Publications by authors named "Huanhuan Wang"

268 Publications

Miniaturized CO Gas Sensor Using 20% ScAlN-Based Pyroelectric Detector.

ACS Sens 2022 Aug 9. Epub 2022 Aug 9.

Institute of Microelectronics, A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, #08-02, Innovis Tower, Singapore 138634, Singapore.

NDIR CO gas sensors using a 10-cm-long gas channel and CMOS-compatible 12% doped ScAlN pyroelectric detector have previously demonstrated detection limits down to 25 ppm and fast response time of ∼2 s. Here, we increase the doping concentration of Sc to 20% in our ScAlN-based pyroelectric detector and miniaturize the gas channel by ∼65× volume with length reduction from 10 to 4 cm and diameter reduction from 5 to 1 mm. The CMOS-compatible 20% ScAlN-based pyroelectric detectors are fabricated over 8-in. wafers, allowing cost reduction leveraging on semiconductor manufacturing. Cross-sectional TEM images show the presence of abnormally oriented grains in the 20% ScAlN sensing layer in the pyroelectric detector stack. Optically, the absorption spectrum of the pyroelectric detector stack across the mid-infrared wavelength region shows ∼50% absorption at the CO absorption wavelength of 4.26 μm. The pyroelectric coefficient of these 20% ScAlN with abnormally oriented grains shows, in general, a higher value compared to that for 12% ScAlN. While keeping the temperature variation constant at 2 °C, we note that the pyroelectric coefficient seems to increase with background temperature. CO gas responses are measured for 20% ScAlN-based pyroelectric detectors in both 10-cm-long and 4-cm-long gas channels, respectively. The results show that for the miniaturized CO gas sensor, we are able to measure the gas response from 5000 ppm down to 100 ppm of CO gas concentration with CO gas response time of ∼5 s, sufficient for practical applications as the average outdoor CO level is ∼400 ppm. The selectivity of this miniaturized CO gas sensor is also tested by mixing CO with nitrogen and 49% sulfur hexafluoride, respectively. The results show high selectivity to CO with nitrogen and 49% sulfur hexafluoride each causing a minimum ∼0.39% and ∼0.36% signal voltage change, respectively. These results bring promise to compact and miniature low cost CO gas sensors based on pyroelectric detectors, which could possibly be integrated with consumer electronics for real-time air quality monitoring.
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http://dx.doi.org/10.1021/acssensors.2c00980DOI Listing
August 2022

Protective effect of ghrelin on intestinal I/R injury in rats.

Open Med (Wars) 2022 20;17(1):1308-1317. Epub 2022 Jul 20.

Department of Emergency Intensive Care Unit, Yangpu Hospital, Tongji University, Shanghai 200090, China.

This study aimed to investigate whether ghrelin affected the autophagy and inflammatory response of intestinal intraepithelial lymphocytes (IELs) by regulating the NOD2/Beclin-1 pathway in an intestinal ischemia-reperfusion (I/R) injury model. Twenty hours after implementing the intestinal I/R injury rat model, the small intestine and both lungs were collected for histological analysis. The morphological changes in the intestinal mucosa epithelium and lung tissues were evaluated using hematoxylin-eosin staining. The activity of autophagic vacuoles and organ injury were evaluated using electron microscopy. The cytokine levels (IL-10 and TNF-α) in IEL cells and lung tissue were determined using enzyme-linked immunosorbent assay. RT-qPCR and western blot assays were conducted to check the NOD2, Beclin-1, and ATG16 levels. Ghrelin relieved the I/R-induced destruction of the intestinal mucosa epithelium and lung tissues. Moreover, ghrelin enhanced autophagy in the intestinal epithelium and lungs of I/R rats. In addition, the levels of autophagy-associated proteins (Beclin-1, ATG16, and NOD2) were higher in the ghrelin treatment group than in rats with I/R. Ghrelin reduced significantly the IL-10 and TNF-α levels. However, these changes were reversed by the NOD2 antagonist. In conclusion, ghrelin may relieve I/R-induced acute intestinal mucosal damage, autophagy disorder, and inflammatory response in IELs by regulating the NOD2/Beclin-1 pathway.
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http://dx.doi.org/10.1515/med-2022-0520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307145PMC
July 2022

Effects of the Chinese herbal medicine Hong Huang decoction, on myocardial injury in breast cancer patients who underwent anthracycline-based chemotherapy.

Front Cardiovasc Med 2022 22;9:921753. Epub 2022 Jul 22.

Department of Breast Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Objective: To assess the effects of Hong Huang Decoction (HHD), a Chinese herbal medicine, on myocardial injury in breast cancer patients who underwent anthracycline (ANT)-based chemotherapy.

Methods: A total of 51 patients with breast cancer who underwent an ANT-based chemotherapy program and met the inclusion/exclusion criteria were allocated to the treatment or placebo groups using a random number generation process. Patients in the treatment group received liquid HHD twice a day. Treatment was given from 1 day prior to chemotherapy up to the end of chemotherapy (after 6 months). Participants in the placebo group received a placebo over the same schedule. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), diagnostic markers of acute myocardial infarction [e.g., lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and B-type natriuretic peptide (BNP)], nitric oxide (NO), superoxide dismutase (SOD), as well as pro-inflammatory cytokines [e.g., tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and human C-reactive protein (CRP)], and anti-inflammatory cytokine interleukin-10 (IL-10), were outcome measures assessed before chemotherapy, 3 and 6 months after chemotherapy.

Results: Compared to the placebo group, the GLS value was significantly higher in the treatment group (19.95 ± 1.16 vs. 19.06 ± 1.64, ≤ 0.001). Significant differences were also noted for levels of SOD (689.71 ± 203.60 vs. 807.88 ± 182.10, < 0.05), IL-6 (58.04 ± 22.06 vs. 194.20 ± 40.14, ≤ 0.001), IL-10 (237.90 ± 94.98 vs. 68.81 ± 32.92, ≤ 0.001), NO (75.05 ± 26.39 vs. 55.83 ± 19.37, ≤ 0.005), and TNF-α (301.80 ± 134.20 vs. 680.30 ± 199.60, ≤ 0.001) in the patients before chemotherapy compared to 6 months after initiating chemotherapy.

Conclusion: HHD regulated the levels of IL-6, IL-10, SOD, NO, and TNF-α. The results demonstrated that GLS is a better indicator of early myocardial injury compared to LVEF, and HHD could modulate oxidative stress to protect against ANT cardio toxicity.

Clinical Trial Registration: Chinese Clinical Trial Registry, identifier ChiCTR1900022394. Date of registration: 2019-04-09.
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http://dx.doi.org/10.3389/fcvm.2022.921753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353583PMC
July 2022

An Energy Metabolism Study on the Efficacy of Naoxintong Capsules against Myocardial Infarction in a Rat Model.

Oxid Med Cell Longev 2022 23;2022:3712500. Epub 2022 Jul 23.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700.

Background: In myocardial ischemia, optimizing the myocardial metabolic phenotype to improve cardiac function is critical. Naoxintong capsules (NXT) are widely prescribed in Chinese medicine for the treatment of cerebrovascular and cardiovascular diseases.

Methods: In this study, a rat model of myocardial infarction was established by ligation of the left anterior descending coronary artery. The structure and function of the heart were evaluated using echocardiography. The pathological changes of the rat myocardium and the myocardial volume collagen fraction (CVF) were examined using hematoxylin-eosin (HE) and Masson's trichrome staining (Masson). The expression of TNF- and IL-6 were detected by immunohistochemistry. The level of cTnT was also measured to evaluate myocardial injury. In order to study the changes in energy metabolism in myocardial infarction and the effects of NXT, a targeted analysis method for detecting the 29 energy metabolites in cardiac muscle tissue was developed based on UPLC-QQQ-MS. Western blotting was used to detect the expression of proteins related to energy metabolism in myocardia.

Results: In the rat model of myocardial infarction, NXT showed obvious effects, such as improving heart function and increasing LVEF and LVFS. HE staining, Masson staining, and immunohistochemical results revealed that NXT decreased inflammatory infiltration, improved myocardial fibrosis, and reduced infarct size. In addition, NXT significantly reduced the level of serum cTnT. The levels of the 29 energy metabolites in cardiac muscle tissue were analyzed using a newly developed targeted analysis method. Compared to the sham group, the levels of 17 metabolites from different energy metabolic pathways, including four compounds in glycolysis metabolism, four compounds in TCA cycle, three compounds in oxidative phosphorylation, four compounds in purine metabolism, and two compounds in glutathione metabolism, displayed obvious changes induced by myocardial ischemia. Expressions of SIRT1, PGC-1, and ATP5D proteins related to energy metabolism were decreased after myocardial infarction. These perturbations could all be reversed by NXT intervention, suggesting that the therapeutic effects of NXT were partially due to interferences with energy metabolisms.

Conclusion: This study provides a useful approach for investigating the mechanism of myocardial infarction and evaluating the efficacy of NXT from energy metabolism.
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http://dx.doi.org/10.1155/2022/3712500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338863PMC
August 2022

An AIE photosensitizer with unquenched fluorescence based on nitrobenzoic acid for tumor-targeting and image-guided photodynamic therapy.

Biomater Sci 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.

Fluorescence quenching occurs in most nitroaromatic compounds due to photoinduced electron transfer (PET) effects, limiting their use as image-guided photosensitizers for anticancer photodynamic therapy (PDT) or as probes for nitroreductase in hypoxic cells. Herein, we developed a tumor-targeting aggregation-induced emission photosensitizer (AIE-PS), Biotin-TTVBA, by binding TTVBA (a nitrobenzoic acid-based AIE-PS with a free carboxylic acid group) to biotin. Biotin-TTVBA has near-infrared emission characteristics in DMSO containing 99% toluene, a large Stoke's shift (210 nm), high photostability, wash-free cell staining ability and type I/II photosensitivity. Compared with TTVBA, Biotin-TTVBA significantly increased cellular uptake (a 60-fold increase) and selective uptake of tumor cells (a 250% increase in the ratio of tumor cells to normal cells), resulting in enhanced antitumor activity against tumor cells (HeLa and MCF-7) and a decreased IC value (from >40 μM to 2.5 μM). Taken together, the results of this study call attention to AIE-PSs based on nitroaromatic groups because of their strong fluorescence and ROS generation ability, which can be used in image-guided photodynamic therapy and provide a new approach for tumor-targeting design of AIE-PSs.
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http://dx.doi.org/10.1039/d2bm00704eDOI Listing
July 2022

Big Endothelin-1 and long-term all-cause death in patients with coronary artery disease and prediabetes or diabetes after percutaneous coronary intervention.

Nutr Metab Cardiovasc Dis 2022 Jun 11. Epub 2022 Jun 11.

National Clinical Research Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Background And Aims: The present study aimed to examine the association between big endothelin-1 (big ET-1) and long-term all-cause death in patients with coronary artery disease (CAD) and different glucose metabolism status.

Methods And Results: We consecutively enrolled 8550 patients from January 2013 to December 2013. Patients were categorized according to both status of glucose metabolism status [Diabetes Mellitus (DM), Pre-Diabetes (Pre-DM), Normoglycemia (NG)] and big ET-1 levels. Primary endpoint was all-cause death. During a median of 5.1-year follow-up periods, 301 all-cause deaths occurred. Elevated big ET-1 was significantly associated with long-term all-cause death (adjusted HR: 2.230, 95%CI 1.629-3.051; p < 0.001). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause death compared with NG group (p < 0.05). When patients were categorized by both status of glucose metabolism and big ET-1 levels, high big ET-1 were associated with significantly higher risk of all-cause death in Pre-DM (adjusted HR: 2.442, 95% CI 1.039-5.740; p = 0.041) and DM (adjusted HR: 3.162, 95% CI 1.376-7.269; p = 0.007). The Kaplan-Meier curve indicated that DM patients with the highest big ET-1 levels were associated with the greatest risk of all-cause death (p < 0.05).

Conclusions: The present data indicate that baseline big ET-1 levels were independently associated with the long-term all-cause death in DM and Pre-DM patients with CAD undergoing PCI, suggesting that big ET-1 may be a valuable marker in patients with impaired glucose metabolism.
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http://dx.doi.org/10.1016/j.numecd.2022.06.002DOI Listing
June 2022

A case report of Klebsiella aerogenes-caused lumbar spine infection identified by metagenome next-generation sequencing.

BMC Infect Dis 2022 Jul 15;22(1):616. Epub 2022 Jul 15.

Department of Emergency Intensive Care Unit, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai, China.

Background: The early clinical diagnosis of spinal infections in elderly patients with recessive or atypical symptoms is difficult. Klebsiella aerogenes is a common opportunistic bacterium that can infect the respiratory tract, urinary tract, and even the central nervous system. However, whether it can infect the lumbar spine has not been previously described.

Case Presentation: In this paper, we report the case of a 69-year-old female patient with osteoporosis who was initially diagnosed with hemolytic anemia. Later, she was diagnosed with K. aerogenes infection of the lumbar spine based on imaging combined with blood culture and metagenome next-generation sequencing (mNGS) detection. After precise medication, the lumbar degeneration was improved.

Conclusions: Bacterial infection should therefore be considered in cases of lumbar degenerative disease in middle-aged and elderly patients.
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http://dx.doi.org/10.1186/s12879-022-07583-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9288078PMC
July 2022

Essential role of Nrf2 in sulforaphane-induced protection against angiotensin II-induced aortic injury.

Life Sci 2022 Jul 13;306:120780. Epub 2022 Jul 13.

Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China. Electronic address:

Aims: Cardiovascular disease (CVD) is the leading cause of death worldwide. Inflammation and oxidative stress are the primary factors underlying angiotensin II (Ang II)-induced aortic damage. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important antioxidative stress factor. Sulforaphane (SFN), which is naturally found in cruciferous vegetables, is an Nrf2 agonist that is safe for oral administration. Here, we aimed to explore the potential of SFN in protecting against Ang II-induced aortic damage by upregulating Nrf2 expression via the extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3 beta (GSK-3β)/Fyn pathway.

Main Methods And Key Findings: Wild-type (WT) C57BL/6J and Nrf2-knockout (Nrf2-KO) mice were injected with Ang II to induce aortic inflammation, oxidative stress, and cardiac remodeling (increased fibrosis and wall thickness). SFN treatment prevented aortic damage via Nrf2 activation in the WT mice. However, the protective effect of SFN on Ang II-induced aortic damage and upregulation of genes downstream of Nrf2 were not observed in Nrf2-KO mice. SFN induced the upregulation of aortic Nrf2 and inhibited the accumulation of ERK, GSK-3β, and Fyn in the nuclei.

Significance: These results revealed that Nrf2 plays a central role in protecting against Ang II-induced aortic injury. Furthermore, SFN prevented Ang II-induced aortic damage by activating Nrf2 through the ERK/GSK-3β/Fyn pathway.
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http://dx.doi.org/10.1016/j.lfs.2022.120780DOI Listing
July 2022

The Differences of Metabolites in Different Parts of the Brain Induced by Shuxuetong Injection against Cerebral Ischemia-Reperfusion and Its Corresponding Mechanism.

Evid Based Complement Alternat Med 2022 29;2022:9465095. Epub 2022 Jun 29.

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100029, China.

Ischemic stroke is often associated with a large disease burden. The existence of ischemia-reperfusion injury brings great challenges to the treatment of ischemic stroke. The purpose of this study was to explore the differences of metabolites in different parts of the brain induced by Shuxuetong injection against cerebral ischemia-reperfusion and to extend the corresponding mechanism. The rats were modeled by transient middle cerebral artery occlusion (-MCAO) operation, and the success of modeling was determined by neurological function score and TTC staining. UPLC-Q/TOF-MS metabolomics technique and multivariate statistical analysis were used to analyze the changes and differences of metabolites in the cortex and hippocampus of cerebral ischemia-reperfusion rats. Compared with the model group, the neurological function score and cerebral infarction volume of the Shuxuetong treatment group were significantly different. There were differences and changes in the metabolic distribution of the cortex and hippocampus in each group, the distribution within the group was relatively concentrated. The separation trend between the groups was obvious, and the distribution of the Shuxuetong treatment group was similar to that of the sham operation group. We identified 13 metabolites that were differentially expressed in the cortex, including glutamine, dihydroorotic acid, and glyceric acid. We also found five differentially expressed metabolites in the hippocampus, including glutamic acid and fumaric acid. The common metabolic pathways of Shuxuetong on the cortex and hippocampus were D-glutamine and D-glutamate metabolism and nitrogen metabolism, which showed inhibition of cortical glutamine and promotion of hippocampal glutamic acid. Specific pathways of Shuxuetong enriched in the cortex included glyoxylate and dicarboxylate metabolism and pyrimidine metabolism, which showed inhibition of glyceric acid and dihydroorotic acid. Specific pathways of Shuxuetong enriched in the hippocampus include arginine biosynthesis and citrate cycle (TCA cycle), which promotes fumaric acid. Shuxuetong injection can restore and adjust the metabolic disorder of the cortex and hippocampus in cerebral ischemia-reperfusion rats. The expression of Shuxuetong in different parts of the brain is different and correlated.
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http://dx.doi.org/10.1155/2022/9465095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259222PMC
June 2022

[Analysis of the molecular pathogenesis of hereditary protein C deficiency due to a p.Gly86Asp variant of the PROC gene].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2022 Jul;39(7):685-688

Department of Clinical Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325015, China.

Objective: To explore the molecular pathogenesis of hereditary protein C (PC) deficiency due to a p.Gly86Asp variant of the PROC gene through in vitro expression experiment.

Methods: Wild type and Gly86Asp mutant expression plasmids of PC were constructed and respectively transfected into HEK 293FT cells. Total RNA was extracted from the transfected cells, and the expression of PROC gene was determined by quantitative real-time PCR (qRT-PCR). PC antigen (PC:Ag) in the supernatant of cell culture and cell lysate was determined by enzyme-linked immunosorbent assay (ELISA), and the level of PC protein was detected by Western blotting.

Results: qRT-PCR has detected no significant difference in the transcription level of wild-type and mutant-type PC. Compared with the wild type, the level of mutant PC:Ag in the supernatant and cell lysate were 81.3%±2.6% and 110.0%±2.8%, respectively. No difference was detected in the molecular weight between the wild-type and mutant-type PC by Western blotting. The PC content of mutant type was higher than wild-type in cell lysate, while the opposite was found with the cell culture supernatant.

Conclusion: The impaired secretion by mutant PC may be the molecular mechanism of PC deficiency caused by the p.Gly86Asp variant.
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http://dx.doi.org/10.3760.cma.j.cn511374-20210525-00440DOI Listing
July 2022

PEGylated Prussian blue nanoparticles for modulating polyethyleneimine cytotoxicity and attenuating tumor hypoxia for dual-enhanced photodynamic therapy.

J Mater Chem B 2022 Jul 20;10(28):5410-5421. Epub 2022 Jul 20.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.

Photodynamic therapy (PDT) is a promising cancer therapy modality due to its intrinsically negligible side effects and treatment resistance. However, the development of the high-efficiency PDT still remains a challenge. Herein, a nanodrug platform [email protected] combined tumor acidity-induced polyethyleneimine (PEI) cytotoxicity with an oxygen self-supply property is developed for dual-enhanced PDT. The obtained [email protected] presents suppressed PEI cytotoxicity and chlorin e6 (Ce6) phototoxicity during the bloodstream before becoming active in tumor tissues/cells. The acidic tumor microenvironment can shed PEG coating to rebound PEI positive charges, facilitating tumor cell uptake and reverting the PEI cytotoxicity to enhance following PDT. Moreover, Prussian blue (PB) nanozymes with catalase-like activity can convert endogenous hydrogen peroxide into oxygen to relieve tumor hypoxia, which is attributed to the photosensitizer Ce6 producing more cytotoxic reactive oxygen species upon laser irradiation to further strengthen PDT. Moreover, [email protected] exhibits good biocompatibility and long blood circulation. More importantly, [email protected] breast cancer cells and tumor-bearing mice present effective therapeutic efficacy upon laser irradiation, verifying the synergistic antitumor effects of PEI cytotoxicity and oxygen self-supplying PDT.
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http://dx.doi.org/10.1039/d2tb00571aDOI Listing
July 2022

ARTS, an unusual septin, regulates tumorigenesis by promoting apoptosis.

Biomed Pharmacother 2022 Aug 14;152:113281. Epub 2022 Jun 14.

Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China; Department of Radiation Oncology, The First Hospital of Jilin University, Changchun 130021, China; NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, Changchun 130021, China. Electronic address:

Apoptosis plays particularly important roles in tumorigenesis through various mechanisms. Apoptosis can be initiated by both extrinsic and intrinsic signals centered in and coming from the mitochondria. Antiapoptotic proteins promote tumor progression, and the occurrence and progression of tumors are closely related to antiapoptotic protein expression. As the only member of the septin gene family with proapoptotic function, apoptosis-related proteins in the TGF-β signaling pathway (ARTS) has received extensive attention for its unique structure. In contrast, unlike other known inhibitors of apoptosis protein (IAP) antagonists, ARTS exhibits a stronger tumor suppressor potential. Recent research has shown that ARTS can bind and inhibit XIAP and Bcl-2 directly or assist p53 in the degradation of Bcl-XL. Here, we review recent advances in the molecular mechanisms by which the proapoptotic protein ARTS, with its unique structure, inhibits tumorigenesis. We also discuss the possibility of mimicking ARTS to develop small-molecule drugs.
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http://dx.doi.org/10.1016/j.biopha.2022.113281DOI Listing
August 2022

Risk factors for prolonged mechanical ventilation in neonates following gastrointestinal surgery.

Transl Pediatr 2022 May;11(5):617-624

Division of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Prolonged mechanical ventilation (MV) should be avoided in neonates. Noninvasive ventilation (NIV) can facilitate weaning from MV but has risks for patients immediately following foregut surgery due to the potential risk of anastomotic leak. We evaluated the risk factors for prolonged MV following intestinal surgery in neonates.

Methods: We retrospectively reviewed 253 neonates undergoing intestinal surgery in 2017-2018 to identify risk factors for prolonged MV, and determine the correlation between NIV and anastomotic leak in a tertiary neonatal intensive care unit that performs the greatest number of neonatal surgeries in Ontario.

Results: The most common diagnoses were necrotizing enterocolitis/spontaneous intestinal perforation (NEC/SIP) 21%, intestinal atresia 16%, esophageal atresia/tracheoesophageal fistula 14%, ano-rectal malformation 13%, malrotation/volvulus 11%, gastroschisis 9% and omphalocele 4%. The median (IQR) duration of MV post-surgery was 3 (1-8) days with 25.7 % (n=65) of neonates on MV for >7 days. Compared to infants on MV post-surgery for ≤7 days, those with MV>7 days were of lower gestational age, birth weight and weight at surgery, but a higher proportion underwent stoma creation, had a longer duration of opioid administration and higher rates of moderate to severe bronchopulmonary dysplasia (BPD) and mortality (P<0.05). Generalized linear regression analysis showed lower gestational age (GA) and longer opioid administration were associated with longer duration of MV (P<0.001), but indication for surgery, weight at surgery and stoma creation didn't correlate with longer duration of MV (P>0.05). Of the 122 patients handled by one-stage resection with primary anastomosis, 22.1% (n=27) received NIV with 74.1% (n=20) commenced on NIV after 7 days post-surgery, anastomotic leak was detected in 2.5 % (3/122) patients and didn't correlate with NIV.

Conclusions: Lower GA and longer opioid administration were risk factors for prolonged MV in neonates following intestinal surgery. Further research is needed to investigate modifiable practices around pain assessment/ventilation in these patients, and the correlation between NIV and anastomotic leak.
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http://dx.doi.org/10.21037/tp-22-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173873PMC
May 2022

, , and Promote Stress Tolerance to Chilling, Heat, Drought, and Salt in Rice.

Front Plant Sci 2022 24;13:851731. Epub 2022 May 24.

The State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, China.

The ()/ () genes are key regulators of cold acclimation and freezing tolerance in the chilling tolerant . Here, we investigated the function of three members of the 10 rice genes, , , and , in the chilling sensitive rice plants. Their loss of function (LOF) mutants were each more chilling susceptible compared to the wild type, and the LOF mutants of all three genes, , were more chilling susceptible than any of the single mutants. Strikingly, these mutants were capable of cold acclimation, indicating that these rice genes are important for basal chilling tolerance but not cold acclimation. Transcriptome and physiology analyses suggest that the // genes are involved in reactive oxygen species (ROS) scavenging and cell death regulation under chilling. Furthermore, these three rice genes are found to promote tolerance to other abiotic stresses: the // genes are positive regulators of heat tolerance, and are positive regulators of salt tolerance, and is a positive regulator of drought tolerance. These findings expand our knowledge of the roles of DREB1 proteins in plants, enhance our mechanistic understanding of abiotic stress tolerance and will facilitate the generation of stress-tolerant crop plants.
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http://dx.doi.org/10.3389/fpls.2022.851731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171204PMC
May 2022

Design, synthesis and activity against drug-resistant bacteria evaluation of C-20, C-23 modified 5-O-mycaminosyltylonolide derivatives.

Eur J Med Chem 2022 Aug 31;238:114495. Epub 2022 May 31.

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, 450001, PR China; Key Laboratory of Henan Province for Drug Quality and Evaluation, Zhengzhou, 450001, PR China; Henan Qunbo Pharmaceutical Research Institute Co. LTD, PR China. Electronic address:

With the increasing incidence of antibiotic resistance, there is an urgent need to develop new antibiotics with excellent activity against drug-resistant bacteria. Three novel series of tylosin semisynthetic derivatives were designed, synthesized and evaluated for their antibacterial activities against various Gram-positive and Gram-negative bacteria. Among these derivatives, compound C-2 demonstrated potent antibacterial activity against both gram-positive and gram negative bacteria, and non mutagenic. More importantly, compound C-2 displayed high antimicrobial potency against Gram-positive bacteria in a murine model, and was found to be more efficient than tildipirosin. Thus, compound C-2 had great potential as a promising lead compound for the treatment of bacterial infection.
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http://dx.doi.org/10.1016/j.ejmech.2022.114495DOI Listing
August 2022

Study on Supramolecules in Traditional Chinese Medicine Decoction.

Molecules 2022 May 19;27(10). Epub 2022 May 19.

Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

With the application of the concept of supramolecular chemistry to various fields, a large number of supramolecules have been discovered. The chemical components of traditional Chinese medicine have various sources and unique structures. During the high-temperature boiling process, various active components form supramolecules due to complex interactions. The supramolecular structure in a traditional Chinese medicine decoction can not only be used as a drug carrier to promote the absorption and distribution of medicinal components but may also have biological activities superior to those of single active ingredients or their physical mixtures. By summarizing the relevant research results over recent years, this paper introduces the research progress regarding supramolecules in various decoctions, laying a foundation for further research into supramolecules in traditional Chinese medicine decoctions, and provides a new perspective for revealing the compatibility mechanisms of traditional Chinese medicine, guiding clinical medications, and developing new nanometers materials.
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http://dx.doi.org/10.3390/molecules27103268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144598PMC
May 2022

MTP8 from Is Primarily Responsible for Manganese Tolerance.

Int J Mol Sci 2022 May 19;23(10). Epub 2022 May 19.

College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.

Mineral nutrients, such as manganese (Mn) and iron (Fe), play essential roles in many biological processes in plants but their over-enrichment is harmful for the metabolism. Metal tolerance proteins (MTPs) are involved in cellular Mn and Fe homeostasis. However, the transporter responsible for the transport of Mn in wheat is unknown. In our study, TuMTP8, a Mn-CDF transporter from diploid wheat (), was identified. Expression of in yeast strains of Δ and Δ and conferred tolerance to elevated Mn and Fe, but not to other metals (zinc, cobalt, copper, nickel, or cadmium). Compared with TuVIT1 (vacuole Fe transporter), TuMTP8 shows a significantly higher proportion in Mn transport and a smaller proportion in Fe transport. The transient analysis in tobacco epidermal cells revealed that TuMTP8 localizes to vacuolar membrane. The highest transcript levels of were in the sheath of the oldest leaf and the awn, suggesting that TuMTP8 sequesters excess Mn into the vacuole in these organs, away from more sensitive tissues. These findings indicate that , a tonoplast-localized Mn/Fe transporter, functions as a primary balancer to regulate Mn distribution in under elevated Mn conditions and participates in the intracellular transport and storage of excess Mn as a detoxification mechanism, thereby conferring Mn tolerance.
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http://dx.doi.org/10.3390/ijms23105683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9144917PMC
May 2022

Prospective Application of Ferroptosis in Hypoxic Cells for Tumor Radiotherapy.

Antioxidants (Basel) 2022 May 7;11(5). Epub 2022 May 7.

Jilin Provincial Key Laboratory of Radiation Oncology & Therapy, The First Hospital of Jilin University, Changchun 130021, China.

Radiation therapy plays an increasingly important role in cancer treatment. It can inhibit the progression of various cancers through radiation-induced DNA breakage and reactive oxygen species (ROS) overload. Unfortunately, solid tumors, such as breast and lung cancer, often develop a hypoxic microenvironment due to insufficient blood supply and rapid tumor proliferation, thereby affecting the effectiveness of radiation therapy. Restraining hypoxia and improving the curative effect of radiotherapy have become difficult problems. Ferroptosis is a new type of cell death caused by lipid peroxidation due to iron metabolism disorders and ROS accumulation. It plays an important role in both hypoxia and radiotherapy and can enhance the radiosensitivity of hypoxic tumor cells by amplifying oxidative stress or inhibiting antioxidant regulation. In this review, we summarize the internal relationship and related mechanisms between ferroptosis and hypoxia, thus exploring the possibility of inducing ferroptosis to improve the prognosis of hypoxic tumors.
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http://dx.doi.org/10.3390/antiox11050921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137794PMC
May 2022

A ROS-Responsive Simvastatin Nano-Prodrug and its Fibronectin-Targeted Co-Delivery System for Atherosclerosis Treatment.

ACS Appl Mater Interfaces 2022 Jun 26;14(22):25080-25092. Epub 2022 May 26.

Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China.

Nanoprodrugs with responsive release properties integrate the advantages of stimuli-responsive prodrugs and nanotechnology. They would provide ultimate opportunity in fighting atherosclerosis. In this study, we synthesized a redox-responsive nanoprodrug of simvastatin (TPTS) by conjugating α-tocopherol polyethylene glycol derivative to the pharmacophore of simvastatin with a thioketal linker. TPTS formed nanoparticles and released parent simvastatin in the presence of hydrogen peroxide. Moreover, by taking advantage of the self-assembly behavior of TPTS, we developed a fibronectin-targeted delivery system (TPTS/C/T) to codelivery simvastatin prodrug and ticagrelor. In vitro and in vivo experiments indicated that TPTS and TPTS/C/T had good stability, which could reduce off-target leakage of drugs. They greatly inhibited the M1-type polarization of macrophages; reduced intracellular reactive oxygen species level and inflammatory cytokine; and TNF-α, MCP-1, and IL-1β were secreted by macrophage cells, thus providing enhanced anti-inflammatory and antioxidant effects compared with free simvastatin. TPTS/C/T realized targeted drug release to plaques and synergistic therapeutic effects of simvastatin and ticagrelor on atherosclerosis treatment in an ApoE-/- mouse model, resulting in excellent atherosclerosis therapeutic efficacy and a promising biosafety profile. Therefore, this study provides a new method for manufacturing statin nanodrugs and a new design idea for related responsive drug release nanosystems for atherosclerosis.
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http://dx.doi.org/10.1021/acsami.2c02354DOI Listing
June 2022

A Secure High-Order Gene Interaction Detecting Method for Infectious Diseases.

Comput Math Methods Med 2022 21;2022:4471736. Epub 2022 Apr 21.

School of Medical Information & Engineering, Xuzhou Medical University, Xuzhou 221000, China.

Infectious diseases pose a serious threat to human life, the Genome Wide Association Studies (GWAS) can analyze susceptibility genes of infectious diseases from the genetic level and carry out targeted prevention and treatment. The susceptibility genes for infectious diseases often act in combination with multiple susceptibility sites; therefore, high-order epistasis detection has become an important means. However, due to intensive computational burden and diversity of disease models, existing methods have drawbacks on low detection power, high computation cost, and preference for some types of disease models. Furthermore, these methods are exposed to repeated query and model inversion attacks in the process of iterative optimization, which may disclose Single Nucleotide Polymorphism (SNP) information associated with individual privacy. Therefore, in order to solve these problems, this paper proposed a safe harmony search algorithm for high-order gene interaction detection, termed as HS-DP. Firstly, the linear weighting method was used to integrate 5 objective functions to screen out high-order SNP sets with high correlation, including K2-Score, JS divergence, logistic regression, mutual information, and Gini. Then, based on the Differential Privacy (DP) theory, the function disturbance mechanism was introduced to protect the security of individual privacy information associated with the objective function, and we proved the rationality of the disturbance mechanism theoretically. Finally, the practicability and superiority of the algorithm were verified by experiments. Experimental results showed that the algorithm proposed in this paper could improve the detection accuracy to the greatest extent while guaranteeing privacy.
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http://dx.doi.org/10.1155/2022/4471736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9050263PMC
May 2022

Intimal Hyperplasia of Arteriovenous Fistula.

Ann Vasc Surg 2022 Apr 23. Epub 2022 Apr 23.

Department of Nephrology, Affiliated Hospital of Chengde Medical University, Chengde, Hebei Province, China.

Intimal hyperplasia (IH), a crucial histopathological injury, forms the basis of vascular stenosis and thrombogenesis. In addition, it is common in maladies such as stenosis at the anastomosis of arteriovenous fistula and restenosis after angioplasty. Various cellular and noncellular components play critical parts in the advancement of IH. This article reviews the distinctive components of IH, such as endothelial dysfunction, multiplication, and movement of vascular smooth muscle cells. Finally, in addition to synthesis of large amounts of extracellular matrix and inflammatory responses, which have frequently been studied in recent years, we offer a premise for clinical treatment with vascular smooth muscle cells.
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http://dx.doi.org/10.1016/j.avsg.2022.04.030DOI Listing
April 2022

Optimizing the Bacteriostatic and Cytocompatibility Properties of Poly(hexamethylene guanidine) Hydrochloride (PHMG) via the Guanidine/Alkane Ratio.

Biomacromolecules 2022 05 24;23(5):2170-2183. Epub 2022 Apr 24.

State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren'ai Road, Suzhou 215123, P. R. China.

The emergence of "superbugs" is not only problematic and potentially lethal for infected subjects but also poses serious challenges for the healthcare system. Although existing antibacterial agents have been effective in some cases, the side effects and biocompatibility generally present difficulties. The development of new antibacterial agents is therefore urgently required. In this work, we have adapted a strategy for the improvement of poly(hexamethylene guanidine) hydrochloride (PHMG), a common antibacterial agent. This involves copolymerization of separate monomer units in varying ratios to find the optimum ratio of the hydrocarbon to guanidine units for antibacterial activity. A series of these copolymers, designated as PGB, was synthesized. By varying the guanidine/hydrophobic ratio and the copolymer molecular weight, a structure-optimized PGB was identified that showed broad-spectrum antibacterial activity and excellent biocompatibility in solution. In an antibacterial assay, the copolymer with the optimum composition (hydrophobic unit content 25%) inhibited >99% and was compatible with mammalian cells. A polyurethane emulsion containing this PGB component formed transparent, flexible films (PGB-PU films) on a wide range of substrate surfaces, including soft polymers and metals. The PGB-PU films showed excellent bacteriostatic efficiency against nosocomial drug-resistant bacteria, such as and methicillin-resistant (MRSA). It is concluded that our PGB polymers can be used as bacteriostatic agents generally and in particular for the design of antibacterial surfaces in medical devices.
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http://dx.doi.org/10.1021/acs.biomac.2c00233DOI Listing
May 2022

Robust, anti-biofouling 2D nanogel films from poly(-vinyl caprolactam--vinylimidazole) polymers.

J Mater Chem B 2022 05 18;10(19):3723-3733. Epub 2022 May 18.

State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China.

In analogy with adsorbed protein films, we have fabricated a family of 2D nanofilms composed of poly(-vinyl caprolactam--vinylimidazole) (PNVCL) nanogels. NVCL was copolymerized with 1-vinylimidazole (VIM), and then cross-linked with α,ω-dibromoalkanes with 2 to 8 carbons quaternization to form the nanogels. The swelling ratio of the gels was precisely controlled by regulating the inter-chain spacing of the polymers at the level of the carbon atom chain length of the cross-linker. The short-chain alkanes used are relatively rigid and their dimensions provide an accurate estimate of the chain spacing in the nanogels. It was shown that small differences in the carbon atom number of the cross-linking agent led to significant differences in the mechanical properties of the nanogels, in particular in the softness, deformability, and contact area (in film form), all of which increased with increasing carbon number. Films of the softer gels not only showed good adhesion to a number of substrates, but were also mechanically robust. In addition, the films showed excellent light transmission and nontoxicity to L929 cells. Nanogels of intermediate softness were shown to inhibit the adhesion of bacteria and human umbilical vein smooth muscle cells (HUVSMCs), and to be resistant to the adsorption of the plasma protein fibrinogen, indicating strong anti-biofouling properties. Gels that were either too stiff or too soft showed somewhat weaker anti-fouling activity in terms both of HUVSMCs adhesion and protein adsorption.
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http://dx.doi.org/10.1039/d1tb02726cDOI Listing
May 2022

Restricting Bond Rotations by Ring Fusion: A Novel Molecular Design Strategy to Improve Photodynamic Antibacterial Efficacy of AIE Photosensitizers.

ACS Appl Mater Interfaces 2022 Apr 5;14(15):17055-17064. Epub 2022 Apr 5.

State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.

In recent years, aggregation-induced emission photosensitizers (AIE-PSs) for antibacterial photodynamic therapy (aPDT) have received increasing attention because of their ability to increase reactive oxygen species (ROS) generation in the aggregation state. However, their antibacterial effect still has great room for improvement. Herein, we propose that if the rotation of some bonds in AIE-PSs is restricted, the nonradiative decay could be further suppressed to boost the generation of fluorescence and ROS, so as to improve their antibacterial efficacy. Following this molecular design strategy, we developed a new class of carbazole group-based AIE-PSs (, , , and ), in which the rotation of phenyl-N bonds is restricted in the carbazole ring. Compared with diphenylamine group-based AIE-PSs with free rotation of phenyl-N bonds, carbazole group-based AIE-PSs showed stronger fluorescence, ROS generation, and antibacterial abilities, demonstrating the feasibility of this new design strategy. Notably, can enter the entire cell of to exert its antibacterial effect, and there are few reports of photosensitizers with similar functions. Furthermore, to the best of our knowledge, the light dose (1.2 J/cm) we used for to kill is much lower than that of many reported photosensitizers, indicating great prospects for AIE antimicrobial photosensitizers.
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http://dx.doi.org/10.1021/acsami.1c24329DOI Listing
April 2022

Etiology of neonatal cholestasis after emerging molecular diagnostics.

Transl Pediatr 2022 Mar;11(3):359-367

Division of Neonatology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.

Background: In the pediatric group, most cholestatic patients had disease onset at 0-3 months of age, and more and more are found to have specific genetic defects after failing to obtain a definite diagnosis by routine evaluation. To investigate the etiological diagnosis for the newborns with cholestasis during the neonatal period after emerging molecular tests comprehensively.

Methods: We conducted a retrospective study to evaluate clinical characteristics, etiologies and outcomes in infants with neonatal cholestasis after emerging molecular diagnostics from January 1st to December 31st, 2019 in Children's Hospital of Fudan University.

Results: There were 160 cases of neonatal cholestasis with mean gestational age (GA) 32.6±4.8 weeks and birth weight (BW) 1,880±991 g, composing 3.4% of total neonatal admissions in 2019. Overall 97.5% (n=156) patients had a definite diagnosis, including 9 obtaining a genetic diagnosis after adding molecular test in routine evaluation, which made the diagnosis rate for cholestasis increased by 5.6%. The most common etiology of cholestasis in the neonatal period was parenteral nutrition-associated cholestasis (PNAC) 48.8% (n=78), followed by cardiovascular and circulatory disorders 18.1%, biliary anatomic obstruction 12.5%, infection 8.7% and genetic disorders 5.6%. PNAC and biliary anatomic obstruction were the most common etiology of cholestasis for preterm and term infants respectively. The mortality rate is 2.5% (n=4) and 91.9% (n=147) patients totally recovery or improve in follow-up.

Conclusions: The causes of cholestasis in neonates are complicated, molecular diagnostics can improve the etiological diagnosis for newborns with cholestasis. But still, quite amount of causes are remediable and transient during the neonatal period, gene test may help to rule out genetic causes and enhance confidence in judging prognosis.
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http://dx.doi.org/10.21037/tp-21-503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976681PMC
March 2022

A ratiometric ESIPT fluorescent probe for detection of anticancer-associated HO level in vitro and in vivo.

Spectrochim Acta A Mol Biomol Spectrosc 2022 Aug 16;276:121163. Epub 2022 Mar 16.

MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China; Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China. Electronic address:

ROS is a significant factor in the cancer treatment mechanism. The monitoring anticancer-associated HO level plays a vital role in the anticancer mechanistic exploration in pathology and physiology. Herein we synthesized a ratiometric fluorescent probe (HBQ-L) to detect and image HO based on excited-state intramolecular proton transfer. HBQ-L had a high sensitivity (231-fold) with a low detection limit (28.5 nM) for monitoring HO in solution. HBQ-L showed good mitochondrial-targeting and successfully detected both exo-/endogenous HO in A549 cells. Furthermore, HBQ-L was used to ratiometric monitor HO level in anticancer reagent DOX-treated cells or zebrafish. Importantly, it was employed to access the monitoring HO in the A549 tumor-bearing mice.
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http://dx.doi.org/10.1016/j.saa.2022.121163DOI Listing
August 2022

TNF-α derived from arsenite-induced microglia activation mediated neuronal necroptosis.

Ecotoxicol Environ Saf 2022 May 1;236:113468. Epub 2022 Apr 1.

Department of Occupational and Environmental Health, Key Laboratory of Liaoning Province on Toxic and Biological Effects of Arsenic, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address:

Arsenic, an identified environmental toxicant, poses threats to the health of human beings through contaminated water and food. Recently, increasing reports focused on arsenic-induced nerve damage, however, the underlying mechanism remains elusive. Microglia are important immune cells in the nervous system, which produce a large number of inflammatory factors including TNF-α when activated. Recent reports indicated that TNF-α is involved in the process of necroptosis, a new type of programmed cell death discovered recently. Although there were evidences suggested that arsenic could induce both microglia activation and TNF-α production in the nervous system, the mechanism of arsenic-induced neurotoxicity due to microglia activation is rarely studied. In addition, the role of microglia-derived TNF-α in response to arsenic exposure in necroptosis has not been documented before. In this study, we found that arsenite induced microglial activation through p38 MAPK signaling pathway, leading to the production of TNF-α. Microglia-derived TNF-α further induced necroptosis in the neuronal cells. Our findings suggested that necroptosis induced by microglia-derived TNF-α upon arsenite exposure partially played a role in arsenic-induced cell death which underlie the fundamental event of arsenic-related neurotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113468DOI Listing
May 2022

Prediction model for different progressions of Atherosclerosis in ApoE mice based on lipidomics.

J Pharm Biomed Anal 2022 May 2;214:114734. Epub 2022 Apr 2.

Institute of Basic Theory of Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China; School of Basic Medicine, Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, 712046, China. Electronic address:

Atherosclerosis (AS) is a progressive disease with a complex pathogenesis which is characterized by dyslipidemia and changes in the vascular wall composition. According to the degree of lesions, atherosclerosis can be divided into four stages: hyperlipidemia, lipid stria, fiber plaque, and atherosclerotic plaque. The present study aimed to establish a prediction model for the different pathological stages of AS based on lipidomics. ApoE mice and C57BL/6 mice fed a normal diet were divided into seven groups according to the feeding time (8, 12, 16, 20, 24, 28, and 32 weeks). The changes in the lipid composition and serum content were detected using ultra-performance liquid chromatography coupled with quadrupole time-of-flight high-definition mass spectrometry (UPLC-Q-TOF/MS). Through the results of serum total cholesterol, triglyceridelow density lipoprotein at each time and HE staining of the head and arm artery, the seven time points of the model group were corresponding to the four courses of atherosclerosis. In accordance with the lipid data of each course of AS and mathematical modeling, this study established a multi-index prediction model of the different processes of AS. Notably, while establishing the model, several indicators were combined with one of four dimension reduction methods, such as principal component logistics regression method, cumulative logistics regression method, Partial least squares-discriminant analysis(PLS-DA), and canonical discriminant analysis (CDA). The error rate of the four methods were 28.5%, 16.22%, 18.24%, and 14.86%, respectively. CDA had the lowest error rate and the best prediction accuracy of the AS different courses for the training and verification sets after 5-fold cross-validation of this model. This study showed that lipidomics combined with mathematical methods could establish a non-invasive and accurate model for the prediction of AS.
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http://dx.doi.org/10.1016/j.jpba.2022.114734DOI Listing
May 2022

Fixed dosing of kukoamine B in sepsis patients: Results from population pharmacokinetic modelling and simulation.

Br J Clin Pharmacol 2022 Apr 3. Epub 2022 Apr 3.

Clinical Pharmacology Research Center, Beijing Key Laboratory of Clinical PK and PD Investigation for Innovative Drugs, Peking Union Medical College Hospital, Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.

Aims: To assess the appropriateness of the body weight or fixed dosing regimen, a population pharmacokinetic (PopPK) model of kukoamine B has been built in sepsis patients.

Methods: Plasma concentrations of kukoamine B and the covariates information were taken from 30 sepsis patients assigned into 0.06 mg/kg, 0.12 mg/kg and 0.24 mg/kg groups in a Phase IIa clinical trial. The PopPK model was built using a nonlinear mixed-effect (NLME) modelling approach. Based on the final model, PK profiles were respectively simulated 500 times applying the body weight and renal function information of 12 sepsis patients from the 0.24 mg/kg group on the body weight or the fixed dosing regimen. For each dosing regimen, PK profiles of 6000 virtual patients were obtained. Statistical analyses for C and C were performed. If the biases of C and C can all meet the criteria of ±15%, the fixed dosing regimen can substitute for the body weight dosing regimen.

Results: The PopPK model was successfully developed using the NLME approach. A bi-compartmental model was selected as the basic model. Renal function was identified as a statistically significant covariate of systemic clearance with the objective function value (OFV) decreasing 8.6, resulting in a 5.2% decrease in inter-individual variability (IIV) of systemic clearance. Body weight was not identified as a statistically significant covariate. Simulation results demonstrated two methods had a bias of 8.1% for C , and 8.6% for C . Furthermore, PK variability was lower on the fixed dosing regimen than the body weight regimen.

Conclusions: Based on the simulation results, a fixed dosing regimen was recommended in the subsequent clinical trials.
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http://dx.doi.org/10.1111/bcp.15342DOI Listing
April 2022

Status of medication literacy and its related factors among undergraduate students in Shanxi Province, China: A cross-sectional study.

J Clin Pharm Ther 2022 Mar 28. Epub 2022 Mar 28.

School of Public Health, Peking University, Beijing, China.

What Is Known And Objective: Medication safety problem has always been the focus of healthcare providers and public health community scholars. As the backbone of the future society, the mastery of college students' knowledge to use medicine will directly affect the level of medication literacy (ML) of the public in the future. The purpose of this study was to investigate the current ML of college students in Shanxi Province and to identify its related factors.

Methods: A cluster random sampling method was utilized to select 800 college students from 10 universities in Shanxi province as participants from 21 March to 10 April 2020. After quality control, 763 valid questionnaires were collected (effective rate 95.4%). This study applied the ML scale adapted from the 14-item health literacy scale (HLS-14) to estimate ML, which contains functional ML, communicative ML and critical ML dimensions to estimate the ML situation. Then, we used structural equation modelling (SEM) to test the hypothesized relationship among three dimensions of ML, self-evaluated health status and safety medication science popularization activities on campus.

Results And Discussion: The results showed that the reliability and validity of the ML scale were good. The average score of ML level of college students in Shanxi Province was 44 points, and the interquartile range was 40-48 points (full score is 65 points). The proportion of high ML level was estimated at as low as 26.7%. 73.1% participants had an average level, and only 1 participant (0.1%) had a low level of ML. Univariate analysis showed that the ML level was significantly influenced by gender, universities, field of study, academic performance and ethnic group (p < 0.05). SEM showed that functional ML (λ = 0.01) and communicative ML (λ = 0.75) had a direct positive association with critical ML. Meanwhile, the model also had a mediating effect. Functional ML had an indirect positive association with critical ML through the mediating effect of communicative ML (λ = 0.11). In addition, both self-evaluated health status and safety medication science popularization activities on campus had an indirect positive association with critical ML through the mediating effect of functional ML and communicative ML.

What Is New And Conclusion: The study revealed that the ML of most college students in Shanxi Province was at the average level. Among them, medical college student (including pharmacy, nursing, public health, preventive medicine, basic medicine and clinical medicine students), the Han nationality students (the students of China's majority ethnic group), students of good self-evaluated health status, and students who were more exposed to safety medication science popularization activities had a relatively higher ML level. Moreover, it highlighted the importance of self-evaluated health status and safety medication science popularization activities on campus to ML.
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http://dx.doi.org/10.1111/jcpt.13655DOI Listing
March 2022
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