Publications by authors named "Peng Luo"

517 Publications

Detection and Quantitation of Adulterated Paprika Samples Using Second-Order HPLC-FLD Fingerprints and Chemometrics.

Foods 2022 Aug 8;11(15). Epub 2022 Aug 8.

State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmacy, Guizhou Medical University, Guiyang 550025, China.

Paprika is a widely consumed spice in the world and its authentication has gained interest considering the increase in adulteration cases in recent years. In this study, second-order fingerprints acquired by liquid chromatography with fluorescence detection (HPLC-FLD) were first used to detect and quantify adulteration levels of Chinese paprika samples. Six different adulteration cases, involving paprika production region, cultivar, or both, were investigated by pairs. Two strategies were employed to reduce the data matrices: (1) chromatographic fingerprints collected at specific wavelengths and (2) fusion of the mean data profiles in both spectral and time dimensions. Afterward, the fingerprint data with different data orders were analyzed using partial least squares (PLS) and n-way partial least squares (N-PLS) regression models, respectively. For most adulteration cases, N-PLS based on second-order fingerprints provided the overall best quantitation results with cross-validation and prediction errors lower than 2.27% and 20.28%, respectively, for external validation sets with 15-85% adulteration levels. To conclude, second-order HPLC-FLD fingerprints coupled with chemometrics can be a promising screening technique to assess paprika quality and authenticity in the control and prevention of food frauds.
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http://dx.doi.org/10.3390/foods11152376DOI Listing
August 2022

Early detection of gram-negative bacteria using metagenomic next-generation sequencing in acute respiratory distress syndrome: A case report.

Exp Ther Med 2022 Sep 15;24(3):573. Epub 2022 Jul 15.

Department of Critical Medicine, Union Jiangbei Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430100, P.R. China.

Metagenomic next-generation sequencing (mNGS) is an effective method that can be used for the identification of early pathogens in patients with suspected severe pneumonia. However, the potential of mNGS for evaluating the prognosis of acute respiratory distress syndrome (ARDS) in patients with severe pneumonia remains unclear. In the present report, hospital-acquired gram-negative bacteria infections were detected in a case using metagenomic next-generation sequencing (mNGS) in a sample of bronchoalveolar fluid. This was obtained from a 58-year-old male patient with traumatic wet lung after a neurosurgery. According to the results, of which the profiles of the resistance genes were detected by mNGS, drugs designed to control infection were adjusted, namely to polymyxin B (500,000 U/12 h), azithromycin (0.5 g/24 h) and ganciclovir (0.25 g/12 h). Following adjusting treatment for 8 days, the symptoms of lung infection and hypoxemia were markedly improved, resulting in the patient being transferred out of the intensive care unit 15 days after treatment. To conclude, observations from the present report suggest that mNGS is a useful method for the early identification of pathogens in patients with pneumonia caused by ARDS. However, further studies are required to identify the complementary role of mNGS in supporting conventional microbiological methods in routine clinical practice.
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http://dx.doi.org/10.3892/etm.2022.11510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353542PMC
September 2022

A New Thinking: Deciphering the Aberrance and Clinical Implication of IGF Axis Regulation Pattern in Clear Cell Renal Cell Carcinoma.

Front Immunol 2022 22;13:935595. Epub 2022 Jul 22.

Department of Urology, Changhai Hospital, Naval Medical University, (Second Military Medical University), Shanghai, China.

Rationale: The recent research found that IGF regulator genes played a pivotal role in multiple biological processes, which may be developed for cancer treatment. However, the characteristics and implication of IGF regulators in cancers, especially in clear cell renal cell carcinoma (ccRCC), remain elusive.

Methods: We systematically analyzed the expression, prognostic valuation, genome variation, and functional implication at pan-cancer level from The Cancer Genome Atlas. According to expression levels of IGF regulator genes, ccRCC could be divided into three different subtypes unsupervised cluster algorithm: IGF pattern cancer type1 (IPCS1), type2 (IPCS2), and type3 (IPCS3). The immune microenvironment, immunotherapy response, metabolic pattern, and tumor progression signature among the three subgroups were investigated. The clinical characteristics, genomic mutations, and potential drug sensitivity were further analyzed. IGF pattern-related risk model was constructed to predict RCC patients' outcome. Finally, SHC1, a potential IGF axis target, was comprehensively investigated in ccRCC.

Results: We found that IGF regulator genes were specifically upregulated in various cancer tissues, which were correlated with copy number variations and dysregulated pathways. IPCS1, IPCS2, and IPCS3 exhibited different clinical profiles and biological characteristics in ccRCC. IPCS3 subtype indicated a higher clinical stage and a worse survival. IPSC3 ccRCC displayed activated metabolic signatures to fuel the cancer progression. IPCS3 subgroup holds a higher tumor mutation burden and lower immune activities, which resulted in a low ICI therapy response and tumor immunity dysfunction state. The genome copy numbers of IPCS2/3, including arm gain and arm loss, were significantly higher than IPCS1. Besides, the drug sensitivity profiles were different among the three subgroups. The prognostic risk model based on subtype's biomarker exerted a promising performance both in training and validation cohorts. Finally, upregulated expression of SHC1 partly induced poorer immunotherapy response and shorter survival of ccRCC patients.

Conclusion: Targeting IGF regulators may be functioned as a treatment approach among multi-cancers. IGF regulator-related signature could reshape the tumor immune microenvironment activating multi-step immune programs. The inhibition of SHC1 may enhance the efficacy of immunotherapy, and SHC1 could be a suitable target for ccRCC therapy.
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http://dx.doi.org/10.3389/fimmu.2022.935595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355597PMC
August 2022

Evolutionarily Ancient Caspase-9 Sensitizes Immune Effector Coelomocytes to Cadmium-Induced Cell Death in the Sea Cucumber, .

Front Immunol 2022 14;13:927880. Epub 2022 Jul 14.

CAS Key Laboratory of Tropical Marine Bio-resources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences (CAS), Guangzhou, China.

Heavy-metal pollution has increasingly jeopardized the habitats of marine organisms including the sea cucumber, a seafloor scavenger vital to seawater bio-decontamination, ocean de-acidification and coral-reef protection. Normal physiology including immune functions of sea cucumbers is toxicologically modulated by marine metal pollutants such as cadmium (Cd). The processes underpinning Cd's toxic effects on immune systems in the sea cucumber, , are still poorly understood. To this end, we cloned and characterized a full-length caspase-9 () cDNA in the sea cucumber, . mRNA levels evolved dynamically during embryonic development. Coelomocytes, a type of phagocytic immune effectors central to immunity, were found to express mRNA most abundantly. Hl-CASP9 protein structurally resembles caspases-2 and -9 in both invertebrate and vertebrate species, comprising a CARD domain and a CASc domain. Remarkably, was transcriptionally sensitive to abiotic oxidative stress inducers including hydrogen peroxide (HO), nitric oxide (NO) and cadmium (Cd), but insensitive to immunostimulants including lipopolysaccharide (LPS), and poly(I:C). Overexpression of augmented mitochondria-dependent apoptosis in HEK293T cells, while knock-down of blunted Cd-induced coelomocyte apoptosis . Overall, we illustrate that an evolutionarily ancient caspase-9-dependent pathway exists to sensitize coelomocytes to premature cell death precipitated by heavy metal pollutants, with important implications for negative modulation of organismal immune response in marine invertebrates.
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http://dx.doi.org/10.3389/fimmu.2022.927880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330033PMC
August 2022

JMJD8 Is an M2 Macrophage Biomarker, and It Associates With DNA Damage Repair to Facilitate Stemness Maintenance, Chemoresistance, and Immunosuppression in Pan-Cancer.

Front Immunol 2022 11;13:875786. Epub 2022 Jul 11.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

Background: JMJD8 has recently been identified as a cancer-related gene, but current studies provide limited information. We aimed to clarify its roles and the potential mechanisms in pan-cancer.

Methods: Pan-cancer bulk sequencing data and online web tools were applied to analyze JMJD8's correlations with prognosis, genome instability, cancer stemness, DNA repair, and immune infiltration. Moreover, single-cell datasets, SpatialDB database, and multiple fluorescence staining were used to validate the association between JMJD8 expression and M2 macrophages. Further, we utilized ROCplotter and cMap web tool to analyze the therapeutic responses and screened JMJD8-targeted compounds, respectively, and we used AlphaFold2 and Discovery Studio to conduct JMJD8 homology modeling and molecular docking.

Results: We first noticed that JMJD8 was an oncogene in many cancer types. High JMJD8 was associated with lower genome stability. We then found that high JMJD8 correlated with high expression of mismatch repair genes, stemness, homologous repair gene signature in more than 9 cancers. ESTIMATE and cytokine analyses results presented JMJD8's association with immunosuppression. Also, immune checkpoint CD276 was positively relevant to JMJD8. Subsequently, we validated JMJD8 as the M2 macrophage marker and showed its connection with other immunosuppressive cells and CD8+ T-cell depression. Finally, potential JMJD8-targeted drugs were screened out and docked to JMJD8 protein.

Conclusion: We found that JMJD8 was a novel oncogene, and it correlated with immunosuppression and DNA repair. JMJD8 was highly associated with immune checkpoint CD276 and was an M2 macrophage biomarker in many cancers. This study will reveal JMJD8's roles in pan-cancer and its potential as a novel therapeutic target.
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http://dx.doi.org/10.3389/fimmu.2022.875786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309472PMC
July 2022

Protective role of TLR9-induced macrophage/microglia phagocytosis after experimental intracerebral hemorrhage in mice.

CNS Neurosci Ther 2022 Jul 25. Epub 2022 Jul 25.

Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Introduction: Intracerebral hemorrhage (ICH) causes devastating morbidity and mortality, and studies have shown that the toxic components of hematomas play key roles in brain damage after ICH. Recent studies have found that TLR9 participates in regulating the phagocytosis of peripheral macrophages. The current study examined the role of TLR9 in macrophage/microglial (M/M) function after ICH.

Methods: RAW264.7 (macrophage), BV2 (microglia), and HT22# (neurons) cell lines were transfected with lentivirus for TLR9 overexpression. Whole blood from C57BL/6 or EGFP mice was infused for phagocytosis and injury experiments, and brusatol was used for the experiments. Intraperitoneal injection of the TLR9 agonist ODN1826 or control ODN2138 was performed on days 1, 3, 5, 7, and 28 after ICH to study the effects of TLR9 in mice. In addition, clodronate was coinjected in M/M elimination experiments. The brains were collected for histological and protein experiments at different time points after ICH induction. Cellular and histological methods were used to measure hematoma/iron residual, M/Ms variation, neural injury, and brain tissue loss. Behavioral tests were performed premodeling and on days 1, 3, 7, and 28 post-ICH.

Results: Overexpression of TLR9 facilitated M/M phagocytosis and protected neurons from blood-derived hazards in vitro. Furthermore, ODN1826 boosted M/M activation and phagocytic function, facilitated hematoma/iron resolution, reduced brain injury, and improved neurological function recovery in ICH mice, which were abolished by clodronate injection. The experimental results indicated that the Nrf2/CD204 pathway participated in TLR9-induced M/M phagocytosis after ICH.

Conclusion: Our study suggests a protective role for TLR9-enhanced M/M phagocytosis via the Nrf2/CD204 pathway after ICH. Our findings may serve as potential targets for ICH treatment.
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http://dx.doi.org/10.1111/cns.13919DOI Listing
July 2022

A Novel Thrombosis-Related Signature for Predicting Survival and Drug Compounds in Glioblastoma.

J Oncol 2022 13;2022:6792850. Epub 2022 Jul 13.

National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Glioblastoma is the most common primary tumor in the central nervous system, and thrombosis-associated genes are related to its occurrence and progression. Univariate Cox and LASSO regression analysis were utilized to develop a new prognostic signature based on thrombosis-associated genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and HALLMARK were used for functional annotation of risk signature. ESTIMATE, MCP-counter, xCell, and TIMER algorithms were used to quantify immune infiltration in the tumor microenvironment. Genomics of Drug Sensitivity in Cancer (GDSC) was used for selecting potential drug compounds. Risk signature based on thrombosis-associated genes shows moderate performance in prognosis prediction. The functional annotation of the risk signature indicates that the signaling pathways related to the cell cycle, apoptosis, tumorigenesis, and immune suppression are rich in the high-risk group. Somatic mutation analysis shows that tumor-suppressive gene and oncogene have higher expression in low-risk and high-risk groups, respectively. Potential drug compounds are explored in risk score groups and show higher AUC values in the low-risk score group. A nomogram with valuable prognostic factors exhibits high sensitivity in predicting the survival outcome of GBM patients. Our research screens out multiple thromboses-associated genes with remarkable clinical significance in GBM and further develops a meaningful prognostic risk signature predicting drug sensitivity and survival outcome.
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http://dx.doi.org/10.1155/2022/6792850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300384PMC
July 2022

Cyclovirobuxine D Ameliorates Experimental Diabetic Cardiomyopathy by Inhibiting Cardiomyocyte Pyroptosis NLRP3 and .

Front Pharmacol 2022 5;13:906548. Epub 2022 Jul 5.

The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.

Diabetic cardiomyopathy (DCM) is one of the common complications of diabetic patients, which can induce myocardial hypertrophy, cardiac fibrosis, and heart failure. Growing evidence has shown that the occurrence and development of DCM are accompanied by pyroptosis which is an NLRP3-mediated intense inflammatory cell death. Cyclovirobuxine D (CVB-D) has been shown to significantly ameliorate DCM and anti-inflammatory effects associated with cardiomyopathy, but it is unclear whether it has an effect on cardiomyocyte pyroptosis accompanying DCM. Therefore, the purpose of the present study was to explore the ameliorating effect of CVB-D on cardiomyocyte pyroptosis associated with DCM and its molecular regulation mechanism. Type 2 diabetes in C57BL/6 mice was reproduced by the high-fat and high-glucose diet (HFD) combined with low-dose streptozotocin (STZ). The characteristics of DCM were evaluated by cardiac ultrasonography, serum detection, and histopathological staining. The results suggested that CVB-D could significantly alleviate the cardiac pathology of DCM. Then, we explored the mechanism of CVB-D on primary neonatal rat cardiomyocyte (PNRCM) injury with high glucose (HG) to simulate the physiological environment of DCM. Preincubation with CVB-D could significantly increase cell viability, attenuate cytopathological changes and inhibit the expression levels of pyroptosis-related proteins. Further research found that the myocardial improvement effect of CVB-D was related to its inhibition of NLRP3 expression. In conclusion, our data suggest that CVB-D can ameliorate DCM by inhibiting cardiomyocyte pyroptosis NLRP3, providing a novel molecular target for CVB-D clinical application.
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http://dx.doi.org/10.3389/fphar.2022.906548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294384PMC
July 2022

Charge reversal hairpin peptide modified synergy therapeutic nanoplatforms for tumor specific drug shuttling.

Biomater Sci 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.

Given the distinct pathological features of neoplasm tissues, multifunctional responsive nanocarriers have been recently considered as promising candidates to optimize the chemotherapy regime. As a result, we propose a graphene oxide-based pH-responsive drug delivery system covalent assembly of "hairpin-like" cell penetrating peptides with acid sensitive and charge reversal properties to realize superior tumor specificity and lower toxicity. Graphene oxide here can serve as high doxorubicin-loading nanosheets and facilitate swift drug release in response to laser irradiation, which provides an efficient platform for the synergy of photo-chemotherapy. Structurally, polyglycol conjugation on the graphene oxide surface fulfils the function of nanocomposite stabilization. After administration, the elaborately acid sensitive cell penetrating peptides maintain the hairpin structure under physiological conditions, while after entering the tumor acidic microenvironment, they undergo charge reversal and structural conversion to promote the cellular uptake of nanoparticles. The evaluation of nanocomposites revealed their negligible systematic toxicity and remarkable antitumor effects. experiments also confirmed the impressive stability and tumor-specific targeting for alleviating breast cancer. In conclusion, hairpin peptide modified graphene oxide nanoparticles show multiple merits including high drug carrying capacity, selective tumor penetration, responsive drug release and effective combination oncotherapy.
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http://dx.doi.org/10.1039/d2bm00817cDOI Listing
July 2022

Revisit causal nexus between financial development and environmental quality in China: a structural shift panel data analysis.

Environ Sci Pollut Res Int 2022 Jul 20. Epub 2022 Jul 20.

Department of Finance, Feng Chia University, Taichung, Republic of China.

Climate change is a challenge for all of humanity. Should financial be environmentally responsible? This paper uses the Toda-Yamamoto test and the extended Fourier Toda-Yamamoto test re-examine the relationship between financial development and environmental quality in 31 provinces and municipalities in China during the period 2000-2018. We find that financial development in certain regions has effectively reduced the concentration of PM2.5, which indicates that it has a significantly positive effect on environmental quality, though with regional differences. After considering structural shifts, the relationship between financial development and environmental improvement is found to be significant in more regions, indicating that China has undergone structural shifts in these aspects. The aforementioned conclusions are also supported by further robustness tests. China can consequently utilize the positive impact of finance for advocating carbon emission reduction and improving environment quality, therefore contributing to the response to global climate change.
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http://dx.doi.org/10.1007/s11356-022-21684-yDOI Listing
July 2022

Relationship between ATOH1 and tumor microenvironment in colon adenocarcinoma patients with different microsatellite instability status.

Cancer Cell Int 2022 Jul 14;22(1):229. Epub 2022 Jul 14.

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou, 510282, Guangdong, China.

Background: Colon adenocarcinoma (COAD) is one of the major varieties of malignant tumors threatening human health today. Immune checkpoint inhibitors (ICIs) have recently begun to emerge as an effective option for the treatment of COAD patients, but not all patients can benefit from ICI treatment. Previous studies have suggested that ICIs boast significant clinical effects on patients with microsatellite instability-high (MSI-H), while conversely patients with microsatellite-stable/microsatellite instability-low (MSS/MSI-L) have shown limited response.

Methods: We used ATAC-seq, RNA-seq, and mutation data from The Cancer Genome Atlas Colon adenocarcinoma (TCGA-COAD) cohort to perform multi-omics differential analysis on COAD samples with different MSI statuses, then further screened genes by additionally combining these results with survival analysis. We analyzed the effects of the screened genes on the tumor microenvironment and immunogenicity of COAD patients, and subsequently determined their influence on the efficacy of ICIs in COAD patients using a series of predictive indexes.

Results: Twelve genes were screened in the TCGA-COAD cohort, and after the combined survival analysis, we identified ATOH1 as having significant effects. ATOH1 is characterized by high chromatin accessibility, high expression, and high mutation in COAD patients in the MSI-H group. COAD patients with high ATOH1 expression are associated with a better prognosis, unique immune microenvironment, and higher efficacy in ICI treatment. Enrichment analysis showed that COAD patients with high ATOH1 expression displayed significant upregulation in their humoral immunity and other related pathways.

Conclusions: We speculate that ATOH1 may influence the efficacy of ICIs therapy in patients with COAD by affecting the immune microenvironment and immunogenicity of the tumor.
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http://dx.doi.org/10.1186/s12935-022-02651-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281179PMC
July 2022

ALOX12: A Novel Insight in Bevacizumab Response, Immunotherapy Effect, and Prognosis of Colorectal Cancer.

Front Immunol 2022 27;13:910582. Epub 2022 Jun 27.

Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Colorectal cancer is a highly malignant cancer with poor prognosis and mortality rates. As the first biological agent approved for metastatic colorectal cancer (mCRC), bevacizumab was confirmed to exhibit good performance when combined with chemotherapy and immunotherapy. However, the efficacy of both bevacizumab and immunotherapy is highly heterogeneous across CRC patients with different stages. Thus, exploring a novel biomarker to comprehensively assess the prognosis and bevacizumab and immunotherapy response of CRC is of great significance. In our study, weighted gene co-expression network analysis (WGCNA) and the receiver operating characteristic (ROC) curves were employed to identify bevacizumab-related genes. After verification in four public cohorts and our internal cohort, ALOX12 was identified as a key gene related to bevacizumab response. Prognostic analysis and experiments further demonstrated that ALOX12 was closely associated with the prognosis, tumor proliferation, invasion, and metastasis. Multi-omics data analysis based on mutation and copy number variation (CNV) revealed that RYR3 drove the expression of ALOX12 and the deletion of 17p12 inhibited ALOX12 expression, respectively. Moreover, we interrogated the relationship between ALOX12 and immune cells and checkpoints. The results exhibited that high ALOX12 expression predicted a higher immune infiltration and better immunotherapy response, which was further validated in Tumor Immune Dysfunction and Exclusion (TIDE) and Subclass Mapping (SubMap) methods. Above all, our study provides a stable biomarker for clinical protocol optimization, prognostic assessment, precise treatment, and individualized treatment of CRC.
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http://dx.doi.org/10.3389/fimmu.2022.910582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271859PMC
July 2022

Pulsed Electromagnetic Fields Protect Against Brain Ischemia by Modulating the Astrocytic Cholinergic Anti-inflammatory Pathway.

Cell Mol Neurobiol 2022 Jul 13. Epub 2022 Jul 13.

Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, 12769 Changle Xi Road, Xi'an, 710032, China.

Neuroinflammation is one of the most important pathological processes following brain ischemia. Pulsed electromagnetic fields (PEMFs) protect against brain ischemia, but their role in regulating neuroinflammation remains unclear. In the present study, we investigated the biological effects of PEMF exposure on brain ischemia-induced neuroinflammation through the astrocytic cholinergic anti-inflammatory pathway. PEMF exposure reduced the activation of astrocytes and neuroinflammation following brain ischemia by directly modulating astrocytic injury and inflammatory cytokine release. Inhibition of nicotinic acetylcholine receptor alpha 7 subunit (α7nAChR) by a specific antagonist reversed the regulatory effects of PEMF on astrocytes. Furthermore, negative regulation of signal transducer and activator of transcription 3 (STAT3) by α7nAChR was found to be an important downstream mechanism through which PEMF regulates astrocyte-related neuroinflammation. PEMF suppressed STAT3 phosphorylation and nuclear translocation by activating α7nAChR. These results demonstrate that PEMF exerts anti-inflammatory effects in the context of brain ischemia by modulating astrocytic α7nAChR/STAT3 signaling.
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http://dx.doi.org/10.1007/s10571-022-01251-2DOI Listing
July 2022

Tc bone scintigraphy does not affect preoperative workup for patients with potentially resectable esophageal squamous cell carcinoma.

Thorac Cancer 2022 Jul 10. Epub 2022 Jul 10.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: Tc bone scintigraphy (BS) is the mainstay and most widely used technique in evaluation of bone metastasis (BM) in China. This study aimed to investigate the value of Tc BS in preoperative workup for patients with potentially resectable (cT N ) esophageal squamous cell carcinoma (ESCC).

Methods: This prospective cross-section clinical trial (ChiCTR1800020304) enrolled a total of 385 patients with ESCC diagnosed at thoracic surgery clinic from October 2018 to September 2020. All patients were diagnosed with stage cT N and were potential candidates for surgical resection. BS was performed preoperatively and the treatment strategy was changed after confirmation of BM. The primary endpoint was the rate of change of the treatment regimen because of BM, while the secondary endpoint was the rate of positive BS findings.

Results: Out of the 385 patients, only two (0.5%) changed their treatment regimen because of BM. The rate of positive BS findings was 1%, while two patients (0.5%) had false-positive or false-negative results. The BS diagnostic performance for BM was sensitivity 50%, specificity 99.5%, positive predictive value 50%, negative predictive value 99.5%, and accuracy 99.0%. There was no significant difference in BM in relation to age, sex, tumor location or clinical stage.

Conclusion: Our data demonstrated that Tc bone scintigraphy does not significantly affect the preoperative workup in patients with potentially resectable ESCC, especially in early clinical stage patients.
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http://dx.doi.org/10.1111/1759-7714.14575DOI Listing
July 2022

Application of ATAC-seq in tumor-specific T cell exhaustion.

Cancer Gene Ther 2022 Jul 6. Epub 2022 Jul 6.

Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Researches show that chronic viral infection and persistent antigen and/or inflammatory signal exposure in cancer causes the functional status of T cells to be altered, mainly by major changes in the epigenetic and metabolic environment, which then leads to T cell exhaustion. The discovery of the immune checkpoint pathway is an important milestone in understanding and reversing T cell exhaustion. Antibodies targeting these pathways have shown superior ability to reverse T cell exhaustion. However, there are still some limitations in immune checkpoint blocking therapy, such as the short-term nature of therapeutic effects and high individual heterogeneity. Assay for transposase-accessible chromatin with sequencing(ATAC-seq) is a method used to analyze the accessibility of whole-genome chromatin. It uses hyperactive Tn5 transposase to assess chromatin accessibility. Recently, a growing number of studies have reported that ATAC-seq can be used to characterize the dynamic changes of epigenetics in the process of T cell exhaustion. It has been determined that immune checkpoint blocking can only temporarily restore the function of exhausted T cells because of an irreversible change in the epigenetics of exhausted T cells. In this study, we review the latest developments, which provide a clearer molecular understanding of T cell exhaustion, reveal potential new therapeutic targets for persistent viral infection and cancer, and provide new insights for designing effective immunotherapy for treating cancer and chronic infection.
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http://dx.doi.org/10.1038/s41417-022-00495-wDOI Listing
July 2022

Reliable Semantic Communication System Enabled by Knowledge Graph.

Entropy (Basel) 2022 Jun 20;24(6). Epub 2022 Jun 20.

College of Electronic Science and Technology, National University of Defense Technology, Changsha 410073, China.

Semantic communication is a promising technology used to overcome the challenges of large bandwidth and power requirements caused by the data explosion. Semantic representation is an important issue in semantic communication. The knowledge graph, powered by deep learning, can improve the accuracy of semantic representation while removing semantic ambiguity. Therefore, we propose a semantic communication system based on the knowledge graph. Specifically, in our system, the transmitted sentences are converted into triplets by using the knowledge graph. Triplets can be viewed as basic semantic symbols for semantic extraction and restoration and can be sorted based on semantic importance. Moreover, the proposed communication system adaptively adjusts the transmitted contents according to channel quality and allocates more transmission resources to important triplets to enhance communication reliability. Simulation results show that the proposed system significantly enhances the reliability of the communication in the low signal-to-noise regime compared to the traditional schemes.
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http://dx.doi.org/10.3390/e24060846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9223175PMC
June 2022

Effects of Total Flavonoids of Epimedium on Bone Marrow Adipose Tissue in Ovariectomized Rats.

Front Endocrinol (Lausanne) 2022 6;13:900816. Epub 2022 Jun 6.

Department of Radiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Bone marrow adipose tissue has brown fat characteristics. Several studies have demonstrated that total flavonoids of Epimedium (TFE) could prevent bone loss and reduce the white adiposity in bone marrow induced by ovariectomy (OVX) in rats. However, the effects of TFE on marrow brown fat in OVX rats remain unclear. In this word, we addressed this question expected to provide a new target for preventing and treating osteoporosis. Thirty-six 3-month-old female Sprague-Dawley rats were equally divided into Sham controls, OVX controls, and OVX treated with TFE. Chemical shift coding magnetic resonance was performed to detect marrow fat fraction at the left femur at baseline, 6 and 12 weeks post-OVX. Bone mineral density at the lumbar spine and femur was measured by dual-energy x-ray absorptiometry. Serum bone biomarkers by ELISA, trabecular bone microarchitecture at the proximal tibia by micro-CT, quantitative parameters of marrow adipocyte by hematoxylin, and eosin staining were evaluated. The marrow adipocyte gene and protein expressions profile were determined by real-time quantitative PCR and immunostaining in whole tibiae. We found that TFE treatment could decrease bone turnover rate and improved bone mineral density and trabecular microarchitecture in OVX rats. OVX resulted in marrow adipogenesis as evidenced by increased marrow fat fraction, larger marrow adipocyte size, increased adipocyte number and percentage of adipocyte area, marrow white adipocyte gene, and protein expression, including PPARγ2 and FABP4. These pathological changes induced by estrogen deficiency were restored by TFE treatment. TFE also increased brown adipocyte expressions of the transcription factor Ucp1 and Prdm16 in whole tibiae. There was no detectible protein expression of brown adipocyte markers in the proximal tibia. Taken together, TFE regulation of bone marrow adiposity in OVX rats is mediated, at least in part, maintaining the reciprocity of white and brown adipose tissue.
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http://dx.doi.org/10.3389/fendo.2022.900816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207204PMC
June 2022

46,XY disorders of sex development: the use of NGS for prevalent variants.

Hum Genet 2022 Jun 21. Epub 2022 Jun 21.

Department of Andrology, First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road 2, Guangzhou, 51080, China.

46,XY disorders of sex development (DSD) present with diverse phenotypes and complicated genetic causes. Precise genetic diagnosis contributes to accurate management, and targeted next-generation sequencing (NGS) and whole-exome sequencing are powerful tools for investigating DSD. However, the prevalent variants resulting in 46,XY DSD remain unclear, especially those associated with mild forms, such as isolated hypospadias, inguinal cryptorchidism, and micropenis. From 2019 to 2021, 74 patients with 46,XY DSD (48 typical and 26 mild) from the First Affiliated Hospital of Sun Yat-sen University were enrolled in our cohort study for targeted NGS or whole-exome sequencing. Our targeted 46,XY DSD panel included 108 genes involved in disorders of gonadal development and differentiation, steroid hormone synthesis and activation, persistent Müllerian duct syndrome, idiopathic hypogonadotropic hypogonadism, syndromic disorder, and others. Variants were classified as pathogenic, likely pathogenic, variant of uncertain significance, likely benign, or benign following the American College of Medical Genetics guidelines. As a result, 28 of 74 (37.8%) patients with pathogenic and/or likely pathogenic variants acquired genetic diagnoses. The Mild DSD patients acquired a diagnosis rate of 30.7%. We detected 44 variants in 28 DSD genes from 31 patients, including 33 novel and 11 reported variants. Heterozygous (65%) and missense (70.5%) variants were the most common. Variants associated with steroid hormone synthesis and activation were the main genetic causes of 46,XY DSD. In conclusion, 46,XY DSD manifests as a series of complicated polygenetic diseases. NGS reveals prevalent variants and improves the genetic diagnoses of 46,XY DSD, regardless of severity.
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http://dx.doi.org/10.1007/s00439-022-02465-6DOI Listing
June 2022

HIF-1α-mediated augmentation of miRNA-18b-5p facilitates proliferation and metastasis in osteosarcoma through attenuation PHF2.

Sci Rep 2022 Jun 21;12(1):10398. Epub 2022 Jun 21.

Department of Orthopedics, The Fifth Hospital of Wuhan/The Second Affiliated Hospital of Jianghan University, Wuhan, 430050, China.

Extensive evidence has explored the involvement of microRNAs (miRNAs) in osteosarcoma (OS). Limitedly, the concrete function of microRNA-18b-5p (miR-18b-5p) in OS remains unexplored and largely elusive. Here, we validated that miR-18b-5p significantly elevated in OS via analyzing the data from GEO database. The results showed that miR-18b-5p was overexpressed in human OS tissues and cell lines. The clinical evidence suggested that high level of miR-18b-5p was negatively correlated with the poor prognosis of OS. Meanwhile, miR-18b-5p upregulation facilitated the proliferation and metastasis of OS cells in vitro and in vivo. The mechanism exploration demonstrated that miR-18b-5p acted as a potential inhibitor of PHF2, a tumor suppressor gene, at post-transcriptional level. Moreover, hypoxia induced gene expression of miR-18b-5p was clarified to be transcriptionally mediated by HIF-1α. The clinicopathological analysis in samples of OS patients further supported that miR-18b-5p had a positive correlation with HIF-1α expression, and negative correlation with PHF2. Collectively, the present study uncovered a new molecular mechanism of OS tumorigenesis and development and miR-18b-5p might be a prognostic biomarker and potential therapeutic target for OS treatment.
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http://dx.doi.org/10.1038/s41598-022-13660-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213540PMC
June 2022

Development of a Novel Rat Intervertebral Disc Degeneration Model by Surgical Multifidus Resection-Induced Instability.

World Neurosurg 2022 Jun 18. Epub 2022 Jun 18.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's, Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Objective: This study aimed to investigate whether surgical resection of multifidus in rats could generate a reliable model of intervertebral disc degeneration (IVDD).

Methods: Instability of the lumbar spine in Sprague-Dawley rats was induced by multifidus resection. Longissimus changes were examined by hematoxylin and eosin staining and immunohistochemistry. Specific protein and mRNA changes in the nucleus pulposus (NP) were quantified by Western blot and reverse transcription-polymerase chain reaction. Bone alterations were assessed using X-ray imaging, and disc changes were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry.

Results: Fat infiltration and increased tumor necrosis factor-α expression in the longissimus were detected following surgery. Reverse transcription-polymerase chain reaction and Western blot results demonstrated that the inflammation and catabolism in the NP were increased after the surgical intervention. Moreover, X-ray imaging showed that the disc height had decreased and bone spurs had formed at the vertebral rims. Histological analyses further revealed degeneration of the annulus fibrosus, endplate, and NP. Furthermore, in contrast to the sham group, the collagen II expression was reduced, while matrix metalloproteinase-13 was increased in the surgery group.

Conclusions: Surgical resection of the multifidus in rats resulted in a reproducible IVDD model. Because the present procedure does not impart direct injury to the intervertebral disc, it can better imitate the pathological states in humans. Therefore, our rat multifidus resection model might help us further understand the intrinsic pathophysiology of IVDD.
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http://dx.doi.org/10.1016/j.wneu.2022.06.051DOI Listing
June 2022

Corrigendum: Antigen Presentation Machinery Signature-Derived CALR Mediates Migration, Polarization of Macrophages in Glioma and Predicts Immunotherapy Response.

Front Immunol 2022 2;13:931433. Epub 2022 Jun 2.

Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.

[This corrects the article DOI: 10.3389/fimmu.2022.833792.].
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http://dx.doi.org/10.3389/fimmu.2022.931433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202315PMC
June 2022

NRBF2 regulates the chemoresistance of small cell lung cancer by interacting with the P62 protein in the autophagy process.

iScience 2022 Jun 26;25(6):104471. Epub 2022 May 26.

Department of Oncology, Zhujiang Hospital, Southern Medical University, 253 Industrial Avenue, Guangzhou 510282, Guangdong, People's Republic of China.

Reversing chemotherapy resistance in small cell lung cancer (SCLC) is crucial to improve patient prognosis. The present study aims to investigate the underlying mechanisms in SCLC chemoresistance. We see that nuclear receptor binding factor 2 (NRBF2) is a poor prognostic factor in SCLC. The effects of NRBF2 on chemoresistance were determined in SCLC. The underlying molecular mechanisms of NRBF2 in the autophagy process in SCLC were examined. NRBF2 positively regulated autophagy, leading to drug resistance in SCLC. The MIT domain of NRBF2 directly interacted with the PB1 domain of P62. This interaction increased autophagic P62 body formation, revealing the regulatory role of NRBF2 in autophagy. Notably, NRBF2 was directly modulated by the transcription factor XRCC6. The MIT domain of NRBF2 interacts with the PB1 domain of P62 to regulate the autophagy process, resulting in SCLC chemoresistance. NRBF2 is likely a useful chemotherapy response marker and therapeutic target in SCLC.
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http://dx.doi.org/10.1016/j.isci.2022.104471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194155PMC
June 2022

Comprehensive Analysis Identifies PI3K/Akt Pathway Alternations as an Immune-Related Prognostic Biomarker in Colon Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitor Treatment.

J Immunol Res 2022 6;2022:8179799. Epub 2022 Jun 6.

Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

Introduction: In recent years, immune checkpoint inhibitors (ICIs) have attracted widespread attention and made breakthroughs in progress towards the treatment of various cancers. However, ICI therapy is selective, and its effects on many patients are not ideal. It is therefore critical to identify prognostic biomarkers of response to ICI therapy. The PI3K/Akt pathway plays important roles in tumor formation and metastasis. However, there are no published reports clarifying the relationship between PI3K/Akt pathway mutations and prognosis for colon adenocarcinoma (COAD) patients receiving immunotherapy.

Methods: We collected data from a COAD cohort from The Cancer Genome Atlas (TCGA) database, including whole-exome sequencing (WES) data, RNA-seq data, and clinical data. We also collected data, including clinical prognosis and targeted sequencing data, from a cohort of COAD patients receiving immunotherapy. We collected 50 COAD patients (Local-COAD) from the Zhujiang Hospital of Southern Medical University and performed targeted sequencing. We analyzed the effects of PI3K/Akt pathway mutations on the patients' clinical prognosis, immunogenicity, and immune microenvironments. Gene set enrichment analysis (GSEA) was used to analyze the significantly upregulated and downregulated signaling pathways. We used these results to hypothesize potential mechanisms by which PI3K/Akt mutations could affect the prognosis of COAD patients.

Results: Univariate and multivariate Cox analyses and Kaplan-Meier (KM) survival curves showed that patients with PI3K-Akt mutations had better overall survival (OS) than those without PI3K-Akt mutations. Genes with significant mutation rates in the two cohorts were screened by panoramic view. CIBERSORT was used to analyze changes in 22 types of immune cells to identify immune activated cells. Similarly, patients in the PI3K/Akt-mutated type (PI3K/Akt-MT) group had significantly increased immunogenicity, including increases in tumor mutation burden (TMB), neoantigen load (NAL), and MANTIS score. Using GSEA, we identified upregulated pathways related to immune response.

Conclusion: PI3K/Akt pathway mutation status can be used as an independent predictor of response to ICI treatment in COAD patients. PI3K/Akt mutations are correlated with improved OS, higher immunogenicity, greater immune response scores, and increases in activated immune cells.
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http://dx.doi.org/10.1155/2022/8179799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9192307PMC
June 2022

Hypomethylation status of miR-657 promoter region as biomarker for diagnosis of hepatocellular carcinoma: a retrospective study.

Transl Cancer Res 2022 May;11(5):1112-1121

Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Background: The purpose of our study was to evaluate whether the methylation status of the miR-657 promoter region could be used as a biomarker for diagnosis of hepatocellular carcinoma (HCC), so as to find alternative biomarkers of early HCC detection.

Methods: Cancerous and paired adjacent noncancerous tissues were collected from 160 patients who had been diagnosed with HCC by histopathology and received surgery. The methylation status of the miR-657 promoter region was measured using a MassARRAY Analyzer 4. Receiver operator characteristic (ROC) curve analysis was used to assess the effectiveness of miR-657 promoter region methylation status as a biomarker for diagnosis of HCC.

Results: The mean methylation level of the miR-657 promoter region was significantly lower in cancerous tissues than in normal tissues of HCC patients (48.91%:67.04%, P<0.0001). ROC curve analysis revealed that the mean methylation level of the miR-657 promoter region could distinguish cancerous tissues from paired normal tissues of HCC patients (area under the curve: 0.847, P<0.001). Using 59.50% as the optimal cut-off, the sensitivity was 95.50% and the specificity was 70.01%.

Conclusions: Methylation levels of the miR-657 promoter region were decreased in HCC patients and could be used as alternative and supplementary biomarkers for diagnosis of HCC.
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http://dx.doi.org/10.21037/tcr-21-2621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189178PMC
May 2022

Effect of ball milling-assisted glycosylation modification on the structure and foaming property of egg white protein.

J Food Sci 2022 Jul 15;87(7):3117-3128. Epub 2022 Jun 15.

School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China.

The effect of different glycosylation degrees on molecular structure and foaming property of egg white protein (EWP) was investigated using ball milling-assisted glycosylation. The results showed the foaming ability (FA) and foam stability (FS) of EWP improved when the degree of glycosylation was increased. In particular, FA of ball milling-assisted glycosylation of EWP enhanced by 39.9% and 28.8%, and the FS increased by 28.7% and 24.0% compared with EWP and ball milling egg white protein (BE) at 150 min of reaction. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis could reflect the grafting degree of EWP and glucose molecules from the side. When EWP was fully grafted with glucose, endogenous fluorescence and free sulfhydryl groups indicated that tertiary structure of EWP was depolymerized, and Fourier transform infrared spectroscopy showed the secondary structure tended to change from order to disorder. The results of this study indicated that ball milling-assisted glycosylation modification was a practical method to improve the foaming property of EWP. PRACTICAL APPLICATION: EWP has great FA and FS, making it indispensable in the baking industry. In this study, ball milling-assisted glycosylation was used to improve the foaming property of EWP, and the molecular structure of EWP with different degrees of glycosylation was fully resolved. The results demonstrated that ball milling, as a physical pretreatment, can fully unfold the structure of EWP. When sugar molecules were fully grafted, the particle size of EWP reduced, solubility increased, and the stability of system improved, thus enhancing the foaming property of EWP. The results can provide theoretical basis for improving the foaming property of EWP and provide a reference value for its industrial application.
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http://dx.doi.org/10.1111/1750-3841.16218DOI Listing
July 2022

THSD7B Mutation Induces Platinum Resistance in Small Cell Lung Cancer Patients.

Drug Des Devel Ther 2022 3;16:1679-1695. Epub 2022 Jun 3.

Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People's Republic of China.

Aim: Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial to the improvement of the overall survival (OS) of SCLC patients to discover the gene mutation inducing platinum resistance within this cohort.

Patients And Methods: We analyzed the gene mutations significantly associated with the OS from 2 cohorts of SCLC platinum-treated patients. And then we screened out THSD7B mutation. In order to understand the mechanism between THSD7B mutation and platinum resistance, we designed gene mutation co-occurrence and mutual exclusivity analysis, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and Connectivity Map (CMap) analysis.

Results: The poor prognosis of THSD7B mutant patients may be related to the inhibition of cell death-related pathways, the up-regulation of cell invasion and metastasis pathways, and the down-regulation of immune response pathways. Lovastatin and cyclooxygenase inhibitors could be used as potential target compounds in THSD7B mutant patients, which provides reference for future research on platinum resistance.

Conclusion: THSD7B can be considered a reliable biomarker that effectively facilitates the prediction of poor survival in SCLC platinum-treated patients.
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http://dx.doi.org/10.2147/DDDT.S363665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172928PMC
June 2022

Analysis of Complete Mitochondrial Genome of (Jaeger, 1833) (Aspidochirotida, Holothuriidae).

Animals (Basel) 2022 Jun 2;12(11). Epub 2022 Jun 2.

CAS Key Laboratory of Tropical Marine Bioresources and Ecology (LMB), South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.

is a kind of sea cucumber with high economic value; it is the only undisputed species in the genus . In this study, the complete mitochondrial genome (mitogenome) of was acquired through high-throughput sequencing. The mitochondrial genome of was 15,656 bp in total length and contained a putative control region (CR) and 37 typical genes of animal mitochondrial genomes, including 13 protein-coding genes (PCGs), 2 ribosomal RNA genes ( and ) and 22 transfer RNA genes (tRNA). The sizes of the PCGs ranged from 168 bp to 1833 bp, and all PCGs except were encoded on the heavy chain (H). Both and were also encoded on the H chain. Twenty-two tRNA genes had positive AT skew and GC skew. All tRNAs had a typical cloverleaf secondary structure except for , in which an arm of dihydrouridine was missing. shared the same gene arrangement order (the echinoderm ground pattern) as other species in Aspidochirotida. Phylogenetic analysis clearly revealed that belongs as a member of the Holothuriidae, and it is closely related to members of and .
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http://dx.doi.org/10.3390/ani12111437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179316PMC
June 2022

Genomic and Transcriptomic Analysis of Neuroendocrine Transformation in -Rearranged Lung Adenocarcinoma After Treatments With Sequential ALK Inhibitors: A Brief Report.

JTO Clin Res Rep 2022 Jun 11;3(6):100338. Epub 2022 May 11.

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People's Republic of China.

Introduction: Neuroendocrine (NE) transformation has been reported in patients with -rearranged NSCLC after ALK inhibition, but unlike -mutant NSCLC, the exact mechanism of NE transformation in -rearranged NSCLC is poorly studied.

Methods: We collected the matched pre- and post-transformation samples from a patient with -rearranged lung adenocarcinoma (LUAD) and performed targeted panel sequencing, whole exome sequencing, and bulk RNA sequencing.

Results: Multiple mutations were shared between the pretransformation and post-transformation samples. Neither nor mutation was detected, but deletion and amplification were found instead. Mismatch repair-associated mutational signature was significantly enriched after transformation. Genes associated with Notch signaling and PI3K/AKT pathway were significantly up-regulated, whereas genes related to lymphocyte activation and NF-kB signaling were down-regulated. Signatures relating to homologous recombination, mismatch repair, and Notch signaling pathways were enriched, which were further validated in The Cancer Genome Atlas cohorts. Macrophages M2 were found to have prominently higher abundance in the tumor immune microenvironment after NE transformation.

Conclusions: The mechanism of NE transformation in -rearranged LUAD may be different from that in -mutant LUAD.
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http://dx.doi.org/10.1016/j.jtocrr.2022.100338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168149PMC
June 2022

Fermented Tratt Juice Alleviates High-Fat Diet-Induced Hyperlipidemia in Rats by Modulating Gut Microbiota and Metabolites.

Front Pharmacol 2022 20;13:883629. Epub 2022 May 20.

State Key Laboratory of Functions and Applications of Medicinal Plants & School of Pharmacy, Guizhou Medical University, Guiyang, China.

Hyperlipidemia endangers human health and has become a significant public health problem. This study aimed to investigate the mechanism of the hypolipidemic effects of Fermented Tratt juice (FRRT) on hyperlipidemic rats and a new hypolipidemic intervention strategy was disclosed. The study revealed 12 weeks FRRT treatment significantly decreased the body weight, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c), while high-density lipoprotein cholesterol (HDL-c) increased. We integrated the 16S rDNA sequencing and metabolomic profiling to evaluate the changes in the gut microbiota and metabolites. Significant changes in microbial composition accompanied marked changes in 56 feces metabolites. The results showed that FRRT could decrease the ratio of to , while increase the abundance of some bacterial genera (, , , ). Metabolomics analysis displayed that the metabolisms of bile acid, amino acid and lipid were significantly affected by FRRT. Correlation analysis suggest that the reductions in serum lipids by FRRT are associated with the gut microbial community and their associated metabolites (amino acid metabolites, bile acid metabolites, and lipid metabolites). This study confirmed FRRT could be used as a new dietary and therapeutic strategy to dyslipidemia by improving the gut microbiota dysbiosis, metabolomic disorders and regulating the dyslipidemia. Our study also extended the understanding of the relationship between gut microbiota, metabolites, and lipid-lowering functions.
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http://dx.doi.org/10.3389/fphar.2022.883629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164371PMC
May 2022

Investigating the interaction between Shewanella oneidensis and phenazine 1-carboxylic acid in the microbial electrochemical processes.

Sci Total Environ 2022 Sep 3;838(Pt 3):156501. Epub 2022 Jun 3.

School of Resources & Environment, Southwest University, Chongqing 400716, PR China. Electronic address:

Many exoelectrogens utilize small redox mediators for extracellular electron transfer (EET). Notable examples include Shewanella species, which synthesize flavins, and Pseudomonas species, which produce phenazines. In natural and engineered environments, redox-active metabolites from different organisms coexist. The interaction between Shewanella oneidensis and phenazine 1-carboxylic acid (PCA, a representative phenazine compound) was investigated to demonstrate exoelectrogens utilizing metabolites secreted by other organisms as redox mediators. After 24 h in a reactor with and without added PCA (1 μM), the anodic current generated by Shewanella was 235 ± 11 and 51.7 ± 2.8 μA, respectively. Shewanella produced oxidative current approximately three times as high with medium containing PCA as with medium containing the same concentration of riboflavin. PCA also stimulated inward EET in Shewanella. The strong effect of PCA on EET was attributed to its enrichment at the biofilm/electrode interface. The PCA voltammetric peak heights with a Shewanella bioanode were 25-30 times higher than under abiotic conditions. The electrochemical properties of PCA were also altered by the transition from two-electron to single-electron electrochemistry, which suggests PCA was bound between the electrode and cell surface redox proteins. This behavior would benefit electroactive bacteria, which usually dwell in open systems where mediators are present in low concentrations. Like flavins, PCA can be immobilized under both bioanode and biocathode conditions but not under metabolically inactive conditions. Shewanella rapidly transfers electrons to PCA via its Mtr pathway. Compared with wild-type Shewanella, the PCA reduction ability was decreased in gene knockout mutants lacking Mtr pathway cytochromes, especially in the mutants with severely undermined electrode-reduction capacities. These strains also lost the ability to immobilize PCA, even under current-generating conditions.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156501DOI Listing
September 2022
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