Publications by authors named "Hao Zhao"

239 Publications

A Robust Seven-Gene Signature Associated With Tumor Microenvironment to Predict Survival Outcomes of Patients With Stage III-IV Lung Adenocarcinoma.

Front Genet 2021 6;12:684281. Epub 2021 Sep 6.

Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, China.

Background: Due to the relatively insidious early symptoms of lung adenocarcinoma (LUAD), most LUAD patients are at an advanced stage at the time of diagnosis and lose the best chance of surgical resection. Mounting evidence suggested that the tumor microenvironment (TME) was highly correlated with tumor occurrence, progress, and prognosis. However, TME in advanced LUAD remained to be studied and reliable prognostic signatures based on TME in advanced LUAD also had not been well-established. This study aimed to understand the cell composition and function of TME and construct a gene signature associated with TME in advanced LUAD.

Methods: The immune, stromal, and ESTIMATE scores of each sample from The Cancer Genome Atlas (TCGA) database were, respectively, calculated using an ESTIMATE algorithm. The LASSO and Cox regression model were applied to select prognostic genes and to construct a gene signature associated with TME. Two independent datasets from the Gene Expression Omnibus (GEO) were used for external validation. Twenty-two subsets of tumor-infiltrating immune cells (Tiics) were analyzed using the CIBERSORT algorithm.

Results: Favorable overall survival (OS) and progression-free survival (PFS) were found in patients with high immune score ( = 0.048 and = 0.028; respectively) and stromal score ( = 0.024 and = 0.025; respectively). Based on the immune and stromal scores, 453 differentially expressed genes (DEGs) were identified. Using the LASSO and Cox regression model, a seven-gene signature containing AFAP1L2, CAMK1D, LOXL2, PIK3CG, PLEKHG1, RARRES2, and SPP1 was identified to construct a risk stratification model. The OS and PFS of the high-risk group were significantly worse than that of the low-risk group ( < 0.001 and < 0.001; respectively). The receiver operating characteristic (ROC) curve analysis confirmed the good potency of the seven-gene signature. Similar findings were validated in two independent cohorts. In addition, the proportion of macrophages M2 and Tregs was higher in high-risk patients ( = 0.041 and = 0.022, respectively).

Conclusion: Our study established and validated a seven-gene signature associated with TME, which might serve as a prognosis stratification tool to predict survival outcomes of advanced LUAD patients. In addition, macrophages M2 polarization may lead to worse prognosis in patients with advanced LUAD.
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http://dx.doi.org/10.3389/fgene.2021.684281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450538PMC
September 2021

Engineering DNA/Fe-N-C single-atom nanozymes interface for colorimetric biosensing of cancer cells.

Anal Chim Acta 2021 Oct 16;1180:338856. Epub 2021 Jul 16.

School of Materials Science and Engineering, Hefei University of Technology, Hefei, 230009, China. Electronic address:

Single atom nanozymes (SAzymes) represent the state-of-the-art technology in nanomaterial-based catalysis, which have attracted attentions in catalysis, cancer treatment, disinfection and biosensing fields. However, numerous SAzymes suffered from low aqueous dispersion and without recognition capacity, which impeded their applications in bioanalysis. Herein, we engineered DNA onto SAzymes to obtain the DNA/SAzymes conjugates, which significantly improved the aqueous dispersion and recognition ability of SAzymes. We synthesized iron SAzymes (Fe-N-C SAzymes) as the catalytic nanomaterials, and investigated the interactions between Fe-N-C SAzymes and DNA. We compared A, T and C adsorption of Fe-N-C SAzymes in HEPES containing 2 mM MgCl. We found that 50 μg mL Fe-N-C SAzymes produced nearly 100% A adsorption, 90% T adsorption and only 69% C adsorption, indicating that adenine and thymine had higher adsorption affinity on Fe-N-C SAzymes. More importantly, DNA modification did not affect the peroxidase-like activity of Fe-N-C SAzymes and the bioactivity of the adsorbed DNA. Taking the advantage of the diblock DNA with one DNA sequence (adenine) binding to Fe-N-C SAzymes and the other DNA sequence (i.e., aptamer) binding to cancer cells, we designed Apt/Fe-N-C SAzymes for colorimetric detection of cancer cells, which offered new insights for the use of SAzymes in biomedicine.
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http://dx.doi.org/10.1016/j.aca.2021.338856DOI Listing
October 2021

Treatment and outcomes of POEMS syndrome: changes in the past 20 years.

Blood Cancer J 2021 Aug 14;11(8):145. Epub 2021 Aug 14.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1038/s41408-021-00540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364551PMC
August 2021

Biliary Neuroendocrine Neoplasms: Analysis of Prognostic Factors and Development and Validation of a Nomogram.

Front Oncol 2021 19;11:654439. Epub 2021 Jul 19.

General Surgery Department, Peking Union Medical College Hospital, China Academy of Medical Science & Peking Union Medical College, Beijing, China.

Background: For this study, we explored the prognostic profiles of biliary neuroendocrine neoplasms (NENs) patients and identified factors related to prognosis. Further, we developed and validated an effective nomogram to predict the overall survival (OS) of individual patients with biliary NENs.

Methods: We included a total of 446 biliary NENs patients from the SEER database. We used Kaplan-Meier curves to determine survival time. We employed univariate and multivariate Cox analyses to estimate hazard ratios to identify prognostic factors. We constructed a predictive nomogram based on the results of the multivariate analyses. In addition, we included 28 biliary NENs cases from our center as an external validation cohort.

Results: The median survival time of biliary NENs from the SEER database was 31 months, and the value of gallbladder NENs (23 months) was significantly shorter than that of the bile duct (45 months) and ampulla of Vater (33.5 months, p=0.023). Multivariate Cox analyses indicated that age, tumor size, pathological classification, SEER stage, and surgery were independent variables associated with survival. The constructed prognostic nomogram demonstrated good calibration and discrimination C-index values of 0.783 and 0.795 in the training and validation dataset, respectively.

Conclusion: Age, tumor size, pathological classification, SEER stage, and surgery were predictors for the survival of biliary NENs. We developed a nomogram that could determine the 3-year and 5-year OS rates. Through validation of our central database, the novel nomogram is a useful tool for clinicians in estimating individual survival among biliary NENs patients.
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http://dx.doi.org/10.3389/fonc.2021.654439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327779PMC
July 2021

Stimuli-responsive Ca-alginate-based photothermal system with enhanced foliar adhesion for controlled pesticide release.

Colloids Surf B Biointerfaces 2021 Jul 27;207:112004. Epub 2021 Jul 27.

Key Laboratory of Tibetan Medicine Research, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining, 810008, PR China.

For minimizing volatilization and leaching of pesticides, and enhancing their residence time on crop surfaces, we synthesized and characterized a novel intelligent pesticide delivery system. Therein, imidacloprid (IMI) was adsorbed by polydopamine modified kaolin (PK) with high adsorption property through hydrogen bonds. Ca-alginate was used as a structural matrix of the system and a protective shell to hinder the pesticide burst release from PK, and endowed the system with unique pH-sensitive property for IMI release. The amino silicone oil (ASO) coating could bind with the waxy layer of crop leaves by the theory of "similarity-intermiscibility", which increased the adhesion of composite on crop leaves. Moreover, by the excellent light-sensitive property of detonation nanodiamond (DND) and temperature-responsive performance of poly(N-isopropylacrylamide) (PNIPAm), the release of IMI from the functional system could be adjusted by sunlight. Besides, the composite displayed high control efficacy. This novel composite can promote the targeting ability and utilization efficiency of pesticides, thus having a huge potential application prospect in agriculture.
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http://dx.doi.org/10.1016/j.colsurfb.2021.112004DOI Listing
July 2021

Bortezomib plus dexamethasone as first-line therapy for patients with POEMS syndrome.

Ann Hematol 2021 Jul 31. Epub 2021 Jul 31.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell dyscrasia without standard front-line treatment. Merely, few studies have reported the responses and outcomes of bortezomib plus dexamethasone (BDex) in POEMS syndrome. In this study, a total of 69 patients (40 males) treated with front-line BDex were included. The median age at diagnosis was 50 years (range, 30-78 years). After a median of 9 cycles BDex (range 1-9), fifty-two (88.1%), thirty-two (46.4%), and forty-seven (71.2%) patients achieved the best neurologic response, hematological complete response, and serum vascular endothelial growth factor (VEGF) response, respectively. The extravascular overload, pulmonary hypertension, and renal impairment also substantially improved. No treatment-related death occurred. Two patients developed grade-1 bortezomib-induced peripheral neuropathy and were reversible after drug withdrawal. After a median follow-up of 22.5 months, the estimated 2-year overall survival and time to next treatment were 95.7% and 65.6%, respectively. In conclusion, the combination of bortezomib and dexamethasone is effective, with a high response rate and safety profile for patients with newly diagnosed POEMS syndrome.
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http://dx.doi.org/10.1007/s00277-021-04609-6DOI Listing
July 2021

Pollutant-removal and DOM characteristics in an urban stormwater wetland.

Environ Technol 2021 Aug 9:1-12. Epub 2021 Aug 9.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, People's Republic of China.

Stormwater wetlands play a crucial role in the urban environment, providing many ecosystem services. In this work, a stormwater wetland was developed to study the effects on the removal of pollutants and the characteristics of dissolved organic matter (DOM) under different operating conditions, such as hydraulic retention time (HRT) and water depth. The results showed that the stormwater wetland exhibited excellent pollutant-removal performance, such as NHN, TN, TP, COD, and suspended solids (SS). The removal rates for these substances reached 79.1%, 73.2%, 89.0%, 84.3%, 80.4%, and 73.77, respectively, with 24 h of HRT and 15 cm of water depth. An increase in HRT can improve the removal rates of TN, TP, COD, and TOC. The removal rates for these parameters decreased with increasing water depth, though, except for TP; the UV-VIS spectral parameters indicated that an obvious decrease occurred in the degrees of humification and aromaticity of DOM with increasing HRT and water depth after the stormwater wetland treatment. Parallel factor (PARAFAC) analysis identified six fluorescent components (one combination of freshly produced biologically labile matter and a tryptophan-like component, one fulvic-like, one humic-like, and three tryptophan-like), whose fluorescence intensity was weakened after the stormwater wetland treatment. The lowest intensity appeared with 24 h of HRT and 15 cm of water depth. This study could be beneficial for understanding and managing stormwater wetlands, thus alleviating the impacts of pollutants on urban environments.
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http://dx.doi.org/10.1080/09593330.2021.1962413DOI Listing
August 2021

Near-Infrared-Light Remote-Controlled Activation of Cancer Immunotherapy Using Photothermal Conjugated Polymer Nanoparticles.

Adv Mater 2021 Aug 18;33(34):e2102570. Epub 2021 Jul 18.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Remote control of the therapeutic process is an ideal strategy for maximizing efficacy and avoiding side effects, especially for cancer immunotherapy. Herein, a conjugated polymer nanoparticles (CPNs)-mediated optogenetic system for in situ activation of immunotherapy under near-infrared laser irradiation is reported. This system is composed of photothermal CPNs and interferon-gamma (IFN-γ) plasmid driven by heat shock promoter HSP70. The photothermally responsive CPNs serve as a photo-heat nanotransducer to trigger the gene transcription of IFN-γ cytokine. The secreted IFN-γ from cancer cells can sufficiently elicit surrounding tumor-associated macrophages activation through IFN-γ-JAK-STAT1 transcription-factor signaling pathway and finally induce cancer cell killing by immunotherapy. Therefore, this synergetic optogenetic system provides a promising approach to remotely control the process of cancer immunotherapy.
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http://dx.doi.org/10.1002/adma.202102570DOI Listing
August 2021

A Data-Driven Scheme for Fault Detection of Discrete-Time Switched Systems.

Sensors (Basel) 2021 Jun 16;21(12). Epub 2021 Jun 16.

School of Electronics and Information, Jiangsu University of Science and Technology, Zhenjiang 212003, China.

This paper is concerned with the fault detection issue for a class of discrete-time switched systems via the data-driven approach. For the fault detection of switched systems, it is inevitable to consider the mode matching problem between the activated subsystem and the executed residual generator since the mode mismatching may cause a false fault alarm in all probability. Frequently, studies assume that the switching laws are available to the residual generator, by which the residual generator keeps the same mode as the system plant and then the mode mismatching is excluded. However, this assumption is conservative and impractical because many switching laws are hard to acquire in practical applications. This work focuses on the case of switched systems with unavailable switching laws. In view of the unavailability of switching information, the mode recognition is considered for the fault detection process and meanwhile, sufficient conditions are presented for the mode distinguishability. Moreover, a novel decision logic for the fault detection is proposed, based on which new algorithms are established for the data-driven realization. Finally, a benchmark case on a three-tank system is used to illustrate the feasibility and usefulness of the obtained results.
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http://dx.doi.org/10.3390/s21124138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235235PMC
June 2021

Polymer nanoparticles regulate macrophage repolarization for antitumor treatment.

Chem Commun (Camb) 2021 Jul 22;57(56):6919-6922. Epub 2021 Jun 22.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China. and College of Chemistry, University of Chinese Academy of Sciences, Beijing 100049, P. R. China.

We demonstrate an intrinsic antitumor effect of polymer nanoparticles (P-NPs), which could re-program tumor-associated macrophages to pro-inflammatory phenotype. The intrinsic effect of P-NPs on macrophage repolarization and its combination with other therapies provide new ideas for drug delivery, macrophage regulation and immunotherapy in cancer treatment.
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http://dx.doi.org/10.1039/d1cc02678jDOI Listing
July 2021

Integrated bioinformatics analysis revealed the regulation of angiogenesis by tumor cells in hepatocellular carcinoma.

Biosci Rep 2021 Jul;41(7)

Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, metastasis accounts for most of the cases. Angiogenesis plays an important role in cancer metastasis, but how tumor cells affect the function of endothelial cells by dictating their microRNA (miRNA) expression remains largely unknown. Differentially expressed miRNAs (DEMs) were identified through dataset downloaded from the Gene Expression Omnibus (GEO) database and analyzed by GEO2R. We then used online tools to obtain potential targets of candidate miRNAs and functional enrichment analysis, as well as the protein-protein interaction (PPI). Finally, the function of miR-302c-3p was validated through in vitro assay. In the current study, we found that HCC cells altered miRNA expression profiles of human umbilical vein endothelial cells (HUVECs) and miR-302c-3p was the most down-regulated miRNA in HUVECs when they were co-cultured with HCC-LM3 cells. Functional enrichment analysis of the candidate targets revealed that these genes were involved in epigenetic regulation of gene expression, in particular, cytosine methylation. In addition, PPI network demonstrated distinct roles of genes targeted by miR-302c-3p. Importantly, inhibition of angiogenesis, migration and permeability by the most down-regulated miR-302c-3p in HUVECs was confirmed in vitro. These findings brought us novel insight into the regulation of angiogenesis by HCC cells and provided potential targets for the development of therapeutic strategies.
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http://dx.doi.org/10.1042/BSR20210126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252189PMC
July 2021

TLR4 signalling via Piezo1 engages and enhances the macrophage mediated host response during bacterial infection.

Nat Commun 2021 06 10;12(1):3519. Epub 2021 Jun 10.

State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

TLR4 signaling plays key roles in the innate immune response to microbial infection. Innate immune cells encounter different mechanical cues in both health and disease to adapt their behaviors. However, the impact of mechanical sensing signals on TLR4 signal-mediated innate immune response remains unclear. Here we show that TLR4 signalling augments macrophage bactericidal activity through the mechanical sensor Piezo1. Bacterial infection or LPS stimulation triggers assembly of the complex of Piezo1 and TLR4 to remodel F-actin organization and augment phagocytosis, mitochondrion-phagosomal ROS production and bacterial clearance and genetic deficiency of Piezo1 results in abrogation of these responses. Mechanistically, LPS stimulates TLR4 to induce Piezo1-mediated calcium influx and consequently activates CaMKII-Mst1/2-Rac axis for pathogen ingestion and killing. Inhibition of CaMKII or knockout of either Mst1/2 or Rac1 results in reduced macrophage bactericidal activity, phenocopying the Piezo1 deficiency. Thus, we conclude that TLR4 drives the innate immune response via Piezo1 providing critical insight for understanding macrophage mechanophysiology and the host response.
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http://dx.doi.org/10.1038/s41467-021-23683-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192512PMC
June 2021

Relationship between multimorbidity, disease cluster and all-cause mortality among older adults: a retrospective cohort analysis.

BMC Public Health 2021 06 5;21(1):1080. Epub 2021 Jun 5.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan, 450001, People's Republic of China.

Background: Previous studies have evaluated the association of multimorbidity with higher mortality, but epidemiologic data on the association between the disease clusters and all-cause mortality risk are rare. We aimed to examine the relationship between multimorbidity (number/ cluster) and all-cause mortality in Chinese older adults.

Methods: We conducted a population-based study of 50,100 Chinese participants. Multiple logistic regression analysis was used to estimate the impact of long-term conditions (LTCs) on all-cause mortality.

Results: The prevalence of multimorbidity was 31.35% and all-cause mortality was 8.01% (50,100 participants). In adjusted models, the odds ratios (ORs) and 95% confidence intervals (CIs) of all-cause mortality risk for those with 1, 2, and ≥ 3 LTCs compared with those with no LTCs was 1.45 (1.32-1.59), 1.72 (1.55-1.90), and 2.15 (1.85-2.50), respectively (P < 0.001). In the LTCs ≥2 category, the cluster of chronic diseases that included hypertension, diabetes, CHD, COPD, and stroke had the greatest impact on mortality. In the stratified model by age and sex, absolute all-cause mortality was higher among the ≥75 age group with an increasing number of LTCs. However, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those < 75 years.

Conclusions: The risk of all-cause mortality is increased with the number of multimorbidity among Chinese older adults, particularly disease clusters.
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http://dx.doi.org/10.1186/s12889-021-11108-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180153PMC
June 2021

Supramolecular Regulation of Catalytic Activity for an Amphiphilic Pyrene-Ruthenium Complex in Water.

Chemistry 2021 Aug 1;27(45):11567-11573. Epub 2021 Jul 1.

Key Laboratory of Organic Solids, Beijing National Laboratory for Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

A switchable catalytic system has been designed and constructed with a host-guest interaction between cucurbituril (CB) and an amphiphilic metal complex pyrene-ruthenium (Py-Ru). Py-Ru can self-assemble into positively charged nanoparticles in water, and exhibits an enhanced catalytic efficiency in the transfer hydrogenation of NAD to NADH. After forming an inclusion complex with CB, Py-Ru aggregates are broken, leading to a decrease in catalytic efficiency, which can be recovered by competitive replacement with amantadine. This supramolecular strategy provides an efficient and flexible method for constructing reversible catalytic system, which also extends the application scope of the host-guest interaction.
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http://dx.doi.org/10.1002/chem.202101668DOI Listing
August 2021

3D Bioprinting of Polythiophene Materials for Promoting Stem Cell Proliferation in a Nutritionally Deficient Environment.

ACS Appl Mater Interfaces 2021 Jun 26;13(22):25759-25770. Epub 2021 May 26.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, P. R. China.

3D printing of stem cells provides a tremendous opportunity to tissue engineering in regenerative medicine. However, developing new bioactive materials to rationally augment stem cell viability is still an enormous challenge owing to the nutritionally deficient environment caused by the limited-penetration distance of nutrition when cells are encapsulated within biomaterials. In this work, a cationic conjugated polythiophene derivative, poly[3-(3'-,,-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrochloride] (PMNT), is designed and integrated into an anionic gelatin/alginate matrix to develop a new 3D bioprintable conjugated polymer ink Gel/Alg/PMNT, while the electrostatic interaction can assist PMNT to anchor inside ink without severe diffusional loss. In principle, PMNT is confirmed to promote human umbilical cord-derived mesenchymal stem cell (hMSC) proliferation in a serum-free medium by driving cell cycles and up-regulating gene expression in the pathways of biosynthesis and the metabolism. By employing the 3D bioprinting strategy together with hMSCs, the accelerated healing of full-thickness excisional wounds is further realized through the augmented-stem cell therapeutics utilizing Gel/Alg/PMNT ink, in which hMSC proliferation can be effectively promoted upon inductive stimulation of PMNT. The inherent highly bioactive and robust proliferation-promoted nature of the developed conjugated polymer ink Gel/Alg/PMNT significantly overcomes the nutritionally deficient environment, especially in 3D-printed large-scale architectures. The bioactive polythiophene material exhibits a unique capacity to promote stem cell proliferation without the need of serum, providing a new bioink for 3D bioprinting in tissue reconstructions.
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http://dx.doi.org/10.1021/acsami.1c04967DOI Listing
June 2021

Downregulation by CNNM2 of ATP5MD expression in the 10q24.32 schizophrenia-associated locus involved in impaired ATP production and neurodevelopment.

NPJ Schizophr 2021 May 21;7(1):27. Epub 2021 May 21.

Department of Medical Genetics, School of Basic Medical Sciences, Guangdong Technology and Engineering Research Center for Molecular Diagnostics of Human Genetic Diseases, and Guangdong Engineering and Technology Research Center for Genetic Testing, Southern Medical University, Guangzhou, China.

Genome-wide association studies (GWAS) have accelerated the discovery of numerous genetic variants associated with schizophrenia. However, most risk variants show a small effect size (odds ratio (OR) <1.2), suggesting that more functional risk variants remain to be identified. Here, we employed region-based multi-marker analysis of genomic annotation (MAGMA) to identify additional risk loci containing variants with large OR value from Psychiatry Genomics Consortium (PGC2) schizophrenia GWAS data and then employed summary-data-based mendelian randomization (SMR) to prioritize schizophrenia susceptibility genes. The top-ranked susceptibility gene ATP5MD, encoding an ATP synthase membrane subunit, is observed to be downregulated in schizophrenia by the risk allele of CNNM2-rs1926032 in the schizophrenia-associated 10q24.32 locus. The Atp5md knockout (KO) in mice was associated with abnormal startle reflex and gait, and ATP5MD knockdown (KD) in human induced pluripotent stem cell-derived neurons disrupted the neural development and mitochondrial respiration and ATP production. Moreover, CNNM2-rs1926032 KO could induce downregulation of ATP5MD expression and disruptions of mitochondrial respiration and ATP production. This study constitutes an important mechanistic component that links schizophrenia-associated CNNM2 regions to disruption in energy adenosine system modulation and neuronal function by long-distance chromatin domain downregulation of ATP5MD. This pathogenic mechanism provides therapeutic implications for schizophrenia.
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http://dx.doi.org/10.1038/s41537-021-00159-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139961PMC
May 2021

Effects of HIF-1α on renal fibrosis in cisplatin-induced chronic kidney disease.

Clin Sci (Lond) 2021 May;135(10):1273-1288

Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Hunan, China.

Cisplatin (Cis) can cause chronic kidney disease (CKD) and promote renal fibrosis, but the underlying mechanism is not fully understood. Hypoxia inducible factor-1α (HIF-1α) can promote renal fibrosis in some kidney diseases, but its role in Cis-induced CKD is still unknown. Notch-1 is a recognized molecule that promotes renal fibrosis under pathological circumstances, and evidence shows that HIF-1α and Notch-1 are closely related to each other. In the present study, mice with HIF-1α gene knockout in proximal tubular cells (PTCs) (PT-HIF-1α-KO) were generated and treated with Cis to induce CKD. A human proximal tubular cell line (HK-2) and primary mouse PTCs were used for in vitro studies. The results showed that HIF-1α was increased in the kidneys of Cis-treated wild-type mice, accompanied by elevated Notch-1, Notch-1 intracellular domain (N1ICD), Hes-1 and renal fibrosis. However, these alterations were partially reversed in PT-HIF-1α-KO mice. Similar results were observed in HK-2 cells and primary mouse PTCs. In addition, treating the cells with Cis induced a marked interaction of HIF-1α and N1ICD. Further inhibiting Notch-1 significantly reduced cellular fibrogenesis but did not affect HIF-1α expression. The data suggested that HIF-1α could promote renal fibrosis in Cis-induced CKD by activating Notch-1 both transcriptionally and post-transcriptionally and that HIF-1α may serve as a potential therapeutic target for Cis-induced CKD.
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http://dx.doi.org/10.1042/CS20210061DOI Listing
May 2021

DsbA-L Ameliorates Renal Injury Through the AMPK/NLRP3 Inflammasome Signaling Pathway in Diabetic Nephropathy.

Front Physiol 2021 30;12:659751. Epub 2021 Apr 30.

Department of Nephrology, Hunan Key Laboratory of Kidney Disease and Blood Purification, The Second Xiangya Hospital, Central South University, Changsha, China.

NLRP3-mediated inflammation is closely related to the pathological progression of diabetic nephropathy (DN). DsbA-L, an antioxidant enzyme, plays a protective role in a variety of diseases by inhibiting ER stress and regulating metabolism. However, the relationship of DsbA-L with inflammation, especially the NLRP3 inflammasome, has not been examined. In this study, we note that activation of the NLRP3 inflammasome and exacerbated fibrosis were observed in the kidneys of diabetic DsbA-L-knockout mice and were accompanied by decreased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, correlation analysis shows that the phosphorylation of AMPK was negatively correlated with NLRP3 expression and tubular damage. In addition, the decreased AMPK phosphorylation and NLRP3 activation induced by high glucose (HG) in HK-2 cells could be alleviated by the overexpression of DsbA-L. Interestingly, the protective effect of DsbA-L was eliminated after treatment with compound C, a well-known AMPK inhibitor. Our findings suggest that DsbA-L inhibits NLRP3 inflammasome activation by promoting the phosphorylation of AMPK.
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http://dx.doi.org/10.3389/fphys.2021.659751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120163PMC
April 2021

Targeted temperature management at 33 degrees Celsius in patients with high-grade aneurysmal subarachnoid hemorrhage: a protocol for a multicenter randomized controlled study.

Ann Transl Med 2021 Apr;9(7):581

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Studies on the use of therapeutic hypothermia (TH) to improve the outcome of high-grade aneurysmal subarachnoid hemorrhage (aSAH), show promising, though conflicting results because of the lack of high-quality trials. The aim of this study is to evaluate the safety and efficacy of TH (maintaining bladder temperature at 33 °C for ≥72 h) to treat patients with high-grade aSAH (Hunt-Hess grade IV-V).

Methods: A multicenter, randomized, controlled clinical trial will be conducted for October 2020 to September 2024 involving 10 clinics. Patients who meet the inclusion criteria will be randomized 1:1 to a TH group and a normothermia group. The trial will enroll 96 participants in TH group and normothermia one, respectively. The trial was registered with ClinicalTrials.gov (NCT03442608) on February 22, 2018. Following conventional treatment for aSAH, patients will undergo either TH for at least 72 h or normothermia. The primary endpoint is the Glasgow outcome scale at 6 months after bleeding. The secondary endpoints are: (I) mortality at 6 months after bleeding; (II) intracranial pressure; (III) intensive care unit stay; and (IV) hospital stay. The safety endpoints include neurological, infectious, intestinal, circulatory, coagulation, and bleeding complications, electrolyte disorders, and other complications.

Discussion: If the study hypothesis is confirmed, TH at 33 °C in patients with high-grade aSAH may become a promising treatment strategy for improving 6-month outcome.

Trial Registration: The trial has been registered at ClinicalTrials.gov (ID: NCT03442608).
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http://dx.doi.org/10.21037/atm-20-4719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105800PMC
April 2021

LncRNA MAFG-AS1 Suppresses the Maturation of miR-34a to Promote Glioblastoma Cell Proliferation.

Cancer Manag Res 2021 22;13:3493-3501. Epub 2021 Apr 22.

Department of Neurosurgery, Zibo Central Hospital, Zibo City, Shandong Province, 255036, People's Republic of China.

Purpose: LncRNA MAFG-AS1 plays critical roles in several types of cancer, while its role in glioblastoma (GBM) is unknown. By analyzing the TCGA dataset, we observed the upregulation of MAFG-AS1 in GBM. This study aimed to investigate the involvement of MAFG-AS1 in GBM cancer.

Methods: The expression levels of MAFG-AS1, mature miR-34a, and miR-34a precursor in GBM and paired non-tumor tissues of 56 GBM patients were determined by RT-qPCR. Correlations are analyzed using linear regression. Overexpression of MAFG-AS1 was achieved in GBM cells, followed by measurement of the expression levels of mature miR-34a, miR-34a precursor, DICER and Drosha by RT-qPCR. The roles of MAFG-AS1 and miR-34a in regulating GBM cell proliferation were evaluated by CCK-8 assay. Flow cytometry was performed to explore the role of MAFG-AS1 and miR-34a in regulating the apoptosis and cell cycle of GBM cells. Cell scratch experiment was performed to determine the role of MAFG-AS1 and miR-34a in regulating the migration of GBM cells. Subcutaneous tumor animal model was used for in vivo study. The expressions levels of BCL-2 and caspase-3 were detected by Western blot analysis.

Results: MAFG-AS1 was upregulated in GBM, while mature miR-34a was downregulated in GBM. Interestingly, MAFG-AS1 was inversely correlated with mature miR-34a but not miR-34a precursor across GBM tissues. In GBM tissues, the overexpression of MAFG-AS1 did not affect the expression levels of miR-34a precursor but reduced the expression levels of mature miR-34a. MAFG-AS1 promoted the expression of DICER and Drosha in GBM cells. Moreover, the overexpression of MAFG-AS1 promoted the proliferation of GBM cells and reduced the inhibitory effects of miR-34a on cell proliferation but did not affect cell cycle, apoptosis and migration. The overexpression of MAFG-AS1 promoted the progression of GBM in vivo by promoting the proliferation of GBM cells while miR-34a reversed the effect of overexpression of MAFG-AS1.

Conclusions: MAFG-AS1 may suppress the maturation of miR-34a to promote GBM cell proliferation.
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http://dx.doi.org/10.2147/CMAR.S274615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075183PMC
April 2021

Association of changes in waist circumference with cardiovascular disease and all-cause mortality among the elderly Chinese population: a retrospective cohort study.

J Geriatr Cardiol 2021 Mar;18(3):185-195

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.

Background: To examine the association of baseline waist circumference (WC) and changes in WC with cardiovascular disease (CVD) and all-cause mortality among elderly people.

Methods: A total of 30,041 eligible participants were included from a retrospective cohort in China. The same questionnaire, anthropometric and laboratory measurements were performed at baseline (2010) and the first follow-up (2013). The percent change in WC between baseline and the first follow-up was calculated to evaluate three years change of WC. We collected the occurrence of CVD and all-cause death from the first follow-up to December 31, 2018. Restricted cubic splines and Cox proportional-hazards regression models were used to evaluate the relationship between baseline WC/ changes in WC and mortality.

Results: The dose-response relationships between baseline WC and CVD mortality were U- or J-shaped. In low WC group, compared with stable group, the fully adjusted hazard ratio (aHR) for CVD mortality was 1.60 (95% CI: 1.24-2.06) in WC gain group among men. In normal WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.86, 95% CI: 1.36-2.56; women: aHR = 1.83, 95% CI: 1.29-2.58). In moderate-high WC group, the CVD mortality risk increased with WC gain (men: aHR = 1.76, 95% CI: 1.08-2.88; women: aHR = 1.46, 95% CI: 1.04-2.05) and risk decreased with WC loss (men: aHR = 0.54, 95% CI: 0.30-0.98; women: aHR = 0.59, 95% CI: 0.37-0.96).

Conclusions: For the elderly population, WC gain may increase CVD mortality risk regardless of baseline WC, whereas WC reduction could decrease the risk only in the moderate-high WC group.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047181PMC
March 2021

Pd Anchored on a Phytic Acid/Thiourea Polymer as a Highly Active and Stable Catalyst for the Reduction of Nitroarene.

ACS Appl Mater Interfaces 2021 May 26;13(17):19904-19914. Epub 2021 Apr 26.

Green Catalysis Center, the College of Chemistry, Zhengzhou University, Zhengzhou, Henan 450001, PR China.

A kind of N, P, C, O-containing polymer was easily prepared via microwave heating of phytic acid and thiourea just for 90 s. After impregnation and reduction of HPdCl, highly dispersed Pd single atoms/sub-nano clusters loaded on the phytic acid/thiourea polymer (Pd-CNSP) were successfully obtained. Owing to the synergetic effect of the polymer support and Pd, the catalyst Pd-CNSP achieves a great atomic efficiency of Pd species and exhibits an outstanding catalytic ability in the reduction of 4-nitrophenol. The value of the catalyst Pd-CNSP (2.17 min mg) is about 19 times higher than that of the commercial Pd/C (5 wt %) catalyst. The turnover frequency value is as high as 848 min, which is the highest value reported so far. Pd-CNSP also has good selectivity for the reduction of halogen-substituted (Cl and Br) nitroaromatics. It is expected to be mass-produced and used in other industrial hydrogenation reactions.
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http://dx.doi.org/10.1021/acsami.0c23007DOI Listing
May 2021

Association of body mass index and waist circumference with high blood pressure in older adults.

BMC Geriatr 2021 04 19;21(1):260. Epub 2021 Apr 19.

Department of Epidemiology and Health Statistics, College of Public Health, Zhengzhou University, Songhe Shi, 100 Kexue Avenue, Zhengzhou, Henan, 450001, People's Republic of China.

Background: The relationship between obesity and prevalent high blood pressure in older adults has predominantly been estimated using categorical measures of body mass index (BMI) and waist circumference (WC), masking the shape of the dose-response relationship. We aimed to examine the precise relationship of BMI, WC with high blood pressure and to assess the appropriate level of BMI and WC for high blood pressure.

Methods: We examined data for 126,123 individuals in Xinzheng city aged ≥60 years from a population based study from January to December 2019. Logistic regression and restricted cubic spline models were applied to assess the relationship and the appropriate level of BMI and WC for high blood pressure. An additive interaction analysis was used to test synergistic effects between a higher BMI and WC for high blood pressure.

Results: The full-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of an increase of 1 kg/m in BMI and 1 cm in WC for high blood pressure were 1.084 (1.080-1.087) and 1.026(1.024-1.027), respectively. Multivariable adjusted restricted cubic spline analyses showed the nonlinear relationships of BMI and WC with high blood pressure in both men and women (all P < 0.001). The risk of high blood pressure increased steeply with increasing BMI from ≥25 kg/m and WC ≥ 88 cm or 86 cm for males and females, respectively. And we observed a significant additive interaction between a higher BMI and WC such that the prevalence of high blood pressure was significantly enhanced.

Conclusion: These findings suggest increased high blood pressure prevalence in the older adults with increased BMI and WC. BMI ≤ 25 kg/m2 and WC ≤ 88 cm or 86 cm for males and females may be the best suggestion with regard to primary prevention of high blood pressure in older adults.
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http://dx.doi.org/10.1186/s12877-021-02154-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056549PMC
April 2021

Identification and Validation of a Tumor Microenvironment-Related Gene Signature for Prognostic Prediction in Advanced-Stage Non-Small-Cell Lung Cancer.

Biomed Res Int 2021 30;2021:8864436. Epub 2021 Mar 30.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The development of immunotherapy has greatly changed the advanced-stage non-small-cell lung cancer (NSCLC) treatment landscape. The complexity and heterogeneity of tumor microenvironment (TME) lead to discrepant immunotherapy effects among patients at the same pathologic stages. This study is aimed at exploring potential biomarkers of immunotherapy and accurately predicting the prognosis for advanced NSCLC patients. RNA-seq data and clinical information on stage III/IV NSCLC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). In TCGA-NSCLC with stage III/IV ( = 192), immune scores and stromal scores were calculated by using the ESTIMATE algorithms. Univariate, LASSO, and multivariate Cox regression analyses were performed to screen prognostic TME-related genes (TMERGs) and constructed a gene signature risk score model. It was validated in external dataset including GSE41271 ( = 91) and GSE81089 ( = 36). Additionally, a nomogram incorporating TMERG signature risk score and clinical characteristics was established. Further, we accessed the proportion of 22 types of tumor-infiltrating immune cells (TIIC) from the CIBERSORT website and analyzed the difference between two risk groups. OS of patients with high immune/stromal scores were higher (log-rank = 0.044/log-rank = 0.048). Multivariate Cox regression identified six prognostic TMERGs, including CD200, CHI3L2, CNTN1, CTSL, FYB1, and SLC52A1. We developed a six-gene risk score model, which was validated as an independent prognostic factor for OS (HR: 3.32, 95% CI: 2.16-5.09). Time-ROC curves showed useful discrimination for TCGA-NSCLC cohort (1-, 2-, and 3-year AUCs were 0.718, 0.761, and 0.750). The predictive robustness was validated in the external dataset. The C-index and 1-, 2-, and 3-year AUCs of nomogram were the largest, which demonstrated the nomogram had the greatest predictive accuracy and effectiveness and could be used for clinical guidance. Besides, the increased infiltration of T cells regulatory (Tregs) and macrophages M2 in the high-risk group suggested that chronic inflammation may reduce survival probability in patients with advanced NSCLC. We conducted a comprehensive analysis of the tumor microenvironment and identified the TMERG signature, which could predict prognosis accurately and provide a reference for the personalized immunotherapy for advanced NSCLC patients.
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http://dx.doi.org/10.1155/2021/8864436DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028741PMC
May 2021

Cereblon expression is a prognostic marker in newly diagnosed POEMS syndrome treated with lenalidomide plus dexamethasone.

Ann Hematol 2021 Jun 10;100(6):1547-1552. Epub 2021 Apr 10.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

POEMS syndrome is a rare plasma cell disorder. Lenalidomide has recently emerged as a therapeutic option for POEMS syndrome. Cereblon has been identified as the direct target of lenalidomide, and high cereblon expression is associated with better response and outcome to lenalidomide therapy in multiple myeloma patients. Here, we analyzed the predictive value of cereblon, IKZF1, and IKZF3 in CD138 selected plasma cells from forty-one newly diagnosed POEMS syndrome patients treated with lenalidomide in combination with dexamethasone at both gene and protein levels. We found that patients with high cereblon expression tended to achieve better hematologic response compared to those with low expression (p = 0.024 for gene expression; p = 0.01 for protein expression). Multivariate Cox regression analysis revealed high cereblon mRNA expression as an independent prognostic marker for longer progression-free survival (hazard ratio 0.542; 95% CI 0.337-0.871; p = 0.011). In conclusion, our results emphasized the role of cereblon mRNA expression as a unique biomarker for predicting the clinical response and outcome of lenalidomide-based therapy in newly diagnosed POEMS syndrome patients.
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http://dx.doi.org/10.1007/s00277-021-04517-9DOI Listing
June 2021

Clinical and Genetic Features of Brainstem Glioma in Adults: A Report of 50 Cases in a Single Center.

J Clin Neurol 2021 Apr;17(2):220-228

Department of Neurosurgery, The Sixth Medical Center of PLA General Hospital, Beijing, China.

Background And Purpose: Brainstem gliomas (BSGs) in adults are rare brain tumors with dismal outcomes. The aim of this study was to determine the clinical and genetic features in a series of BSGs and their association with the prognosis.

Methods: Fifty patients who underwent a stereotactic biopsy between January 2016 and April 2018 at a single institution were collected. Data on clinicopathological characteristics were analyzed and factors associated with patient survival were identified using a Cox regression model.

Results: The median age at diagnosis was 55.5 years, and 62% of the patients were male. Glioblastoma (44%) accounted for the largest proportion of BSGs, and oligodendroglioma (2 of 50) was rarely encountered. The mutation (6 of 44) occurred infrequently in astrocytomas, and -mutant tumors harbored both loss and promoter methylation at a relatively low level. Wild-type astrocytomas were identified as having high rates of 1p/19q codeletion (5 of 38) and loss of heterozygosity 1p (8 of 38) or 19q (8 of 38) only. In diffuse midline glioma mutant, promoter methylation occurred in three of four cases. Patients were offered radiotherapy and/or concurrent/adjuvant temozolomide chemotherapy, and their median survival time was 13 months. Multivariate analysis revealed that a low tumor grade, absence of tumor enhancement, duration of symptoms ≥3 months, Karnofsky performance status ≥70, and loss conferred a survival advantage.

Conclusions: Adult BSGs showed different molecular genetic characteristics, but also resembled supratentorial gliomas in their clinical features associated with oncological outcomes.
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http://dx.doi.org/10.3988/jcn.2021.17.2.220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053546PMC
April 2021

Nonlinear dynamic control of GaAs nanomechanical resonators using lasers.

Nanotechnology 2021 Apr 27;32(29). Epub 2021 Apr 27.

College of Electronic and Optical Engineering and College of Microelectronics, Nanjing University of Posts and Telecommunications, Nanjing 210023, People's Republic of China.

The ability to control, manipulate, and read out nanomechanical resonators is of great significance for many applications. In this work, we start by constructing a nonlinear dynamic model that is deduced from the fundamental beam-photon-electron interaction and energy band theories, with the aim of describing a complicated cavity-free optomechanical coupling process. Based on the model established, we first reveal the manipulation of a resonator's response, including softening and hardening effects due to laser injection. By driving the laser parametrically, we comprehensively investigate the control of the resonator's dynamics, in particular, in the nonlinear regime. It is found that both the laser power and frequency can be used to directly manipulate the NEMS resonator's dynamics, e.g., by amplitude amplification, periodicity changes, and periodic-chaotic state conversion. We then provide bifurcation diagrams, which evidence a deterministic evolution of dynamics. Finally, we perform a special study of the control of chaotic states of the nanomechanical resonator using laser parametric driving. The maximal Lyapunov exponents together with time series calculation show that the chaotic states can be controlled at a few specific frequency points of the injecting laser. This work not only provides guidance for using lasers to control nanoscale resonators, but also sheds light on the exploration of novel applications based on nonlinear NEMS resonators.
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http://dx.doi.org/10.1088/1361-6528/abf3f1DOI Listing
April 2021

Revealing serum lipidomic characteristics and potential lipid biomarkers in patients with POEMS syndrome.

J Cell Mol Med 2021 05 28;25(9):4307-4315. Epub 2021 Mar 28.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

POEMS syndrome is a rare plasma cell dyscrasia with distinct lipid metabolism abnormalities at disease onset. However, the serum lipidomic characteristics in patients with POEMS syndrome were not investigated. The study performed an untargeted lipidome screening by liquid chromatography-tandem mass spectrometry (LS-MS/MS) in the pre- and post-treatment serum of 24 patients with POEMS syndrome, together with the serum of 24 paired healthy controls. Patients with POEMS syndrome had a distinct serum lipid composition compared with healthy controls, and a 3-lipid model had a predictive accuracy of 93.5% in distinguishing patients and healthy controls consisting of fatty acyl 17-oxo-20Z-hexacosenoic acid, phosphatidylcholine(16:0/18:1(9Z)) and sterol lipid 5b-pregnanediol. Four lipids including 17-oxo-20Z-hexacosenoic acid (r = 0.423, P = .040) were correlated with risk stratification, and 2 lipids including Cer(d18:0/13:0) were inversely related to serum vascular endothelial growth factor level (r=-0.465, P = .022). Eleven lipids were related to disease activity, including arachidonic acid which was inversely related and lysoPC(20:4) which was positively related. The study indicated a distinct lipid characteristic profile of patients with POEMS syndrome different from healthy controls and identified several lipids that may serve as potential diagnostic markers and monitors of therapeutic efficacy, as well as indicating potential metabolism pathways involved in the pathological process.
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http://dx.doi.org/10.1111/jcmm.16486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093959PMC
May 2021

Identification of a Prognostic Signature Model with Tumor Microenvironment for predicting Disease-free Survival after Radical Prostatectomy.

J Cancer 2021 22;12(8):2371-2384. Epub 2021 Feb 22.

Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

The tumor microenvironment (TME) and immune checkpoint inhibitors have been shown to promote active immune responses through different mechanisms. We attempted to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa). The gene transcriptome profiles and clinical information of PCa patients were obtained from The Cancer Genome Atlas (TCGA) database, and the immune and stromal scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of the risk score (RS) model based on univariate Cox analysis and least absolute shrinkage and selection operation (LASSO) Cox regression analysis and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 dataset was utilized for external validation. Twenty-two subsets of tumor-infiltrating immune cells were analyzed using the CIBERSORT algorithm. In this study, the patients with higher immune/stromal scores were associated with a worse DFS, higher Gleason score, and higher pathological T stage. Based on the immune and stromal scores, 515 differentially expressed genes (DEGs) were identified. The univariate Cox and LASSO Cox regression models were employed to select 18 DEGs from 515 DEGs and construct an RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (<0.001). The AUCs for the 1-year, 3-year and 5-year DFS rates in the RS model were 0.890, 0.877 and 0.841, respectively. A nomogram of DFS was established based on the RS and Gleason score, and the AUCs for the 1-year, 3-year and 5-year DFS rates in the nomogram were 0.907, 0.893, and 0.872, respectively. These results were further validated in the GSE70768 dataset. In addition, the proportion of Tregs was determined to be higher in high-RS patients (<0.05), and the expression levels of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) were observed to be higher in high-RS patients (<0.05). Our study established and validated an 18-gene prognostic signature model associated with TME, which might serve as a prognosis stratification tool to predict DFS in PCa patients after radical prostatectomy.
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http://dx.doi.org/10.7150/jca.51173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974886PMC
February 2021

MAMs Protect Against Ectopic Fat Deposition and Lipid-Related Kidney Damage in DN Patients.

Front Endocrinol (Lausanne) 2021 19;12:609580. Epub 2021 Feb 19.

Department of Nephrology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, China.

Ectopic fat deposition (EFD) in the kidney plays a key role in the development of diabetic nephropathy (DN). Mitochondria-associated ER membranes (MAMs) are structures that connect to the endoplasmic reticulum (ER) and are involved in lipid metabolism. However, there are few studies on MAMs in the field of kidney disease, and the relationship between EFD and MAMs in DN is still unclear. In this study, increased EFD in the kidneys of DN patients was observed, and analysis showed that the degree of EFD was positively correlated with renal damage. Then, the MAMs were quantified by an proximity ligation assay (PLA). The MAMs in the kidneys were found to gradually decrease through the different stages of DN, while the expression of ADRP (a marker of lipid droplets) and tubulointerstitial damage increased. Moreover, correlation analysis showed that the MAMs were negatively correlated with serum lipid levels, the EFD in the kidney and renal damage. Finally, we observed decreased expression of MAM-control proteins (DsbA-L, PACS-2, and MFN-2) in different stages of DN and they were associated with lipid deposition and renal damage. These data showed that the destruction of MAMs in DN might be the cause of EFD and interstitial damage in the kidney.
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http://dx.doi.org/10.3389/fendo.2021.609580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933555PMC
February 2021
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