Publications by authors named "Chen Huang"

943 Publications

Effects of exenatide on urinary albumin in overweight/obese patients with T2DM: a randomized clinical trial.

Sci Rep 2021 Oct 8;11(1):20062. Epub 2021 Oct 8.

Department of Endocrinology of Xinqiao Hospital, Army Medical University, Chongqing, China.

In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM). A total of 159 overweight/obese patients with T2DM were randomized to the EXE group or insulin glargine (GLAR) control group for a total treatment period of 24 weeks. EXE intervention significantly reduced the urine albumin concentration (UAC) at week 12 and 24 endpoints (P < 0.001 at week 12 and 24). The levels of the anthropometric, glucose and lipid parameters (TG and HDL-c), and inflammation biomarkers (CRP and TNF-α) in the EXE group were improved at 12 weeks or 24 weeks, respectively. Meanwhile, a comparison between two groups showed significant changes in anthropometric parameters, glucose parameters, lipid parameters (TG and HDL-c), and Inflammation biomarkers (CRP, IL-6, and TNF-α). Serum fibroblast growth factor 21 (FGF21) was increased in the EXE group (P = 0.005) at week 24, and the change was significantly improved compared with GLAR group (P = 0.003). Correlation network analysis showed that FGF21 had a more central role in improving metabolism in the EXE group, and the change of FGF 21 was significantly negatively correlated with UAC at week 12 and week 24, respectively (r = - 0.297, P = 0.010; r = - 0.294, P = 0.012). Our results showed that EXE could help patients improve UAC, glycemic levels, and inflammatory biomarkers after a follow-up period of 24 weeks intervention. These EXE effects may be partly mediated by FGF 21, indicating that EXE is an effective and safe way to control albuminuria in overweight/obese patients with T2DM.
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http://dx.doi.org/10.1038/s41598-021-99527-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501012PMC
October 2021

Study of the Effect of Nutrient Environment on the Biological Characteristics of Clinical Corneal Isolates.

J Ophthalmol 2021 23;2021:6666303. Epub 2021 Sep 23.

Department of Ophthalmology, Peking University Third Hospital, Beijing, China.

Purpose: The biological characteristics of clinical corneal isolates growing in different nutritional conditions in vitro were studied in order to find out the key point of pathogenicity.

Methods: Five kinds of media with different glucose and nitrogen concentrations were prepared as the liquid and solid forms. The clinical isolates were as follows: 2 strains. The clinical corneal isolates and the standard strains were inoculated in the solid and liquid media. They were all incubated at 296 for 96 h and observed at defined time points. The optical density was recorded to generate the growth curves in liquid media. Morphologic changes of colonies in the solid media were determined under the light microscope.

Results: The clinical isolates of showed stronger reproductive capacity in the abominable nutritional condition. Besides, when the glucose concentration in the medium was consistent with the glucose concentration of aqueous in diabetic patients, the clinical isolates would show the biological features of quicker growth rate and stronger reproductive capacity.

Conclusions: Nitrogen source is essential for fungus reproduction. The clinical isolates showed stronger environmental adaptability under different nutritional conditions and more sensitive to environmental changes.
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http://dx.doi.org/10.1155/2021/6666303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487384PMC
September 2021

Clinical and Bacterial Characteristics of Affecting 30-Day Mortality in Patients With Bloodstream Infection.

Front Cell Infect Microbiol 2021 16;11:688989. Epub 2021 Sep 16.

Department of Respiratory Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, China.

Background: There is a paucity of studies using clinical characteristics and whole-genome sequencing together to fully identify the risk factors of patients with (KP) bloodstream infection (BSI).

Methods: We retrospectively analyzed the clinical and microbiological characteristics of patients with KP BSI. Isolates were processed using Illumina NGS, and relevant bioinformatics analysis was conducted (multi-locus sequence typing, serotype, phylogenetic reconstruction, detection of antibiotic resistance, and virulence genes). A logistic regression model was used to evaluate the risk factors of hosts and causative KP isolates associated with 30-day mortality in patients infected with KP BSI.

Results: Of the 79 eligible patients, the 30-day mortality rate of patients with KP BSI was 30.4%. Multivariate analysis showed that host-associated factors (increased APACHE II score and septic shock) were strongly associated with increased 30-day mortality. For the pathogenic factors, carriage of (OR, 1.46; 95% CI, 1.11-1.81, = 0.002) or (OR, 1.31; 95% CI, 1.02-1.69, = 0.043) was an independent risk factor, especially when accompanied by a multidrug-resistant phenotype. In addition, ST11-K64 hypervirulent carbapenem-resistant KP co-harbored acquired together with (76.5%, 13/17) and (100%, 17/17) genes. Comparative genomic analysis showed that they were clustered together based on a phylogenetic tree, and more virulence genes were observed in the group of ST11-K64 strains compared with ST11-non-K64. The patients infected with ST11-K64 strains were associated with relatively high mortality (47.2%, 7/17).

Conclusion: The carriage of and was seen to be an independent mortality risk factor in patients with KP BSI. The identification of hypervirulent and carbapenem-resistant KP strains associated with high mortality should prompt surveillance.
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http://dx.doi.org/10.3389/fcimb.2021.688989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482843PMC
October 2021

Atovaquone-HSA nano-drugs enhance the efficacy of PD-1 blockade immunotherapy by alleviating hypoxic tumor microenvironment.

J Nanobiotechnology 2021 Oct 2;19(1):302. Epub 2021 Oct 2.

Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.

Background: Hypoxia is inherent character of most solid malignancies, leading to the failure of chemotherapy, radiotherapy and immunotherapy. Atovaquone, an anti-malaria drug, can alleviate tumor hypoxia by inhibiting mitochondrial complex III activity. The present study exploits atovaquone/albumin nanoparticles to improve bioavailability and tumor targeting of atovaquone, enhancing the efficacy of anti-PD-1 therapy by normalizing tumor hypoxia.

Methods: We prepared atovaquone-loaded human serum albumin (HSA) nanoparticles stabilized by intramolecular disulfide bonds, termed HSA-ATO NPs. The average size and zeta potential of HSA-ATO NPs were measured by particle size analyzer. The morphology of HSA-ATO NPs was characterized by transmission electron microscope (TEM). The bioavailability and safety of HSA-ATO NPs were assessed by animal experiments. Flow cytometry and ELISA assays were used to evaluate tumor immune microenvironment.

Results: Our data first verified that atovaquone effectively alleviated tumor hypoxia by inhibiting mitochondrial activity both in vitro and in vivo, and successfully encapsulated atovaquone in vesicle with albumin, forming HSA-ATO NPs of approximately 164 nm in diameter. We then demonstrated that the HSA-ATO NPs possessed excellent bioavailability, tumor targeting and a highly favorable biosafety profile. When combined with anti-PD-1 antibody, we observed that HSA-ATO NPs strongly enhanced the response of mice bearing tumor xenografts to immunotherapy. Mechanistically, HSA-ATO NPs promoted intratumoral CD8 T cell recruitment by alleviating tumor hypoxia microenvironment, thereby enhancing the efficacy of anti-PD-1 immunotherapy.

Conclusions: Our data provide strong evidences showing that HSA-ATO NPs can serve as safe and effective nano-drugs to enhance cancer immunotherapy by alleviating hypoxic tumor microenvironment.
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http://dx.doi.org/10.1186/s12951-021-01034-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487475PMC
October 2021

Enhanced light extraction of the deep-ultraviolet micro-LED via rational design of chip sidewall.

Opt Lett 2021 Oct;46(19):4809-4812

In this Letter, we perform a comprehensive investigation on the optical characterization of micro-sized deep-ultraviolet (DUV) LEDs (micro-LEDs) emitting below 280 nm, highlighting the light extraction behavior in relation to the design of chip sidewall angle. We found that the micro-LEDs with a smaller inclined chip sidewall angle (∼33) have improved external quantum efficiency (EQE) performance 19% more than that of the micro-LEDs with a larger angle (∼75). Most importantly, the EQE improvement by adopting an inclined sidewall can be more outstanding as the diameter of the LED chip reduces from 40 to 20 . The enhanced EQE of the micro-LEDs with smaller inclined chip sidewall angles can be attributed to the stronger reflection of the inclined sidewall, leading to enhanced light extraction efficiency (LEE). In the end, the numerical optical modeling further reveals and verifies the impact of the sidewall angles on the LEE of the micro-LEDs, corroborating our experiment results. This Letter provides a fundamental understanding of the light extraction behavior with optimized chip geometry to design and fabricate highly efficient micro-LEDs in a DUV spectrum of the future.
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http://dx.doi.org/10.1364/OL.441285DOI Listing
October 2021

3-Epipachysamine B suppresses proliferation and induces apoptosis of breast cancer cell via PI3K/AKT/mTOR signaling pathway.

Life Sci 2021 Sep 28;285:119995. Epub 2021 Sep 28.

School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; Shaanxi Key Laboratory of "Qiyao" Resources and Anti-tumor Acitivities/Shaanxi Plant Extract Engineering Technology Research Center, Xi'an 710061, China. Electronic address:

3-Epipachysamine B is a natural steroidal alkaloid isolated from Pachysandra terminalis Sieb. et Zucc. (known locally as Kunxianqi). Kunxianqi contains numerous compounds with demonstrated activity against breast cancer (BRCA). However, it is unknown whether 3-epipachysamine B also has anti-BRCA efficacy. In the present study, we employed network pharmacology technology to search and find potential molecular targets of 3-epipachysamine B. We applied cell proliferation, apoptosis, and western blotting assays to test the predicted key targets and the effects of 3-epipachysamine B against BRCA. Network pharmacology disclosed 80 potential BRCA-related targets of 3-epipachysamine B and assigned them to 75 signaling pathways. Of these, the most highly enriched was the PI3K/AKT signaling pathway. PIK3R1, AKT1, and mTOR had high degrees and betweenness centrality in protein-protein interaction network and are associated with PI3K/AKT signaling. Molecular docking and molecular dynamics simulation indicated strong binding between 3-epipachysamine B and PIK3R1, AKT1, and mTOR. 3-Epipachysamine B repressed the proliferation and induced the apoptosis of BRCA cells, as well as downregulated P-AKT/AKT, P-mTOR/mTOR, and P-PI3K/PI3K in the cells. The PI3K inhibitor LY294002 augmented these changes. Hence, 3-epipachysamine could also prove effective as an anticancer agent in future animal tumor model and human clinical breast cancer trials. Successful validation results could lead to a safe and effective new breast cancer treatment that improves patient prognosis and quality of life.
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http://dx.doi.org/10.1016/j.lfs.2021.119995DOI Listing
September 2021

Maternal hypertensive disorder of pregnancy and offspring early-onset cardiovascular disease in childhood, adolescence, and young adulthood: A national population-based cohort study.

PLoS Med 2021 Sep 28;18(9):e1003805. Epub 2021 Sep 28.

Department of Biostatistics, School of Public Health, and The Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China.

Background: The prevalence of cardiovascular disease (CVD) has been increasing in children, adolescents, and young adults in recent decades. Exposure to adverse intrauterine environment in fetal life may contribute to the elevated risk of early-onset CVD. Many studies have shown that maternal hypertensive disorders of pregnancy (HDP) are associated with increased risks of congenital heart disease, high blood pressure, increased BMI, and systemic vascular dysfunction in offspring. However, empirical evidence on the association between prenatal exposure to maternal HDP and early-onset CVD in childhood and adolescence remains limited.

Methods And Findings: We conducted a population-based cohort study using Danish national health registers, including 2,491,340 individuals born in Denmark from 1977 to 2018. Follow-up started at birth and ended at the first diagnosis of CVD, emigration, death, or 31 December 2018, whichever came first. Exposure of maternal HDP was categorized as preeclampsia or eclampsia (n = 68,387), gestational hypertension (n = 18,603), and pregestational hypertension (n = 15,062). Outcome was the diagnosis of early-onset CVD from birth to young adulthood (up to 40 years old). We performed Cox proportional hazards regression to evaluate the associations and whether the association differed by maternal history of CVD or diabetes before childbirth. We further assessed the association by timing of onset and severity of preeclampsia. The median follow-up time was 18.37 years, and 51.3% of the participants were males. A total of 4,532 offspring in the exposed group (2.47 per 1,000 person-years) and 94,457 in the unexposed group (2.03 per 1,000 person-years) were diagnosed with CVD. We found that exposure to maternal HDP was associated with an increased risk of early-onset CVD (hazard ratio [HR]: 1.23; 95% CI = 1.19 to 1.26; P < 0.001). The HRs for preeclampsia or eclampsia, gestational hypertension, and pregestational hypertension were 1.22 (95% CI, 1.18 to 1.26; P < 0.001), 1.25 (95% CI, 1.17 to 1.34; P < 0.001), and 1.28 (95% CI, 1.15 to 1.42; P < 0.001), respectively. We also observed increased risks for type-specific CVDs, in particular for hypertensive disease (HR, 2.11; 95% CI, 1.96 to 2.27; P < 0.001) and myocardial infarction (HR, 1.49; 95% CI, 1.12 to 1.98; P = 0.007). Strong associations were found among offspring of mothers with CVD history (HR, 1.67; 95% CI, 1.41 to 1.98; P < 0.001) or comorbid diabetes (HR, 1.56; 95% CI, 1.34 to 1.83; P < 0.001). When considering timing of onset and severity of preeclampsia on offspring CVD, the strongest association was observed for early-onset and severe preeclampsia (HR, 1.48, 95% CI, 1.30 to 1.67; P < 0.001). Study limitations include the lack of information on certain potential confounders (including smoking, physical activity, and alcohol consumption) and limited generalizability in other countries with varying disparities in healthcare.

Conclusions: Offspring born to mothers with HDP, especially mothers with CVD or diabetes history, were at increased risks of overall and certain type-specific early-onset CVDs in their first decades of life. Further research is warranted to better understand the mechanisms underlying the relationship between maternal HDP and early-onset CVD in offspring.
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http://dx.doi.org/10.1371/journal.pmed.1003805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478255PMC
September 2021

Proteogenomic characterization of pancreatic ductal adenocarcinoma.

Cell 2021 Sep;184(19):5031-5052.e26

Department of Oncology, Johns Hopkins University, Baltimore, MD 21205, USA.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.
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http://dx.doi.org/10.1016/j.cell.2021.08.023DOI Listing
September 2021

Glucose Metabolism Reprogramming of Regulatory T Cells in Concanavalin A-Induced Hepatitis.

Front Pharmacol 2021 31;12:726128. Epub 2021 Aug 31.

Department of Gastroenterology and Hepatology, Sichuan University-University of Oxford Huaxi Joint Centre for Gastrointestinal Cancer, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.

Autoimmune hepatitis (AIH) is an inflammatory liver disease caused by a dysregulated immune response. Although the pathogenesis of AIH remains unclear, impaired regulatory T cells (Tregs) have been considered a driver of AIH development. Unlike autoreactive T cells, Tregs mainly utilize oxidative phosphorylation (OXPHOS) as their energy supply. Elevated glycolysis has been reported to limit the suppressive functions of Tregs. However, whether glucose metabolism reprogramming in Tregs is involved in AIH etiology remains unknown. The aim of this study was to examine alternations in Treg numbers and functions in AIH patients and concanavalin A (Con A)-induced hepatitis, while exploring associations between impaired Tregs and glucose metabolism. The frequency of Tregs was decreased in the peripheral blood but increased in liver biopsies of AIH patients. Moreover, immunosuppressive therapy rescued circulating Tregs in AIH. In Con A-induced immune hepatitis, enhanced intrahepatic Treg accumulation was observed over time, accompanied by reduced splenic Treg numbers. To investigate whether functional impairment of Tregs occurs in AIH, Tregs were isolated from experimental AIH (EAH) model mice and normal controls and the former displayed downregulated mRNA levels of FOXP3, CTLA4, CD103, TIGIT, CD39, and CD73. EAH model-derived Tregs also produced fewer anti-inflammatory mediators (TGF-β and IL-35) than control Tregs. Moreover, enhanced glycolysis and reduced OXPHOS were found in Tregs from EAH model mice, as reflected by elevated levels of key glycolytic enzymes (HK2, PK-M2, and LDH-A) and a decreased ATP concentration. This study revealed a decreased peripheral Treg frequency and abnormal intrahepatic Treg infiltration in AIH. It is first reported that glucose metabolism reprogramming is associated with decreases and functional impairments in the Treg population, promoting AIH development. Targeting glucose metabolism may provide novel insights for the treatment of AIH.
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http://dx.doi.org/10.3389/fphar.2021.726128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438122PMC
August 2021

Treating Chronic Wounds Using Photoactive Metabolites: Data Mining the Chinese Pharmacopoeia for Potential Lead Species.

Planta Med 2021 Sep 15. Epub 2021 Sep 15.

Research Group "Pharmacognosy and Phytotherapy", UCL School of Pharmacy, London, UK.

Efficient wound treatment that addresses associated infections and inflammation remains one of the big unmet needs, especially in low- and middle-income countries. One strategy for securing better healthcare can be using medicinal plants if sufficient evidence on their safety and therapeutic benefits can be ascertained. A unique novel opportunity could be photo-enhanced wound treatment with a combination of light-sensitive plant preparations and local exposure to daylight. Data mining strategies using existing resources offer an excellent basis for developing such an approach with many potential plant candidates. In the present analysis, we researched the 535 botanical drugs included in the Chinese pharmacopeia and identified 183 medicinal plant species, 82 for treating open wounds caused by trauma and 101 for inflammatory skin conditions. After further screening for reports on the presence of known photoactive compounds, we determined a core group of 10 scientifically lesser-known botanical species that may potentially be developed into more widely used topical preparations for photodynamic treatment of infected wounds. Our predictive approach may contribute to developing a more evidence-based use of herbal medicines.
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http://dx.doi.org/10.1055/a-1578-8778DOI Listing
September 2021

TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity.

Sci Adv 2021 Sep 15;7(38):eabi6515. Epub 2021 Sep 15.

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

[Figure: see text].
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http://dx.doi.org/10.1126/sciadv.abi6515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443187PMC
September 2021

Clinicopathologic features and BRAF mutation status of tracheal glomus tumors - Characterization of 4 cases and the distinction from low-grade neuroendocrine tumors.

Ann Diagn Pathol 2021 Jul 31;55:151797. Epub 2021 Jul 31.

Departments of Pathology, China-Japan Friendship Hospital, Beijing, China. Electronic address:

Background: Glomus tumors are uncommon and mostly benign mesenchymal neoplasms of the perivascular family. To date, only a few cases of glomus tumors occurring in the trachea have been reported. Tracheal glomus tumors simulated low-grade neuroendocrine tumors on clinical and histomorphological examination, so the differential diagnosis between these two entities is very necessary. The latest studies showed that BRAF mutation may be associated with a malignant phenotype of glomus tumors.

Methods: We investigated the clinical, histopathologic, immunohistochemical, and BRAF V600E mutation status of four cases of tracheal glomus tumors.

Results: The cases showed a female predilection (male:female, 1:3) with a median age of 35.5. All of the cases had the typical morphological characteristics of glomus tumors, such as uniform round tumor cells with nest-like distribution surrounding thin-walled vessels; two of them met the malignant diagnostic criteria based on the 5th edition of WHO classification, including marked nuclear atypia and any level of mitotic activity. Immunohistochemistry showed diffusely positive for vimentin (4/4), α-SMA (4/4) and collagen IV (4/4), variably reactive for synaptophysin (3/4) and SSTR2 (2/2), and negative for AE1/AE3 (0/4) and chromogranin A (0/4). Three tested cases harbored no BRAF V600E mutation. Three follow-up cases were alive and free of disease with an average follow-up of 89.3 months.

Conclusions: Tracheal glomus tumors are rare mesenchymal tumors that have overlapping morphologic and immunohistochemical features with neuroendocrine neoplasms. Our cases highlight the importance of careful histomorphological examination and comprehensive immunohistochemical study in reaching a correct diagnosis of glomus tumors of the trachea. Other than BRAF mutation, malignant glomus tumors may have a complex mutational profile.
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http://dx.doi.org/10.1016/j.anndiagpath.2021.151797DOI Listing
July 2021

Epidemiology and factors predicting survival of amyotrophic lateral sclerosis in a large Chinese cohort.

Chin Med J (Engl) 2021 Sep 2;134(18):2231-2236. Epub 2021 Sep 2.

Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing 100191, China.

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS.

Methods: We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors.

Results: The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17-49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46-63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS.

Conclusions: Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.
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http://dx.doi.org/10.1097/CM9.0000000000001679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478368PMC
September 2021

Reversible Immunoaffinity Interface Enables Dynamic Manipulation of Trapping Force for Accumulated Capture and Efficient Release of Circulating Rare Cells.

Adv Sci (Weinh) 2021 Sep 2:e2102070. Epub 2021 Sep 2.

The MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, The Key Laboratory of Chemical Biology of Fujian Province, State Key Laboratory of Physical Chemistry of Solid Surfaces, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.

Controllable assembly and disassembly of recognition interface are vital for bioanalysis. Herein, a strategy of dynamic manipulation of trapping force by engineering a dynamic and reversible immunoaffinity microinterface (DynarFace) in a herringbone chip (DynarFace-Chip) for liquid biopsy is proposed. The DynarFace is assembled by magnetically attracting immunomagnetic beads (IMBs) on chip substrate, with merits of convenient operation and reversible assembly. The DynarFace allows accumulating attachment of IMBs on circulating rare cell (CRC) surfaces during hydrodynamically enhanced interface collision, where accumulatively enhanced magnetic trapping force improves capture efficiency toward CRCs with medium expression of biomarkers from blood samples by 134.81% compared with traditional non-dynamic interfaces. Moreover, magnet withdrawing-induced disappearance of trapping force affords DynarFace disassembly and CRC release with high efficiency (>98%) and high viability (≈98%), compatible with downstream in vitro culture and gene analysis of CRCs. This DynarFace strategy opens a new avenue to accumulated capture and reversible release of CRCs, holding great potential for liquid biopsy-based precision medicine.
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http://dx.doi.org/10.1002/advs.202102070DOI Listing
September 2021

Use of mineral element profiling coupled with chemometric analysis to distinguish Zanthoxylum bungeanum cultivars and health risks of potentially toxic elements in pericarps.

J Sci Food Agric 2021 Aug 31. Epub 2021 Aug 31.

College of Forestry, Northwest A&F University, Yangling, China.

Background: Zanthoxylum bungeanum pericarps (ZBP) are commonly used as food additives and traditional herbal medicines. Several mineral elements are known to have important physiological functions in organisms, whereas others are reported to have toxic effects. We determined levels of macro elements (Mg, S and Ca), essential trace elements (B, Mn, Fe, Cu, Zn, Se and Mo) and toxic elements (Ni, Al, Cr, As, Cd, Hg and Pb) in the pericarps of 19 Z. bungeanum cultivars. Hazard index values and incremental lifetime cancer risks were calculated to express health risks associated with pericarp consumption. Moreover, several chemometric analyses based on the mineral elements were used to distinguish Z. bungeanum cultivars.

Results: The concentrations of 17 determined elements in the pericarps were ranked: Ca > Mg > S > Fe > Al > Mn > Zn > B > Cu > Ni > Pb > Cr > Mo > As > Cd > Hg > Se. The elements Zn, Cr and As had the highest variations in their concentrations. Cu, Mn, Se, Zn, Al, As, Cd, Cr, Hg, Ni and Pb posed some non-cancer risks, while As and Cd posed cancer risks. Mn, Fe, Zn, and Al were chosen as critical element markers for assessing ZBP using chemometric analyses.

Conclusion: Chemometric analyses could highlight mineral concentration differentiation among the 19 cultivars. The Z. bungeanum cultivar Z12 (from Wudu, Gansu) is best for producing ZBP, and cultivar Z18 (Guanling, Guizhou) can be a reference to classify and evaluate ZBP quality. The results provide valuable information for evaluating the potential safety risks of ZBP and contribute to inter-cultivar discrimination. © 2021 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.11517DOI Listing
August 2021

Effect of 580 °C (20 h) Heat Treatment on Mechanical Properties of 25Cr2NiMo1V Rotor-Welded Joints of Oscillating Arc (MAG) Narrow Gap Thick Steel.

Materials (Basel) 2021 Aug 11;14(16). Epub 2021 Aug 11.

Shanghai Turbine Factory, Shanghai Electric Power Station Equipment Co., Ltd., Shanghai 201100, China.

The thick plate narrow gap welding of 25Cr2NiMo1V rotor steel is achieved by metal active gas arc welding, in which the weld gap was 18.04-19.9 mm. After welding, the weldment was heat treated at 580 °C (20 h). The impact and tensile properties in the as-welded and heat-treated were studied. The results show that after heat treatment, the coarse carbides in the center of the weld were transformed into fine granular carbides distributed along the grain boundaries, and the quantity of carbide precipitates in the weld near the fusion line was reduced. The tensile fracture mode changed from a ductile fracture to a combination of brittle and ductile fractures, and the tensile strength of the weld metal changed from 605 MPa to 543 MPa. After heat-treated, the radiation zone of the weld center changed from a brittle fracture to a combination of brittle and ductile fractures, and the impact energy changed from 141 J to 183 J; the characteristics of the brittle fracture in the radial zone of the fusion line were more obvious, and the impact energy changed from 113 J to 95 J. Therefore, after heat treatment, the toughness of the welded metal was improved, without reducing the strength and hardness of the welded metal to a large extent.
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http://dx.doi.org/10.3390/ma14164498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400107PMC
August 2021

Indoor exposure levels of radon in dwellings, schools, and offices in China from 2000 to 2020: A systematic review.

Indoor Air 2021 Aug 25. Epub 2021 Aug 25.

School of Environment and Architecture, University of Shanghai for Science and Technology, Shanghai, China.

After decades of development, the indoor environment in China has changed. A systematic review was conducted from peer-reviewed scientific papers with field test data of indoor radon in China from 2000 to 2020 for three types of buildings. The mean concentrations of indoor radon for dwellings, school buildings, and office buildings are 54.6, 56.1, and 54.9 Bq/m . The indoor radon concentration was related to seasons, climate regions, ventilation, decoration, and other factors such as soil and outdoor air. Colder seasons, especially in severe colder areas of China, newer decorated buildings, closed windows, and doors were all associated with higher indoor radon concentrations. Variables like climate region and ventilation showed statistical significance in the correlation analysis. Regarding the increasing trend of indoor radon concentration in China during the last two decades, further study of indoor radon is necessary especially for school buildings and office buildings, and will help access its environmental burden of disease in China more accurately.
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http://dx.doi.org/10.1111/ina.12920DOI Listing
August 2021

LncRNA SNHG17 regulates cell proliferation and invasion by targeting miR-338-3p/SOX4 axis in esophageal squamous cell carcinoma.

Cell Death Dis 2021 08 24;12(9):806. Epub 2021 Aug 24.

Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

Small nucleolar RNA host gene 17 (SNHG17), a novel functional long noncoding RNA, has been demonstrated to play an essential role in the oncogenesis of several tumors. However, for esophageal squamous cell carcinoma (ESCC) the expression pattern and detailed function of SNHG17 are largely unknown. Hence, we conducted this study to explore potential roles and underlying oncogenic mechanisms for SNHG17 in ESCC progression. Results demonstrated SNHG17 to be markedly upregulated in ESCC. Knockdown of SNHG17 significantly suppressed ESCC cell proliferation, invasion, and epithelial-mesenchymal transition in vitro and tumor growth in vivo. Online database software analysis found miR-338-3p to interact with SNHG17 with the level of miR-338-3p negatively correlated with SNHG17 levels in ESCC samples. Further, miR-338-3p was found to directly target SRY-box transcription factor 4 (SOX4) in ESCC cells. Mechanistic analysis suggested that SNHG17 acts as an endogenous "sponge" competing with miR-338-3p to regulate SOX4, thereby promoting tumor progression. These results suggest that these molecular interactions may be potential therapeutic targets for ESCC.
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http://dx.doi.org/10.1038/s41419-021-04093-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384996PMC
August 2021

Overview on the Role of E-Cadherin in Gastric Cancer: Dysregulation and Clinical Implications.

Front Mol Biosci 2021 30;8:689139. Epub 2021 Jul 30.

Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Gastric cancer is the fifth most common cancer and the third most common cause of cancer death all over the world. E-cadherin encoded by human gene plays important roles in tumorigenesis as well as in tumor progression, invasion and metastasis. Full-length E-cadhrin tethered on the cell membrane mainly mediates adherens junctions between cells and is involved in maintaining the normal structure of epithelial tissues. After proteolysis, the extracellular fragment of the full-length E-cadhein is released into the extracellular environment and the blood, which is called soluble E-cadherin (sE-cadherin). sE-cadherin promots invasion and metastasis as a paracrine/autocrine signaling molecule in the progression of various types of cancer including gastric cancer. This review mainly summarizes the dysregulation of E-cadherin and the regulatory roles in the progression, invasion, metastasis, and drug-resistance, as well as its clinical applications in diagnosis, prognosis, and therapeutics of gastric cancer.
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http://dx.doi.org/10.3389/fmolb.2021.689139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371966PMC
July 2021

Acquisition of the Gene Lowers the Target Mutation to Impede the Evolution of a High-Level Colistin-Resistant Mutant in .

Infect Drug Resist 2021 10;14:3041-3051. Epub 2021 Aug 10.

State Key Laboratory for Diagnosis and Treatment of Infectious Disease, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People's Republic of China.

Objective: The spread of the plasmid-mediated colistin resistance gene poses a significant public health threat. Little information is available on the development of high-level colistin-resistant mutants (HLCRMs) in MCR-1-producing (MCRPEC). The present study was designed to evaluate the impact of chromosomal modifications in , and combined with on colistin resistance in .

Methods: Five MCRPEC and three non-MCRPEC ( ATCC25922 and two plasmid-curing) strains were used. The HLCRMs were selected through multi-stepwise colistin exposure. Moreover, two C600-pMCRs were constructed and used for selection of HLCRMs. Further analysis included mutation rates and DNA sequencing. Transcripts of , and were quantified by real-time quantitative PCR.

Results: All tested HLCRMs were successfully isolated from their parental strains. Non-MCRPEC strains had higher minimum inhibitory concentrations (MICs) and mutation rates than MCRPEC strains. Nineteen amino acid substitutions were identified: seven in PmrA, six in PmrB, one in PhoP, three in PhoQ, and two in MgrB. Most were detected in non-MCRPEC strains. Sorting Intolerant From Tolerant predicted that four substitutions, PmrA Gly15Arg, Gly53Arg, PmrB Pro94Gln, and PhoP Asp86Gly, affected protein function. Two HLCRM isolates did not show amino acid substitutions in contrast to their parental MCRPEC isolates. No further mutations were detected in the second- and third-step mutants. Further transcriptional analysis showed that the up-regulation of expression was greater in the mutant of C600 than in C600-pMCR.

Conclusion: Acquisition of the gene had a negative impact on the development of HLCRMs in , but was associated with low-level colistin resistance. Thus, colistin-based combination regimens may be effective against infections with MCR-1-producing isolates.
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http://dx.doi.org/10.2147/IDR.S324303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364431PMC
August 2021

Prognostic implications of ENE and LODDS in relation to lymph node-positive colorectal cancer location.

Transl Oncol 2021 Nov 14;14(11):101190. Epub 2021 Aug 14.

Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai 201600, China. Electronic address:

Background: Extranodal extension (ENE) and log odds of positive lymph nodes (LODDS) are associated with the aggressiveness of both colon and rectal cancers. The current study evaluated the clinicopathological significance and the prognostic impact of ENE and LODDS in the colon and rectal patients independently.

Methods: The clinical and histological records of 389 colorectal cancer (CRC) patients who underwent curative surgery were reviewed.

Results: For the ENE system, 244 patients were in the ENE1 group and 145 in the ENE2 system. Compared with the ENE1 system, the patients included in the ENE2 system were prone to nerve invasion (P < 0.001) and vessel invasion (P < 0.001) with higher TNM (P = 0.009), higher T category (P = 0.003), higher N category (P < 0.001), advanced differentiation (P = 0.013), more number of positive lymph nodes (NPLN) (P < 0.001), more lymph node ratio (LNR) (P < 0.001), and a higher value of LODDS (P < 0.001). ENE was more frequent in patients with left and rectal than right cancer. For the LODDS system, 280 patients were in the LODDS1 group, and 109 in the LODDS2 group. Compared to the LODDS1 group, the patients included in the LODDS2 group were more prone to nerve invasion (P = 0.0351) and vessel invasion (P < 0.001) with a higher rate of N2 stage, less NDLN (P < 0.001), more NPLN (P < 0.001), more LNR (P < 0.001), and a higher value of ENE (P < 0.001). Based on the results in the univariable analysis, the N, NPLN, LNR, LODDS, and ENE were separately incorporated into five different Cox regression models combined with the same confounders. The multivariable Cox regression analysis demonstrated that all the five staging systems were independent prognostic factors for overall survival.

Conclusion: The current study confirmed that the LODDS stage is an independent influence on the prognosis of both CRC and CC patients. ENE is an independent influencing factor on the prognosis of both CRC and CC patients, and the prognostic impact of extracapsular lymph node was observed in both CRC and CC. The frequency of ENE increases from the proximal (right) to the distal (left) colon as well as the rectum. Therefore, combining ENE and LODDS into the current TNM system to compensate for the inadequacy of pN staging needs further investigation.
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http://dx.doi.org/10.1016/j.tranon.2021.101190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8367836PMC
November 2021

Long noncoding RNA NEAT1 promotes tumorigenesis in H. pylori gastric cancer by sponging miR-30a to regulate COX-2/BCL9 pathway.

Helicobacter 2021 Aug 16:e12847. Epub 2021 Aug 16.

Department of Medical Oncology and Cancer Institute, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Background: Helicobacter pylori (H. pylori) is a carcinogenic factor for gastric cancer. Our previous study demonstrated that H. pylori decreased the expression of micro-RNA (miRNA)-30a to promote the tumorigenesis of gastric cancer. However, the upstream regulatory molecules of miR-30a are not well elucidated. In this study, we found the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) may sponge miR-30a to regulate COX-2/BCL9 pathway.

Methods: The expression of NEAT1 was detected in gastric cancer tissues and tumor-adjacent tissues by fluorescence in situ hybridization (FISH) analysis and RT-qPCR. LncRNA-miRNA interaction networks were constructed using the RNAhybrid and starBase v.2.0. and then validated using a dual-luciferase reporter assay. The effects of NEAT1 dysregulation on the proliferative, migratory, and invasive abilities of H. pylori filtrate-infected gastric cancer cells were observed by cell counting kit-8 (CCK-8), colony formation, wound healing test, and transwell assays. Western blot and RT-qPCR were performed to detect protein and RNA expression. Immunohistochemistry (IHC) was carried out to analyze the localization and expression of COX-2 and BCL9.

Results: FISH and RT-qPCR demonstrated that the expression of NEAT1 was up-regulated in gastric cancer tissues, especially in H. pylori-infected gastric cancer tissues, and the expression of NEAT1 was negatively correlated with miR-30a (miR-30a-3p and miR-30a-5p). The upregulation of NEAT1 enhanced proliferation, migration, and invasion of H. pylori filtrate-infected gastric cancer cells, while the downregulation of NEAT1 decreased these abilities, and miR-30a could reverse the effect of NEAT1 on these abilities. The dual-luciferase reporter assay identified that NEAT1 directly targeted miR-30a (miR-30a-3p and miR-30a-5p). Because miR-30a (miR-30a-3p and miR-30a-5p) negatively regulates the expression of downstream COX-2 and BCL9, NEAT1 was identified to upregulate indirectly the expression of COX-2 and BCL9. IHC showed that the expression of COX-2 and BCL9 was increased in H. pylori gastric cancer tissues.

Conclusion: The study demonstrated that lncRNA NEAT1 may act as a promoter of tumorigenesis in H. pylori gastric cancer, by sponging miR-30a (miR-30a-3p and miR-30a-5p) to regulate the COX-2/BCL9 pathway.
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http://dx.doi.org/10.1111/hel.12847DOI Listing
August 2021

Exploring the relationship between pain intensity and knee moments in participants with medial knee osteoarthritis: a cross-sectional study.

BMC Musculoskelet Disord 2021 Aug 12;22(1):685. Epub 2021 Aug 12.

Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China.

Background: High biomechanical loading is believed to be a risk factor to pain in people with knee osteoarthritis (OA), but controversial findings have been reported on the relationship between external knee adduction moment (KAM) and pain. A more comprehensive analysis considering other factor such as external knee flexion moment (KFM) could help better reveal this relationship. This study explored the relationship between external knee adduction moment and pain intensity in participants with knee osteoarthritis (OA) using an integrated path analysis model.

Methods: This was a cross-sectional study based on laboratory setting. Forty-seven participants with clinical and radiographic medial knee OA were analyzed for their external knee adduction moment (KAM) and knee flexion moment (KFM) during walking using a motion analysis system. Pain intensity was measured by visual analogue scale (VAS) and the pain subscale of the Knee Injury and Osteoarthritis Outcome Score. Varus/valgus alignment was captured and quantified using a bi-planar X-ray system. Using a path analysis model, the relationships between pain intensity, KAM, KFM, OA radiographic severity, knee varus angle and walking speed were examined.

Results: The proposed path model met the goodness-of-fit criteria. Based on this model, KAM had a negative effect on VAS pain indirectly through the mediation of KFM. The model indicated KAM and KFM were negatively related to one another; and KFM was positively related to VAS. The KAM index, defined as (KAM/ (KAM + KFM)), was negatively related to VAS.

Conclusions: Path analysis enabled the construction of a more integrated pathokinematic framework for people with knee OA. The KAM index which reflected the load sharing on the frontal and sagittal planes also revealed its relationship with pain. Re-distribution of mechanical loading from frontal to sagittal plane might be a strategy for pain avoidance associated with mechanical irritation.
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http://dx.doi.org/10.1186/s12891-021-04587-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361612PMC
August 2021

Low-Cost, Unsinkable, and Highly Efficient Solar Evaporators Based on Coating MWCNTs on Nonwovens with Unidirectional Water-Transfer.

Adv Sci (Weinh) 2021 Oct 11;8(19):e2101727. Epub 2021 Aug 11.

Engineering Research Center of Technical Textiles, Ministry of Education, College of Textiles, Donghua University, Shanghai, 201620, China.

Solar vapor generation technology is promising in seawater desalination, sewage purification, and other fields. However, wide application of this technology is still largely confined due to its high cost and difficulties for scalable production. In this study, an ever-floating solar evaporator is fabricated by coating multiwall carbon nanotubes on a bicomponent nonwoven composed of polypropylene/polyethylene core-sheath fibers. This all-fiber structure is highly porous and ultralight, with large specific area (for efficient water evaporation), interconnected channels (for easy vapor escape), and low thermal conductivity (to avoid heat loss). The unique unidirectional water-transfer behavior of the nonwoven enables it to spontaneously pump an adjustable amount of water for interfacial solar heating and a delicate balance between water supply and loss may accelerate the evaporation speed of water. These distinct benefits endow the solar evaporator with excellent evaporation rates of 1.44 kg m  h under the simulated irradiation of 1 sun and 12.81 kg m  d under natural sunlight. Moreover, the evaporator can be fabricated by using low-cost materials and industrialized methods (overall cost ≈2.4 USD m ), making one believe its practical significance for commercial solar steam evaporation.
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http://dx.doi.org/10.1002/advs.202101727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498870PMC
October 2021

Neutrophil-to-Lymphocyte Ratio and Treatment Failure in Peritoneal Dialysis-Associated Peritonitis.

Front Med (Lausanne) 2021 26;8:699502. Epub 2021 Jul 26.

Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

We sought to explore if there is an association between neutrophil-to-lymphocyte ratio (NLR) and treatment failure in patients with peritoneal dialysis-associated peritonitis (PDAP). Our cohort involved 337 episodes of PDAP experienced by 202 patients who were undergoing continuous ambulatory peritoneal dialysis at a single center from 1 July 2013 to 30 June 2018. The exposures were log-transformed NLR and a categorical variable grouped by the tertiles of NLR levels (T1, <3.75; T2, 3.75-6.53; and T3, >6.53) at baseline. Generalized estimating equation (GEE) and restricted cubic spline (RCS) analyses were done to determine the association between NLR and treatment failure, defined as catheter removal or all-cause mortality during therapy. After adjusting for other potential predictors, the log-transformed NLR exhibited an incremental relationship with the risk of treatment failure (odds ratio, 1.82; 95% confidence interval, 1.05-3.15). RCS analyses showed that the relationship was positively and linearly correlated ( for nonlinearity = 0.104). As a three-level categorical variable, in reference to T1, the T3 of NLR showed a 3.41-fold increased venture of treatment failure in fully adjusted model. Subgroup analyses suggested that the prognostic relevance of NLR in PDAP was particularly significant in gram-negative peritonitis. A greater level of NLR at baseline was remarkably associated with a higher incidence of treatment failure among PDAP episodes regardless of other potential risk factors.
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http://dx.doi.org/10.3389/fmed.2021.699502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350030PMC
July 2021

A 3D Bioprinted In Vitro Model of Pulmonary Artery Atresia to Evaluate Endothelial Cell Response to Microenvironment.

Adv Healthc Mater 2021 Aug 8:e2100968. Epub 2021 Aug 8.

Department of Biomedical Engineering, Emory University School of Medicine and Georgia Institute of Technology, Atlanta, GA, 30322, USA.

Vascular atresia are often treated via transcatheter recanalization or surgical vascular anastomosis due to congenital malformations or coronary occlusions. The cellular response to vascular anastomosis or recanalization is, however, largely unknown and current techniques rely on restoration rather than optimization of flow into the atretic arteries. An improved understanding of cellular response post anastomosis may result in reduced restenosis. Here, an in vitro platform is used to model anastomosis in pulmonary arteries (PAs) and for procedural planning to reduce vascular restenosis. Bifurcated PAs are bioprinted within 3D hydrogel constructs to simulate a reestablished intervascular connection. The PA models are seeded with human endothelial cells and perfused at physiological flow rate to form endothelium. Particle image velocimetry and computational fluid dynamics modeling show close agreement in quantifying flow velocity and wall shear stress within the bioprinted arteries. These data are used to identify regions with greatest levels of shear stress alterations, prone to stenosis. Vascular geometry and flow hemodynamics significantly affect endothelial cell viability, proliferation, alignment, microcapillary formation, and metabolic bioprofiles. These integrated in vitro-in silico methods establish a unique platform to study complex cardiovascular diseases and can lead to direct clinical improvements in surgical planning for diseases of disturbed flow.
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http://dx.doi.org/10.1002/adhm.202100968DOI Listing
August 2021

Commentary: Live long and prosper: Enhanced biomechanics of pulmonary autograft using inclusion technique in Ross procedure.

J Thorac Cardiovasc Surg 2021 Jul 15. Epub 2021 Jul 15.

Department of Thoracic Surgery, Fujian Provincial Hospital, Shengli Clinical College of Fujian Medical University, Fuzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2021.07.014DOI Listing
July 2021

A proteogenomic portrait of lung squamous cell carcinoma.

Cell 2021 Aug;184(16):4348-4371.e40

Department of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.
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http://dx.doi.org/10.1016/j.cell.2021.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475722PMC
August 2021

Eczema, facial erythema, and seborrheic dermatitis symptoms among young adults in China in relation to ambient air pollution, climate, and home environment.

Indoor Air 2021 Aug 1. Epub 2021 Aug 1.

Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden.

A questionnaire survey on dermal symptoms and home environment was performed in eight Chinese cities (40 279 participants). Data on city level temperature, precipitation, PM , NO and gross domestic product (GDP) per capita were collected. In total, 2.2% had eczema, 2.4% facial erythema (FE) and 2.6% seborrheic dermatitis symptoms (SD). Higher temperature was associated with eczema (OR = 1.09). Higher GDP per capita was related to less SD. Higher PM was related to SD. Suburban living was protective for eczema (OR = 0.77) (vs. urban). Living in old buildings (built before 1991) was related to eczema (OR = 1.42). Living near heavily trafficked roads was related to FE (OR = 1.33) and SD (OR = 1.35). Having new furniture was related to all symptoms (OR = 1.26-1.47). Burning mosquito coils (OR = 1.37-1.57) and incense (OR = 1.33-1.37) were associated with eczema, FE, or SD. Presence of cockroaches and rats/mice was associated with FE or SD (OR = 1.31-1.40). Using air conditioner, daily cleaning and frequently exposing bedding to sunshine were protective (OR = 0.60-0.83). In conclusion, higher temperature, higher PM , urban living, living near heavily trafficked roads, old buildings, new furniture, burning mosquito coils and incense, and presence of cockroaches/rats/mice increased the risk of eczema, FE, or SD. Higher GDP, air conditioner, daily cleaning, and exposing bedding to sunshine were protective.
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http://dx.doi.org/10.1111/ina.12918DOI Listing
August 2021

Dichloroacetate enhances the anti-tumor effect of sorafenib via modulating the ROS-JNK-Mcl-1 pathway in liver cancer cells.

Exp Cell Res 2021 09 29;406(1):112755. Epub 2021 Jul 29.

Department of Clinical Biochemistry, Army Medical University (Third Military Medical University), Chongqing, 400038, China; Department of Biochemistry and Molecular Biology, Army Medical University (Third Military Medical University), Chongqing, 400038, China. Electronic address:

Liver cancer is one of the most common and high recurrence malignancies. Besides radiotherapy and surgery, chemotherapy also plays an essential role in the treatment of liver cancer. Sorafenib and sorafenib-based combination therapies have been proven efficacy against tumors. However, previous clinical studies have indicated that some patients with liver cancer are resistant to sorafenib treatment and the existing strategies are not satisfactory in the clinic. Therefore, it is urgent to investigate strategies to improve the effectiveness of sorafenib for liver cancer and to explore effective drug combinations. In the present study, we found that dichloroacetate (DCA) could significantly enhance the anti-tumor effect of sorafenib on liver cancer cells, including reduced viability and dramatically promoted apoptosis in liver cancer cells. Moreover, compared to sorafenib alone, the combination of DCA and sorafenib markedly increased the degradation of anti-apoptotic protein Mcl-1 by enhancing its phosphorylation. Overexpression of Mcl-1 could significantly attenuate the synergetic effect of DCA and sorafenib on apoptosis induction in liver cancer cells. Furthermore, we found that the ROS-JNK pathway was obviously activated in the DCA combined sorafenib group. The levels of ROS and p-JNK were dramatically up-regulated in the two drug combination groups. Antioxidant NAC could alleviate the synergetic effects of DCA and sorafenib on ROS generation, JNK activation, Mcl-1 degradation, and cell apoptosis. Moreover, DCA and sorafenib's effects on Mcl-1 degradation and apoptosis could also be inhibited by JNK inhibitor 'SP'600125. Finally, the synergetic effects of DCA and sorafenib on tumor growth suppression, Mcl-1 degradation and induction of apoptosis were also validated in liver cancer xenograft in vivo. These findings indicate that DCA enhances the anti-tumor effect of sorafenib via the ROS-JNK-Mcl-1 pathway in liver cancer cells. This study may provide new insights to improve the chemotherapeutic effect of sorafenib, which may be beneficial for further clinical application of sorafenib in liver cancer treatment.
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http://dx.doi.org/10.1016/j.yexcr.2021.112755DOI Listing
September 2021
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