Publications by authors named "Liang Liu"

1,575 Publications

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miR-542-3p Attenuates Bone Loss and Marrow Adiposity Following Methotrexate Treatment by Targeting sFRP-1 and Smurf2.

Int J Mol Sci 2021 Oct 12;22(20). Epub 2021 Oct 12.

UniSA Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.

Intensive methotrexate (MTX) treatment for childhood malignancies decreases osteogenesis but increases adipogenesis from the bone marrow stromal cells (BMSCs), resulting in bone loss and bone marrow adiposity. However, the underlying mechanisms are unclear. While microRNAs (miRNAs) have emerged as bone homeostasis regulators and miR-542-3p was recently shown to regulate osteogenesis in a bone loss context, the role of miR-542-3p in regulating osteogenesis and adipogenesis balance is not clear. Herein, in a rat MTX treatment-induced bone loss model, miR-542-3p was found significantly downregulated during the period of bone loss and marrow adiposity. Following target prediction, network construction, and functional annotation/ enrichment analyses, luciferase assays confirmed sFRP-1 and Smurf2 as the direct targets of miR-542-3p. miRNA-542-3p overexpression suppressed sFRP-1 and Smurf2 expression post-transcriptionally. Using in vitro models, miR-542-3p treatment stimulated osteogenesis but attenuated adipogenesis following MTX treatment. Subsequent signalling analyses revealed that miR-542-3p influences Wnt/β-catenin and TGF-β signalling pathways in osteoblastic cells. Our findings suggest that MTX treatment-induced bone loss and marrow adiposity could be molecularly linked to miR-542-3p pathways. Our results also indicate that miR-542-3p might be a therapeutic target for preserving bone and attenuating marrow fat formation during/after MTX chemotherapy.
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http://dx.doi.org/10.3390/ijms222010988DOI Listing
October 2021

Pathological changes in the lungs and lymphatic organs of 12 COVID-19 autopsy cases.

Natl Sci Rev 2020 Dec 29;7(12):1868-1878. Epub 2020 Sep 29.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Systematic autopsy and comprehensive pathological analyses of COVID-19 decedents should provide insights into the disease characteristics and facilitate the development of novel therapeutics. In this study, we report the autopsy findings from the lungs and lymphatic organs of 12 COVID-19 decedents-findings that evaluated histopathological changes, immune cell signature and inflammatory factor expression in the lungs, spleen and lymph nodes. Here we show that the major pulmonary alterations included diffuse alveolar damage, interstitial fibrosis and exudative inflammation featured with extensive serous and fibrin exudates, macrophage infiltration and abundant production of inflammatory factors (IL-6, IP-10, TNFα and IL-1β). The spleen and hilar lymph nodes contained lesions with tissue structure disruption and immune cell dysregulation, including lymphopenia and macrophage accumulation. These findings provide pathological evidence that links injuries of the lungs and lymphatic organs with the fatal systematic respiratory and immune malfunction in critically ill COVID-19 patients.
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http://dx.doi.org/10.1093/nsr/nwaa247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543449PMC
December 2020

SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation.

Cell Res 2021 Oct 18. Epub 2021 Oct 18.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 100 Haike Rd, Pudong, Shanghai, China.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.
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http://dx.doi.org/10.1038/s41422-021-00578-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8522117PMC
October 2021

FGF14-AS2 accelerates tumorigenesis in glioma by forming a feedback loop with miR-320a/E2F1 axis.

J Cancer 2021 3;12(21):6429-6438. Epub 2021 Sep 3.

Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, Jiangsu, China.

Glioma is the most common primary tumour in the central nervous system in adults, and at present, there is no effective treatment to cure this malignancy. Long noncoding RNAs (lncRNAs) are closely related to tumour progression and have attracted increasing attention in tumour research. However, the role of lncRNA FGF14-AS2 in glioma tumorigenesis has not been determined. In the present study, we found that FGF14-AS2 expression was significantly elevated in glioma tissues and was associated with poor survival in glioma patients. Silencing FGF14-AS2 inhibited the proliferation, migration and invasion ability of glioma cells. assay showed that silencing FGF14-AS2 led to inhibition of tumour growth. In addition, FGF14-AS2 was observed to promote glioma progression via the miR-320a/E2F1 axis. Moreover, E2F1 could bind to the promoter region of FGF14-AS2, thereby enhancing FGF14-AS2 expression. In conclusion, FGF14-AS2 could accelerate tumorigenesis of glioma by forming a feedback loop with the miR-320a/E2F1 axis which suggested that FGF14-AS2 could serve as a therapeutic target for glioma.
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http://dx.doi.org/10.7150/jca.62120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489148PMC
September 2021

Patterns and predictors of pancreatic neuroendocrine tumor prognosis: Are no two leaves alike?

Crit Rev Oncol Hematol 2021 Oct 12;167:103493. Epub 2021 Oct 12.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 20032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China; Shanghai Pancreatic Cancer Institute, Shanghai, 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai, 200032, PR China. Electronic address:

Pancreatic neuroendocrine tumors (PanNETs) are heterogeneous; thus, individual prognostic prediction is important. Clinicopathological features, like TNM stage, grade, and differentiation, are independent clinical predictors. However, single predictors are insufficient, as patients sharing similar clinicopathological features usually show distinct prognoses. Accordingly, novel nomograms and risk stratifications have been developed for more accurate PanNET prognostic prediction. Moreover, the exploration of molecular mechanisms has identified novel prognostic predictors for PanNET. Multi-analyte assays of molecular biomarkers provide a deeper understanding of PanNET features; however, the priority, and the optimal combination of classic and novel predictors for PanNET prognosis prediction remain unclear. In this review, we summarized the patterns and predictors of PanNET prognosis and discussed their clinical utility; we emphasized that PanNET at different stages have different superior predictor, and that multi-analyte assays are more sensitive than mono-analyte biomarkers. Therefore, combined biomarkers improve the accuracy of surveillance and optimize decision-making in clinical practice.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103493DOI Listing
October 2021

C,C- and C,N-Chelated Organocopper Compounds.

Molecules 2021 Sep 25;26(19). Epub 2021 Sep 25.

Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China.

Copper-catalyzed and organocopper-involved reactions are of great significance in organic synthesis. To have a deep understanding of the reaction mechanisms, the structural characterizations of organocopper intermediates become indispensable. Meanwhile, the structure-function relationship of organocopper compounds could advance the rational design and development of new Cu-based reactions and organocopper reagents. Compared to the mono-carbonic ligand, the C,N- and C,C-bidentate ligands better stabilize unstable organocopper compounds. Bidentate ligands can chelate to the same copper atom via -mode, forming a mono-cupra-cyclic compounds with at least one acute C-Cu-C angle. When the bidentate ligands bind to two copper atoms via -mode at each coordinating site, the bimetallic macrocyclic compounds will form nearly linear C-Cu-C angles. The anionic coordinating sites of the bidentate ligand can also bridge two metals via -mode, forming organocopper aggregates with Cu-Cu interactions and organocuprates with contact ion pair structures. The reaction chemistry of some selected organocopper compounds is highlighted, showing their unique structure-reactivity relationships.
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http://dx.doi.org/10.3390/molecules26195806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510249PMC
September 2021

Long non-coding RNA CRNDE as potential biomarkers facilitate inflammation and apoptosis in alcoholic liver disease.

Aging (Albany NY) 2021 Oct 11;13(19):23233-23244. Epub 2021 Oct 11.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Due to persistent inconsistencies in the expression data of alcoholic liver disease (ALD), it is necessary to turn to "pre-laboratory" comprehensive analysis in order to accelerate effective precision medicine and transformation research. We screened pseudogene-derived lncRNA associated with ALD by comparative analysis of 2 independent data sets from GEO. Three lncRNAs (CRNDE, RBMS3-AS3, and LINC01088) were demonstrated to be potentially useful diagnostic markers in ALD. Among them, the expression of CRNDE is up-regulated. Therefore, we focus on CRNDE. Kyoto Encyclopedia of Genes and Genomes pathways analysis revealed higher CRNDE can activate MAPK signaling pathway, apoptosis, wnt signaling pathway, and hematopoietic cell lineage. Next, we established ALD animal model and verified the success of the modeling. The result showed ALD tissues in mice had significantly higher CRNDE levels than normal tissues. Moreover, the increase of IL-6 in the serum of mice in the low-dose group is related to the activation of inflammatory factors after alcohol-induced liver injury. In addition, alcohol can induce apoptosis, and knockdown of CRNDE can reduce apoptosis. Our integrated expression profiling identified CRNDE independently associated with ALD. CRNDE can facilitate inflammation and apoptosis in ALD.
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http://dx.doi.org/10.18632/aging.203614DOI Listing
October 2021

Novel DIP2C gene splicing variant in an individual with focal infantile epilepsy.

Am J Med Genet A 2021 Oct 7. Epub 2021 Oct 7.

Department of Pediatric neurology, Xi'an Children's Hospital, Xi'an, China.

Disco-interacting protein 2 C (DIP2C) encodes a disco-interacting protein and is highly expressed in the nervous system. Most variants of DIP2C are microdeletions on chromosome 10p15.3. This study reports a 17-month-old infant with focal infantile epilepsy who has a single-nucleotide variation in DIP2C that results in alternative splicing. The de novo variation (NM_014974.3: c.1057+2T>G) in DIP2C was uncovered through whole-exome sequencing. Minigene assays were performed and verified the alternative splicing caused by the variation. Finally, an 80-bp nucleotide deletion in the 3' end of Exon 8 was detected. Our study identified a de novo splicing variant that affects the coding length of DIP2C. This finding provides a new candidate gene for focal infantile epilepsy. Importantly, our finding is the first to associate a single nucleotide variant in DIP2C with focal infantile epilepsy.
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http://dx.doi.org/10.1002/ajmg.a.62524DOI Listing
October 2021

Cell death and pathological findings of the spleen in COVID-19 patients.

Pathol Res Pract 2021 Sep 8;227:153610. Epub 2021 Sep 8.

Hubei AIDS Clinical Training Center, Department of Infectious Disease, Zhongnan Hospital of Wuhan University, Wuhan, PR China; Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, PR China; Cancer Research Institute, General Hospital, Ningxia Medical University, Yinchuan, PR China. Electronic address:

The coronavirus disease 2019(COVID-19) is recognized as systemic inflammatory response syndrome. It was demonstrated that a rapid increase of cytokines in the serum of COVID-19 patients is associated with the severity of disease. However, the mechanisms of the cytokine release are not clear. By using immunofluorescence staining we found that the number of CD11b positive immune cells including macrophages in the spleens of died COVID-19 patients, was significantly higher than that of the control patients. The incidence of apoptosis as measured by two apoptotic markers, TUNEL and cleaved caspase-3, in COVID-19 patients' spleen cells is higher than that in control patients. By double immunostaining CD11b or CD68 and SARS-CoV-2 spike protein, it was found that up to 67% of these immune cells were positive for spike protein, suggesting that viral infection might be associated with apoptosis in these cells. Besides, we also stained the autophagy-related molecules (p-Akt、p62 and BCL-2) in spleen tissues, the results showed that the number of positive cells was significantly higher in COVID-19 group. And compared with non-COVID-19 patients, autophagy may be inhibited in COVID-19 patients. Our research suggest that SARS-CoV-2 may result in a higher rate of apoptosis and a lower rate of autophagy of immune cells in the spleen of COVID-19 patients. These discoveries may increase our understanding of the pathogenesis of COVID-19.
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http://dx.doi.org/10.1016/j.prp.2021.153610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423775PMC
September 2021

The Effect of Combination Therapy on Mortality and Adverse Events in Patients with Staphylococcus aureus Bacteraemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Infect Dis Ther 2021 Oct 1. Epub 2021 Oct 1.

Department of Pharmacy, People's Hospital of Ningxiang City Affiliated to Hunan University of Chinese Medicine, Changsha, Hunan, People's Republic of China.

Introduction: The findings of randomized controlled trials (RCTs), observational studies, and meta-analyses vary regarding the effectiveness and safety of combination therapy for patients with Staphylococcus aureus bacteraemia (SAB). We aimed to identify the effectiveness and safety of combination therapy in patients with SAB compared with those of monotherapy.

Methods: We performed a systematic review and meta-analysis to compare combination therapy versus monotherapy in patients with SAB. Two authors independently searched PubMed, Embase, and the Cochrane Library of clinical trials until 17 February 2021. Any RCT comparing mortality or adverse events (AEs) of combination therapy versus monotherapy for patients with SAB was eligible. Summary risk ratios (RRs) and 95% confidence intervals (CIs) were evaluated using a random-effects model. The primary outcome was all-cause mortality at any time point. This meta-analysis is registered with the PROSPERO database (CRD42020188176) and reported according to PRISMA guidelines.

Results: In total, 1906 articles were identified and screened, and 14 studies (2367 patients) were included in the meta-analysis. There was no significant difference in the risk of all-cause mortality between the two groups (RR = 1.00; 95% CI 0.83-1.20; P = 0.99; I = 0%). Similar results were obtained by subgroup analysis of mortality recording time, endocarditis, pathogen resistance, article publication time, number of patients, and adjuvant antibiotics. Notably, combination treatment might significantly increase the risk of drug-related AEs (RR = 1.68; 95% CI 1.06-2.66; P = 0.03; I = 67%) and nephrotoxicity (RR = 2.30; 95% CI 1.68-3.16; P < 0.00001; I = 0%), although the occurrences of AEs leading to treatment discontinuation and serious AEs were not significantly different between the two groups.

Conclusions: The meta-analysis suggested that combination therapy could not reduce mortality but might increase the risk of drug-related AEs and nephrotoxicity and should be applied very cautiously. Future studies on combined drug therapy for SAB need careful and rigorous design for specific antibiotic combinations.
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http://dx.doi.org/10.1007/s40121-021-00539-yDOI Listing
October 2021

Progressive brain structural abnormality in depression assessed with MR imaging by using causal network analysis.

Psychol Med 2021 Sep 29:1-10. Epub 2021 Sep 29.

Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: As a neuroprogressive illness, depression is accompanied by brain structural abnormality that extends to many brain regions. However, the progressive structural alteration pattern remains unknown.

Methods: To elaborate the progressive structural alteration of depression according to illness duration, we recruited 195 never-treated first-episode patients with depression and 130 healthy controls (HCs) undergoing T1-weighted MRI scans. Voxel-based morphometry method was adopted to measure gray matter volume (GMV) for each participant. Patients were first divided into three stages according to the length of illness duration, then we explored stage-specific GMV alterations and the causal effect relationship between them using causal structural covariance network (CaSCN) analysis.

Results: Overall, patients with depression presented stage-specific GMV alterations compared with HCs. Regions including the hippocampus, the thalamus and the ventral medial prefrontal cortex (vmPFC) presented GMV alteration at onset of illness. Then as the illness advanced, others regions began to present GMV alterations. These results suggested that GMV alteration originated from the hippocampus, the thalamus and vmPFC then expanded to other brain regions. The results of CaSCN analysis revealed that the hippocampus and the vmPFC corporately exerted causal effect on regions such as nucleus accumbens, the precuneus and the cerebellum. In addition, GMV alteration in the hippocampus was also potentially causally related to that in the dorsolateral frontal gyrus.

Conclusions: Consistent with the neuroprogressive hypothesis, our results reveal progressive morphological alteration originating from the vmPFC and the hippocampus and further elucidate possible details about disease progression of depression.
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http://dx.doi.org/10.1017/S0033291721003986DOI Listing
September 2021

A Computable Gaussian Quantum Correlation for Continuous-Variable Systems.

Entropy (Basel) 2021 Sep 9;23(9). Epub 2021 Sep 9.

School of Mathematical Science, Shanxi University, Taiyuan 030006, China.

Generally speaking, it is difficult to compute the values of the Gaussian quantum discord and Gaussian geometric discord for Gaussian states, which limits their application. In the present paper, for any (n+m)-mode continuous-variable system, a computable Gaussian quantum correlation M is proposed. For any state ρAB of the system, M(ρAB) depends only on the covariant matrix of ρAB without any measurements performed on a subsystem or any optimization procedures, and thus is easily computed. Furthermore, M has the following attractive properties: (1) M is independent of the mean of states, is symmetric about the subsystems and has no ancilla problem; (2) M is locally Gaussian unitary invariant; (3) for a Gaussian state ρAB, M(ρAB)=0 if and only if ρAB is a product state; and (4) 0≤M((ΦA⊗ΦB)ρAB)≤M(ρAB) holds for any Gaussian state ρAB and any Gaussian channels ΦA and ΦB performed on the subsystem A and B, respectively. Therefore, M is a nice Gaussian correlation which describes the same Gaussian correlation as Gaussian quantum discord and Gaussian geometric discord when restricted on Gaussian states. As an application of M, a noninvasive quantum method for detecting intracellular temperature is proposed.
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http://dx.doi.org/10.3390/e23091190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467257PMC
September 2021

The transcriptional characteristics of mast cells derived from skin tissue in type 2 diabetes patients at the single-cell level.

Acta Histochem 2021 Oct 22;123(7):151789. Epub 2021 Sep 22.

Wound Treatment Department, TCM-Integrated Hospital of Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address:

Objectives: The mechanisms underlying the role of mast cells in wound healing have not been thoroughly studied, and even fewer data are available on studies related to mast cells in the skin of patients with type 2 diabetes mellitus (T2DM). Therefore, this study aims to explore the transcriptional characteristics of mast cells at the single-cell level in patients with T2DM and provide experimental data for studying mast cell behaviors under abnormal glucose metabolism.

Methods: Two patients with T2DM and one trauma patient without diabetes were enrolled. Samples were derived from skin tissue resected at the time of surgery and were isolated by single cell capture technology on BD platform to prepare single cell cDNA library. Seurat was used to process raw reads and analyze data downstream of single-cell RNA sequencing, including removal of low-quality cells, identification of cell clusters at the single-cell level, and screening for differential genes with fold change > 1.5 and p < 0.05 by two-sided t-test. We performed single-cell RNA sequencing on skin tissues of T2DM patients and non-diabetics and identified the cell cluster of skin, single-cell subsets, and transcriptional characteristics of mast cells at a single-cell level. Meanwhile, gene set enrichment(GSEA) analysis was performed on the differentially expressed genes.

Results: A total of 8888 cells were obtained from skin tissue. Clustering analysis revealed eight-cell clusters, identified as smooth muscle cells, dendritic cells, mast cells, and T cells, respectively. Cluster 6 was identified as mast cells with the marker genes TPSAB1, CPA3, TPSB2, MS4A2,KIT, etc., which accounting for 2.7% of the total cell number.Compared with the control group, the genes highly expressed in MCs from T2DM patients, include ADH1C, PAXIP1, HAS1, ARG1, etc., and the low expression genes include PHACTR2, GGA1, RASSF2, etc. GSEA analysis suggested that the signal pathways of MCS in T2DM patients included VEGF signaling pathway, Fc gamma R-mediated phagocytosis, the B cell receptor signaling pathway, natural killer cell-mediated cytotoxicity.

Conclusions: The characteristic genes of MCs in the skin tissues of T2DM patients were described at the single-cell level. These genes and enriched signaling pathways provide a theoretical basis and data support for further researches on dermatopathy in patients with diabetes mellitus.
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http://dx.doi.org/10.1016/j.acthis.2021.151789DOI Listing
October 2021

A case of meningoencephalocele in the nasal cavity 6 years after skull base fracture.

Neurol Sci 2021 Sep 23. Epub 2021 Sep 23.

Department of Neurosurgery, Affiliated Hospital of Southwest Medical University, Xianglin Road, Luzhou, 646000, Sichuan, China.

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http://dx.doi.org/10.1007/s10072-021-05604-5DOI Listing
September 2021

Ni-In Synergy in CO Hydrogenation to Methanol.

ACS Catal 2021 Sep 29;11(18):11371-11384. Epub 2021 Aug 29.

Laboratory of Inorganic Materials and Catalysis, Department of Chemical Engineering and Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.

Indium oxide (InO) is a promising catalyst for selective CHOH synthesis from CO but displays insufficient activity at low reaction temperatures. By screening a range of promoters (Co, Ni, Cu, and Pd) in combination with InO using flame spray pyrolysis (FSP) synthesis, Ni is identified as the most suitable first-row transition-metal promoter with similar performance as Pd-InO. NiO-InO was optimized by varying the Ni/In ratio using FSP. The resulting catalysts including InO and NiO end members have similar high specific surface areas and morphology. The main products of CO hydrogenation are CHOH and CO with CH being only observed at high NiO loading (≥75 wt %). The highest CHOH rate (∼0.25 g/(g h), 250 °C, and 30 bar) is obtained for a NiO loading of 6 wt %. Characterization of the as-prepared catalysts reveals a strong interaction between Ni cations and InO at low NiO loading (≤6 wt %). H-TPR points to a higher surface density of oxygen vacancy (O) due to Ni substitution. X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and electron paramagnetic resonance analysis of the used catalysts suggest that Ni cations can be reduced to Ni as single atoms and very small clusters during CO hydrogenation. Supportive density functional theory calculations indicate that Ni promotion of CHOH synthesis from CO is mainly due to low-barrier H dissociation on the reduced Ni surface species, facilitating hydrogenation of adsorbed CO on O.
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http://dx.doi.org/10.1021/acscatal.1c03170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453486PMC
September 2021

Transcriptome Analysis of Immune Receptor Activation and Energy Metabolism Reduction as the Underlying Mechanisms in Interleukin-6-Induced Skeletal Muscle Atrophy.

Front Immunol 2021 6;12:730070. Epub 2021 Sep 6.

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-Innovation Center of Neuroregeneration, Nantong University, National Medical Products Administration Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong, China.

Background: Inflammation may trigger skeletal muscle atrophy induced by cancer cachexia. As a pro-inflammatory factor, interleukin-6 may cause skeletal muscle atrophy, but the underlying molecular mechanisms have not been explored.

Methods: In this experimental study, we used adult male ICR mice, weighing 25 ± 2 g, and the continuous infusion of interleukin-6 into the tibialis anterior muscle to construct a skeletal muscle atrophy model (experimental group). A control group received a saline infusion. RNA-sequencing was used to analyze the differentially expressed genes in tissue samples after one and three days. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis were applied to define the function of these genes, and protein-protein interaction analysis was performed to identify potential transcription factors. Fluorescence microscopy was used to determine the muscle fiber cross-sectional area after 14 days.

Results: Continuous infusion of interleukin-6 for 14 days caused significant muscle atrophy. RNA-sequencing found 359 differentially expressed genes in the 1- and 3-day tissue samples and 1748 differentially expressed genes only in the 3-day samples. Functional analysis showed that the differentially expressed genes found in both the 1- and 3-day samples were associated with immune receptor activation, whereas the differentially expressed genes found only in the 3-day sample were associated with reduced energy metabolism. The expression of multiple genes in the oxidative phosphorylation and tricarboxylic acid cycle pathways was down-regulated. Furthermore, differentially expressed transcription factors were identified, and their interaction with interleukin-6 and the differentially expressed genes was predicted, which indicated that STAT3, NF-κB, TP53 and MyoG may play an important role in the process of interleukin-6-induced muscle atrophy.

Conclusions: This study found that interleukin-6 caused skeletal muscle atrophy through immune receptor activation and a reduction of the energy metabolism. Several transcription factors downstream of IL-6 have the potential to become new regulators of skeletal muscle atrophy. This study not only enriches the molecular regulation mechanism of muscle atrophy, but also provides a potential target for targeted therapy of muscle atrophy.
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http://dx.doi.org/10.3389/fimmu.2021.730070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450567PMC
September 2021

Circ_0007534 Silencing Inhibits the Proliferation, Migration and Invasion and Induces the Apoptosis of Glioma Cells Partly Through Down-Regulating PROX1 Via Elevating miR-22-3p Level.

Cell Mol Neurobiol 2021 Sep 18. Epub 2021 Sep 18.

Department of Neurosurgery, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), No. 118, Longjing Second Road, Xin'an Street, Baoan District, Shenzhen, 518101, China.

Glioma is a common malignant brain neoplasm. The role and mechanism of circular RNA 0,007,534 (circ_0007534) in glioma progression were investigated in this study. The expression of circ_0007534, microRNA-22-3p (miR-22-3p) and prospero homeobox protein 1 (PROX1) messenger RNA (mRNA) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration and invasion abilities were analyzed by colony formation assay, transwell migration assay and transwell invasion assay. Cell apoptosis was assessed through measuring the activity of Caspase-3 using the Caspase-3 kit and the apoptosis rate using flow cytometry. Dual-luciferase reporter assay was used to confirm the target interaction between miR-22-3p and circ_0007534 or PROX1. The protein level of PROX1 was examined by Western blot assay. Animal studies were conducted to analyze the influence of circ_0007534 interference on xenograft tumor growth in vivo. Circ_0007534 was highly expressed in glioma tissues and cell lines relative to that in normal tissues and NHA cell line. Circ_0007534 knockdown suppressed the proliferation and motility while induced the apoptosis of glioma cells. Circ_0007534 negatively regulated miR-22-3p level through targeting it in glioma cells. Circ_0007534 interference-induced influences in glioma cells were partly overturned by the silencing of miR-22-3p. PROX1 was a target of miR-22-3p, and circ_0007534 interference-mediated effects in glioma cells were largely diminished by the overexpression of PROX1. Circ_0007534 interference restrained glioma development in vivo. Circ_0007534 aggravated glioma progression through elevating PROX1 expression via targeting miR-22-3p, which provided new targets for the diagnosis and treatment of glioma.
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http://dx.doi.org/10.1007/s10571-021-01150-yDOI Listing
September 2021

Weighted gene co-expression network analysis reveals that CXCL10, IRF7, MX1, RSAD2, and STAT1 are related to the chronic stage of spinal cord injury.

Ann Transl Med 2021 Aug;9(15):1248

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.

Background: The process of spinal cord injury involves acute, subacute, and chronic stages; however, the specific pathological mechanism remains unclear. In this study, weighted gene co-expression network analysis (WGCNA) was used to clarify specific modules and hub genes that associated with SCI.

Methods: The gene expression profiles GEO Series (GSE)45006 and GEO Series (GSE)2599 were downloaded, and the co-expression network modules were identified by the WGCNA package. The protein-protein interaction (PPI) network and Venn diagram were constructed to identify hub genes. Quantitative real-time polymerase chain reaction (QRT-PCR) was used to quantify the degree of the top five candidate genes. Correlation analysis was also carried out between hub genes and immune infiltration.

Results: In total, 14,402 genes and seven modules were identified. The brown module was considered to be the most critical module for the chronic stage of SCI, which contained 775 genes that were primarily associated with various biological processes, including extracellular structure organization, lysosome, isoprenoid biosynthesis, response to nutrients, response to wounding, sulfur compound metabolic process, cofactor metabolic process, and ossification. Furthermore, C-X-C motif chemokine ligand 10 (), myxovirus (influenza virus) resistance 1 (), signal transducer and activator of transcription 1 (), interferon regulatory factor 7 () and radical S-adenosyl methionine domain containing 2 () were identified as the hub genes in the PPI and Venn diagram network, and verified by qRT-PCR. Immune infiltration analysis revealed that CD8+ T cells, macrophages, neutrophils, plasmacytoid dendritic cells, helper T cells, Th2 cells, and tumor-infiltrating lymphocytes may be involved in the SCI process.

Conclusions: There were significant differences among the five hub genes (, , , , and ) of the brown module, which may be potential diagnostic and prognostic markers of SCI, and immune cell infiltration may play an important role in the chronic stage of SCI.
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http://dx.doi.org/10.21037/atm-21-3586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421925PMC
August 2021

Mechanism of Intervention in Cerebral Infarction: A Research Based on Chemoinformatics and Systematic Pharmacology.

Evid Based Complement Alternat Med 2021 6;2021:6789835. Epub 2021 Sep 6.

Hunan University of Chinese Medicine, Changsha, Hunan Province, China.

Objective: To explore the therapeutic targets, network modules, and coexpressed genes of intervention in cerebral infarction (CI), and to predict significant biological processes and pathways through network pharmacology. To explore the differential proteins of intervention in CI, conduct bioinformatics verification, and initially explain the possible therapeutic mechanism of intervention in CI through proteomics.

Methods: The TCM database was used to predict the potential compounds of Radix Rhei Et Rhizome, and the PharmMapper was used to predict its potential targets. GeneCards and OMIM were used to search for CI-related genes. Cytoscape was used to construct a protein-protein interaction (PPI) network and to screen out core genes and detection network modules. Then, DAVID and Metascape were used for enrichment analysis. After that, in-depth analysis of the proteomics data was carried out to further explore the mechanism of intervention in CI.

Results: (1) A total of 14 potential components and 425 potential targets were obtained. The core components include sennoside A, palmidin A, emodin, toralactone, and so on. The potential targets were combined with 297 CI genes to construct a PPI network. The targets shared by and CI include ALB, AKT1, MMP9, IGF1, CASP3, etc. The biological processes that may treat CI include platelet degranulation, cell migration, fibrinolysis, platelet activation, hypoxia, angiogenesis, endothelial cell apoptosis, coagulation, and neuronal apoptosis. The signaling pathways include Ras, PI3K-Akt, TNF, FoxO, HIF-1, and Rap1 signaling pathways. (2) Proteomics shows that the top 20 proteins in the differential protein PPI network were Syp, Syn1, Mbp, Gap43, Aif1, Camk2a, Syt1, Calm1, Calb1, Nsf, Nefl, Hspa5, Nefh, Ncam1, Dcx, Unc13a, Mapk1, Syt2, Dnm1, and Cltc. Differential protein enrichment results show that these proteins may be related to synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, synaptic vesicle endocytosis, axon guidance, calcium signaling pathway, and so on.

Conclusion: This study combined network pharmacology and proteomics to explore the main material basis of for the treatment of CI such as sennoside A, palmidin A, emodin, and toralactone. The mechanism may be related to the regulation of biological processes (such as synaptic vesicle cycle, vesicle-mediated transport in synapse, presynaptic endocytosis, and synaptic vesicle endocytosis) and signaling pathways (such as Ras, PI3K-Akt, TNF, FoxO, HIF-1, Rap1, and axon guidance).
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http://dx.doi.org/10.1155/2021/6789835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440083PMC
September 2021

Impaired bone healing by enoxaparin via inhibiting the differentiation of bone marrow mesenchymal stem cells towards osteoblasts.

J Bone Miner Metab 2021 Sep 15. Epub 2021 Sep 15.

Orthopedics Department, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, Shanxi, 030001, People's Republic of China.

Introduction: Enoxaparin is widely used to prevent venous thromboembolism after orthopedic surgery and has some adverse effects, such as osteoporosis and delay in fracture healing. However, the exact mechanism delaying bone healing by enoxaparin is still unclear.

Materials And Methods: X-ray and Micro-CT scanning were performed to detect the effects of enoxaparin on bone healing at rat model of bone defeat. CCK-8 assay and flow cytometry were conducted to measure the effects of enoxaparin on bone marrow mesenchymal stem cells (BMSCs). The mRNA/protein levels of osteocalcin (OCN), runt-related transcription factor 2 (Runx2) and bone morphogenetic protein 2 (BMP2) were analyzed by real-time PCR and western blotting, respectively. Alizarin red staining was used to observe the mineralized nodules.

Results: Enoxaparin (2000 AXaIU/kg) not only profoundly increased the trabecular separation, but also notably decreased the trabecular bone volume/tissue volume, trabecular thickness, trabecular number and OCN level, in vivo. Additionally, significantly inhibiting proliferation of BMSCs by enoxaparin (1.0 and 10 AXaIU/ml) was detected. The apoptosis and the ratio of G phase cells in enoxaparin (0.1, 1.0 and 10 AXaIU/ml) group were obviously higher than that in control group. While the ratio of S phase cells was downregulated markedly by enoxaparin (0.1,1.0 and 10 AXaIU/ml) compared with the control group. Most importantly, inducing significant decreases of OCN/Runx2 mRNA/protein expression and formation of mineralized nodules by enoxaparin (0.1, 1.0 and 10 AXaIU/ml) were observed compared with the control group. While the notable decreases of BMP2 mRNA/protein level were only detected in enoxaparin (10 AXaIU/ml) group.

Conclusion: It was suggested that enoxaparin impaired bone healing through suppressing the differentiation of BMSCs towards osteoblasts.
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http://dx.doi.org/10.1007/s00774-021-01268-5DOI Listing
September 2021

A Distance-Learning Approach to Point-of-Care Ultrasound Training (ADAPT): A Multi-Institutional Educational Response During the COVID-19 Pandemic.

Acad Med 2021 Sep 14. Epub 2021 Sep 14.

K. Nix is assistant professor, Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia; ORCID: https://orcid.org/0000-0002-8412-9682. E.L. Liu is assistant professor, Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia; ORCID: https://orcid.org/0000-0003-3273-9021. L. Oh is associate professor, Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia; ORCID: https://orcid.org/0000-0002-4566-2580. Y. Duanmu is clinical assistant professor, Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, California; ORCID: https://orcid.org/0000-0002-3430-7866. T. Fong is assistant professor, Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland; ORCID: https://orcid.org/0000-0002-8843-5177. N. Ashenburg is clinical assistant professor, Department of Emergency Medicine, Stanford University School of Medicine, Palo Alto, California; ORCID: https://orcid.org/0000-0002-9996-6248 R.B. Liu is associate professor, Department of Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut; ORCID: https://orcid.org/0000-0002-3997-0325.

Problem: The COVID-19 pandemic significantly disrupted point-of-care ultrasound (POCUS) education. Medical schools and residency programs placed restrictions on bedside teaching and clinical scanning as part of risk mitigation. In response, POCUS faculty nationwide from 15 institutions collaborated on an alternative model of ultrasound education, A Distance-learning Approach to POCUS Training (ADAPT).

Approach: ADAPT was repeated monthly from April 1 through June 30, 2020. It accommodated 70 learners, who included 1- to 4-week rotators and asynchronous learners. The curriculum included assigned pre-work and learning objectives covering 20 core POCUS topics. A rotating group of 30 faculty and fellows delivered daily virtual teaching sessions that included gamification to increase learner engagement and hands-on instruction through teleguidance. After participation, faculty and learners completed anonymous surveys.

Outcomes: Educators reported a significant decrease in preparatory time (6.2 vs. 3.1 hours per week, P < .001) dedicated to ultrasound education after implementing ADAPT. The majority of 29 learners who completed surveys felt "somewhat confident" or "very confident" in their ability to acquire (n = 25, 86.2%) and interpret (n = 27, 93.1%) ultrasound images after the intervention; the majority of 22 educators completing surveys rated the program "somewhat effective" or "very effective" at contributing to learner's ability to acquire (n = 13, 59.1%) and interpret (n = 20, 90.9%) images. Most learners (n = 28, 96.6%) and all educators (n = 22, 100%) were "satisfied" or "very satisfied" with ADAPT as a whole, and the large majority of educators were "very likely" (n = 18, 81.8%) to recommend continued use of this program.

Next Steps: A virtual curriculum that pools the efforts of multiple institutions nationwide was implemented rapidly and effectively while satisfying educational expectations of both learners and faculty. This collaborative framework can be replicated and may be generalizable to other educational objectives.
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http://dx.doi.org/10.1097/ACM.0000000000004399DOI Listing
September 2021

Differentially expressed miRNAs in bone after methotrexate treatment.

J Cell Physiol 2021 Sep 12. Epub 2021 Sep 12.

Clinical and Health Sciences, University of South Australia, Adelaide, South Australia, Australia.

Previous studies have shown that administration of antimetabolite methotrexate (MTX) caused a reduced trabecular bone volume and increased marrow adiposity (bone/fat switch), for which the underlying molecular mechanisms and recovery potential are unclear. Altered expression of microRNAs (miRNAs) has been shown to be associated with dysregulation of osteogenic and/or adipogenic differentiation by disrupting target gene expression. First, the current study confirmed the bone/fat switch following MTX treatment in precursor cell culture models in vitro. Then, using a rat intensive 5-once daily MTX treatment model, this study aimed to identify miRNAs associated with bone damage and recovery (in a time course over Days 3, 6, 9, and 14 after the first MTX treatment). RNA isolated from bone samples of treated and control rats were subjected to miRNA array and reverse transcription-polymerase chain reaction validation, which identified five upregulated miRNA candidates, namely, miR-155-5p, miR-154-5p, miR-344g, miR-6215, and miR-6315. Target genes of these miRNAs were predicted using TargetScan and miRDB. Then, the protein-protein network was established via STRING database, after which the miRNA-key messenger RNA (mRNA) network was constructed by Cytoscape. Functional annotation and pathway enrichment analyses for miR-6315 were performed by DAVID database. We found that TGF-β signaling was the most significantly enriched pathway and subsequent dual-luciferase assays suggested that Smad2 was the direct target of miR-6315. Our current study showed that miR-6315 might be a vital regulator involved in bone and marrow fat formation. Also, this study constructed a comprehensive miRNA-mRNA regulatory network, which may contribute to the pathogenesis/prognosis of MTX-associated bone loss and bone marrow adiposity.
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http://dx.doi.org/10.1002/jcp.30583DOI Listing
September 2021

Prevalence, Clinical Features, and In-hospital Outcome of Fatty Liver Disease in Acute Aortic Dissection: A Single-Center Retrospective Study.

Front Cardiovasc Med 2021 13;8:698285. Epub 2021 Aug 13.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.

Fatty liver disease (FLD) has emerged as a major public issue in China. We aim to investigate prevalence, clinical features, and in-hospital outcome of FLD in acute aortic dissection (AAD) patients. Data of 379 AAD patients from 2017 to 2019 at Renmin hospital of Wuhan University was retrospectively collected and divided according to age and FLD absence. Propensity score matching was used for minimal confounding. We compared their physical environmental parameter of onset, clinical features, and in-hospital outcome. The mean age was 52.0 ± 11.5 years in type A and 55.1 ± 11.4 in type B. 25.0% of type A and 19.2% of type B AAD patients had FLD. Logistic regression indicated a negative association between FLD and age, both in type A [unadjusted odds ratio (OR) 0.958 (per 1 year), 95% confidence interval (CI) 0.930-0.988, = 0.0064] and type B [unadjusted OR 0.943 (per 1 year), 95% CI 0.910-0.978, = 0.0013]. After matching, type A with FLD had onset with a lower air quality index (AQI) of 68.5 [interquartile range (IQR) 46.0-90.0] and a lower Pm 2.5 concentration of 36.0 μg/m (IQR 23.0-56.0) compared with non-FLD group. In Kaplan-Meier estimation, FLD was associated with higher risk of in-hospital mortality in type B AAD ( = 0.0297). The prevalence of FLD in AAD decrease with age, both in type A and type B AAD. Type A AAD patients with FLD had onset with better air quality parameters compared with non-FLD group. FLD was associated with higher risk of in-hospital mortality in type B AAD.
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http://dx.doi.org/10.3389/fcvm.2021.698285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414544PMC
August 2021

Water-Soluble Humic Materials Modulating Metabolism and Triggering Stress Defense in Sinorhizobium fredii.

Microbiol Spectr 2021 09 25;9(1):e0029321. Epub 2021 Aug 25.

State Key Laboratory of Agrobiotechnology and Key Laboratory of Soil Microbiology, Ministry of Agriculture, College of Biological Sciences, China Agricultural Universitygrid.22935.3f, Beijing, China.

Bacteria have evolved a series of mechanisms to maintain their survival and reproduction in changeable and stressful environments. In-depth understanding of these mechanisms can allow for better developing and utilizing of bacteria with various biological functions. In this study, we found that water-soluble humic materials (WSHM), a well-known environment-friendly plant growth biostimulant, significantly promoted the free-living growth and survival of Sinorhizobium fredii CCBAU45436 in a bell-shaped, dose-dependent manner, along with more-efficient carbon source consumption and relief of medium acidification. By using RNA-Seq analysis, a total of 1,136 genes significantly up-/downregulated by external addition of WSHM were identified under test conditions. These differentially expressed genes (DEGs) were enriched in functional categories related to carbon/nitrogen metabolism, cellular stress response, and genetic information processing. Further protein-protein interaction (PPI) network analysis and reverse genetic engineering indicated that WSHM might reprogram the transcriptome through inhibiting the expression of key hub gene , which encodes a bifunctional enzyme catalyzing synthesis and hydrolysis of the "magic spot" (p)ppGpp. In addition, the root colonization and viability in soil of S. fredii CCBAU45436 were increased by WSHM. These findings provide us with new insights into how WSHM benefit bacterial adaptations and demonstrate great application value to be a unique inoculant additive. Sinorhizobium fredii CCBAU45436 is a highly effective, fast-growing rhizobium that can establish symbiosis with multiple soybean cultivars. However, it is difficult to maintain the high-density effective viable cells in the rhizobial inoculant for the stressful conditions during production, storage, transport, and application. Here, we showed that WSHM greatly increased the viable cells of S. fredii CCBAU45436 in culture, modulating metabolism and triggering stress defense. The root colonization and viability in soil of CCBAU45436 were also increased by WSHM. Our results shed new insights into the effects of WSHM on bacteria and the importance of metabolism and stress defense during the bacteria's whole life. In addition, the functional mechanism of WSHM may provide candidate genes for improving environmental adaptability and application potential of bacteria through genetic engineering.
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http://dx.doi.org/10.1128/Spectrum.00293-21DOI Listing
September 2021

Putative regulatory role of hexokinase and fructokinase in terpenoid aroma biosynthesis in Lilium 'Siberia'.

Plant Physiol Biochem 2021 Oct 30;167:619-629. Epub 2021 Aug 30.

The Research Center for Ornamental Plants, College of Forestry and Landscape Architecture, South China Agricultural University, Guangzhou, 510642, China; Guangdong Key Laboratory for Innovative Development and Utilization of Forest Plant Germplasm, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

Lily is one of the most economically important flowers worldwide due to its elegant appearance and appealing scent, which is mainly composed of monoterpene ocimene, linalool and benzenoids. Sugars are the primary products of plants, with fructose and hexose sugars being the substrate material for most organic compounds and metabolic pathways in plants. Herein, we isolated and functionally characterized hexokinase (LoHXK) and fructokinase (LoFRK) from Lilium 'Siberia' flower, which indicated their potential roles in floral aroma production. Real-time PCR analysis showed that LoHXK and LoFRK were highly expressed in the flower filament. Overexpression and virus-induced gene silencing (VIGS) assays revealed that LoHXK and LoFRK significantly modified the emission of β-ocimene and linalool contents via regulation of expression of key structural volatile synthesis genes (LoTPS1 and LoTPS3). Under exogenous glucose and fructose application, the volatile contents of β-ocimene and linalool were increased and the expression levels of key structural genes were upregulated. The emission of β-ocimene and linalool followed a diurnal circadian rhythm. Determination of carbon fluxes via C-labeled glucose and C-labeled fructose experiments showed that the mass spectra of ocimene and linalool significantly increased, however, the m/z ratio of ethyl benzoate did not change. Furthermore, yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) assays showed that LoFRK interacted with LoMYB1 and LoMYB2 proteins. Together, these results suggest that hexokinase and fructokinase may play significant roles in the regulation of ocimene and linalool biosynthesis in Lilium 'Siberia'.
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http://dx.doi.org/10.1016/j.plaphy.2021.08.042DOI Listing
October 2021

One-Step Preparation of Chitin Nanofiber Dispersion in Full pH Surroundings Using Recyclable Solid Oxalic Acid and Evaluation of Redispersed Performance.

Biomacromolecules 2021 10 3;22(10):4373-4382. Epub 2021 Sep 3.

Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, International Innovation Center for Forest Chemicals and Materials, College of Chemical Engineering, Nanjing Forestry University, Longpan Road 159, Nanjing 210037, China.

This study proposed an efficient and economical preparation pathway from purified chitin to nanofibers that can be dispersed in full pH surroundings. Recyclable oxalic acid was applied to prepare chitin nanofibers in a mild environment along with concurrent modifications of the carboxylic groups on the surface. Pretreatment with oxalic acid significantly improved the mechanical disintegration of chitin into nanofibers, the length of nanofibers reached ∼1100 nm, and the crystallinity and thermal stability of the chitin were basically unchanged with mild treatment. Oxalic acid can be reused many times with a high recovery of over 91%. Most importantly, the obtained nanofibers can be fabricated into films and hydrogels with certain mechanical properties, which can be redispersed into nanofibers using mild mechanical treatment. This method not only produces nanofibers in a green, reusable system but also provides a reference for the potential application of chitin nanofibers in commercial transportation and wide applicability.
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http://dx.doi.org/10.1021/acs.biomac.1c00938DOI Listing
October 2021

Carrelizumab combined with anlotinib in the treatment of extensive-stage small cell lung cancer: A case report.

Medicine (Baltimore) 2021 Sep;100(35):e27138

Lianyungang Clinical College of Nanjing Medical University/ The First People's Hospital of Lianyungang, Lianyungang, Jiangsu, China.

Rationale: The emergence of immune checkpoint inhibitors has brought new breakthroughs in the treatment of small cell lung cancer (SCLC). Programmed cell death-ligand 1 inhibitors combined with chemotherapy have been approved for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). However, programmed death 1 inhibitors have limited efficacy in the treatment of SCLC. The reason may be related to the abnormal vascular state in the tumor microenvironment.

Patient Concerns: A 55-year-old male patient, presenting cough and sputum for 1 month.

Diagnoses: The patient was clinically diagnosed with SCLC and staged as ES-SCLC.

Interventions: Etoposide combined with lobaplatin treatment every 3 weeks for 4 cycles, evaluate as progressive disease. On the basis of the original plan, combined with camrelizumab for 2 cycles, evaluation as progressive disease. Then, the patient was treated with intravenous infusion of camrelizumab plus oral anlotinib. After 4 cycles, evaluation as partial response. Then we continued to use camrelizumab combined with anlotinib treatment for the patient. At the end of 26 cycles, the chest computed tomography examination revealed that the patient had achieved complete remission.

Outcomes: After treated with carrelizumab combined with anlotinib for 26 cycles, the curative effect was evaluated as complete remission, progression-free survival was 24 months and there was no immune-related adverse reaction during treatment period. Besides, the patient developed complicated hand-foot syndrome, but this symptom was significantly relieved after reducing the dosage of anlotinib.

Lessons: In this case, antiangiogenesis combined with programmed death 1 inhibitors significantly inhibited tumor progression. It also indicated that anlotinib concurrent carrelizumab may be a superior choice for ES-SCLC. Further clinical trials required to confifirm its effificacy and safety.
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http://dx.doi.org/10.1097/MD.0000000000027138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416004PMC
September 2021

Sequential Capecitabine/Temozolomide (CAPTEM) and Sunitinib Treatment in Patients with Metastatic Well-differentiated G1/G2 Pancreatic Neuroendocrine Tumors.

Endocr Pract 2021 Aug 25. Epub 2021 Aug 25.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 20032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, PR China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, PR China. Electronic address:

Objective: The role of alternate sequential administration of sunitinib and capecitabine/temozolomide (CAPTEM) in metastatic Pancreatic Neuroendocrine Tumors (PanNET) remains unexplored. We thus aimed to analyze the efficacy and tolerability of this strategy in advanced G1/G2 PanNET.

Methods: In total, data of 43 patients with metastatic PanNET were collected from a real-world database of a cancer center. Twenty-four patients were treated with sunitinib followed by CAPTEM (group I), and 19 were treated with CAPTEM followed by sunitinib (group II).

Results: Twenty-three patients were treated with first-line sunitinib or CAPTEM, and twenty were pretreated with somatostatin analog (SSA) or SSA plus transcatheter arterial chemoembolization. The objective response rate (ORR) with first-line treatment was similar in both groups, whereas ORR with second-line treatment was higher in group I than in group II albeit with no significant differences (21.1% vs. 5.3%, P=0.205). Median progression-free survival (PFS) for first-line and second-line treatments did not differ between two groups (11 and 12 months vs. 12 and 8 months, respectively). In subgroup analyses, first-line sunitinib and sunitinib after pretreated SSA had longer mPFS compared to second-line sunitinib after CAPTEM (11 vs. 8 months, P=0.046), whereas first-line CAPTEM and CAPTEM after pretreated SSA had mPFS similar to that of second-line CAPTEM after sunitinib. CAPTEM and sunitinib had similar tolerability.

Conclusion: Alternating sunitinib and CAPTEM were well-tolerated and associated with similar mPFS in G1/G2 PanNETs. However, larger prospective studies are required to investigate the efficacy of alternate sequential therapies for metastatic PanNET.
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http://dx.doi.org/10.1016/j.eprac.2021.08.008DOI Listing
August 2021

Optical coherence tomographic angiography study of perfusion recovery after surgical lowering of intraocular pressure.

Sci Rep 2021 08 26;11(1):17251. Epub 2021 Aug 26.

Casey Eye Institute and Department of Ophthalmology, Oregon Health and Science University, 515 SW Campus Drive, Portland, OR, 97239-4197, USA.

We investigated the time and location of retinal perfusion recovery after surgical intraocular pressure (IOP) lowering in glaucoma by using optical coherent tomography angiography (OCTA). Seventeen patients were analyzed. The 4.5 × 4.5-mm OCTA scans centered on the disc were performed preoperatively and postoperatively at 6 weeks, 3 months, and 6 months. The peripapillary retinal nerve fiber layer (NFL) thickness, NFL plexus capillary density (NFLP-CD) and visual field (VF) were measured overall and in 8 corresponding sectors. The low-perfusion area (LPA) was used to assess the cumulative area where local NFLP-CD was significantly below normal. At 6 months, the average IOP decreased 5.3 mmHg (P = 0.004), LPA decreased by 15% (P = 0.005), and NFLP-CD improved by 12% (P < 0.001). The NFL thickness and VF mean deviation didn't change significantly at any time point. Among the sectors with significant preoperative NFLP-CD loss, the recovery at 6 months was greatest in sectors with minimal preoperative NFL thinning (P < 0.001). In conclusion, surgical IOP lowering may improve NFLP capillary perfusion after 6 months. The perfusion recovery tended to occur in areas with minimal NFL thinning at baseline. OCTA parameters may have potential usefulness as pharmacodynamic biomarkers for glaucoma therapy.
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http://dx.doi.org/10.1038/s41598-021-96225-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390670PMC
August 2021

PTENα functions as an immune suppressor and promotes immune resistance in PTEN-mutant cancer.

Nat Commun 2021 08 26;12(1):5147. Epub 2021 Aug 26.

Institute of Systems Biomedicine, Department of Pathology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.

PTEN is frequently mutated in human cancers and PTEN mutants promote tumor progression and metastasis. PTEN mutations have been implicated in immune regulation, however, the underlying mechanism is largely unknown. Here, we report that PTENα, the isoform of PTEN, remains active in cancer bearing stop-gained PTEN mutations. Through counteraction of CD8 T cell-mediated cytotoxicity, PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Clinical analysis further uncovers that PTENα-active mutations suppress host immune responses and result in poor prognosis in cancer as relative to PTENα-inactive mutations. Furthermore, germline deletion of Ptenα in mice increases cell susceptibility to immune attack through augmenting stress granule formation and limiting synthesis of peroxidases, leading to massive oxidative cell death and severe inflammatory damage. We propose that PTENα protects tumor from T cell killing and thus PTENα is a potential target in antitumor immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-25417-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390757PMC
August 2021
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