enlarged and irregular colonies, and decreased biofilm formation ability. These results suggest that YiaD responds to MEM stimulus in A. baumannii and participates in the adaptive resistance of MEM in both carbapenem-sensitive and -resistant strains.
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http://dx.doi.org/10.1128/spectrum.00173-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045393PMC
April 2022

Extensive secretion of phenolic acids and fatty acids facilitates rhizosphere pH regulation in halophyte Puccinellia tenuiflora under alkali stress.

Physiol Plant 2022 Mar;174(2):e13678

Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, China.

Puccinellia tenuiflora is a forage grass with high nutritional value that is an extreme alkali-tolerant halophyte: it can survive at pH 10-11. Root secretion is perceived as a major plant alkali tolerance mechanism. In the present study, we applied a widely targeted metabolomic approach to identify and quantify the root exudates of P. tenuiflora under alkali stress. We also surveyed the transcriptional and metabolic profiling of P. tenuiflora roots under salt (96-mM Na , pH 6.8) and alkali (96-mM Na , pH 9.6) stresses to reveal the biological processes mediating root secretion. In P. tenuiflora plants, 493 root exudates were detected under control conditions, 544 root exudates under salt stress conditions, and 607 root exudates under alkali stress conditions. Salt-stressed plants and alkali-stressed plants shared 64 root exudates, and 60 root exudates were unique to alkali-stressed plants. The secretion rate of 56 phenolic acids, 43 fatty acids, and 9 organic acids was faster in alkali-stressed roots than in control and salt-stressed roots. In P. tenuiflora roots, alkali stress enhanced the accumulation of 23 phenolic acids, five organic acids, and only one fatty acid. In addition, transcriptomic analysis revealed that alkali stress upregulated glycolysis and phenylpropanoid biosynthesis pathways in P. tenuiflora roots. Taken together, extensive secretion of phenolic acids and fatty acids promotes rhizosphere pH regulation of P. tenuiflora under alkali stress, which contributes to its strong alkali tolerance. The root secretion of P. tenuiflora upon alkali stress is highly organized. Enhanced glycolysis, phenylpropanoid biosynthesis, and organic acid synthesis in the roots provide more reducing power and carbon source for the root secretion process of alkali-stressed P. tenuiflora.
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http://dx.doi.org/10.1111/ppl.13678DOI Listing
March 2022

Graphene-Based Nanomaterials for Dental Applications: Principles, Current Advances, and Future Outlook.

Front Bioeng Biotechnol 2022 10;10:804201. Epub 2022 Mar 10.

College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, China.

With the development of nanotechnology, nanomaterials have been used in dental fields over the past years. Among them, graphene and its derivatives have attracted great attentions, owing to their excellent physicochemical property, morphology, biocompatibility, multi-differentiation activity, and antimicrobial activity. In our review, we summarized the recent progress about their applications on the dentistry. The synthesis methods, structures, and properties of graphene-based materials are discussed. Then, the dental applications of graphene-based materials are emphatically collected and described. Finally, the challenges and outlooks of graphene-based nanomaterials on the dental applications are discussed in this paper, aiming at inspiring more excellent studies.
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http://dx.doi.org/10.3389/fbioe.2022.804201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961302PMC
March 2022

Branched chain and other amino acid intakes are inversely associated with sarcopenia among community elders in Qingdao, China.

Asia Pac J Clin Nutr 2022 Mar;31(1):97-107

Institute of Nutrition & Health, Qingdao University, Qingdao, China.

Background And Objectives: The present study aimed to investigate the hypothesis that dietary amino acid intakes are associated with the risk of sarcopenia through a community-based observational study.

Methods And Study Design: A total of 1,140 participants (72.7±6.3 y) were recruited from an annual health check-up program in Qingdao, China. Skeletal muscle mass, muscle mass functions and biochemical parameters were measured by standard methods. Dietary intake was assessed by 3-day, 24-hour food records. The odds ratios (ORs) and 95% confidence intervals (CIs) of sarcopenic risk across quartiles of amino acid intakes were calculated using a multivariable- adjusted logistic regression model. Generalized linear models were used to assess the associations between dietary amino acid intakes and muscle mass functions.

Results: The prevalence of sarcopenia was 4.1%. Compared with the lowest category intake, the highest category of branched chain amino acids (BCAAs) (OR=0.11; 95% CI: 0.01, 0.90; p for trend=0.119), isoleucine (OR=0.11; 95% CI: 0.01, 0.89; p for trend=0.122) and tryptophan (OR=0.10; 95% CI: 0.01, 0.87; p for trend=0.176) was negatively correlated with sarcopenic risk with adjustment for potential confounding factors. Generalized linear model analysis showed that gait speed was positively correlated with dietary intakes of lysine, threonine, leucine, valine, tryptophan, BCAAs and aromatic amino acids (p<0.05).

Conclusions: Higher intakes of BCAAs were associated with a lower risk of sarcopenia, which might beneficially protect against sarcopenia and improve physical function of the elderly.
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http://dx.doi.org/10.6133/apjcn.202203_31(1).0011DOI Listing
March 2022

Skeletal muscle index and muscle attenuation with liver cirrhosis as survival prognosticators by sex.

Asia Pac J Clin Nutr 2022 Mar;31(1):24-32

Department of Nutrition, The Affiliated Hospital of Qingdao University, Qingdao, China. Email:

Background And Objectives: It has been proven that skeletal muscle index (SMI) and muscle attenuation (MA) are correlated with outcomes in liver cirrhosis. However, whether there are sex differences in these factors re-mains unknown. We aimed to analyze the predictive ability of SMI and MA for the prognosis of cirrhotic patients of different sexes and promote computed tomography (CT) use in body composition assessment.

Methods And Study Design: CT images taken at the 3rd lumbar vertebra from 223 patients were quantified for body composi-tion. A Cox regression model was used to assess associations between mortality and body composition. Time-dependent receiver operating characteristic curves were calculated to evaluate the predictive ability of SMI and MA for the 1-, 3- and 5- year mortality of cirrhotic patients.

Results: The majority of patients with liver cirrhosis were male (64.6%), and there was a weak linear correlation between SMI and MA in males (r=0.33, p<0.001). In the sex stratified multivariate Cox regression analysis, SMI in males (HR=0.95; 95% CI, 0.91-0.98; p=0.002) and MA in females (HR=0.91; 95% CI, 0.87-0.96; p<0.001) were independently associated with mortality. The areas under the curve (AUCs) of SMI (AUC=0.718) and MA (AUC=0.705) were similar in the 5-year mortality predic-tion of males, while in females, MA (AUC=0.797) had a stronger predictive ability than SMI (AUC=0.541).

Conclusions: SMI in males and MA in females are independent prognostic factors for liver cirrhosis. For females, MA may be a more sensitive indicator of mortality prediction than SMI, while in males, they are equivalent.
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http://dx.doi.org/10.6133/apjcn.202203_31(1).0003DOI Listing
March 2022

Fuzzy C-Means Algorithm-Based ARM-Linux-Embedded System Combined with Magnetic Resonance Imaging for Progression Prediction of Brain Tumors.

Comput Math Methods Med 2022 15;2022:4224749. Epub 2022 Mar 15.

Information Section, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, 157009 Heilongjiang, China.

The aim of this research was to analyze the application of fuzzy C-means (FCM) algorithm-based ARM-Linux-embedded system in magnetic resonance imaging (MRI) images for prediction of brain tumors. The optimized FCM (OFCM) algorithm was proposed based on kernel function, and the ARM-Linux-embedded imaging system was designed under ARM9 chip and Linux recorder, which were applied in MRI images of brain tumor patients. It was found that the sensitivity, specificity, and accuracy of the OFCM algorithm (90.46%, 88.97%, and 97.46%) were greater obviously than those of the deterministic C-means clustering algorithm (80.38%, 77.98%, and 85.24%) and the traditional FCM algorithm (83.26%, 79.56%, and 86.45%), and the difference was statistically substantial ( < 0.05). The ME and running time of the OFCM algorithm decreased sharply in contrast to those of the deterministic C-means clustering algorithm and the traditional FCM algorithm ( < 0.05). There were great differences in fraction anisotropy (FA) and mean diffusion (MD) of tumor parenchymal area, surrounding edema area, and normal white matter area ( < 0.05). FA of stage III+IV was smaller than those of stage I and II ( < 0.05), while the apparent diffusion coefficient (ADC) of stage III+IV was greater than that of stage I and II ( < 0.05). In conclusion, the poor update data processing and low data clustering efficiency of FCM were solved by OFCM. Moreover, computational efficiency of ARM-Linux-embedded imaging system was improved, so as to better realize the prediction of brain tumor patients through ARM-Linux-embedded system based on adaptive FCM incremental clustering algorithm.
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http://dx.doi.org/10.1155/2022/4224749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941506PMC
April 2022

The single nucleotide polymorphism rs1814521 in long non-coding RNA ADGRG3 associates with the susceptibility to silicosis: a multi-stage study.

Environ Health Prev Med 2022 ;27(0)

Department of Occupational Health, Center for Disease Control and Prevention of Wuxi.

Background: This study aimed to evaluate the correlation between long non-coding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) and susceptibility to silicosis.

Methods: First, RNA-sequencing (RNA-seq) data were comprehensively analyzed in the peripheral blood lymphocytes of eight participants (four silicosis cases and four healthy controls) exposed to silica dust to identify differentially expressed lncRNAs (DE-lncRNAs). The functional SNPs in the identified DE-lncRNAs were then identified using several databases. Finally, the association between functional SNPs and susceptibility to silicosis was evaluated by a two-stage case-control study. The SNPs of 155 silicosis cases and 141 healthy silica-exposed controls were screened by genome-wide association study (GWAS), and the candidate SNPs of 194 silicosis cases and 235 healthy silica-exposed controls were validated by genotyping using the improved Mutiligase Detection Reaction (iMLDR) system.

Results: A total of 76 DE-lncRNAs were identified by RNA-seq data analysis (cut-offs: fold change > 2 or fold change < 0.5, P < 0.05), while 127 functional SNPs among those 76 DE-lncRNAs were identified through multiple public databases. Furthermore, five SNPs were found to be significantly correlated with the risk of silicosis by GWAS screening (P < 0.05), while the results of GWAS and iMLDR validation indicated that the variant A allele of rs1814521 was associated with a reduced risk of silicosis (OR = 0.76, 95% CI = 0.62-0.94, P = 0.011).

Conclusion: The presence of the SNP rs1814521 in the lncRNA ADGRG3 is associated with susceptibility to silicosis. Moreover, ADGRG3 was found to be lowly expressed in silicosis cases. The underlying biological mechanisms by which lncRNA ADGRG3 and rs1814521 regulate the development of silicosis need further study.
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http://dx.doi.org/10.1265/ehpm.21-00338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093617PMC
March 2022

Understanding the influence of AMG 510 on the structure of KRAS empowered by molecular dynamics simulation.

Comput Struct Biotechnol J 2022 24;20:1056-1067. Epub 2022 Feb 24.

State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

The KRAS mutant is often associated with human cancers, and AMG 510 as a promising covalent inhibitor of KRAS has achieved surprising efficacy in clinical trials. However, the interaction mechanism between KRAS and AMG 510 is not completely understood. Here, we performed all-atom molecular dynamics simulations on the complex of KRAS-AMG 510 to explore the influence of this covalent inhibitor on the conformational change of KRAS. A PCA (Principal Component Analysis) model was constructed based on known KRAS crystal structures to distinguish different conformations (active, inactive, and other). By mapping simulation trajectories onto the PCA model, we observed that the conformations of KRAS bound with AMG 510 were mainly concentrated in the inactive conformation. Further analysis demonstrated that AMG 510 reduced the flexibility of two switch regions to make the complex of KRAS-AMG 510 restricted in the inactive conformation. In the meantime, we also identified key interacting residues between KRAS and AMG 510 through the calculation of binding energy. Finally, we built a series of KRAS second-site mutation systems (i.e. KRAS) to conduct large-scale screening of potential resistance mutations. By further combining MD simulations and the PCA model, we not only recapitulated the currently known resistance mutations of AMG 510 successfully but also proposed some novel potential resistant mutations. Taken together, these results broaden our insight into the influence of AMG 510 on the conformational change of the KRAS mutant at the atomic level, thereby providing crucial hints for the improvement and optimization of drug candidates.
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http://dx.doi.org/10.1016/j.csbj.2022.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8894142PMC
February 2022

Vasohibin 2 promotes lymphangiogenesis of lung squamous cell carcinoma through snail-dependent vascular endothelial growth factor-D (VEGF-D) signaling pathway.

Ann Transl Med 2022 Jan;10(2):39

Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Caner, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China.

Background: Tumor lymphatic metastasis is mostly dependent on lymphangiogenesis, which was less studied compared to angiogenesis and the molecular mechanisms involved remained unclear.

Methods: We analyzed the mRNA expression profiles of 937 primary lung squamous cell carcinoma (LUSC) samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to explore the genes related to lymphatic metastasis in LUSC. We focused on vasohibin 2 (VASH2) and investigated its biological functions in LUSC proliferation, apoptosis, migration, invasion, as well as lymphangiogenesis capacity by forced over-expressing VASH2 in LUSC cell line H520 and . We also evaluated the anti-tumor efficacy of specific anti-VASH2 antibody in LUSC xenograft-bearing mice models.

Results: Vasohibin2 (VASH2) was filtered out as a significant predictive factor of poor prognosis and lymphatic metastasis in LUSC patients both in public datasets and an independent Chinese LUSC cohort. VASH2 promoted the proliferation and invasion of LUSC cells in vitro and vivo. Forced over-expression of VASH2 in LUSC cells promoted the amplification and tube formation capacity of human umbilical vein endothelial cells (HUVECs) and human lymphatic endothelial cells (HLECs) via up-regulating vascular endothelial growth factor-D (VEGF-D), which could be reversed via Snail inhibition. Furthermore, blocking VASH2/VEGF-D signaling using specific antibodies dramatically inhibited tumor growth in mice by interfering with the proliferation of cancer cells and lymphangiogenesis in tumor tissues.

Conclusions: In conclusion, VASH2 facilitated lymphangiogenesis and tumor growth in a Snail-dependent manner and might serve as a novel biomarker for early diagnosis and prognosis prediction, as well as a potential therapeutic target in LUSC.
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http://dx.doi.org/10.21037/atm-21-4865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848404PMC
January 2022
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