Publications by authors named "Qun Zhang"

572 Publications

High alcohol-producing causes fatty liver disease through 2,3-butanediol fermentation pathway .

Gut Microbes 2021 Jan-Dec;13(1):1979883

Bacteriology Laboratory, Capital Institute of Pediatrics, Beijing, China.

High alcohol-producing (HiAlc ) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) and constructed an (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc W14 strain (W14) using CRISPR-Cas9 system. Subsequently, we established the mouse model gavage administration of HiAlc W14 and W14 strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc W14-fed mice, W14-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol the 2,3-butanediol fermentation pathway in HiAlc , which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes .
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http://dx.doi.org/10.1080/19490976.2021.1979883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510565PMC
October 2021

Explore the Usefulness of Concurrent Chemotherapy in Stage II Nasopharyngeal Carcinoma: A Retrospective Study.

Front Pharmacol 2021 21;12:688528. Epub 2021 Sep 21.

Department of Radiotherapy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

This study aims to compare the treatment outcomes of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in stage II nasopharyngeal carcinoma (NPC) patients. We retrospectively collected 601 stage II NPC patients treated in two hospitals between June 2003 to June 2016. All patients were divided into the CCRT group ( = 255) and the RT group ( = 346). Overall survival (OS), locoregional failure-free survival (LRFFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method. The log-rank test was used to compare the differences between the groups. The Cox-regression hazards model was performed to determine potential prognostic factors. The median follow-up was 99 months. No significant difference was found in locoregional recurrence, distant metastasis, disease progression, and death between the two groups (all > 0.05). In univariate analysis, the 5-years OS, PFS, LRFFS, and DMFS had no significant differences between the CCRT and RT groups (all > 0.05). Two-dimensional radiotherapy (2DRT) sub-analysis showed that CCRT remarkably increased DMFS, PFS, and OS rates (all < 0.05) but not LRFFS ( = 0.258) compared with RT alone. While intensity-modulated radiotherapy (IMRT) sub-analysis showed that the prognosis of the two groups had no significant differences (all > 0.05). In multivariate analyses, age was significantly and inversely related to OS, PFS, LRFFS, and DMFS. IMRT was an independent favorable factor for improving LRFFS, PFS, and OS. Concurrent chemotherapy was an independent protective factor for DMFS. In the context of 2DRT, it is definite that concurrent chemotherapy provides survival benefits for patients with stage II NPC. While in the IMRT era, the impact of chemotherapy on survival in patients with stage II NPC is weakened. Prospective randomized controlled studies are required to confirm these results.
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http://dx.doi.org/10.3389/fphar.2021.688528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490628PMC
September 2021

Ajuba functions as a co-activator of C/EBPβ to induce expression of PPARγ and C/EBPα during adipogenesis.

Mol Cell Endocrinol 2021 Oct 5;539:111485. Epub 2021 Oct 5.

Hongqiao International Institute of Medicine, Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry & Molecular Cellular Biology, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. Electronic address:

Adipogenesis is regulated by a complicated network of transcription factors among which PPARγ and C/EBP family members are the major regulators. During adipogenesis, C/EBPβ is induced early and then transactivates PPARγ and C/EBPα, which cooperatively induce genes whose expressions give rise to the mature adipocyte phenotype. Identifying the factors that influence the expression and activity of C/EBPβ should provide additional insight into the mechanisms regulating adipogenesis. Here, we demonstrate that depletion of Ajuba in 3T3-L1 cells significantly decreases mRNA and protein levels of PPARγ and C/EBPα and impairs adipocyte differentiation, while overexpression increases expression of these genes and promotes adipocyte differentiation. Moreover, restoration of C/EBPα or PPARγ expression in Ajuba-deficient 3T3-L1 cells improves the impaired lipid accumulation. Mechanistically, Ajuba interacts with C/EBPβ and recruits CBP to facilitate the binding of C/EBPβ to the promoter of PPARγ and C/EBPα, resulting in increased H3 histone acetylation and target gene expression. Collectively, these data indicate that Ajuba functions as a co-activator of C/EBPβ, and may be an important therapeutic target for combating obesity-related diseases.
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http://dx.doi.org/10.1016/j.mce.2021.111485DOI Listing
October 2021

Real-time reception of 106 Gbps PAM-4 transmission over an 80 km SSMF link enabled by CD pre-compensation.

Opt Express 2021 Jul;29(15):23517-23523

In this study, we report, to the best of our knowledge, the first experimental demonstration of the real-time reception of a 106 Gbps PAM-4 transmission over an 80 km dispersion uncompensated standard single-mode fiber (SSMF) link. In the transmitter, a chromatic dispersion (CD) pre-compensation, aided by an optical IQ modulator, is implemented. The optimization guideline of driver signal amplitudes and bias voltages is proposed to enable optimal CD pre-compensation. In the receiver, a real-time PAM-4 module including simple feed-forward equalization (FFE) is used. After the transmission, the required optical signal-to-noise ratio (OSNR) at a bit error rate (BER) below 3.8 × 10 is determined to be 35 dB for 106 Gbps PAM-4 signals. The better BER of 6.9 × 10 is achieved successfully compared to the previously reported off-line reception. The demonstration confirms the feasibility of 80 km DCI based on CD pre-compensation under real-time reception.
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http://dx.doi.org/10.1364/OE.430956DOI Listing
July 2021

The mechanism of nicotinamide on reducing acute lung injury by inhibiting MAPK and NF-κB signal pathway.

Mol Med 2021 09 20;27(1):115. Epub 2021 Sep 20.

Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun, 130000, Jilin, China.

Background: Acute lung injury is an important factor that leads to the death of patients with pneumonia. Previous studies have shown that nicotinamide (NAM) plays a role in reducing cell damage, so this study explored the mechanism by which NAM functions in acute lung injury.

Methods: We explored the mechanism by which NAM affects acute lung injury in vivo and in vitro by qRT-PCR, western blotting and ELISA.

Results: The results showed that NAM could significantly reduce lung injury and proinflammatory mediator accumulation. Further mechanistic studies showed that NAM could significantly inhibit the MAPK and AKT/NF-κB signaling pathways.

Conclusion: These results suggested that NAM may reduce the release of proinflammatory mediators by inhibiting the MAPK and AKT/NF-κB signaling pathways and ultimately alleviate lung injury.
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http://dx.doi.org/10.1186/s10020-021-00376-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451170PMC
September 2021

Convenient synthesis of zwitterionic calcium(II)-carboxylate metal organic frameworks with efficient activities for the treatment of osteoporosis.

Int J Pharm 2021 Oct 16;608:121083. Epub 2021 Sep 16.

Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China. Electronic address:

Calcium supplementation is effective in alleviating the process of osteoporosis and the occurrence of osteoporotic fractures for people with long-term calcium deficiency. Herein, five water-stable calcium carboxylate compounds, that is, mononuclear coordination compound [Ca(Cbdcp)(HO)]·0.5HO (1, HCbdcpBr = N-(4-carboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide), and metal organic frameworks (MOFs) {[Ca(Dcbdcp)(HO)]·2HO} (2, HDcbdcpBr = N-(3,5-dicarboxybenzyl)-(3,5-dicarboxyl)pyridinium bromide), {[Ca(Cmdcp)(HO)]·3HO} (3, HCmdcpBr = N-carboxymethyl-(3,5-dicarboxyl)pyridinium bromide), {[Ca(Cdcbp)]·2HO} (4, HCdcbpBr = 3-carboxyl-(3,5-dicarboxybenzyl)-pyridinium bromide) and {[Ca(Cmcp)]·2HO} (5, HCmcpBr = N-carboxymethyl-(3-carboxyl)pyridinium bromide), were synthesized from the reaction of CaCl with five different kinds of zwitterionic carboxylate ligands in the presence of NaOH, respectively. Compounds 1-5 were characterized by Fourier-transform infrared (FTIR) spectroscopy, elemental analyses, single-crystal X-ray crystallography, and inductively coupled plasma mass spectrometry (ICP-MS). Compound 1 features a mononuclear structure and MOF 2 with a one-dimensional (1D) structure while MOFs 3 and 5 with 2D layer structures and MOF 4 showing a 3D structure. Compounds 1-5 exhibited good water stability and possessed considerable biocompatibility with primary mice osteoblasts. The in vitro ability of compounds 1-5 in regulating osteoblastic differentiation was studied via alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, and quantitative real-time polymerase chain reaction (qPCR). Among these 5 compounds, MOF 4 showed the overall best in vitro osteogenic effects. Then, we administrated MOF 4 intragastrically to bilaterally ovariectomized mice for 8 weeks and found that bone loss caused by ovariectomy (OVX) was significantly alleviated. Besides, MOF 4 administration showed no toxic effects in the main organs of the mice. Altogether, zwitterionic carboxylate ligands-based calcium compounds provide a new strategy for calcium agents development.
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http://dx.doi.org/10.1016/j.ijpharm.2021.121083DOI Listing
October 2021

Baseline Neutrophil-to-Lymphocyte Ratio Is Independently Associated With 90-Day Transplant-Free Mortality in Patients With Cirrhosis.

Front Med (Lausanne) 2021 31;8:726950. Epub 2021 Aug 31.

Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Patients with cirrhosis have an increased risk of short-term mortality, however, few studies quantify the association between neutrophil-to-lymphocyte ratio (NLR) and 90-day transplant-free mortality in cirrhotic patients. We prospectively analyzed 3,970 patients with chronic liver diseases from two multicenter cohorts in China (January 2015 to December 2016 and July 2018 to January 2019). Restricted cubic splines (RCS) were used to analyze the relation of NLR and all-causes 90-day transplant-free mortality in cirrhosis. A total of 2,583 cirrhotic patients were enrolled in our study. Restricted cubic splines showed that the odds ratio (OR) of all causes 90-day transplant-free mortality started to increase rapidly until around NLR 6.5, and then was relatively flat ( for non-linearity <0.001). The risk of 90-day transplant-free mortality in cirrhotic patients with NLR < 6.5 increased with an increment of 23% for every unit increase in NLR ( < 0.001). The patients with NLR < 4.5 had the highest risk (OR: 2.34, 95% CI 1.66-3.28). In multivariable-adjusted stratified analyses, the increase in the incidence of 90-day transplant-free mortality with NLR increasing was consistent (OR >1.0) across all major prespecified subgroups, including infection group (OR: 1.04, 95% CI 1.00-1.09) and non-infection (OR: 1.06, 95% CI 1.02-1.11) group. The trends for NLR and numbers of patients with organ failure varied synchronously and were significantly increased with time from day 7 to day 28. We found a non-linear association between baseline NLR and the adjusted probability of 90-day transplant-free mortality. A certain range of NLR is closely associated with poor short-term prognosis in patients with cirrhosis.
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http://dx.doi.org/10.3389/fmed.2021.726950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438214PMC
August 2021

A dual-targeted molecular therapy of PP242 and cetuximab plays an anti-tumor effect through EGFR downstream signaling pathways in colorectal cancer.

J Gastrointest Oncol 2021 Aug;12(4):1625-1642

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: Epidermal growth factor receptor (EGFR) and its downstream Ras-mitogen-activated protein kinase kinase (MAPKK, MEK)-extracellular regulated protein kinase (ERK) signaling pathway and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway play important roles in the pathogenesis of colorectal cancer (CRC). The combination therapy of anti-EGFR and anti-mTOR needs to be explored.

Methods: Here we combined the anti-EGFR monoclonal antibody cetuximab (CTX) with the mTOR inhibitor PP242 in CRC cell lines and mouse xenograft models and discussed the changes of EGFR downstream signaling pathways of CRC cell lines.

Results: In HT-29 cells and Caco-2 cells, combined application of CTX and PP242 significantly inhibited the proliferation of CRC cells in vivo and in vitro. In BRAF wild-type Caco-2 cells, combined application of CTX and PP242 inhibited the activation of the EGFR and its downstream signaling pathways.

Conclusions: Our research further demonstrates the effectiveness of the combined application of CTX and PP242 in inhibiting CRC cell lines from the perspective of cell proliferation, cell cycle, apoptosis, and mouse xenografts. We revealed that the combined application of CTX and PP242 can inhibit tumor growth and proliferation by inhibiting the phosphorylation of key molecules in EGFR downstream MEK-ERK and MEK 4/7 (MKK)-c-Jun N-terminal kinase (JNK) signaling pathways in BRAF wild-type CRC cells. In addition, we found that in BRAF mutant CRC cells, the monotherapy of PP242 resulted in negative feedback increased EGFR phosphorylation rates, accompanied by significant up-regulation of downstream MEK and ERK phosphorylation.
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http://dx.doi.org/10.21037/jgo-21-467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421906PMC
August 2021

Geographic Variation of Mitogenomes: Genetic Differentiation and Phylogeny.

Front Genet 2021 31;12:711992. Epub 2021 Aug 31.

Department of Ecology, Jinan University, Guangzhou, China.

(Copepoda: Calanoida) is largely endemic to and widespread in freshwater in southern China, where it inhabits a complex landscape from lowland to highland across an elevation gradient of 2000m. A deep genetic differentiation can be expected between its most distant geographic populations. Here, we sequenced nine mitogenomes from diverse populations. All mitogenomes contained 37 genes, including 13 protein-coding genes (PCG), two rRNA genes, 22 tRNA genes and one control region. Their base composition, genetic distance and tRNA structure indeed revealed a wide differentiation between mitogenomes. Two from Guangxi near Vietnam differed from the other seven by up to 10.1%. Their tRNA-Arg had a complete clover-leaf structure, whereas that of the others did not contain an entire dihydrouridine arm. The nine mitogenomes also differed in the length of rRNA. NJ, ML, and Bayesian analyses all split them into two clades, the two from Guangxi (Clade 1), and the other seven (Clade 2). Both the structure and phylogeny of the mitogenomes suggest that has complex geographic origin, and its populations in Clade 1 have long lived in isolation from those in Clade 2. They currently reach the level of subspecies or cryptic species. An extensive phylogenetic analysis of Copepoda further verified that Diaptomidae is the most recently diverging family in Calanoida and that is at the evolutionary apex of the family.
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http://dx.doi.org/10.3389/fgene.2021.711992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439380PMC
August 2021

Explore the Value of Adding Induction Chemotherapy to Concurrent Chemoradiotherapy in T3-4N0M0 Nasopharyngeal Carcinoma Patients: A Retrospective Study.

Cancer Manag Res 2021 9;13:7067-7076. Epub 2021 Sep 9.

Department of Radiation Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, 310000, People's Republic of China.

Purpose: Patients with T3-4N0M0 nasopharyngeal carcinoma (NPC) are a unique subgroup of locoregional advanced NPC, which generally have a better prognosis than others and are often excluded in most randomized controlled clinical trials focusing on locoregional advanced NPC. The management of this population is still controversial. This study aims to evaluate the outcomes of T3-4N0M0 NPC patients treated with sequential induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT) or chemoradiotherapy (CCRT) alone.

Patients And Methods: We included 362 patients diagnosed with T3-4N0M0 NPC from two hospitals between December 2005 and December 2014. All patients were received IC + CCRT (n=146) or CCRT (n=216). Locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were retrospectively estimated.

Results: The median follow-up was 95 (range: 11-168) months. Univariable analyses have shown that 5-year LRFFS, DFS and OS in the IC+CCRT group and the CCRT group were 87.4% vs 93.4% (P = 0.035), 80.4% vs 87.0% (P = 0.047) and 86.3% vs 93.0% (P = 0.040). Multivariate analyses demonstrated that only the T stage was the independent prognostic factor for LRFFS, DFS, and OS in the entire group analysis. Subgroup analysis revealed that patients with T3 tumors who received IC+CCRT had significantly lower LRFFS, DFS, and OS than those treated with CCRT. For T4 patients, the outcomes had no significant difference between the two groups.

Conclusion: This retrospective study showed that T3N0M0 patients who received CCRT had better prognosis than those treated with IC+CCRT. In terms of T4N0M0 disease, treatment outcomes are similar in both treatment groups. However, these results require further confirmation of large sample size, prospectively, randomized controlled trials.
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http://dx.doi.org/10.2147/CMAR.S321471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437383PMC
September 2021

Cost-effective and robust DSP scheme for a short-reach coherent system in the presence of transmitter IQ skew and chromatic dispersion.

Opt Lett 2021 Sep;46(18):4606-4609

A cost-effective and robust digital signal processing (DSP) scheme is proposed and demonstrated experimentally in a coherent 61 GBaud PDM 16QAM system. In our scheme, multi-stage DSP blocks are used to deal with channel effects, transceiver in-phase and quadrature (IQ) skew, and phase noise. A 4×4 real-valued multiple-input multiple-output (RV-MIMO) with taps is for polarization recovery and receiver IQ skew calibration. After frequency offset compensation, two 2×2 RV-MIMO with taps are used to compensate for chromatic dispersion (CD), inter-symbol interference, transmitter IQ skew, and phase noise. Finally, the residual phase noise is eliminated by the maximum likelihood (ML) estimator. The experimental results indicate that the proposed scheme provides better received optical power sensitivity and CD tolerance than the existing simplified DSP schemes. In addition, the proposed scheme can tolerate transmitter IQ skew up to 7 ps in a 10 km case, which outperforms both simplified and conventional DSP schemes. Meanwhile, the proposed scheme can keep the same transceiver IQ skew and CD tolerance and has reduced complexity by 25% after 10 km links, compared to 4×4 RV-MIMO followed by a transmitter skew compensator. To the best of our knowledge, the proposed scheme is the most cost-effective solution for a high baud rate datacenter interconnects where transmitter IQ skew and CD have to be dealt with.
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http://dx.doi.org/10.1364/OL.434977DOI Listing
September 2021

Functional analysis of indole 3-hexanoic acid as a novel auxin from Arabidopsis thaliana.

Planta 2021 Sep 8;254(4):69. Epub 2021 Sep 8.

College of Life Sciences, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, People's Republic of China.

Main Conclusion: Indole 3-hexanoic acid is a novel auxin and regulates plant growth and development. Auxin is a signaling molecule that influences most aspects of plant development. Although many small bioactive molecules have been developed as auxin analogues, naturally occurring auxin and the detailed mechanisms of its specific actions in plants remain to be fully elucidated. In this study, to screen auxin responses, we used a novel picolinate synthetic auxin, 3-indole hexanoic acid (IHA), which is similar in structure to indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA). IHA showed classical auxin activity in the regulation of root growth, gene expression, and PIN-FORMED abundance. Physiological and genetic analyses indicated that IHA may be perceived by the auxin receptor TIR1 and transported by the G-class ATP-binding cassette protein ABCG36 and its homolog ABCG37. Importantly, IHA was detected in planta and converted into IBA depending on the peroxisomal β-oxidation. Together, these findings reveal a novel auxin pathway component and suggest possible undiscovered modes of auxin metabolism regulation in plants.
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http://dx.doi.org/10.1007/s00425-021-03719-9DOI Listing
September 2021

A rice mTERF protein V14 sustains photosynthesis establishment and temperature acclimation in early seedling leaves.

BMC Plant Biol 2021 Sep 6;21(1):406. Epub 2021 Sep 6.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Life Sciences, South China Agricultural University, Guangzhou, 510642, China.

Background: Plant mitochondrial transcription termination factor (mTERF) family members play important roles in development and stress tolerance through regulation of organellar gene expression. However, their molecular functions have yet to be clearly defined.

Results: Here an mTERF gene V14 was identified by fine mapping using a conditional albino mutant v14 that displayed albinism only in the first two true leaves, which was confirmed by transgenic complementation tests. Subcellular localization and real-time PCR analyses indicated that V14 encodes a chloroplastic protein ubiquitously expressed in leaves while spiking in the second true leaf. Chloroplastic gene expression profiling in the pale leaves of v14 through real-time PCR and Northern blotting analyses showed abnormal accumulation of the unprocessed transcripts covering the rpoB-rpoC1 and/or rpoC1-rpoC2 intercistronic regions accompanied by reduced abundance of the mature rpoC1 and rpoC2 transcripts, which encode two core subunits of the plastid-encoded plastid RNA polymerase (PEP). Subsequent immunoblotting analyses confirmed the reduced accumulation of RpoC1 and RpoC2. A light-inducible photosynthetic gene psbD was also found down-regulated at both the mRNA and protein levels. Interestingly, such stage-specific aberrant posttranscriptional regulation and psbD expression can be reversed by high temperatures (30 ~ 35 °C), although V14 expression lacks thermo-sensitivity. Meanwhile, three V14 homologous genes were found heat-inducible with similar temporal expression patterns, implicating their possible functional redundancy to V14.

Conclusions: These data revealed a critical role of V14 in chloroplast development, which impacts, in a stage-specific and thermo-sensitive way, the appropriate processing of rpoB-rpoC1-rpoC2 precursors and the expression of certain photosynthetic proteins. Our findings thus expand the knowledge of the molecular functions of rice mTERFs and suggest the contributions of plant mTERFs to photosynthesis establishment and temperature acclimation.
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http://dx.doi.org/10.1186/s12870-021-03192-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420055PMC
September 2021

Free Triiodothyronine Is Associated With Hepatic Steatosis and Liver Stiffness in Euthyroid Chinese Adults With Non-Alcoholic Fatty Liver Disease.

Front Endocrinol (Lausanne) 2021 12;12:711956. Epub 2021 Aug 12.

Department of Health Promotion Center, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China.

Objective: The association between non-alcoholic fatty liver disease (NAFLD) and thyroid hormones in euthyroid subjects is unclear. We investigated the relationship between thyroid function and the severity of hepatic steatosis and liver fibrosis in a large cohort of euthyroid Chinese adults.

Methods: A total of 3496 participants were enrolled. Liver ultrasonography was used to define the presence of NAFLD (n=2172) or the absence of NAFLD (n=1324). Anthropometric and biochemical measurements were made and thyroid function parameters including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH) were measured. The severity of hepatic steatosis and liver stiffness was assessed by transient elastography.

Results: Levels of FT3 were significantly higher in the severe NAFLD group and moderate NAFLD group than in the mild NAFLD group (5.18 ± 0.58 5.11 ± 0.57 4.98 ± 0.60 pmol/L, <0.001). Participants with F4 and F3 liver fibrosis had higher FT3 levels than those with F2 fibrosis (6.33 ± 0.39 5.29 ± 0.48 5.20 ± 0.50 pmol/L, <0.001). However, FT4 and TSH levels did not correlate with hepatic steatosis or liver fibrosis severity. In addition, the proportions of participants with NAFLD (46.0% 63.1% 73.3%, <0.001) and liver fibrosis (11.5% 18.6% 20.8%, <0.001) increased as FT3 levels increased. Logistic regression analysis showed that FT3 levels were positively associated with the severity of hepatic steatosis and liver fibrosis presence, even after adjustment for metabolic risk factors including BMI. In non-obese participants, the FT3 level was an independently risk factor for the severity of hepatic steatosis.

Conclusions: There are positive associations of FT3 levels with the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD with euthyroidism.
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http://dx.doi.org/10.3389/fendo.2021.711956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387962PMC
August 2021

Characterization of allelopathic compounds from the harmful dinoflagellate, Cochlodinium geminatum.

Harmful Algae 2021 07 26;107:102069. Epub 2021 Jun 26.

Institute of Hydrobiology/Key Laboratory of Eutrophication and Red Tide Prevention of Guangdong Higher Education Institutes, Jinan University, 510632 Guangzhou, PR China. Electronic address:

In 2006, species of Cochlodinium geminatum were first recorded as new, harmful algal bloom (HAB)-forming dinoflagellate, in the Pearl River Estuary, China. Previous studies indicated that allelopathy (the release of chemical compounds) is an important competitive strategy for C. geminatum in inhibiting the growth of phytoplankton competitors, however, little is known about the allelochemicals produced by this species. In this study, allelopathic compounds were characterized using a series of chromatographic techniques. Methanol extracts from cultures showed significant inhibitory effects towards the co-occurring phytoplankton, Akashiwo sanguinea, and potent hemolytic activity against rabbit erythrocytes. Solid phase extraction (SPE) fractions from a reverse phase SPE column, exhibited inhibitory and synergistic effects on A. sanguinea growth, of which fractions eluted in 80% and 100% methanol showed the strongest allelopathic activity. These fractions were further purified using reverse phase high performance liquid chromatography (HPLC), and six fractions were collected. Three fractions displayed strong inhibitory effects towards A. sanguinea, with 14%-25% inhibitory rates, but a higher 35% inhibitory rate was observed when fractions were combined, suggesting allelochemicals had synergistic allelopathic effects. Allelopathic activity also exhibited time dependent reduction when stored at -20°C. Furthermore, trypsin digestion and dialysis assays indicated C. geminatum produced multiple allelopathic compounds. Our study demonstrated that species of C. geminatum produced and released multiple allelopathic compounds of low polarity and sufficient hydrophilicity, which elicit important competitive advantages by inhibiting co-occurring phytoplankton, and promoting population growth.
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http://dx.doi.org/10.1016/j.hal.2021.102069DOI Listing
July 2021

Mesenchymal stem cells plus bone repair materials as a therapeutic strategy for abnormal bone metabolism: Evidence of clinical efficacy and mechanisms of action implied.

Pharmacol Res 2021 Oct 24;172:105851. Epub 2021 Aug 24.

Office of Clinical Trial of Drug, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou 510000, China. Electronic address:

The regeneration process of human bones is very complicated, the management and treatment of bone damage caused by diseases are the main problems faced by clinicians worldwide. It is known that cell-based stem cell therapy together with biomaterials is a fast-developing method of tissue regeneration. This review focuses on the different types and main characteristics of scaffolds and stem cells suitable for bone regeneration, and aims to provide a state-of-the-art description of the current treatment of common bone metabolism related diseases such as osteoarthritis, osteoporosis and osteosarcoma and the strategies based on stem cell biological scaffolds used in bone tissue engineering. This method may provide a new treatment option for the treatment of common bone metabolism-related diseases that cannot be cured by ordinary and routine applications. Three databases (PubMed, CNKI and Web of Science) search terms used to write this review are: "arthritis", "osteoporosis", "osteosarcoma", "bone tissue engineering", "mesenchymal stem cells", "materials", "bioactive scaffolds" and their combinations, and the most relevant studies are selected. As a conclusion, it needs to be emphasized that despite the encouraging results, further development is needed due to the need for more in-depth research, standardization of stem cell manufacturing processes, large-scale development of clinical methods for bone tissue engineering, and market regulatory approval. Although the research and application of tissue regeneration technology and stem cells are still in their infancy, the application prospect is broad and it is expected to solve the current clinical problems.
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http://dx.doi.org/10.1016/j.phrs.2021.105851DOI Listing
October 2021

Effect of short-term ambient PM exposure on fasting blood glucose levels: A longitudinal study among 47,471 people in eastern China.

Environ Pollut 2021 Dec 17;290:117983. Epub 2021 Aug 17.

Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Department of Health Management, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

As a common health indicator in physical examinations, fasting blood glucose (FBG) level measurements are widely applied as a diagnostic method for diabetes mellitus. Uncertain conclusions remained regarding the relationship between PM exposure and FBG levels. We enrolled 47,471 subjects who participated in annual physical examinations between 2017 and 2019. We collected their general characteristics and FBG levels, and environmental factors simultaneously. We applied the generalized additive model to evaluate the impact of short-term outdoor PM exposure on FBG levels. Among the entire population, the single-pollutant models showed that a 10 μg/m increase in PM significantly contributed to 0.0030, 0.0233, and 0.0325 mmol/L increases in FBG at lag 0-7 days, lag 0-21 days, and lag 0-28 days, respectively. Accordingly, in multipollutant models, when PM increased by 10 μg/m, there was an elevation of 0.0361, 0.0315, 0.0357, and 0.0387 mmol/L in FBG for 8-day, 15-day, 22-day, and 29-day moving averages, respectively. Similarly, we observed a significant positive association between them in the normal population. Moreover, the effects could be modified by age in both the entire and normal populations. Decreasing the ambient PM concentrations can alleviate the elevation of FBG, which may significantly impact the burden of diabetes mellitus.
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http://dx.doi.org/10.1016/j.envpol.2021.117983DOI Listing
December 2021

Negative/Zero Thermal Quenching of Luminescence Electronic Structural Transition in Copper-Iodide Cluster-Based Coordination Networks.

J Phys Chem Lett 2021 Sep 23;12(34):8237-8245. Epub 2021 Aug 23.

Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology, Advanced Catalysis & Green Manufacturing Collaborative Innovation Center, School of Petrochemical Engineering, Changzhou University, Changzhou, Jiangsu 213164, P. R. China.

Photoluminescence (PL) intensity in organic or metal-organic emitters usually suffers from thermal quenching (TQ), which severely hinders their industrial applications. The development of negative thermal quenching (NTQ) and/or zero thermal quenching (ZTQ) materials depends on a better understanding of the mechanisms underpinning TQ in luminescent solids. In this work, we investigated the temperature dependence of thermally activated delayed fluorescence (TADF) in copper(I)-organic coordination polymers (CP) ligated with an imidazole or triazole derivative over a broad temperature range. The efficient PL emission of is heavily quenched as the crystalline samples are cooled to 77 K; the PL intensity shows the NTQ effect in the region of 77-238 K followed by a ZTQ effect in the temperature range of 238-318 K. No NTQ or ZTQ effect is observed for reference coordination polymer , where the 1,2,4-triazole group was used instead of the imidazole one. Our work highlights the important role of the ligand's electronic structure in optimizing photophysical properties of coordination polymer emitters and may stimulate new efforts to design luminescent materials exhibiting NTQ and ZTQ effect at higher temperature.
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http://dx.doi.org/10.1021/acs.jpclett.1c02426DOI Listing
September 2021

Impact of Hepatic Encephalopathy on Clinical Characteristics and Adverse Outcomes in Prospective and Multicenter Cohorts of Patients With Acute-on-Chronic Liver Diseases.

Front Med (Lausanne) 2021 2;8:709884. Epub 2021 Aug 2.

Department of Gastroenterology, School of Medicine, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, China.

Hepatic encephalopathy is a severe complication, and its contribution to clinical adverse outcomes in patients with acute-on-chronic liver diseases from the East is unclear. We aimed to investigate the impact of hepatic encephalopathy on clinical characteristics and adverse outcomes in prospective and multicenter cohorts of patients with acute-on-chronic liver diseases. We conducted a cohort study of two multicenter prospective cohorts. China. Acute-on-chronic liver disease patients with various etiologies. The diagnosis and severity of hepatic encephalopathy were assessed using the West Haven scale. The correlation between clinical adverse outcomes and varying hepatic encephalopathy grades was analyzed in the target patients. A total of 3,949 patients were included, and 340 of them had hepatic encephalopathy. The incidence of hepatic encephalopathy was higher in patients with alcohol consumption (9.90%) than in those with hepatitis B virus infection (6.17%). The incidence of 28- and 90-day adverse outcomes increased progressively from hepatic encephalopathy grades 1-4. Logistic regression analysis revealed that hepatic encephalopathy grades 3 and 4 were independent risk factors for the 28- and 90-day adverse outcome in the fully adjusted model IV. Stratified analyses showed similar results in the different subgroups. Compared to grades 1-2 and patients without hepatic encephalopathy, those with grade 3 hepatic encephalopathy had a significant increase in clinical adverse outcomes, independent of other organ failures. Hepatic encephalopathy grades 3-4 were independent risk factors for 28- and 90-day adverse outcomes. Hepatic encephalopathy grade 3 could be used as an indicator of brain failure in patients with acute-on-chronic liver disease.
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http://dx.doi.org/10.3389/fmed.2021.709884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365160PMC
August 2021

Combining electrochemical nitrate reduction and anammox for treatment of nitrate-rich wastewater: A short review.

Sci Total Environ 2021 Dec 11;800:149645. Epub 2021 Aug 11.

Civil & Environmental Engineering Dept., University of Nebraska-Lincoln, Omaha, NE 68182-0178, USA.

Treatment of nitrate-rich wastewater is important but challenging for the conventional biological denitrification process. Here, we propose combining the electrochemical reduction and anaerobic ammonium oxidation (anammox) processes together for treatment of nitrate-rich wastewater. This article reviews the mechanism and current research status of electrochemical reduction of nitrate to ammonium as well as the mechanism and applicability of the anammox process. This article discusses the principles, superiorities and challenges of this combined process. The feasibility of the combined process depends on the efficiency of electrochemical nitrate reduction to ammonium and the conditions in the anammox process to use the reduced ammonium as the substrate to achieve deep nitrogen removal. The article provides a feasible strategy for using the electrochemical reduction and anammox combined process to treat nitrate-rich wastewater.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149645DOI Listing
December 2021

New strategies for base frame fabrication in microtia reconstruction.

Sci Rep 2021 08 5;11(1):15947. Epub 2021 Aug 5.

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai, 200011, People's Republic of China.

The base frame provides a stable support for the helix, antihelix, and tragus-antitragus complex in microtia reconstruction, and this support is vital to attain a highly defined outline for a reconstructed auricle. The success of base frame sculpting depends on appropriate treatment of the cartilage, mainly the sixth and seventh costal cartilages, which may have different characteristics. The aim of this study was to demonstrate the relevant details for base frame fabrication under various scenarios. Between 2016 and 2019, a total of 352 patients with microtia underwent autologous auricular reconstruction. Concerning the different sizes and characteristics of the costal cartilage used for the base frame reconstruction, we describe the related methods for fabrication and introduce corresponding strategies for proper management. We found that 90% of the patients responded at follow-up, and 76% of them were satisfied with the cosmetically refined auricle with harmonious integrity. The elaborate design and appropriate utilization of costal cartilage for base frame sculpting is one of the most significant and fundamental processes in microtia reconstruction. It contributes to achieving a clearly defined outline of the auricle with harmonious integrity, which is as important as the other projected subunits.
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http://dx.doi.org/10.1038/s41598-021-95613-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342471PMC
August 2021

Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.

Front Cell Dev Biol 2021 19;9:720111. Epub 2021 Jul 19.

Department of Tissue Engineering and Regeneration, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

Mutations of H-Ras, a member of the RAS family, are preferentially found in cutaneous squamous cell carcinomas (SCCs). H-Ras has been reported to induce autophagy, which plays an essential role in tissue homeostasis in multiple types of cancer cells and in fibroblasts, however, the potential role of H-Ras in regulating autophagy in human keratinocytes has not been reported. In this study, we found that the stable expression of the G12V mutant of H-RAS (H-Ras ) induced autophagy in human keratinocytes, and interestingly, the induction of autophagy was strongly blocked by inhibiting the calcineurin/nuclear factor of activated T cells (NFAT) pathway with either a calcineurin inhibitor (Cyclosporin A) or a NFAT inhibitor (VIVIT), or by the small interfering RNA (siRNA) mediated knockdown of calcineurin B1 or NFATc1 , as well as To characterize the role of the calcineurin/NFAT pathway in H-Ras induced autophagy, we found that H-Ras promoted the nuclear translocation of NFATc1, an indication of the activation of the calcineurin/NFAT pathway, in human keratinocytes. However, activation of NFATc1 either by the forced expression of NFATc1 or by treatment with phenformin, an AMPK activator, did not increase the formation of autophagy in human keratinocytes. Further study revealed that inhibiting the calcineurin/NFAT pathway actually suppressed H-Ras expression in H-Ras overexpressing cells. Finally, chromatin immunoprecipitation (ChIP) assays showed that NFATc1 potentially binds the promoter region of H-Ras and the binding efficiency was significantly enhanced by the overexpression of H-Ras , which was abolished by treatment with the calcineurin/NFAT pathway inhibitors cyclosporine A (CsA) or VIVIT. Taking these data together, the present study demonstrates that the calcineurin/NFAT signaling pathway controls H-Ras expression and interacts with the H-Ras pathway, involving the regulation of H-Ras induced autophagy in human keratinocytes.
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http://dx.doi.org/10.3389/fcell.2021.720111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328491PMC
July 2021

Rationality and Regulation Needed to Contain China's Dangerous Infatuation with "Elf Ears".

Aesthetic Plast Surg 2021 Jul 30. Epub 2021 Jul 30.

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai, 200011, China.

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http://dx.doi.org/10.1007/s00266-021-02505-yDOI Listing
July 2021

Changes in Direct Medical Cost and Medications for Managing Diabetes in Beijing, China, 2016 to 2018: Electronic Insurance Data Analysis.

Ann Fam Med 2021 Jul-Aug;19(4):332-341

Department of Endocrinology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China.

Purpose: Although the cost and complexity of managing diabetes is increasing around the world, placing greater burden on patients and their families, the cost of drug regimens prescribed to Chinese patients has not been evaluated. This study was conducted to evaluate the temporal changes in the costs and drugs used for people with diabetes.

Methods: Patients enrolled in Beijing Medical Insurance with outpatient medical records from 2016 through 2018 were included in this study. The outcomes of interest were: (1) the number of outpatient medications, (2) the number of comorbidities diagnosed, (3) the estimated annual cost of the outpatient drug regimen, (4) the drug therapy strategies used for diabetic patients, and (5) the most commonly prescribed classes of drugs.

Results: Over the 3-year period, there was a significant decrease (9.0%, <.001) in the average number of diabetes medications used. Both antiglycemic and non-antiglycemic drug use decreased by 3.6% and 12.9%, respectively. Similarly, for estimated annual costs of medication, an 18.4% ( <.05) decrease was observed, with a gradual decreased from ¥6,868 ($1,059) in 2016 to ¥5,605 ($865) in 2018.

Conclusion: This is the first large-scale cost analysis of the medical management of diabetes since the implementation of medical insurance in China. Despite the increasing availability of newer, more expensive diabetes drugs, there was a significant reduction in the number of diabetes medications used, that may be due to a more rational approach to optimizing metabolic targets.
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http://dx.doi.org/10.1370/afm.2686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282297PMC
October 2021

Different Effects of Total Bilirubin on 90-Day Mortality in Hospitalized Patients With Cirrhosis and Advanced Fibrosis: A Quantitative Analysis.

Front Med (Lausanne) 2021 23;8:704452. Epub 2021 Jun 23.

Department of Liver Intensive Care Unit, Shanghai Public Health Clinical Centre, Fudan University, Shanghai, China.

Total bilirubin (TB) is a major prognosis predictor representing liver failure in patients with acute on chronic liver failure (ACLF). However, the cutoff value of TB for liver failure and whether the same cutoff could be applied in both cirrhotic and non-cirrhotic patients remain controversial. There is a need to obtain the quantitative correlation between TB and short-term mortality evidence-based methods, which is critical in establishing solid ACLF diagnostic criteria. Patients hospitalized with cirrhosis or advanced fibrosis (FIB-4 > 1.45) were studied. TB and other variables were measured at baseline. The primary outcome was 90-day transplantation-free mortality. Multi-variable Cox proportional hazard model was used to present the independent risk of mortality due to TB. Generalized additive model and second derivate (acceleration) were used to plot the "TB-mortality correlation curves." The mathematical (maximum acceleration) and clinical (adjusted 28-day transplantation-free mortality rate reaching 15%) TB cutoffs for liver failure were both calculated. Among the 3,532 included patients, the number of patients with cirrhosis and advanced fibrosis were 2,592 and 940, respectively, of which cumulative 90-day mortality were 16.6% (430/2592) and 7.4% (70/940), respectively. Any increase of TB was found the independent risk factor of mortality in cirrhotic patients, while only TB >12 mg/dL independently increased the risk of mortality in patients with advanced fibrosis. In cirrhotic patients, the mathematical TB cutoff for liver failure is 14.2 mg/dL, with 23.3% (605/2592) patients exceeding it, corresponding to 13.3 and 25.0% adjusted 28- and 90-day mortality rate, respectively. The clinical TB cutoff for is 18.1 mg/dL, with 18.2% (471/2592) patients exceeding it. In patients with advanced fibrosis, the mathematical TB cutoff is 12.1 mg/dL, 33.1% (311/940) patients exceeding it, corresponding to 2.9 and 8.0% adjusted 28- and 90-day mortality rate, respectively; the clinical TB cutoff was 36.0 mg/dL, 1.3% (12/940) patients above it. This study clearly demonstrated the significantly different impact of TB on 90-day mortality in patients with cirrhosis and advanced fibrosis, proving that liver failure can be determined by TB alone in cirrhosis but not in advanced fibrosis. The proposed TB cutoffs for liver failure provides solid support for the establishment of ACLF diagnostic criteria.
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http://dx.doi.org/10.3389/fmed.2021.704452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260970PMC
June 2021

A New Method of Correcting Cryptotia by Changing Mechanical Fulcrum After Constricted Cartilage Overturned.

Aesthetic Plast Surg 2021 Jul 9. Epub 2021 Jul 9.

Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639, Zhi Zao Ju Rd., Shanghai, 200011, China.

Background: Many techniques have been introduced to correct cryptotia. The previous methods are releasing the constricted cartilage and changing the mechanical fulcrum partly to the right position. However, some patients are still not satisfied with the treatment results, due to cryptotia recurrence and insufficient superior 1/3 width. This study aimed to develop a new method for completely changing the mechanical direction of constricted cartilage for correcting cryptotia.

Methods: From 2007 to 2020, twenty-four cryptotia patients were treated. During surgical reconstruction, the retroauricular skin flap was elevated, the posterior aspect of the upper auricular cartilage was completely exposed, and the abnormal insertion of the auricular intrinsic muscles detached. The sharply curved antihelical cartilage was cut and overturned, and the scalp skin flap was undermined and advanced toward the postauricular sulcus. The edge of the retroauricular scalp flap is fixed on the mastoid periosteum. The incision was closed.

Results: Eighteen patients had unilateral cryptotia, and six had bilateral cryptotia. Relatively favorable results were obtained in the follow-up period (range, 6-48 months). There were no cases of skin necrosis, complications, or revision surgery.

Conclusions: The main advantages of this technique are the surgically reproducible results, and that it can be applied to most cases. The method described in this paper could potentially increase the width of the upper third of the auricle and reduce recurrence rate, while also leaving an inconspicuous scar and a satisfactory auricular contour. It is suggested that this technique could be an alternative method of cryptotia correction.

Level Of Evidence Iv: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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http://dx.doi.org/10.1007/s00266-021-02413-1DOI Listing
July 2021

Seed specifically over-expressing DGAT2A enhances oil and linoleic acid contents in soybean seeds.

Biochem Biophys Res Commun 2021 Sep 30;568:143-150. Epub 2021 Jun 30.

College of Life Sciences, State Key Laboratory of Crop Genetics and Germplasm Enhancement, Nanjing Agricultural University, Nanjing, 210095, PR China.

Triacylglycerol (TAG), a main component of oil, is mainly biosynthesized by diacylglycerol acyltransferase (DGAT), which is critical for oil accumulation in plants. Intensive focus has been on DGAT2 functioning in unsaturated fatty acids biosynthesis. In this study, we analyzed the coding sequence (CDS) and amino acid sequence of GmDGAT2A and determined its key active sites through site-directed mutagenesis. As a consequence, H132, G201, and P152-X-I154-K155 were found to be essential active sites for GmDGAT2A. The spatial structure of the protein may bring the three active sites into close proximity, constituting an active domain. Additionally, N-terminus of GmDGAT2A was found to be an important regulator for the activity. Further, in vitro activity results uncovered GmDGAT2A was prone to utilize C18:2-CoA as the substrate. Consequently, overexpression of GmDGAT2A driven by a seed-specific promoter of Gmole1 in soybean significantly increased linoleic acid content specifically and total oil content, concomitant with accelerated elongation.
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http://dx.doi.org/10.1016/j.bbrc.2021.06.087DOI Listing
September 2021

Long noncoding RNA BS-DRL1 modulates the DNA damage response and genome stability by interacting with HMGB1 in neurons.

Nat Commun 2021 07 1;12(1):4075. Epub 2021 Jul 1.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese academy of Science, Shanghai, 200032, China.

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration.
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http://dx.doi.org/10.1038/s41467-021-24236-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249382PMC
July 2021

Snail enhances arginine synthesis by inhibiting ubiquitination-mediated degradation of ASS1.

EMBO Rep 2021 08 29;22(8):e51780. Epub 2021 Jun 29.

Tongren Hospital/Faculty of Basic Medicine, Hongqiao International Institute of Medicine, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Snail is a dedicated transcriptional repressor and acts as a master inducer of EMT and metastasis, yet the underlying signaling cascades triggered by Snail still remain elusive. Here, we report that Snail promotes colorectal cancer (CRC) migration by preventing non-coding RNA LOC113230-mediated degradation of argininosuccinate synthase 1 (ASS1). LOC113230 is a novel Snail target gene, and Snail binds to the functional E-boxes within its proximal promoter to repress its expression in response to TGF-β induction. Ectopic expression of LOC113230 potently suppresses CRC cell growth, migration, and lung metastasis in xenograft experiments. Mechanistically, LOC113230 acts as a scaffold to facilitate recruiting LRPPRC and the TRAF2 E3 ubiquitin ligase to ASS1, resulting in enhanced ubiquitination and degradation of ASS1 and decreased arginine synthesis. Moreover, elevated ASS1 expression is essential for CRC growth and migration. Collectively, these findings suggest that TGF-β and Snail promote arginine synthesis via inhibiting LOC113230-mediated LRPPRC/TRAF2/ASS1 complex assembly and this complex can serve as potential target for the development of new therapeutic approaches to treat CRC.
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http://dx.doi.org/10.15252/embr.202051780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339691PMC
August 2021

Fe-doped chrysotile nanotubes containing siRNAs to silence SPAG5 to treat bladder cancer.

J Nanobiotechnology 2021 Jun 23;19(1):189. Epub 2021 Jun 23.

Department of Oncology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha, 410013, Hunan, China.

Background: For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically.

Results: The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15-25 nm) and inner diameter (7-8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells.

Conclusions: The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer.
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http://dx.doi.org/10.1186/s12951-021-00935-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220725PMC
June 2021
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