Publications by authors named "Wei He"

2,279 Publications

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Inhibition of PHLPP1/2 phosphatases rescues pancreatic β-cells in diabetes.

Cell Rep 2021 Aug;36(5):109490

Centre for Biomolecular Interactions Bremen, University of Bremen, 28359 Bremen, Germany; Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran 1449614535, Iran. Electronic address:

Pancreatic β-cell failure is the key pathogenic element of the complex metabolic deterioration in type 2 diabetes (T2D); its underlying pathomechanism is still elusive. Here, we identify pleckstrin homology domain leucine-rich repeat protein phosphatases 1 and 2 (PHLPP1/2) as phosphatases whose upregulation leads to β-cell failure in diabetes. PHLPP levels are highly elevated in metabolically stressed human and rodent diabetic β-cells. Sustained hyper-activation of mechanistic target of rapamycin complex 1 (mTORC1) is the primary mechanism of the PHLPP upregulation linking chronic metabolic stress to ultimate β-cell death. PHLPPs directly dephosphorylate and regulate activities of β-cell survival-dependent kinases AKT and MST1, constituting a regulatory triangle loop to control β-cell apoptosis. Genetic inhibition of PHLPPs markedly improves β-cell survival and function in experimental models of diabetes in vitro, in vivo, and in primary human T2D islets. Our study presents PHLPPs as targets for functional regenerative therapy of pancreatic β cells in diabetes.
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http://dx.doi.org/10.1016/j.celrep.2021.109490DOI Listing
August 2021

Mendelian randomisation study of smoking exposure in relation to breast cancer risk.

Br J Cancer 2021 Aug 2. Epub 2021 Aug 2.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk.

Methods: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy.

Results: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect.

Conclusion: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
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http://dx.doi.org/10.1038/s41416-021-01432-8DOI Listing
August 2021

TSPO deficiency accelerates amyloid pathology and neuroinflammation by impairing microglial phagocytosis.

Neurobiol Aging 2021 Jul 3;106:292-303. Epub 2021 Jul 3.

Department of Immunology, CAMS Key Laboratory for T Cell and Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing, China. Electronic address:

Increasing evidence has placed inflammation and immune dysfunction at the center of the pathogenesis of Alzheimer's disease (AD). The mitochondrial protein translocator protein (18 kDa) (TSPO) is highly upregulated in microglia and astrocytes in response to inflammatory stimulation. However, the biological action of TSPO in the pathogenesis of AD has not been determined to date. In this study, we showed that TSPO expression was upregulated in brain tissues from AD patients and AD model mice. APP/PS1 mice lacking TSPO generated significantly higher levels of Aβ and Aβ peptides and more Aβ plaques, as well as enhanced microglial activation, in the brain. TSPO-deficient microglia cultured in vitro showed a significant decrease in the ability to phagocytose Aβ peptides or latex beads and generated more proinflammatory cytokines (TNF-α and IL-1β) in response to Aβ peptides. Our findings suggest that TSPO has protective functions against neuroinflammation and Aβ pathogenesis in AD. TSPO may be a potential drug target for the development of drugs that have therapeutic or preventive effects in neuroinflammatory diseases.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.06.020DOI Listing
July 2021

Bisepoxide-Jeffamine microgel synthesis and application toward heterogeneous surface morphology for differential neuronal/non-neuronal cell responses in vitro.

Colloids Surf B Biointerfaces 2021 Jul 26;207:112009. Epub 2021 Jul 26.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian, Liaoning, 116023, China; School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning, 116023, China. Electronic address:

Herein, a new non-vinylic type of cationic microgels (MG) was readily prepared from ethylene glycol diglycidyl ether and Jeffamine T-403 in water. The MG was responsive to both temperature and pH, and oxidatively stable as demonstrated by the hydrogen peroxide study. Using glass as a model substrate, its surface was easily imparted with a heterogeneous morphology by simply adsorbing MG dispersed in basic solution. Specifically, the morphology features patches made of a monolayer of connected yet individually recognizable MG. Through in vitro cell studies, we show that a mere change of the extent of surface coverage by such a patchy morphology can strike a balance in promoting adhesion and differentiation of neuron-like PC-12 cells and primary cortical neurons of chick embryo, without soliciting proliferative response from non-neuronal cells of NIH3T3 fibroblast and CTX astrocyte. This simple yet unconventional surface morphology created by MG could be leveraged in the future as an alternative strategy for neural interface engineering.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112009DOI Listing
July 2021

A Universal Strategy toward the Precise Regulation of Initial Coulombic Efficiency of Li-Rich Mn-Based Cathode Materials.

Adv Mater 2021 Aug 1:e2103173. Epub 2021 Aug 1.

State Key Laboratory of Physical Chemistry of Solid Surface Fujian Key Laboratory of Materials Genome Collaborative Innovation Center of Chemistry for Energy Materials College of Materials, Xiamen University, Xiamen, 361005, China.

Li-rich Mn-based cathode materials (LRMs) are potential cathode materials for high energy density lithium-ion batteries. However, low initial Coulombic efficiency (ICE) severely hinders the commercialization of LRM. Herein, a facile oleic acid-assisted interface engineering is put forward to precisely control the ICE, enhance reversible capacity and rate performance of LRM effectively. As a result, the ICE of LRM can be precisely adjusted from 84.1% to 100.7%, and a very high specific capacity of 330 mAh g at 0.1 C, as well as outstanding rate capability with a fascinating specific capacity of 250 mAh g at 5 C, are harvested. Theoretical calculations reveal that the introduced cation/anion double defects can reduce the diffusion barrier of Li ions, and in situ surface reconstruction layer can induce a self-built-in electric field to stabilize the surface lattice oxygen. Moreover, this facile interface engineering is universal and can enhance the ICEs of other kinds of LRM effectively. This work provides a valuable new idea for improving the comprehensive electrochemical performance of LRM through multistrategy collaborative interface engineering technology.
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http://dx.doi.org/10.1002/adma.202103173DOI Listing
August 2021

Electroacupuncture and Moxibustion-Like Stimulation Relieves Inflammatory Muscle Pain by Activating Local Distinct Layer Somatosensory Afferent Fibers.

Front Neurosci 2021 15;15:695152. Epub 2021 Jul 15.

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.

Recent studies have shown that both superficial and deep acupuncture produced clinically relevant and persistent effect on chronic pain, and several subtypes of somatic primary afferents played critical roles in acupuncture and moxibustion analgesia. However, which kind of primary afferents in the superficial and deep tissue of the acupoint is activated by acupuncture or moxibustion to relieve pain persistently remains unclear. The aim of this study is to investigate the roles of distinct peripheral afferents in different layers of the tissue (muscle or skin) in the acupoint for pain relief. Muscular A-fibers activated by deep electroacupuncture (dEA) with lower intensity (approximately 1 mA) persistently alleviated inflammatory muscle pain. Meanwhile, cutaneous C-nociceptors excited by noxious moxibustion-like stimulation (MS) and topical application of capsaicin (CAP) on local acupoint area produced durable analgesic effect. Additionally, spontaneous activity of C-fibers caused by muscular inflammation was also inhibited by dEA and CAP. Furthermore, decreases in pain behavior induced by dEA disappeared after deep A-fibers were demyelinated by cobra venom, whereas CAP failed to relieve pain following cutaneous denervation. Collectively, these results indicate that dEA and MS ameliorate inflammatory muscle pain through distinct primary afferents in different layers of somatic tissue; the former is achieved by activating muscular A-fibers, while the latter is mediated by activating cutaneous C-fibers.
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http://dx.doi.org/10.3389/fnins.2021.695152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8319633PMC
July 2021

Severe fetal anemia and hydrops fetalis associated with compound heterozygosity for Hb Zurich-Albisrieden (:c.178G>C) and Hb Quong Sze (:c.377T>C).

J Int Med Res 2021 Jul;49(7):3000605211031429

Medical Genetic Center, 90405Guangdong Women and Children Hospital, Guangdong Women and Children Hospital, Guangzhou, Guangdong, China.

We report on a fetus with cardiomegaly and increased middle cerebral artery-peak systolic velocity at 25 weeks of gestation. Severe fetal anemia (hemoglobin (Hb) level 37 g/L) was confirmed by cordocentesis. Hb analysis showed that Hb Bart's was 9% in cord blood. Molecular analysis of the proband's family found that the mother was a carrier of Hb Quong Sze (Hb QS, :c.377T>C), the father was a carrier of Hb Zurich-Albisrieden (Hb ZA, :c.178G>C), and the fetus was a compound heterozygote for Hb ZA and Hb QA. Despite intrauterine blood transfusions, the fetus experienced problems including oligohydramnios, growth retardation, placental thickening, and heart enlargement in the third trimester. The couple chose to terminate the pregnancy, and fetal autopsy confirmed the above diagnosis. This is the first report of a case of Hb ZA compounded with Hb QS, and provides a reference for genetic counselling and prenatal diagnosis in the Chinese population.
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http://dx.doi.org/10.1177/03000605211031429DOI Listing
July 2021

Cryptotanshinone inhibits cytotoxin-associated gene A-associated development of gastric cancer and mucosal erosions.

World J Gastrointest Oncol 2021 Jul;13(7):693-705

Department of General Surgery, Fourth Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China.

Background: Approximately 90% of new cases of noncardiac gastric cancer (GC) are related to , and cytotoxin-associated gene A (CagA) is one of the main pathogenic factors. Recent studies have shown that the pharmacological effects of cryptotanshinone (CTS) can be used to treat a variety of tumors. However, the effects of CTS on , especially CagA+ strain-induced gastric mucosal lesions, on the development of GC is unknown.

Aim: To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells, and determine if CagA+ strains causes pathological changes in the gastric mucosa of mice.

Methods: The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, and the abnormal growth, migration and invasion caused by CagA were detected by CCK-8 and transwell assays. After transfection with pSR-HA-CagA and treatment with CTS, proliferation and metastasis were evaluated by CCK-8 and transwell assays, respectively, and the expression of Src homology 2 (SH2) domain-containing phosphatase 2 (SHP2) and phosphorylated SHP2 (p-SHP2) was detected using western blotting in AGS cells. The enzyme-linked immunosorbent assay was used to determine the immunoglobulin G (IgG) level against CagA in patient serum. Mice were divided into four groups and administered strains (CagA+ or CagA-) and CTS (or PBS) intragastrically, and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains. Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney.

Results: CTS inhibited the growth of GC cells in dose- and time-dependent manners. Overexpression of CagA promoted the growth, migration, and invasion of GC cells. Importantly, we demonstrated that CTS significantly inhibited the CagA-induced abnormal proliferation, migration, and invasion of GC cells. Moreover, the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients. Additionally, CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells. CTS suppressed CagA+ strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA- strain group.

Conclusion: CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro, and CagA+ strains caused mucosal erosions of the stomach by decreasing the protein expression of SHP2.
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http://dx.doi.org/10.4251/wjgo.v13.i7.693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299932PMC
July 2021

Behavior Characteristics and Risk for Metabolic Syndrome Among Women in Rural Communities in China.

J Cardiovasc Nurs 2021 Jul 23. Epub 2021 Jul 23.

Jyu-Lin Chen, PhD, RN, CNS, FAAN Professor, Department of Family Health Care Nursing, School of Nursing, University of California, San Francisco. Jia Guo, PhD, RN Professor, Xiangya School of Nursing, Central South University, Changsha, China. Chen-Xi Lin, MS School of Nursing, University of California, San Francisco. Jundi Yang, BSN Xiangya School of Nursing, Central South University, Changsha, China. Ping Mao, PhD, RN Professor, Nursing Department, Third Xiangya Hospital, Central South University, Changsha, China. Shan Jiang, BSN, RN Xiangya School of Nursing, Central South University, Changsha, China. Wei He, MS, RN, Third Xiangya Hospital and Xiangya School of Nursing, Central South University, Changsha, China. Kathy Lien, BA, RN Department of Family Health Care Nursing, School of Nursing, University of California, San Francisco.

Background: Rapid economic growth and lifestyle changes in China have resulted in increased metabolic syndrome (MetS) rates. Few investigators have examined sex-specific risk factors and the role of menopause, stress, and sleep on MetS among women in China.

Objective: In this study, we aimed to identify the risk factors for MetS among women in rural China.

Methods: A cross-sectional study design was used, and participants were recruited from rural areas in China. Female participants older than 18 years were eligible to participate. Participants had their weight, height, waist circumference, blood pressure, and fasting blood measured at study sites. They also completed validated questionnaires regarding sociodemographic information and MetS-related health behaviors.

Results: A total of 646 women were included in this study. The overall prevalence of MetS was 26.2%. The MetS group had a greater number of overweight/obese women than the non-MetS group did. For premenopausal women, a higher income, being overweight/obese, and eating salty/marinated food increased their risk for MetS (odds ratio [OR], 2.56, 4.55, and 3.1, respectively). For postmenopausal women, a low level of education (OR, 0.44) and being overweight/obese (OR, 4.98) increased their risk of MetS.

Conclusion: Almost half of the women in this study were overweight/obese, and many of them did not meet the national recommendations for a healthy lifestyle, increasing their risk for MetS. Developing cultural and behavioral interventions tailored for overweight/obese women is critical in reducing MetS.
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http://dx.doi.org/10.1097/JCN.0000000000000836DOI Listing
July 2021

Persistent deficiency of mucosa-associated invariant T (MAIT) cells during alcohol-related liver disease.

Cell Biosci 2021 Jul 28;11(1):148. Epub 2021 Jul 28.

Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, Anhui, China.

Background: Alcohol-related liver disease (ALD) is a major cause of chronic liver diseases. Inflammatory response is a basic pathological feature of ALD. Mucosal-associated invariant T(MAIT) cells are a novel population of innate immune cells, which may be depleted in various inflammatory diseases. However, the changes of MAIT cell in ALD remains unclear.

Results: In this study, the levels of MAIT cell were significantly decreased in patients with alcoholic fatty liver disease, alcoholic cirrhosis, and mixed cirrhosis (alcoholic + viral). Furthermore, the reduction of circulating MAIT cells was correlated with liver function in patients with cirrhosis. Functional changes among circulating MAIT cells in patients with alcoholic cirrhosis, including increased production of IL-17A and perforin, and reduced production of TNF-α. Plasma cytokine and chemokine levels were quantified using multiple immunoassays and ELISA. Serum levels of chemokine IL-8 were correlated with MAIT cell frequency in patients with alcoholic cirrhosis. Moreover, no differences were observed in the expression of CCR6, CXCR6, and PD-1 in circulating MAIT cells of patients with alcoholic cirrhosis. The MAIT cells in patients with alcoholic cirrhosis were prone to apoptosis, which was promoted by IL-12, IL-18, and IL-8.

Conclusions: Our findings indicate persistent MAIT cell loss during alcohol-related liver disease and suggest that MAIT cells can be promising indicator and therapeutic targets in ALD.
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http://dx.doi.org/10.1186/s13578-021-00664-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320031PMC
July 2021

Impacts of stand density on diversity of understory plant and soil seed banks in a plantation.

Ying Yong Sheng Tai Xue Bao 2021 Jul;32(7):2355-2362

College of Horticulture, Huazhong Agricultural University, Wuhan 430070, China.

Stand density is a critical factor impacting the diversity of understory plants. We analyzed the diversity of understory plants and soil seed banks, as well as their relationship by setting up three planting densities in a plantation, including low density (1575 trees·hm, D), medium (2474 trees·hm, D), and high (3550 trees·hm, D). It aimed to provide a scientific basis for the implementation of the multi-objective sustainable development of plantations. The results showed that there were 70 species of herbs and shrubs belonging to 42 families and 62 genera. D was dominated by heliophiles, whereas both the D and D were dominated by shade-tolerant species. The Margalef (), Shannon (), Simpson (), Pielou (), and Altalo () indices of the herbs and shrubs exhibited a downward trend with increasing stand den-sity. In the herb layer, D and D showed significant difference in , , and . There were significant differences of and in the shrub layer among the three stand densities, but no diffe-rence of and . , , and in the soil seed bank first decreased and then increased with increasing stand density, with species richness and diversity being the highest in D. The similarity coefficient of Jaccard and Sorensen among different stand densities was low. In the herb layer, was positively correlated with . The correlations between stand density and , , and were greater in the shrub layer than in the herb layer. There was significant negative correlation between stand density and both in the shrub and herb layers. The stand density of 1575 trees·hm was comparatively beneficial for the development of understory, plant diversity, and sustainability of plantation.
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http://dx.doi.org/10.13287/j.1001-9332.202107.004DOI Listing
July 2021

Cascade catalytic nanoplatform based on ions interference strategy for calcium overload therapy and ferroptosis.

Int J Pharm 2021 Jul 24;606:120937. Epub 2021 Jul 24.

College of Pharmacy, Xinxiang Medical University, Xinxiang 453003, China. Electronic address:

Intracellular ions played prominent part in cell function and behavior. Disrupting intracellular ions homeostasis might switch ions signal from "regulating" to "destroying". Inspired by this, we introduced the ions interference strategy for tumor therapy. Herein, curcumin (CUR) and transferrin (Tf) co-loaded calcium peroxide nanoparticles (CaO NPs) were formulated. With tumor targeting ability, CaO/Tf/CUR pinpointed tumor cells and then instantaneously decomposed in acidic lysosomes, concurrently accompanying with the release of Ca and CUR, as well as the production of HO. Then HO not only damaged structure of Tf to release Fe, but also was converted to hydroxyl radicals via ferric ions mediated Fenton reaction for ferroptosis. In addition, the released Ca and CUR induced Ca overload via exogenous and endogenous calcium ions accumulation, respectively, further activating mitochondria apoptosis signaling pathway for cell injury. Therefore, based on calcium and ferric ions interference strategy, the cascade catalytic CaO/Tf/CUR offered synergistic combination of ferroptosis, Ca overload therapy and chemotherapy, which held a great promise in cancer treatment.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120937DOI Listing
July 2021

Adenosine A receptor neurons in the olfactory bulb mediate odor-guided behaviors in mice.

Brain Res 2021 Jul 24;1768:147590. Epub 2021 Jul 24.

Department of Pharmacology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai 200032, China. Electronic address:

Depression, rapid eye movement (REM) sleep behavior disorder, and altered olfaction are often present in Parkinson's disease. Our previous studies demonstrated the role of the olfactory bulb (OB) in causing REM sleep disturbances in depression. Furthermore, adenosine A receptors (AR) which are richly expressed in the OB, play an important role in the regulation of REM sleep. Caffeine, an adenosine A receptors and AR antagonist, and other AR antagonists were reported to improve olfactory function and restore age-related olfactory deficits. Therefore, we hypothesized that the AR neurons in the OB may regulate olfaction or odor-guided behaviors in mice. In the present study, we employed chemogenetics to specifically activate or inhibit neuronal activity. Then, buried food test and olfactory habituation/dishabituation test were performed to measure the changes in the mice's olfactory ability. We demonstrated that activation of OB neurons or OB AR neurons shortened the latency of buried food test and enhanced olfactory habituation to the same odors and dishabituation to different odors; inhibition of these neurons showed the opposite effects. Photostimulation of ChR2-expressing OB AR neuron terminals evoked inward current in the olfactory tubercle (OT) and the piriform cortex (Pir), which was blocked by glutamate receptor antagonists 2-amino-5-phosphonopentanoic acid and 6-cyano-7nitroquinoxaline-2,3-dione. Collectively, these results suggest that the OB mediates olfaction via AR neurons in mice. Moreover, the excitatory glutamatergic release from OB neurons to the OT and the Pir were found responsible for the olfaction-mediated effects of OB AR neurons.
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http://dx.doi.org/10.1016/j.brainres.2021.147590DOI Listing
July 2021

Comprehensive analysis of a new prognosis signature based on histone deacetylases in clear cell renal cell carcinoma.

Cancer Med 2021 Jul 26. Epub 2021 Jul 26.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, P.R. China.

Histone deacetylases (HDAC) family is vital for tumorigenesis and tumor progression. However, the exact role of the HDAC family in clear cell renal cell carcinoma (ccRCC) remains unclear. Based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and The Human Protein Atlas (HPA) database, we investigated and validated the expression profile, clinical significance and prognostic value of HDAC family members in ccRCC. Moreover, we further explored the correlation between HDACs and tumor microenvironment, tumor stemness, drug activity and immune subtype. The HDAC8, HDAC10, and HDAC11 manifested potential clinical value for prognosis, and the correlation analyses reveals underlying molecular mechanisms, which deserve further investigation for ccRCC. This Integrated bioinformatics analysis, based on transcriptomics and proteomics, implied that HDAC8, HDAC10, and HDAC11 may serve as potential molecular biomarkers and therapeutic targets for ccRCC, but some underlying molecular mechanisms still need to be elucidated.
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http://dx.doi.org/10.1002/cam4.4156DOI Listing
July 2021

Electroacupuncture-Induced Muscular Inflammatory Pain Relief Was Associated With Activation of Low-Threshold Mechanoreceptor Neurons and Inhibition of Wide Dynamic Range Neurons in Spinal Dorsal Horn.

Front Neurosci 2021 8;15:687173. Epub 2021 Jul 8.

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.

Acupuncture is an effective alternative therapy for pain management. Evidence suggests that acupuncture relieves pain by exciting somatic afferent nerve fibers. However, the mechanism underlying the interaction between neurons in different layers of the spinal dorsal horn induced by electroacupuncture (EA) remains unclear. The aim of this study was to explore the mechanism of EA relieving inflammatory muscle pain, which was associated with activation of the spontaneous firing of low-threshold mechanoreceptor (LTM) neurons and inhibition of wide dynamic range (WDR) neuronal activities in the spinal dorsal horn of rats. Inflammatory muscle pain was induced by injecting complete Freund's adjuvant into the right biceps femoris muscle. EA with intensity of threshold of A fibers (Ta) in Liangqiu (ST34) muscle considerably inhibited the abnormal spontaneous activities of electromyography (EMG) due to muscle inflammation. While EA with intensity of C-fiber threshold (Tc) increased the abnormal activities of EMG. EA with Ta also ameliorated the imbalance of weight-bearing behavior. A microelectrode array with 750-μm depth covering 32 channels was used to record the neuronal activities of WDR and LTM in different layers of the spinal dorsal horn. The spontaneous firing of LTM neurons was enhanced by EA-Ta, while the spontaneous firing of WDR neurons was inhibited. Moreover, EA-Ta led to a significant inverse correlation between changes in the frequency of WDR and LTM neurons ( = -0.64, < 0.05). In conclusion, the results indicated that EA could alleviate inflammatory muscle pain, which was associated with facilitation of the spontaneous firing of LTM neurons and inhibition of WDR neuronal activities. This provides a promising evidence that EA-Ta could be applied to relieve muscular inflammatory pain in clinical practice.
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http://dx.doi.org/10.3389/fnins.2021.687173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295590PMC
July 2021

Effect of the attachments on clinical outcomes of mandibular distal extension implant-supported removable partial dentures: A systematic review.

J Prosthet Dent 2021 Jul 20. Epub 2021 Jul 20.

Lecturer, The First Affiliated Hospital of Nanchang University, Nanchang, PR China; Visiting Scholar, Department of Restorative Dentistry, School of Dentistry, University of Washington, Seattle, Wash.

Statement Of Problem: Healing abutments and attachments have been used for implant-supported removable partial dentures (ISRPDs). However, the effects of these abutments and attachments on the clinical outcomes of the implants and prostheses are elusive because of the lack of standardized research protocols.

Purpose: The purpose of this systematic review was to determine the clinical outcomes of mandibular distal extension ISRPDs with healing abutments and attachments by analyzing qualified studies.

Material And Methods: An electronic and manual literature search was conducted on PubMed, Web of Science, Scopus, Embase, and Cochrane Library databases including articles published in English from 1980 to 2020. Publications of clinical outcome studies on the mandibular distal extension ISRPDs with healing abutments or attachments were screened by inclusion and exclusion criteria. Clinical outcomes of removable partial dentures (RPDs) and ISRPDs with different types of abutments or attachments were compared by using patient-reported outcome measures, implant survival rate, masticatory performance, and implant- or prosthesis-related complications. Study designs and clinical outcome data were extracted and analyzed. The evidence of the selected studies and degree of recommendation were made according to the Oxford Centre for Evidence-based Medicine, and the risk of bias of the studies was assessed based on Newcastle-Ottawa criteria.

Results: Of 541 articles initially identified after removing duplicate records, 11 articles were selected by applying the inclusion and exclusion criteria, by inter-viewer agreement, and by hand searching. Nine prospective cohort studies, 1 retrospective cohort study, and 1 randomized controlled trial were included with evidence levels assessed at 1b, 2b, and 2c. The risk of bias varied from 5 to 8 out of 9. Patient overall satisfaction, oral health-related quality of life (OHRQoL) scores, and masticatory ability were significantly improved for ISRPDs with either healing abutments, ball, or LOCATOR attachments when compared with RPDs. The implant survival rate varied from 92% to 97% at 2 to 10 years for ball attachment and was 100% at 1 year for LOCATOR attachment-supported ISRPDs. Marginal bone loss (MBL) varied from 0 to 1 mm in all studies, although LOCATOR attachments had significantly less MBL compared with ball attachments. The maximal pocket depth and bleeding on probing index around implants at 1 year were 1.7 to 1.8 mm and 0.1 to 0.3. Loose healing caps were the main mechanical complication of implants. There were more prosthetic complications in ISRPDs with ball attachments than RPDs at 10-year follow-up, including gold matrix loosening, loss of retention, and denture base fractures. No direct comparisons were made of patient-reported outcomes or prosthetic complications between ball and LOCATOR attachment-supported ISRPDs.

Conclusions: Healing abutments and attachments (ball or LOCATOR) improved patient-reported outcomes and the masticatory function of mandibular distal extension ISRPDs. However, insufficient evidence was found to determine the relative effectiveness of different attachment systems on the clinical outcomes of mandibular distal extension ISRPDs. Abutment loosening was the most frequent mechanical complication for healing abutments. More prosthetic complications were associated with ball attachment-supported ISRPDs than RPDs. The major weaknesses of this systematic review were the relatively moderate level of evidence and the publication language, since implant attachments are used in many non-English speaking countries.
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http://dx.doi.org/10.1016/j.prosdent.2021.04.008DOI Listing
July 2021

The Effects of La Doping on the Crystal Structure and Magnetic Properties of NiIn-Type MnCoGeLa (x = 0, 0.01, 0.03) Alloys.

Materials (Basel) 2021 Jul 16;14(14). Epub 2021 Jul 16.

School of Resources, Environment and Materials, Guangxi University, Nanning 530004, China.

In this experiment, a series of MnCoGeLa (x = 0, 0.01, 0.03) alloy samples were prepared using a vacuum arc melting method. The crystal structure and magnetic properties of alloys were investigated using X-ray diffraction (XRD), Rietveld method, physical property measurement system (PPMS), and vibrating sample magnetometer (VSM) analyses. The results show that all samples were of high-temperature NiIn-type phases, belonging to space group P6/mmc (194) after 1373 K annealing. The results of Rietveld refinement revealed that the lattice constant and the volume of MnCoGeLa increased along with the values of La constants. The magnetic measurement results show that the Curie temperatures (T) of the MnCoGeLa series alloys were 294, 281, and 278 K, respectively. The maximum magnetic entropy changes at 1.5T were 1.64, 1.53, and 1.56 J·kg·K, respectively. The respective refrigeration capacities (RC) were 60.68, 59.28, and 57.72J·kg, with a slight decrease along the series. The experimental results show that the doping of La results in decreased T, basically unchanged magnetic entropy, and slightly decreased RC.
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http://dx.doi.org/10.3390/ma14143998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306495PMC
July 2021

mA mRNA Methylation Regulates Epithelial Innate Antimicrobial Defense Against Cryptosporidial Infection.

Front Immunol 2021 6;12:705232. Epub 2021 Jul 6.

Department of Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, NE, United States.

Increasing evidence supports that N6-methyladenosine (mA) mRNA modification may play an important role in regulating immune responses. Intestinal epithelial cells orchestrate gastrointestinal mucosal innate defense to microbial infection, but underlying mechanisms are still not fully understood. In this study, we present data demonstrating significant alterations in the topology of host mA mRNA methylome in intestinal epithelial cells following infection by , a coccidian parasite that infects the gastrointestinal epithelium and causes a self-limited disease in immunocompetent individuals but a life-threatening diarrheal disease in AIDS patients. Altered mA methylation in mRNAs in intestinal epithelial cells following infection is associated with downregulation of alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 and the fat mass and obesity-associated protein with the involvement of NF-кB signaling. Functionally, mA methylation statuses influence intestinal epithelial innate defense against infection. Specifically, expression levels of immune-related genes, such as the immunity-related GTPase family M member 2 and interferon gamma induced GTPase, are increased in infected cells with a decreased mA mRNA methylation. Our data support that intestinal epithelial cells display significant alterations in the topology of their mA mRNA methylome in response to infection with the involvement of activation of the NF-кB signaling pathway, a process that modulates expression of specific immune-related genes and contributes to fine regulation of epithelial antimicrobial defense.
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http://dx.doi.org/10.3389/fimmu.2021.705232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291979PMC
July 2021

GLP-2 Is Locally Produced From Human Islets and Balances Inflammation Through an Inter-Islet-Immune Cell Crosstalk.

Front Endocrinol (Lausanne) 2021 5;12:697120. Epub 2021 Jul 5.

Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.

Glucagon-like peptide-1 (GLP-1) shows robust protective effects on β-cell survival and function and GLP-1 based therapies are successfully applied for type-2 diabetes (T2D) and obesity. Another cleavage product of pro-glucagon, Glucagon-like peptide-2 (GLP-2; both GLP-1 and GLP-2 are inactivated by DPP-4) has received little attention in its action inside pancreatic islets. In this study, we investigated GLP-2 production, GLP-2 receptor (GLP-2R) expression and the effect of GLP-2R activation in human islets. Isolated human islets from non-diabetic donors were exposed to diabetogenic conditions: high glucose, palmitate, cytokine mix (IL-1β/IFN-γ) or Lipopolysaccharide (LPS) in the presence or absence of the DPP4-inhibitor linagliptin, the TLR4 inhibitor TAK-242, the GLP-2R agonist teduglutide and/or its antagonist GLP-2(3-33). Human islets under control conditions secreted active GLP-2 (full-length, non-cleaved by DPP4) into the culture media, which was increased by combined high glucose/palmitate, the cytokine mix and LPS and highly potentiated by linagliptin. Low but reproducible GLP-2R mRNA expression was found in all analyzed human islet isolations from 10 donors, which was reduced by pro-inflammatory stimuli: the cytokine mix and LPS. GLP-2R activation by teduglutide neither affected acute or glucose stimulated insulin secretion nor insulin content. Also, teduglutide had no effect on high glucose/palmitate- or LPS-induced dysfunction in cultured human islets but dampened LPS-induced macrophage-dependent expression, while its antagonist GLP-2(3-33) abolished such reduction. In contrast, the expression of islet macrophage-independent cytokines , and was not affected by teduglutide. Medium conditioned by teduglutide-exposed human islets attenuated M1-like polarization of human monocyte-derived macrophages, evidenced by a lower mRNA expression of pro-inflammatory cytokines, compared to vehicle treated islets, and a reduced production of itaconate and succinate, marker metabolites of pro-inflammatory macrophages. Our results reveal intra-islet production of GLP-2 and GLP-2R expression in human islets. Despite no impact on β-cell function, local GLP-2R activation reduced islet inflammation which might be mediated by a crosstalk between endocrine cells and macrophages.
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http://dx.doi.org/10.3389/fendo.2021.697120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287580PMC
July 2021

A scalable and reproducible preparation for the antitumor protein TLC, a human-derived telomerase inhibitor.

Protein Expr Purif 2021 Jul 17;187:105942. Epub 2021 Jul 17.

Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou, 313000, China; School of Medicine, Huzhou University, Huzhou, 313000, China. Electronic address:

Telomerase, which is overexpressed in approximately 90% of liver cancer cells, is an ideal target for anti-liver cancer therapy. LPTS, a putative liver tumor suppressor, is the only human-derived protein that can bind telomerase directly and inhibit the extension of telomere activity. Our previous studies demonstrated that TAT-LPTS-LC (TLC), a recombinant protein fused by the C-terminal 133-328 fragment of LPTS and TAT peptides, could be delivered into cells to inhibit telomerase-positive hepatoma cell growth in vitro and in vivo with very low toxicity. In the present study, E. coli strains which expressed TLC in abundance were screened and cultured in a laboratory bioreactor. A reproducible protein separation process was built, and this process was suitable for industrial amplification. The yields of TLC protein were up to 184 mg in one batch with a purity of approximately 95%. The purified TLC protein had a similar inhibitory effect on telomerase activity in vitro compared with those purified by Ni-affinity chromatography. Furthermore, TLC protein could be delivered into the cell nucleus to increase the doubling time of the cell and suppress cell growth in telomerase-positive liver cancer cell lines. Cell growth inhibition was negatively correlated with telomere length, suggesting that TLC is a highly targeted telomerase-telomere anticancer agent. These results will contribute to future preclinical studies of the TLC protein.
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http://dx.doi.org/10.1016/j.pep.2021.105942DOI Listing
July 2021

Targeting WEE1 Inhibits Growth of Breast Cancer Cells That Are Resistant to Endocrine Therapy and CDK4/6 Inhibitors.

Front Oncol 2021 1;11:681530. Epub 2021 Jul 1.

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, United States.

Despite the success of antiestrogens in extending overall survival of patients with estrogen receptor positive (ER+) breast tumors, resistance to these therapies is prevalent. ER+ tumors that progress on antiestrogens are treated with antiestrogens and CDK4/6 inhibitors. However, 20% of these tumors never respond to CDK4/6 inhibitors due to intrinsic resistance. Here, we used endocrine sensitive ER+ MCF7 and T47D breast cancer cells to generate long-term estrogen deprived (LTED) endocrine resistant cells that are intrinsically resistant to CDK4/6 inhibitors. Since treatment with antiestrogens arrests cells in the G1 phase of the cell cycle, we hypothesized that a defective G1 checkpoint allows resistant cells to escape this arrest but increases their dependency on G2 checkpoint for DNA repair and growth, and hence, targeting the G2 checkpoint will induce cell death. Indeed, inhibition of WEE1, a crucial G2 checkpoint regulator, with AZD1775 (Adavosertib), significantly decreased cell proliferation and increased G2/M arrest, apoptosis and gamma-H2AX levels (a marker for DNA double stranded breaks) in resistant cells compared with sensitive cells. Thus, targeting WEE1 is a promising anti-cancer therapeutic strategy in standard therapy resistant ER+ breast cancer.
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http://dx.doi.org/10.3389/fonc.2021.681530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281892PMC
July 2021

Characterization of the Exometabolome of SCM1 by Liquid Chromatography-Ion Mobility Mass Spectrometry.

Front Microbiol 2021 1;12:658781. Epub 2021 Jul 1.

Shenzhen Key Laboratory of Marine Geo-Omics Research, Southern University of Science and Technology, Shenzhen, China.

Marine (formerly known as the marine group I archaea) have received much research interest in recent years since these chemolithoautotrophic organisms are abundant in the subsurface ocean and oxidize ammonium to nitrite, which makes them a major contributor to the marine carbon and nitrogen cycles. However, few studies have investigated the chemical composition of their exometabolome and their contributions to the pool of dissolved organic matter (DOM) in seawater. This study exploits the recent advances in ion mobility mass spectrometry (IM-MS) and integrates this instrumental capability with bioinformatics to reassess the exometabolome of a model ammonia-oxidizing archaeon, strain SCM1. Our method has several advantages over the conventional approach using an Orbitrap or ion cyclotron resonance mass analyzer and allows assignments or annotations of spectral features to known metabolites confidently and indiscriminately, as well as distinction of biological molecules from background organics. Consistent with the results of a previous report, the SPE-extracted exometabolome of is dominated by biologically active nitrogen-containing metabolites, in addition to peptides secreted extracellularly. Cobalamin and associated intermediates, including α-ribazole and α-ribazole 5'-phosphate, are major components of the SPE-extracted exometabolome of . This supports the proposition that have the capacity of biosynthesizing cobalamin. Other biologically significant metabolites, such as agmatidine and medicagenate, predicted by genome screening are also detected, which indicates that have remarkable metabolic potentials, underlining their importance in driving elemental cycles critical to biological processes in the ocean.
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http://dx.doi.org/10.3389/fmicb.2021.658781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281238PMC
July 2021

Ultrasound-mediated microbubbles cavitation enhanced chemotherapy of advanced prostate cancer by increasing the permeability of blood-prostate barrier.

Transl Oncol 2021 Jul 13;14(10):101177. Epub 2021 Jul 13.

Department of Urology, Peking University Third Hospital, Beijing 100191, China. Electronic address:

Although chemotherapy is an important treatment for advanced prostate cancer, its efficacy is relatively limited. Ultrasound-induced cavitation plays an important role in drug delivery and gene transfection. However, whether cavitation can improve the efficacy of chemotherapy for prostate cancer remains unclear. In this study, we treated RM-1 mouse prostate carcinoma cells with a combination of ultrasound-mediated microbubble cavitation and paclitaxel. Our results showed that combination therapy led to a more pronounced inhibition of cell viability and increased cell apoptosis. The enhanced efficacy of chemotherapy was attributed to the increased cell permeability induced by cavitation. Importantly, compared with chemotherapy alone (nab-paclitaxel), chemotherapy combined with ultrasound-mediated microbubble cavitation significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice in an orthotopic mouse model of RM-1 prostate carcinoma, indicating the synergistic effects of combined therapy on tumor reduction. Furthermore, we analyzed tumor-infiltrating lymphocytes and found that during chemotherapy, the proportions of CTLA4 cells and PD-1/CTLA4 cells in CD8 T cells slightly increased after cavitation treatment.
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http://dx.doi.org/10.1016/j.tranon.2021.101177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287239PMC
July 2021

Toward Efficient Oil Energy Recovery: Eco-Friendly Fabrication of a Biomimetic Durable Metal Mesh with a Moss-Like Silver Nanocluster Structure.

Langmuir 2021 07 16;37(29):8776-8788. Epub 2021 Jul 16.

State Key Laboratory of Oil and Gas Reservoir Geology and Exploitation, Southwest Petroleum University, Chengdu, Sichuan 610500, China.

With the purpose of oil energy recovery as well as achieving efficiency of oil/water separation, hydrophobic mesh materials have attracted extensive attention. However, fabrication of the current methods is not environmentally friendly, has high energy consumption, and creates serious pollution. Inspired by lotus leaves and rose petals, a biomimetic superhydrophobic surface was fabricated prepared on a stainless steel mesh by an in situ chemical reduction method with simple operation and mild conditions. The results of SEM, XRD, and XPS demonstrated that the mesh shows a stable and uniform moss-like rough structured surface. The SSM/Ag/ODA mesh, which was modified by moss-like Ag nanoclusters and low surface energy agents, has excellent superhydrophobicity with an excellent oil/water separation efficiency that reached up to 99.8%. The silver mirror phenomenon formed by the Ag nanoclusters further confirmed that silver ions were reduced and attached to the surface of the mesh. Moreover, the mesh can maintain superhydrophobicity under harsh conditions, such as a high concentration of a salty solution, organic solvents, alkaline, acidic solution, and even long-time UV irradiation, etc. More importantly, the modified mesh has excellent physical stability, in which the water contact angle on the mesh can be maintained above 150° after harsh mechanical wear. The hydrophobic mesh showed great potential to be applied for highly efficient oil/water separation and oil energy recovery even under complex and harsh conditions.
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http://dx.doi.org/10.1021/acs.langmuir.1c01125DOI Listing
July 2021

Management of a COVID-19-infected critically ill patient treated by extracorporeal membrane oxygenation: a case report.

Ann Palliat Med 2021 Jul 1. Epub 2021 Jul 1.

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Coronavirus disease 2019 (COVID-19) is a new type of respiratory infectious disease that spreads among humans. People infected with COVID-19 present with severe acute respiratory symptoms, fever, cough, breathlessness and dyspnea, impaired physical conditions, kidney failure, and even death. Chest radiographs suggest diffuse inflammation in both lungs and show "white lung" changes. Patients may even experience multiple organ failures within a short period. The effects of general ventilator-assisted treatment are poor. While the application of extracorporeal membrane oxygenation (ECMO) for adjuvant therapy in COVID-19 patients may benefit, there is still a lack of clinical management experience to guide the treatment of the disease. Therefore, in this case, report, we describe the case of a COVID-19-infected patient who was managed with ECMO. During treatment, the patient's vital signs, biochemical indicators, and hemodynamic changes were closely monitored, with strengthening the operation of ECMO and mechanical ventilation, the patients bleeding, infection and other related complications were actively prevented and managed. After active treatment and careful management, the patient was successfully weaned from ECMO after 13 days. This report has summarized the management experience of a severe case with ECMO management, which can provide a reference for the diagnosis and treatment of severe COVID-19 patients in the future.
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http://dx.doi.org/10.21037/apm-20-1176DOI Listing
July 2021

Redox-sensitive irinotecan liposomes with active ultra-high loading and enhanced intracellular drug release.

Colloids Surf B Biointerfaces 2021 Jul 6;206:111967. Epub 2021 Jul 6.

School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, PR China. Electronic address:

In this report, a novel irinotecan (IR) encapsulated redox-responsive liposome was developed. The redox-responsive liposomes were prepared based on disulfide phosphatidylcholine (SS-PC), DSPC, DSPE-PEG2000 and cholesterol by ethanol injection method. IR was actively loaded by triethylammonium sucrose octasulfate (TEA8-SOS) gradient method to generate IR/SS-PC liposomes (IR/SS-LP). The particle size of IR/SS-PC was characterized by using dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that IR/SS-LP with 30 % content of SS-PC (IR/SS30-LP) had an average size of 125.5 ± 5.8 nm with a negative zeta potential of -19.5 ± 0.1. The encapsulation efficiency (EE) was further determined to be 98.1 ± 0.8 % and drug loading (DL) was 31.8 ± 0.1 %. The redox-responsiveness of IR/SS-LP was investigated by observing the change of particle size and morphology as well as the release behavior of IR triggered by glutathione (GSH). The data indicated GSH breaks the disulfide bonds in SS-PC and leads to the controlled release of IR. At 1 mM GSH, 60.2 % irinotecan was released from IR/SS30-LP within 24 h. Finally, the effects of IR/SS-LP in cell and animal experiments were evaluated in detail. The results showed that IR/SS30-LP had superior pharmacokinetic and antitumor efficacy compared to free irinotecan and traditional irinotecan liposome (ONIVYDE®-like). Taken together, IR/SS30-LP displayed redox-responsive release of IR, ultra-high loading and enhanced anti-tumor activity, which has great potential for clinical application as a new generation of IR liposomal formulation.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111967DOI Listing
July 2021

TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling.

Bone Res 2021 Jul 12;9(1):33. Epub 2021 Jul 12.

Department of Orthopaedics, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, Zhejiang, PR China.

Osteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo signaling pathway; it was suggested to be involved in the regulation of bone homeostasis. However, the exact role of TAZ in osteoclasts has not yet been established. In this study, we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation, which was further evidenced by in vitro osteoclast formation assays. Moreover, the overexpression of TAZ inhibited RANKL-induced osteoclast formation, whereas silencing of TAZ reduced it. Mechanistically, TAZ bound to TGF-activated kinase 1 (TAK1) and reciprocally inhibited NF-κB signaling, suppressing osteoclast differentiation. Collectively, our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.
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http://dx.doi.org/10.1038/s41413-021-00151-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275679PMC
July 2021

Density Functional Theory Investigation of the [email protected] Composite as a Urea Oxidation Catalyst in the Alkaline Electrolyte.

ACS Omega 2021 Jun 26;6(22):14648-14654. Epub 2021 May 26.

Department of Agricultural and Biosystems Engineering, South Dakota State University, Brookings, South Dakota 57007, United States.

Developing efficient and low-cost urea oxidation reaction (UOR) catalysts is a promising but still challenging task for environment and energy conversion technologies such as wastewater remediation and urea electrolysis. In this work, NiO nanoparticles that incorporated graphene as the [email protected] composite were constructed to study the UOR process in terms of density functional theory. The single-atom model, which differed from the previous heterojunction model, was employed for the adsorption/desorption of urea and CO in the alkaline media. As demonstrated from the calculated results, [email protected] prefers to adsorb the hydroxyl group than urea in the initial stage due to the stronger adsorption energy of the hydroxyl group. After [email protected] was formed in the alkaline electrolyte, it presents excellent desorption energy of CO in the rate-determining step. Electronic density difference and the d band center diagram further confirmed that the Ni(III) species is the most favorable site for urea oxidation while facilitating charge transfer between urea and [email protected] Moreover, graphene provides a large surface for the incorporation of NiO nanoparticles, enhancing the electron transfer between NiOOH and graphene and promoting the mass transport in the alkaline electrolyte. Notably, this work provides theoretical guidance for the electrochemical urea oxidation work.
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http://dx.doi.org/10.1021/acsomega.1c01758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260271PMC
June 2021

Microfluidic synthesis of pyrrolidin-2-ones photoinduced organocatalyzed cyclization of styrene, α-bromoalkyl esters and primary amines.

Org Biomol Chem 2021 Jul;19(29):6468-6472

College of Biotechnology and Pharmaceutical Engineering Nanjing Tech University, 30 Puzhu Rd S., Nanjing, 211816, China. and State Key Laboratory of Materials-Oriented Chemical Engineering, 30 Puzhu Rd S., Nanjing, 211816, China.

A green and efficient reaction route for the synthesis of pyrrolidin-2-ones via photoinduced organocatalyzed three-component cyclization of styrene, tertiary α-bromoalkyl esters and primary amines in a microchannel reactor under visible light conditions has been developed. Moreover, the overall process can be carried out under mild conditions without using a metal. In addition, a reasonable reaction mechanism was proposed based on control experiments.
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http://dx.doi.org/10.1039/d1ob01082dDOI Listing
July 2021

Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer's Disease in an APP/PS1 Mouse Model.

Neuropsychiatr Dis Treat 2021 30;17:2129-2139. Epub 2021 Jun 30.

College of Medical Technology, Qiqihar Medical University, Qiqihar City, Heilongjiang Province, 161000, People's Republic of China.

Purpose: Alzheimer's disease (AD) is a complex neurodegenerative disorder, which is characterized by memory loss and cognitive deficits. The neuroprotective role of milrinone on the injury of spinal cord or cerebral ischemia-reperfusion has been confirmed. However, the accurate function of milrinone on AD pathogeny is still unclear.

Methods: APP/PS1 transgenic mouse was used to explore the role of milrinone in behaviour tests, and the effects on histopathologic features of AD such as the formation of neuronal amyloid-β (Aβ) plaque, microglial activation, tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Lipopolysaccharide (LPS)/Aβ-treated BV-2 cells were used to understand the anti-inflammation mechanism of milrinone on AD in vitro.

Results: Our in vivo results showed that milrinone ameliorates the memory functions of AD mice. Meanwhile, milrinone reduced Aβ deposits, repressed microglial activation and tau protein hyperphosphorylation, attenuated the oxidative stress, and decreased the levels of inflammatory cytokines. The in vitro results demonstrated that milrinone could inhibit the secretion of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α via regulation of NLRP3 inflammasomes and TLR4/MyD88/NF-κB signalling pathway.

Conclusion: Overall, milrinone could ameliorate the memory loss and cognitive deficits through repressing the multiple pathological processes of AD, suggesting that milrinone may be an underlying and effective drug for treating AD clinically.
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http://dx.doi.org/10.2147/NDT.S312648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256386PMC
June 2021
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