Publications by authors named "Wei Tang"

1,640 Publications

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Fucoidan Extracted From Sporophyll of Grown in Weihai, China - Chemical Composition and Comparison of Antioxidant Activity of Different Molecular Weight Fractions.

Front Nutr 2021 28;8:636930. Epub 2021 May 28.

Faculty of Health and Environmental Sciences, School of Public Health and Interdisciplinary Studies, Auckland University of Technology, Auckland, New Zealand.

Fucoidan is a multifunctional marine carbohydrate polymer that differs in its chemical composition and bioactivity both between seaweed species and within species from different locations across the globe. In this study, fucoidan was extracted from the sporophyll of grown in Weihai, Shandong Province, China. Fucoidan fractions with molecular weight cutoffs (MWCO) of >300 kDa and <10 kDa were obtained via dialysis. The fucoidan standard from Sigma (Fstd, ≥95, CAS: 9072-19-9), fucoidan crude extract (WH), >300 kDa fraction (300k) and <10 kDa fraction (10k) were compared in terms of chemical composition and antioxidant capacity. Based on Fourier transform infrared spectroscopy (FT-IR) analysis, Fstd, WH, and 300k all showed strong bands around 830 cm, corresponding to the sulfate substituent in the molecule. The results showed that compared with WH and 300 k, the degree of sulfation at 10k was the lowest. From Nuclear magnetic resonance spectroscopy (NMR) result, the four fucoidan samples all contain α--fucose. The primary antioxidant ability of the 10k is significantly higher than that of the 300k, WH, and Fstd, but the secondary antioxidant capabilities of the 10k and 300k were similar, and both were higher than that of the butylated hydroxyanisole (BHA). The ferric reducing antioxidant ability was higher in the 300k and WH fractions. This demonstrates that fucoidan extracted from grown in Weihai, China should be a useful nutraceutical resource.
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http://dx.doi.org/10.3389/fnut.2021.636930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193228PMC
May 2021

Discovery of chiral N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones with anti-inflammatory activity from the nucleophilic addition reactions of the thiophenols and oxazolinium.

Eur J Med Chem 2021 Jun 1;222:113583. Epub 2021 Jun 1.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China. Electronic address:

Herein we disclosed the novel nucleophilic addition reactions of the thiophenols and oxazolinium (DCZ0358) to produce N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones. After evaluating the anti-inflammatory activity in vitro, 2d was found having significant anti-TNFα activity. Through the amplified synthesis of 2d, four monomers (3a-b and 4a-d) were obtained by chiral separation of the product. The reaction mechanism was proposed and explored by the control experiments. However, only the R-stereoisomers 3b and 4b have significant anti-TNFα activity in vitro (IC = 56 and 14 nM, respectively). Moreover, 4b exerts potent therapeutic effects on ulcerative colitis in vivo (30 mg/kg bw, qd, i. g.). The subsequent bio-target exploration of compound 4bvia molecular docking and the experimental validation disclosed that 4b has 3-fold selectivity of binding activity on estrogen receptor (ER) beta (β) (Ki = 760.86 nM) vs. alpha (α) (Ki = 2320.58 nM). Thus, it provides a novel type of non-steroidal leads for developing anti-inflammatory drugs.
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http://dx.doi.org/10.1016/j.ejmech.2021.113583DOI Listing
June 2021

CLEC14A protects against podocyte injury in mice with adriamycin nephropathy.

FASEB J 2021 Jul;35(7):e21711

Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China.

Podocyte injury is a major determinant of focal segmental glomerular sclerosis (FSGS) and the identification of potential therapeutic targets for preventing podocyte injury has clinical importance for the treatment of FSGS. CLEC14A is a single-pass transmembrane glycoprotein belonging to the vascular expressed C-type lectin family. CLEC14A is found to be expressed in vascular endothelial cells during embryogenesis and is also implicated in tumor angiogenesis. However, the current understanding of the biological functions of CLEC14A in podocyte is very limited. In this study, we found that CLEC14A was expressed in podocyte and protected against podocyte injury in mice with Adriamycin (ADR)-induced FSGS. First, we observed that CLEC14A was downregulated in mice with ADR nephropathy and renal biopsies from individuals with FSGS and other forms of podocytopathies. Moreover, CLEC14A deficiency exacerbated podocyte injury and proteinuria in mice with ADR nephropathy accompanied by enhanced inflammatory cell infiltration and inflammatory responses. In vitro, overexpression of CLEC14A in podocyte had pleiotropic protective actions, including anti-inflammatory and anti-apoptosis effects. Mechanistically, CLEC14A inhibited high-mobility group box 1 protein (HMGB1) release, at least in part by directly binding HMGB1, and suppressed HMGB1-mediated signaling, including NF-κB signaling and early growth response protein 1 (EGR1) signaling. Taken together, our findings provide new insights into the pivotal role of CLEC14A in maintaining podocyte function, indicating that CLEC14A may be an innovative therapeutic target in FSGS.
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http://dx.doi.org/10.1096/fj.202100283RDOI Listing
July 2021

Neat1 decreases neuronal apoptosis after oxygen and glucose deprivation.

Neural Regen Res 2022 Jan;17(1):163-169

Department of Neurosurgery, First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Studies have shown that downregulation of nuclear-enriched autosomal transcript 1 (Neat1) may adversely affect the recovery of nerve function and the increased loss of hippocampal neurons in mice. Whether Neat1 has protective or inhibitory effects on neuronal cell apoptosis after secondary brain injury remains unclear. Therefore, the effects of Neat1 on neuronal apoptosis were observed. C57BL/6 primary neurons were obtained from the cortices of newborn mice and cultured in vitro, and an oxygen and glucose deprivation cell model was established to simulate the secondary brain injury that occurs after traumatic brain injury in vitro. The level of Neat1 expression in neuronal cells was regulated by constructing a recombinant adenovirus to infect neurons, and the effects of Neat1 expression on neuronal apoptosis after oxygen and glucose deprivation were observed. The experiment was divided into four groups: the control group, without any treatment, received normal culture; the oxygen and glucose deprivation group were subjected to the oxygen and glucose deprivation model protocol; the Neat1 overexpression and Neat1 downregulation groups were treated with Neat1 expression intervention techniques and were subjected to the in oxygen and glucose deprivation protocol. The protein expression levels of neurons p53-induced death domain protein 1 (PIDD1, a pro-apoptotic protein), caspase-2 (an apoptotic priming protein), cytochrome C (a pro-apoptotic protein), and cleaved caspase-3 (an apoptotic executive protein) were measured in each group using the western blot assay. To observe changes in the intracellular distribution of cytochrome C, the expression levels of cytochrome C in the cytoplasm and mitochondria of neurons from each group were detected by western blot assay. Differences in the cell viability and apoptosis rate between groups were detected by cell-counting kit 8 assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, respectively. The results showed that the apoptosis rate, PIDD1, caspase-2, and cleaved caspase-3 expression levels significantly decreased, and cell viability significantly improved in the Neat1 overexpression group compared with the oxygen and glucose deprivation group; however, Neat1 downregulation reversed these changes. Compared with the Neat1 downregulation group, the cytosolic cytochrome C level in the Neat1 overexpression group significantly decreased, and the mitochondrial cytochrome C level significantly increased. These data indicate that Neat1 upregulation can reduce the release of cytochrome C from the mitochondria to the cytoplasm by inhibiting the PIDD1-caspase-2 pathway, reducing the activation of caspase-3, and preventing neuronal apoptosis after oxygen and glucose deprivation, which might reduce secondary brain injury after traumatic brain injury. All experiments were approved by the Animal Ethics Committee of the First Affiliated Hospital of Chongqing Medical University, China, on December 19, 2020 (approval No. 2020-895).
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http://dx.doi.org/10.4103/1673-5374.314313DOI Listing
January 2022

Anatomical basis of the support of fibula to tibial plateau and its clinical significance.

J Orthop Surg Res 2021 May 29;16(1):346. Epub 2021 May 29.

Department of Anatomy, College of Basic Medicine, Dalian Medical University, Dalian, 116044, China.

Background: The fibula is only indirectly involved in the composition of the human knee joint and has therefore been neglected in the research on knee osteoarthritis. Nonuniform settlement of the proximal tibia plateau is clinically defined as when the height of the medial tibial plateau is lower than that of the lateral side in medial compartment knee osteoarthritis (KOA). The non-uniform settlement of the proximal tibia plateau may be caused by fibular support on the lateral side. Orthopedic surgeons practice partial fibulectomy based on the clinical manifestation of nonuniform settlement, and this technique has been shown to reduce pain and improve function in patients with medial compartment KOA. However, this hypothesis of the mechanism of nonuniform settlement lacks an anatomical basis.

Methods: The P45 polyester plastination technique was used to prepare sections of the proximal tibiofibular joint to investigate the distribution of the bone trabeculae in the region of the lateral tibial plateau.

Results: There was uneven distribution of trabeculae in the lateral condyle of the tibia and the head and neck of the fibula. The fibula and the posterolateral cortex of the shaft of the tibia united to form an arch beam via the tibiofibular joint. Many thick, dense trabeculae were present in a longitudinal direction above the tibiofibular arch.

Conclusions: The fibula supports the lateral tibial plateau, and the trabeculae were concentrated above the tibiofibular arch.
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http://dx.doi.org/10.1186/s13018-021-02500-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164332PMC
May 2021

Structural characteristics of three pectins isolated from white kidney bean.

Int J Biol Macromol 2021 May 27;182:2151-2161. Epub 2021 May 27.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology (Nanchang), Nanchang University, Nanchang, Jiangxi Province 330047, China.

Three water-soluble pectic polysaccharides (WKBP-P2, P3 and P4) were isolated from white kidney bean by ion exchange combined with size-exclusion methods. The structural features were characterized by GC-MS, NMR spectroscopy and HPSEC-MALLS-RI. It was found that three pectic polysaccharides were the major water-extracted polysaccharides in white kidney bean. All the WKBP-P2, P3 and P4 were probably composed of various structural regions including homogalacturonan (HG), xylogalacturonan (XGA), rhamnogalacturonan I (RG-I) regions in backbone, and arabinan region mainly as side chain. However, these pectic polysaccharides were significantly different in molar ratios of these structural regions and molecular size. WKBP-P2 was HG-predominant pectin (partially methyl-esterified) with weight-average molecular weight (M) of 1.2 × 10 g/mol, and contained minor RG-I, arabinan and probable XGA regions. WKBP-P3 (M of 4.0 × 10 g/mol) primarily embraced XGA, HG, arabinan regions and minor RG-I region. WKBP-4 with highest M (4.5 × 10 g/mol) had the most arabinan region (51.3%), which was probably the side chain linked to the backbone composed of RG-I, HG and slight XGA regions. These findings provided a structural basis for study on polysaccharides from white kidney bean, which was benefit for development of functional food.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.154DOI Listing
May 2021

Synthesis and Pharmacological Evaluation of Tetrahydro-γ-carboline Derivatives as Potent Anti-inflammatory Agents Targeting Cyclic GMP-AMP Synthase.

J Med Chem 2021 06 27;64(11):7667-7690. Epub 2021 May 27.

Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

The activation of cyclic GMP-AMP synthase (cGAS) by double-stranded DNA is implicated in the pathogenesis of many hyperinflammatory and autoimmune diseases, and the cGAS-targeting small molecule has emerged as a novel therapeutic strategy for treating these diseases. However, the currently reported cGAS inhibitors are far beyond maturity, barely demonstrating in vivo efficacy. Inspired by the structural novelty of compound (G140), we conducted a structural optimization on both its side chain and the central tricyclic core, leading to several subseries of compounds, including those unexpectedly cyclized complex ones. Compound bearing an -glycylglycinoyl side chain was identified as the most potent one with cellular IC values of 1.38 and 11.4 μM for h- and m-cGAS, respectively. Mechanistic studies confirmed its direct targeting of cGAS. Further, compound showed superior in vivo anti-inflammatory effects in the lipopolysaccharide-induced mouse model. The encouraging result of compound provides solid evidence for further pursuit of cGAS-targeting inhibitors as a new anti-inflammatory treatment.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00398DOI Listing
June 2021

Clinical application of "Double R" anastomosis technique in laparoscopic pancreaticoduodenectomy procedure.

Medicine (Baltimore) 2021 May;100(21):e26204

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University.

Abstract: Laparoscopic pancreaticoduodenectomy (LPD) is widely used as a treatment for periampullary tumors and pancreatic head tumors. However, postoperative pancreatic fistula (POPF), which significantly affects mortality and length of hospital stay of patients, remains one of the most common and serious complications following LPD. Though numerous technical modifications for pancreaticojejunostomy (PJ) have been proposed, POPF is still the "Achilles heel" of LPD.To reduce POPF rate and other postoperative complications following LPD by exploring the best approach to manage with the pancreatic remnant, a novel duct-to-mucosa anastomosis technique named Double Layer Running Suture (Double R) for the PJ was established. During 2018 and 2020, a totally 35 patients who underwent LPD with Double R were included, data on the total operative time, PJ duration, estimated blood loss, recovery of bowel function, postoperative complications, and length of hospital stay were collected and analyzed.The average duration of surgery was (380 ± 69) minutes. The mean time for performing PJ was (34 ± 5) minutes. The average estimated blood loss was (180 ± 155) mL. The overall POPF rate was 8.6% (3/35), including 8.6% (3/35) for the biochemical leak, 0% (0/35) for Grade B, and 0% (0/35) for Grade C. No patient suffered from biliary fistula, post-pancreatectomy hemorrhage, and intra-abdominal infection, the 30-day mortality was 0%.Double R anastomosis is potentially a safe, reliable, and rapid anastomosis with a low rate of POPF and post-pancreatectomy hemorrhage. It provides surgeons more options when performing LPD. However, its safety and effectiveness should be verified further by a larger prospective multicenter study.
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http://dx.doi.org/10.1097/MD.0000000000026204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154374PMC
May 2021

Rhodomentosones A and B: Two Pairs of Enantiomeric Phloroglucinol Trimers from and Their Asymmetric Biomimetic Synthesis.

Org Lett 2021 Jun 25;23(11):4499-4504. Epub 2021 May 25.

Center for Bioactive Natural Molecules and Innovative Drugs Research, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.

Rhodomentosones A and B ( and ), two pairs of novel enantiomeric phloroglucinol trimers featuring a unique 6/5/5/6/5/5/6-fused ring system were isolated from . Their structures with absolute configurations were elucidated by NMR spectroscopy, X-ray crystallography, and ECD calculation. The bioinspired syntheses of and were achieved in six steps featuring an organocatalytic asymmetric dehydroxylation/Michael addition/Kornblum-DeLaMare rearrangement/ketalization cascade reaction. Compounds and exhibited promising antiviral activities against respiratory syncytial virus (RSV).
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http://dx.doi.org/10.1021/acs.orglett.1c01616DOI Listing
June 2021

The Rise and Fall of Hydroxychloroquine with the COVID-19 Pandemic: Narrative Review of Selected Data.

Rheumatol Ther 2021 Jun 24;8(2):681-691. Epub 2021 May 24.

Division of Rheumatology, Department of Medicine, Columbia University Irving Medical Center, 161 Fort Washington Avenue, 2nd Floor, New York, NY, 10032, USA.

Since the first outbreak of Coronavirus Disease-2019 (COVID-19) in January 2020, the medical community has been pursuing effective countermeasures. Early in the pandemic, several small clinical and in vitro studies from France and China reported on the efficacy of chloroquine (CQ) and hydroxychloroquine (HCQ) against SARS-CoV-2 infections, which generated global attention towards these decades-old antimalarials (AM) and heralded numerous studies investigating their role in treating COVID-19. Despite several observational studies early in the pandemic affirming their beneficial role in treating COVID-19, 12 clinical studies reported no mortality benefits for CQ/HCQ in COVID-19 patients. The excitement over CQ/HCQ was ultimately quenched after three large randomized clinical trials, the COALITION-I trial in Brazil, the RECOVERY trial in the United Kingdom (UK), and the SOLIDARITY trial from World Health Organization (WHO) consistently reported no beneficial effects for CQ/HCQ in hospitalized COVID-19 patients. While initial studies suggested that CQ/HCQ might have a role in treating the early phases of infection, the results from three rigorously designed studies investigating their role in non-hospitalized COVID-19 patients were equivocal and inconsistent. Here we review the major social events related to the therapeutic use of CQ/HCQ in COVID-19, and the data from selected clinical studies evaluating their efficacy in hospitalized and non-hospitalized COVID-19 patients along with the major safety concerns.
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http://dx.doi.org/10.1007/s40744-021-00315-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142615PMC
June 2021

Selective intra-arterial brain cooling induces cerebral protection against ischemia/reperfusion injury through SENP1-Sirt3 signaling.

Free Radic Biol Med 2021 Aug 18;171:272-283. Epub 2021 May 18.

Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China; Liaoning Clinical Medical Research Center in Nervous System Disease, Shenyang, 110004, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China. Electronic address:

Background: Although it is well known that selective intra-arterial cooling (SI-AC) elicits cerebral protection against ischemia/reperfusion (I/R) injury, the underlying mechanism remains unclear. This study aimed to determine whether SI-AC can protect against cerebral I/R injury by inhibiting oxidative stress and mitochondrial dysfunction through regulation of Sirt3 deSUMOylation via SENP1.

Methods: All mice were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion. SI-AC treatment was performed by infusion with cold saline (10 °C, 20 mL/kg) for 15 min through a microcatheter placed in the internal carotid artery immediately before reperfusion. The infarct volume, survival rate, neurological deficit scores, behavioral parameters, histopathology findings, and apoptosis were assessed. HT22 cells were subjected to 2 h of oxygen and sugar deprivation (OGD) and 22 h of reoxygenation. HA-SUMO1, Flag-Sirt3, a Sirt3 mutation plasmid (Flag-Sirt3 K288R), His-SENP1, and SENP1 small interfering RNA were transfected into HT22 cells 48 h before OGD. Apoptosis-related proteins were analyzed by western blotting. SUMOylation of Sirt3, acetylation of cyclooxygenase 1 (COX1), superoxide dismutase 2 (SOD2), and isocitrate dehydrogenase 2 (IDH2), the activities of COX1, SOD2, and IDH2, oxidative stress, and mitochondrial dysfunction were evaluated.

Results: Compared with the I/R group, SI-AC decreased cerebral infarct volume and neurological deficit scores and increased motor coordination, exploratory behavior, and memory. Hematoxylin and eosin and Nissl staining showed that SI-CA decreased karyopyknosis, nuclear fragmentation, and nucleolysis, increased neuron density, and decreased the cell apoptosis rate. In addition, Sirt3 was revealed as a target protein of SUMO1. SI-AC attenuated cerebral I/R injury through Sirt3 deSUMOylation via SENP1.

Conclusions: SENP1-mediated deSUMOylation of Sirt3 plays an essential role in SI-AC-induced cerebral protection against I/R injury. Our findings provide a promising therapeutic approach for treatment of acute cerebral I/R injury.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.05.026DOI Listing
August 2021

Triptolide analog LLDT-8 ameliorates psoriasis-like dermatitis in BALB/c mice via suppressing the IL-36α signaling pathway.

Pharmacol Res 2021 Jul 17;169:105678. Epub 2021 May 17.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address:

Triptolide has shown a good immunosuppressive effect on autoimmune diseases. However, the toxicity limited its widely clinical practice. In this study, we investigated the effects and underlying mechanisms of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative, on a murine psoriasis-like dermatitis model and related cell lines. Here, we showed that LLDT-8 significantly attenuated symptoms of psoriasis-like dermatitis induced by imiquimod (IMQ, a TLR7 agonist) by reducing the psoriasis area and severity index (PASI) score and inflammatory parameters. The action of LLDT-8 was involved in down-regulated interleukin (IL)-36α expression and blocked IL-36α pathway by LC-MS-based label-free quantitative (LFQ) proteomic approach and further experiments. Meanwhile, we observed that LLDT-8 significantly inhibited the expression of IL-36α in R837-treated bone marrow-derived dendritic cells (BMDCs). In conclusion, LLDT-8 notably alleviated IMQ-induced psoriasis-like skin inflammation via suppressing the IL-36α signaling pathway, suggesting LLDT-8 might be a potential drug for the treatment of psoriasis.
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http://dx.doi.org/10.1016/j.phrs.2021.105678DOI Listing
July 2021

Sensing of joint and spinal bending or stretching via a retractable and wearable badge reel.

Nat Commun 2021 05 19;12(1):2950. Epub 2021 May 19.

CAS Center for Excellence in Nanoscience, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, China.

Human motions, such as joint/spinal bending or stretching, often contain information that is useful for orthopedic/neural disease diagnosis, rehabilitation, and prevention. Here, we show a badge-reel-like stretch sensing device with a grating-structured triboelectric nanogenerator exhibiting a stretching sensitivity of 8 V mm, a minimum resolution of 0.6 mm, a low hysteresis, and a high durability (over 120 thousand cycles). Experimental and theoretical investigations are performed to define the key features of the device. Studies from human natural daily activities and exercise demonstrate the functionality of the sensor for real-time recording of knee/arm bending, neck/waist twisting, and so on. We also used the device in a spinal laboratory, monitoring human subjects' spine motions, and validated the measurements using the commercial inclinometer and hunchback instrument. We anticipate that the lightweight, precise and durable stretch sensor applied to spinal monitoring could help mitigate the risk of long-term abnormal postural habits induced diseases.
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http://dx.doi.org/10.1038/s41467-021-23207-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136475PMC
May 2021

Association between gonadal hormones and osteoporosis in schizophrenia patients undergoing risperidone monotherapy: a cross-sectional study.

PeerJ 2021 27;9:e11332. Epub 2021 Apr 27.

Department of Psychiatry, Suzhou Guangji Hospital, the Affiliated Guangji Hospital of Soochow University, Suzhou, Jiangsu, China.

Objective: Patients with schizophrenia are at increased risk of osteoporosis. This study first determined the osteoporosis rate in patients with schizophrenia and then then explored the association between serum gonadal hormone levels and osteoporosis among these patients.

Methods: A total of 250 patients with schizophrenia and 288 healthy controls were recruited. Osteoporosis was defined by decreased bone mineral density (BMD) of the calcaneus. Serum fasting levels of gonadal hormones (prolactin, estradiol, testosterone, progesterone, follicle-stimulating hormone, luteinizing hormone) were determined. The relationship between osteoporosis and hormone levels was statistically analyzed by binary logistic regression analysis.

Results: Our results showed that patients with schizophrenia had a markedly higher rate of osteoporosis (24.4% vs. 10.1%) than healthy controls ( < 0.001). Patients with osteoporosis were older, had a longer disease course, and had a lower body mass index (BMI) than patients without osteoporosis (all  < 0.05). Regarding gonadal hormones, we found significantly higher prolactin, but lower estradiol, levels in patients with osteoporosis than in those without osteoporosis (both  < 0.05). The regression analysis revealed that PRL (OR = 1.1, 95% CI [1.08-1.15],  < 0.001) and E2 level (OR = 0.9, 95%CI [0.96-0.99],  = 0.011) were significantly associated with osteoporosis in patients with schizophrenia.

Conclusion: Our results indicate that patients with schizophrenia who are being treated with risperidone have a high rate of osteoporosis. Increased prolactin and reduced estradiol levels are significantly associated with osteoporosis.
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http://dx.doi.org/10.7717/peerj.11332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086585PMC
April 2021

A new mechanism of obeticholic acid on NASH treatment by inhibiting NLRP3 inflammasome activation in macrophage.

Metabolism 2021 Jul 10;120:154797. Epub 2021 May 10.

Laboratory of Anti-inflammation, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address:

Objective: Obeticholic acid (OCA) has been proved to play potential therapeutic effect on nonalcoholic steatohepatitis (NASH). Up to now, the study of OCA on NLRP3 inflammasome activation in macrophage is still blank and merits great attention. Here, we aimed to better characterize the role and mechanism of OCA on NASH treatment focusing on NLRP3 inflammasome activation in macrophages.

Methods: The effects of OCA on inflammasome activation were investigated in BMDM, Kupffer cell, BMDC and LX2 cell. Preconditioned media from BMDM culture was used to treat primary hepatocytes to explore the effects of macrophage NLRP3 inflammasome activation on the function of hepatocytes. In vivo, high fat diet plus CCl (DIO + CCl) induced murine NASH model and choline-deficient and amino acid-defined (CDA) diet-induced NASH mice were used to verify the inhibitory effect of OCA on inflammasome activation in liver macrophages and recapitulate its protective role on NASH progressing. To clear up the effect of OCA on macrophage is FXR dependent or not, FXR siRNA was introduced into BMDMs.

Results: OCA blockaded NLRP3 inflammasome in BMDMs by impacting on the activation stage and disrupting ASC oligomerization. Preconditioned supernatant from LPS + ATP treated BMDMs increased mRNA expression of lipogenic enzymes and lipid content, whereas preconditioned supernatant from OCA treated BMDM blocked these effects in both normal and the FXR knockdown hepatocytes. In DIO + CCl mice, the population of inflammatory myeloid lineage cells in livers was decreased upon OCA treatment. Accordingly, the level of IL-1β and IL-18 in liver, the hepatic expression of ASC, pro-caspase-1 and active caspase-1, the expression of caspase 1 p20 in liver macrophages were also reduced. Similar results were obtained in CDA diet-fed mice. Furthermore, OCA maintained the inhibition on NLRP3 inflammasome activation in FXR knockdown BMDMs, suggesting FXR could be dispensable in this effect.

Conclusions: This finding brings up a new mechanism of OCA on NASH treatment, suggested by direct inhibition on NLRP3 inflammasome activation in macrophage, further suppression on inflammasome activation-elicited hepatic lipid accumulation, and contributing to the amelioration of NASH.
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http://dx.doi.org/10.1016/j.metabol.2021.154797DOI Listing
July 2021

Seeding depth and seeding rate regulate apical hook formation by inducing GhHLS1 expression via ethylene during cotton emergence.

Plant Physiol Biochem 2021 Jul 30;164:92-100. Epub 2021 Apr 30.

Cotton Research Center, Shandong Key Lab for Cotton Culture and Physiology, Shandong Academy of Agricultural Sciences, Jinan, 250100, PR China; School of Life Science, Shandong Normal University, Jinan, 250014, PR China. Electronic address:

Apical hook formation is essential for the emergence and stand establishment of cotton plants. Searching for agronomic measures to regulate apical hook formation and clarifying its mechanism are important for full stand establishment in cotton. In this study, cotton seeds were sown at varying seeding rates or depths in sand to determine if and how apical hook formation was regulated by seeding rates or depths. The results showed that deep seeding or low seeding rates increased mechanical pressure and then increased ethylene content by increasing GhACO1 and GhACS2 expression to improve apical hook formation. Silencing of the GhACO1 and GhACS2 genes or exogenous application of 1-methylcyclopropene (1-MCP) decreased the ethylene content and inhibited apical hook formation in the cotton seedlings. Deep seeding, a low seeding rate, or 1-amino cyclopropane-1-carboxylic acid (ACC) treatment increased the expression of GhHLS1 and GhPIF3 genes, but their expression was decreased in theVIGS-ACO1 and VIGS-ACS2 seedlings. Silencing of the GhHLS1 and GhPIF3 genes inhibited apical hook formation, although the expression of GhACO1 and GhACS2 was unchanged. GhPIF3 may act upstream of GhHLS1, as the expression of GhPIF3 in the VIGS-HLS1 seedlings was unchanged, while the expression of GhHLS1 in the VIGS-PIF3 seedlings decreased. These results suggested that raised mechanical pressure could increase ethylene content by inducing GhACO1 and GhACS2 gene expression, which promoted apical hook formation by increasing the expression of GhHLS1. Therefore, adjusting the mechanical pressure through changing the seeding depth or seeding rate is an important means to regulate apical hook formation and emergence.
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http://dx.doi.org/10.1016/j.plaphy.2021.04.030DOI Listing
July 2021

Weakly Supervised Temporal Action Localization through Contrast based Evaluation Networks.

IEEE Trans Pattern Anal Mach Intell 2021 May 11;PP. Epub 2021 May 11.

Given only video-level action categorical labels during training, weakly-supervised temporal action localization (WS-TAL) learns to detect action instances and locates their temporal boundaries in untrimmed videos. Compared to its fully supervised counterpart, WS-TAL is more cost-effective in data labeling and thus favorable in practical applications. However, the coarse video-level supervision inevitably incurs ambiguities in action localization, especially in untrimmed videos containing multiple action instances. To overcome this challenge, we observe that significant temporal contrasts among video snippets, i.e., caused by temporal discontinuities and sudden changes, often occur around true action boundaries. This motivates us to introduce a Contrast-based Localization EvaluAtioN Network (CleanNet), whose core is a new temporal action proposal evaluator, which provides fine-grained pseudo supervision by leveraging the temporal contrasts among snippet-level classification predictions. Moreover, the new action localization module is an integral part of CleanNet which enables end-to-end training. This is in contrast to many existing WS-TAL methods where action localization is merely a post-processing step. Besides, we also explore the usage of temporal contrast on temporal action proposal generation task, which we believe is the first attempt with the weak supervision setting. Experiments on the THUMOS14, ActivityNet v1.2 and v1.3 datasets validate the efficacy of our method.
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http://dx.doi.org/10.1109/TPAMI.2021.3078798DOI Listing
May 2021

Isolation and structure characterization of a low methyl-esterified pectin from the tuber of Dioscorea opposita Thunb.

Food Chem 2021 Oct 20;359:129899. Epub 2021 Apr 20.

State Key Laboratory of Food Science and Technology, China-Canada Joint Lab of Food Science and Technology Nanchang, Nanchang University, Nanchang, Jiangxi Province 330047, China. Electronic address:

A low methyl-esterified pectin (33.2% methyl-esterification degree) was isolated from the tuber of Dioscorea opposita Thunb., which was an edible and medicinal material in China. This pectin (M of 1.3 × 10 g/mol) contained the ~59.1% homogalacturonan (HG) and ~38.1% highly branched rhamnogalacturonan I (RG-I) region with possible side chains embracing arabinogalactan II, arabinan or arabinogalactan I. The fragments including HG backbone consisting of → 4)-α-GalpA-(1 → and → 4)-α-GalpA-6-O-methyl-(1 → with molar ratio of ~2:1, and repeating unit of arabinogalactan II side chain composed of α-Araf-(1 → and → 3,6)-β-Galp-(1→, were speculated through methylation analysis and NMR spectra. However, the linkage pattern for RG-I backbone and side chains were indiscernible due to limited resolution of NMR spectra. Besides, the pectin adopted a flexible chain conformation in 0.1 M NaNO solution. These results provided a structural basis for study on polysaccharide from D. opposite, which was benefit for development of functional food of yam.
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http://dx.doi.org/10.1016/j.foodchem.2021.129899DOI Listing
October 2021

A Programmed Cell-Mimicking Nanoparticle Driven by Potato Alkaloid for Targeted Cancer Chemoimmunotherapy.

Adv Healthc Mater 2021 May 8:e2100311. Epub 2021 May 8.

Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.

Membrane camouflaged-nanoparticles (CM-NPs) have been exploited to inherit desired functionalities from source cells. Despite those advantages, membrane cloak may play a "double-edged sword" role in tumor-targeting therapy, as the intact membrane coating may hinder function-exertion of loaded drugs after reaching predetermined site. Therefore, further optimization of CM-NPs is still needed to enhance their delivery efficiency. Herein, natural product, Solamargine (SM), a cholesterol-affiliative amphiphilic potato alkaloid is first applied as core component of "inner core," to design a cell-mimicking "core-shell" nanoparticle (RBC-SLip) with acid-responsive off-coating properties for tumor-targeted therapy. Owing to red blood cell membrane (RBCm)-derived outer coating, it circulates stably in physiological conditions. While it would undergo an off-coating morphological change in response to acid stimuli in tumor microenvironment (TME), afterwards, the resulting off-coating liposome (SLip) shows active tumor-targeting and endosomal escape abilities, thus contributing to superior antitumor efficacy. In addition, SM also possesses natural TME-modulating ability; therefore, RBC-SLip can synergize with the PD1/PD-L1 blockade immunotherapy when encapsulated with PTX to achieve enhanced chemoimmunotherapy. The off-coating strategy developed by natural products SM, provide a brand-new perspective to optimize CM-NPs, and it also embodies application value of "unification of medicines and excipients" of natural products.
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http://dx.doi.org/10.1002/adhm.202100311DOI Listing
May 2021

Epithelial exosomal contactin-1 promotes monocyte-derived dendritic cell-dominant T-cell responses in asthma.

J Allergy Clin Immunol 2021 May 4. Epub 2021 May 4.

Department of Pediatrics, Ruijin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai, China. Electronic address:

Background: Exosomes have emerged as a vital player in cell-cell communication; however, whether airway epithelial cell (AEC)-generated exosomes participate in asthma development remains unknown.

Objective: Our aims were to characterize the AEC-secreted exosomes and the potentially functional protein(s) that may contribute to the proinflammatory effects of AEC exosomes in the dendritic cell (DC)-dominant airway allergic models and to confirm their clinical significance in patients with asthma.

Methods: Mice were treated with exosomes derived from house dust mite (HDM)-stimulated AECs (HDM-AEC-EXOs) or monocyte-derived DCs primed by HDM and/or contactin-1 (CNTN1). The numbers of DCs in the lung were determined by flow cytometry. Proteomic analysis of purified HDM-AEC-EXOs was performed. CNTN1 small interfering RNA was designed to probe its role in airway allergy, and γ-secretase inhibitor was used to determine involvement of the Notch pathway.

Results: HDM-AEC-EXOs facilitate the recruitment, proliferation, migration, and activation of monocyte-derived DCs in cell culture and in mice. CNTN1 in exosomes is a critical player in asthma pathology. RNA interference-mediated silencing and pharmaceutical inhibitors characterize Notch2 receptor as necessary for relaying the CNTN1 signal to activate T2 cell/T17 cell immune response. Studies of patients with asthma also support existence of the CNTN1-Notch2 axis that has been observed in cell and mouse models.

Conclusion: This study's findings reveal a novel role for CNTN1 in asthma pathogenesis mediated through exosome secretion, indicating a potential strategy for the treatment of allergic airway inflammation.
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http://dx.doi.org/10.1016/j.jaci.2021.04.025DOI Listing
May 2021

The feasibility of a public-private mix program on pulmonary tuberculosis screening in Penang: A pilot study.

Malays Fam Physician 2021 Mar 31;16(1):75-83. Epub 2021 Jan 31.

M.D.(UNIMAS), Master in Family Medicine (UKM), Jalan Perak Health Clinic.

Background: The low detection rate of tuberculosis (TB) cases in Malaysia remains a challenge in the effort to end TB by 2030. The collaboration between private and public health care facilities is essential in addressing this issue. As of now, no private-public health care collaborative program in pulmonary tuberculosis (PTB) screening exists in Malaysia.

Aim: To determine the feasibility of a collaborative program between private general practitioners (GPs) and the public primary health clinics in PTB screening and to assess the yield of smear-positive PTB from this program.

Methods: A prospective cohort study using convenient sampling was conducted involving GPs and public health clinics in the North-East District, Penang, from March 2018 to May 2019. In this study, GPs could direct all suspected PTB patients to perform a sputum acid fast bacilli (AFB) direct smear in any of the dedicated public primary health clinics. The satisfaction level of both the GPs and their patients were assessed using a self-administered client satisfaction questionnaire. IBM SPSS Statistical Software was used to analyze the data.

Results: Out of a total of 31 patients who underwent the sputum investigation for PTB, one (3.2%) was diagnosed to have smear-positive PTB. Most of the patients (>90%) and GPs (66.7%) agreed to continue with this program in the future. Furthermore, most of the patients (>90%) were satisfied with the program structure.

Conclusion: It is potentially feasible to involve GPs in combating TB. However, a more structured program addressing the identified issues is needed to make the collaborative program a success.
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http://dx.doi.org/10.51866/oa1096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088739PMC
March 2021

Blockade of TLRs-triggered macrophage activation by caffeic acid exerted protective effects on experimental ulcerative colitis.

Cell Immunol 2021 Jul 22;365:104364. Epub 2021 Apr 22.

Laboratory of Anti-inflammation and Immunopharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Ulcerative colitis (UC) represents a relapsing and inflammatory bowel disease which is commonly linked with the communications between dysfunction of epithelium and mucosal immune responses. Though caffeic acid (CA) has numerous pharmacological capacities, whether CA demonstrates immunoregulation on the mucosal immune responses remains ill-defined. Herein, the present research demonstrated that CA could dramatically attenuate the mucosal inflammation, as evidenced by improving the disease severity, serum biochemical indexes, mucosal ulcerations, loss of epithelium and crypts, and secretion of inflammatory cytokines in the colonic homogenates and explants culture. Consistently, CA could interfere with the infiltration and function of mononuclear macrophages in the mucosa, MLNs, and spleens of UC. Furthermore, CA exerted direct suppressive effects on the activation of BMDMs upon the exposure of TLRs agonists in vitro. Taken together, CA could attenuate DSS-induced murine UC through interfering with the activation of macrophages, which might provide an alternative therapeutic option for UC.
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http://dx.doi.org/10.1016/j.cellimm.2021.104364DOI Listing
July 2021

Correction to: Exosomes from tamoxifen-resistant breast cancer cells transmit drug resistance partly by delivering miR-9-5p.

Cancer Cell Int 2021 Apr 29;21(1):240. Epub 2021 Apr 29.

The First Department of Breast Surgery, Guangxi Medical University Cancer, Hospital, Nanning, 530021, People's Republic of China.

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http://dx.doi.org/10.1186/s12935-021-01944-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082645PMC
April 2021

A Smart Sensing System of Water Quality and Intake Monitoring for Livestock and Wild Animals.

Sensors (Basel) 2021 Apr 20;21(8). Epub 2021 Apr 20.

College of Agricultural, Consumer, and Environmental Sciences, New Mexico State University, 940 College Dr, Las Cruces, NM 88003, USA.

This paper presents a water intake monitoring system for animal agriculture that tracks individual animal watering behavior, water quality, and water consumption. The system is deployed in an outdoor environment to reach remote areas. The proposed system integrates motion detectors, cameras, water level sensors, flow meters, Radio-Frequency Identification (RFID) systems, and water temperature sensors. The data collection and control are performed using Arduino microcontrollers with custom-designed circuit boards. The data associated with each drinking event are water consumption, water temperature, drinking duration, animal identification, and pictures. The data and pictures are automatically stored on Secure Digital (SD) cards. The prototypes are deployed in a remote grazing site located in Tucumcari, New Mexico, USA. The system can be used to perform water consumption and watering behavior studies of both domestic animals and wild animals. The current system automatically records the drinking behavior of 29 cows in a two-week duration in the remote ranch.
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http://dx.doi.org/10.3390/s21082885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074319PMC
April 2021

A General Temperature-Dependent Stress-Strain Constitutive Model for Polymer-Bonded Composite Materials.

Polymers (Basel) 2021 Apr 25;13(9). Epub 2021 Apr 25.

Graduate School of China Academy of Engineering Physics, 10 Xibeiwang E. Rd., Beijing 100193, China.

This study develops a general temperature-dependent stress-strain constitutive model for polymer-bonded composite materials, allowing for the prediction of deformation behaviors under tension and compression in the testing temperature range. Laboratory testing of the material specimens in uniaxial tension and compression at multiple temperatures ranging from -40 ∘C to 75 ∘C is performed. The testing data reveal that the stress-strain response can be divided into two general regimes, namely, a short elastic part followed by the plastic part; therefore, the Ramberg-Osgood relationship is proposed to build the stress-strain constitutive model at a single temperature. By correlating the model parameters with the corresponding temperature using a response surface, a general temperature-dependent stress-strain constitutive model is established. The effectiveness and accuracy of the proposed model are validated using several independent sets of testing data and third-party data. The performance of the proposed model is compared with an existing reference model. The validation and comparison results show that the proposed model has a lower number of parameters and yields smaller relative errors. The proposed constitutive model is further implemented as a user material routine in a finite element package. A simple structural example using the developed user material is presented and its accuracy is verified.
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http://dx.doi.org/10.3390/polym13091393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123350PMC
April 2021

ZIF-Derived Carbon Nanoframes as a Polysulfide Anchor and Conversion Mediator for High-Performance Lithium-Sulfur Cells.

ACS Appl Mater Interfaces 2021 May 28;13(18):21544-21555. Epub 2021 Apr 28.

State Key Laboratory of Environmentally-Friendly Energy Materials, School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010, China.

Improving the redox kinetics of sulfur species, while suppressing the "shuttle effects" to achieve stable cycling under high sulfur loading is an inevitable problem for lithium-sulfur (Li-S) cells to commercialization. Herein, the three-dimensional Zn, Co, and N codoped carbon nanoframe (3DZCN-C) was successfully synthesized by calcining precursor which protected by mesoporous SiO and was used as cathode host for the first time to improve the performance of Li-S cells. Combining the merits of strong lithium polysulfides (LiPSs) anchoring and accelerating the conversion kinetics of sulfur species, 3DZCN-C effectively inhibit the shuttling of LiPSs and achieves excellent cyclability with capacity fading rate of 0.03% per cycle over 1000 cycles. Furthermore, the Li-S pouch cell has been assembled and has been shown to operate reliably with high energy density (>300 Wh kg) even under a high sulfur loading of 10 mg cm. This work provides a simple and effective way for the promotion and commercial application of Li-S cells.
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http://dx.doi.org/10.1021/acsami.1c04194DOI Listing
May 2021

Effects of Shuanghuanglian oral liquids on patients with COVID-19: a randomized, open-label, parallel-controlled, multicenter clinical trial.

Front Med 2021 Apr 28. Epub 2021 Apr 28.

Division of Cardiology, Department of Internal Medicine and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
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http://dx.doi.org/10.1007/s11684-021-0853-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079840PMC
April 2021

NPRL2 reduces the niraparib sensitivity of castration-resistant prostate cancer via interacting with UBE2M and enhancing neddylation.

Exp Cell Res 2021 Jun 24;403(2):112614. Epub 2021 Apr 24.

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China. Electronic address:

In this study, we explored the regulatory effects of nitrogen permease regulator 2-like (NPRL2) on niraparib sensitivity, a PARP inhibitor (PARPi) in castrate-resistant prostate cancer (CRPC). Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) program were retrospectively examined. Gene-set enrichment analysis (GSEA) was conducted between high and low NRPL2 expression prostate adenocarcinoma (PRAD) cases in TCGA. CCK-8 assay, Western blot analysis of apoptotic proteins, and flow cytometric analysis of apoptosis were applied to test niraparib sensitivity. Immunofluorescent (IF) staining and co-immunoprecipitation (co-IP) were conducted to explore the proteins interacting with NPRL2. Results showed that the upregulation of a canonical protein-coding transcript of NPRL2 (ENST00000232501.7) is associated with an unfavorable prognosis. Bioinformatic analysis predicts a physical interaction between NPRL2 and UBE2M, which is validated by a following Co-IP assay. This interaction increases NPRL2 stability by reducing polyubiquitination and proteasomal degradation. Depletion of NPRL2 or UBE2M significantly increases the niraparib sensitivity of CRPC cells and enhances niraparib-induced tumor growth inhibition in vivo. NPRL2 cooperatively enhances UBE2M-mediated neddylation and facilitates the degradation of multiple substrates of Cullin-RING E3 ubiquitin ligases (CRLs). In conclusion, this study identified a novel NPRL2-UBE2M complex in modulating neddylation and niraparib sensitivity of CRPC cells. Therefore, targeting NPRL2 might be considered as an adjuvant strategy for PARPi therapy.
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http://dx.doi.org/10.1016/j.yexcr.2021.112614DOI Listing
June 2021

MYC-Protein Arginine Methyltransferase 5 Axis Defines the Tumorigenesis and Immune Response in Hepatocellular Carcinoma.

Hepatology 2021 Apr 25. Epub 2021 Apr 25.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally with poor outcome and limited therapeutic options. Although the MYC oncogene is frequently dysregulated in HCC, it is thought to be undruggable. Thus, the current study aimed to identify the critical downstream metabolic network of MYC and develop new therapies for MYC-driven HCC. Liver cancer was induced in mice with hepatocyte-specific disruption of Myc and control mice by administration of diethylnitrosoamine (DEN). Liquid chromatography coupled with mass spectrometry-based metabolomic analyses revealed that urinary dimethylarginine, especially symmetric dimethylarginine (SDMA), was increased in the HCC mouse model in a MYC-dependent manner. Analyses of human samples demonstrated a similar induction of SDMA in the urines from HCC patients. Mechanistically, Prmt5, encoding protein arginine methyltransferase 5, which catalyzes SDMA formation from arginine, was highly induced in HCC and identified as a direct MYC target gene. Moreover, GSK3326595, a PRMT5 inhibitor, suppressed the growth of liver tumors in human MYC-overexpressing transgenic mice that spontaneously develop HCC. Inhibition of PRMT5 exhibited anti-proliferative activity via upregulation of the tumor suppressor gene Cdkn1b/p27. In addition, GSK3326595 induced lymphocyte infiltration and MHC II expression, which might contribute to the enhanced anti-tumor immune response. Combination of GSK3326595 with anti-PD-1 immune checkpoint therapy (ICT) improved therapeutic efficacy in HCC. This study revealed that PRMT5 is an epigenetic executer of MYC leading to repression of the transcriptional regulation of downstream genes that promote hepatocellular carcinogenesis, highlights a mechanism-based therapeutic strategy for MYC-driven HCC via PRMT5 inhibition through synergistically suppressed proliferation and enhanced anti-tumor immunity, and finally provides an opportunity to mitigate the resistance of "immune-cold" tumor to ICT.
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http://dx.doi.org/10.1002/hep.31864DOI Listing
April 2021

Promoting enzymatic hydrolysis of aggregated bamboo crystalline cellulose by fast microwave-assisted dicarboxylic acid deep eutectic solvents pretreatments.

Bioresour Technol 2021 Aug 6;333:125122. Epub 2021 Apr 6.

Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

Deep eutectic solvents (DESs) have received considerable interests as pretreatment solvents for biorefinery. In the present work, five kinds of dicarboxylic acids based DESs were introduced to pretreatments on moso bamboo (MB) with microwave irradiation assistance. Factors influencing the enzymatic conversion of MB cellulose to glucose were determined. With the fast heating, pretreated samples all present significant delignification and hemicelluloses matrix removal, thus improving the enzymatic conversion yield from 15% of MB to ~60%. For the DESs, hydrogen donors with less carbon atoms (oxalic acid) and more hydroxyl groups (tartaric acid) displayed higher efficiency due to separation of aggregated cellulose microfibrils. The microwave assisted DESs (MW-DESs) pretreatments also contributed to cellulose crystal variations including decrystallization and more exposure of hydrophobic surfaces, which are beneficial for followed cellulase adsorption and hydrolysis. The exploration of fast MW-DESs pretreatments may expand the potentials of lignocellulose biomass on effective and applicable biorefinery.
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http://dx.doi.org/10.1016/j.biortech.2021.125122DOI Listing
August 2021