Publications by authors named "Chong Wang"

1,080 Publications

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Phase Ib/II study of Cetuximab Plus Pembrolizumab in Patients with Advanced RAS wild-type Colorectal Cancer.

Clin Cancer Res 2021 Oct 13. Epub 2021 Oct 13.

Medical Oncology, Rutgers Cancer Institute of New Jersey.

Purpose: We evaluated the antitumor efficacy of cetuximab in combination with pembrolizumab in patients with wild-type (RASwt), metastatic colorectal adenocarcinoma (mCRC).

Experimental Design: In this phase Ib/II study, cetuximab was combined with pembrolizumab in patients with RASwt mCRC with {greater than or equal to} one prior line of therapy for advanced disease. We analyzed baseline on-treatment tumor tissues for changes in the tumor microenvironment (TME), using flow cytometry and multispectral immunofluorescence.

Results: Forty-four patients were evaluable for efficacy. The study was negative for the primary efficacy endpoint (overall response rate: 2.6%, 6-month progression-free survival: 31%; p=0.52). Median PFS was 4.1 months (95% CI: 3.9-5.5 months). No increase in adverse effects was identified. We observed favorable immunomodulation with 47% increase in the number of intratumoral cytotoxic T-cell lymphocytes post-treatment (p=0.035). These changes were more pronounced in patients with tumor shrinkage (p=0.05). The TME was characterized by high numbers of TIM3 and CTLA4 cells; there were few activated OX40 cells. PD-L1 expression was higher in pre-treatment tumor cells from metastatic sites vs. primary tumor samples (p<0.05). Higher numbers of PD-L1 tumor cells at baseline were associated with tumor shrinkage (p=0.04). Analysis of immune populations in the blood demonstrated decreases in PD-1 memory effector cells (p=0.04) and granulocytic MDSCs (p=0.03), with simultaneous increases in CD4/CTLA4 cells (p=0.01).

Conclusions: The combination of cetuximab and pembrolizumab is inactive in patients with RASwt mCRC, despite its partial local immunologic efficacy. Further development of immuno-oncology combinations with enhanced efficacy and/or targeting additional or alternative immune checkpoints merits investigation.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-1650DOI Listing
October 2021

Integrating Multilevel Functional Characteristics Reveals Aberrant Neural Patterns during Audiovisual Emotional Processing in Depression.

Cereb Cortex 2021 Jun 30. Epub 2021 Jun 30.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, University of Electronic Science and Technology of China, Chengdu, 610054, PR China.

Emotion dysregulation is one of the core features of major depressive disorder (MDD). However, most studies in depression have focused on unimodal emotion processing, whereas emotional perception in daily life is highly dependent on multimodal sensory inputs. Here, we proposed a novel multilevel discriminative framework to identify the altered neural patterns in processing audiovisual emotion in MDD. Seventy-four participants underwent an audiovisual emotional task functional magnetic resonance imaging scanning. Three levels of whole-brain functional features were extracted for each subject, including the task-evoked activation, task-modulated connectivity, combined activation and connectivity. Support vector machine classification and prediction models were built to identify MDD from controls and evaluate clinical relevance. We revealed that complex neural networks including the emotion regulation network (prefrontal areas and limbic-subcortical regions) and the multisensory integration network (lateral temporal cortex and motor areas) had the discriminative power. Moreover, by integrating comprehensive information of local and interactive processes, multilevel models could lead to a substantial increase in classification accuracy and depression severity prediction. Together, we highlight the high representational capacity of machine learning algorithms to characterize the complex network abnormalities associated with emotional regulation and multisensory integration in MDD. These findings provide novel evidence for the neural mechanisms underlying multimodal emotion dysregulation of depression.
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http://dx.doi.org/10.1093/cercor/bhab185DOI Listing
June 2021

Risk factors affect accurate prognosis in ASXL1-mutated acute myeloid leukemia.

Cancer Cell Int 2021 Oct 9;21(1):526. Epub 2021 Oct 9.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The epigenetic regulator additional sex combs-like 1 (ASXL1) is an adverse prognostic factor in acute myeloid leukemia (AML). However, the mutational spectrum and prognostic factors of ASXL1-mutated (ASXL1+) AML are largely unknown. We aim to evaluate the risk factors influencing the prognosis of ASXL1+ AML.

Methods: We performed next-generation sequencing (NGS) in 1047 cases of de novo AML and discovered 91 ASXL1+ AML (8.7%). The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis.

Results: In a total of 91 ASXL1+ AML, 86% had one or more co-mutations. The factors that had adverse impact on overall survival (OS) and event-free survival (EFS) are defined as high risk factors, including age ≥ 60 years, WBC count ≥ 50 × 10/L, FLT3-ITD mutations, RUNX1 mutations, and absence of AML1-ETO fusion gene. ASXL1 mutations without any risk factor were classified as single-hit ASXL1+ AML; ASXL1 mutations accompanied with one of the risk factors was referred to as double-hit ASXL1+ AML; ASXL1 mutations with two or more of the risk factors were designated as triple-hit ASXL1+ AML. The combination of these risk factors had a negative influence on the prognosis of ASXL1+ AML. The median OS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 6.67 months in triple-hit ASXL1+ AML (P = 0.003). The median EFS was not attained in single-hit ASXL1+ AML, 29.53 months in double-hit ASXL1+ AML, and 5.47 months in triple-hit ASXL1+ AML (P = 0.002). Allogenic hematopoietic stem cell transplantation (allo-HSCT) improved the prognosis of double/triple-hit ASXL1+ AML patients.

Conclusions: Our study provided new insights into the mutational spectrum and prognostic factors of ASXL1+ AML patients. Our primary data suggest that the risk factors in ASXL1+ AML contribute to the poor outcome of these patients. The management of ASXL1+ AML patients should be based on the risk factors and allo-HSCT is highly recommended for consolidation.
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http://dx.doi.org/10.1186/s12935-021-02233-yDOI Listing
October 2021

Global optimization for light concentrators of a Geiger-mode cosmic-ray Cherenkov calorimeter.

Opt Express 2021 Aug;29(16):25876-25893

Light concentrators are crucial devices for photon-counting instruments, the optical characteristics of which affect the photoelectric response for the sensors. The designs that only aim to the light transmission have been proved far from optimum for the Geiger-mode calorimeters due to the significant influence from the angle-dependent reflectance, versatile light trajectories, and saturation of fired avalanche photodiodes (APDs). In this paper, we took into account these coupling effects, presented a novel approach to solve the problems in global optimization for light concentrators in combination with silicon photomultiplier (SiPM). In addition, a new probability method is studied and used to restore the photon counting for precise reconstruction of cosmic-ray air showers. The Monte-Carlo experiment verified that the new system design features a high accurate energy scaling for cosmic-ray measurement. The results also indicate that the precision is able to be improved by at least one order in magnitude.
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http://dx.doi.org/10.1364/OE.432981DOI Listing
August 2021

NOL6 promotes the proliferation and migration of endometrial cancer cells by regulating expression.

Epigenomics 2021 Oct 5. Epub 2021 Oct 5.

Department of Obstetrics & Gynecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.

To investigate the role and function of NOL6, a protein related to ribosome biogenesis, in endometrial cancer. Methyl thiazolyl tetrazolium assay, colony formation assay, flow cytometry apoptosis assay, transwell and wound healing assays were carried out for evaluating cell proliferation, migration and apoptosis. Immunohistochemistry, western blot and tumor xenograft assays were carried out for detecting the level of protein expression and tumor formation. We demonstrated that NOL6 is overexpressed in endometrial cancer and promotes cell proliferation and migration while reducing apoptosis. NOL6 regulates the expression of , which can restore the changes in cells caused by knockdown. NOL6 can promote the proliferation and migration of endometrial cancer cells by regulating expression.
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http://dx.doi.org/10.2217/epi-2021-0218DOI Listing
October 2021

The immunomodulatory activity of lenvatinib prompts the survival of patients with advanced hepatocellular carcinoma.

Cancer Med 2021 Oct 4. Epub 2021 Oct 4.

Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Lenvatinib is a novel multiple receptor tyrosine kinase inhibitor used for hepatocellular carcinoma (HCC) treatment. Although its main function is to suppress VEGFR and FGFR pathway, its immunomodulatory activity in HCC is not elucidated. Thus, this study aimed to investigate the immunomodulatory capability of lenvatinib in HCC.

Material And Methods: Totally 47 patients with HCC were enrolled in this study, and the immune cells and serum cytokine profiles before initiation of treatment and after 1 and 3 months were measured. The immune checkpoint receptors on the immune cells were also evaluated. Kaplan-Meier survival estimate and log rank tests were used to assess the prognostic value.

Result: The frequency of T helper (Th) cells and T regulatory (Treg) cells reduced after lenvatinib treatment, while cytotoxic T lymphocyte (CTL) cells increased significantly. The cytokine profiles showed IL-2, IL-5, IFN-γ increased; other cytokines including IL-6, IL-10, TNF- α and TNF- β decreased with lenvatinib therapy. Furthermore, the PD-1 and TIM-3 expressed on CTL had greatly decreased; the expression of TIM-3 and CTLA-4 was reduced on Treg cells as well. Besides, the new index CTL/Treg ratio was created, and low ratio was associated with the unfavorable outcome of HCC patients.

Conclusion: Our results confirmed that lenvatinib is capable of improving patients' immune status, saving the effector cells from exhaustion status and inhibiting the number and function of immunosuppressive cells. The novel index CTL/Treg ratio qualifies as a predictor for the outcome of patients with lenvatinib therapy.
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http://dx.doi.org/10.1002/cam4.4312DOI Listing
October 2021

IL-13 Alleviates Cardiomyocyte Apoptosis by Improving Fatty Acid Oxidation in Mitochondria.

Front Cell Dev Biol 2021 17;9:736603. Epub 2021 Sep 17.

Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Sepsis-induced cardiac injury () is one of the most common complications in the intensive care unit (ICU) with high morbidity and mortality. Mitochondrial dysfunction is one of the main reasons for , and Interleukin-13 (IL-13) is a master regulator of mitochondria biogenesis. The aim of the present study was to investigate the role of IL-13 in and explore the underlying mechanism. It was found that reactive oxygen species (ROS) production and apoptosis were significantly increased in lipopolysaccharide (LPS)-stimulated primary cardiomyocytes, which was accompanied with obvious mitochondria dysfunction. The results of RNA-sequencing (RNA-seq), mitochondrial membrane potential, fatty acid uptake and oxidation rate suggested that treatment with IL-13 could restore the function and morphology of mitochondria, indicating that it played an important role in protecting septic cardiomyocytes. These findings demonstrated that IL-13 alleviated sepsis-induced cardiac inflammation and apoptosis by improving mitochondrial fatty acid uptake and oxidation, suggesting that IL-13 may prove to be a potential promising target for treatment.
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http://dx.doi.org/10.3389/fcell.2021.736603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8484794PMC
September 2021

Larval metamorphosis is inhibited by methimazole and propylthiouracil that reveals possible hormonal action in the mussel Mytilus coruscus.

Sci Rep 2021 Sep 29;11(1):19288. Epub 2021 Sep 29.

International Research Center for Marine Biosciences, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.

Larval metamorphosis in bivalves is a key event for the larva-to-juvenile transformation. Previously we have identified a thyroid hormone receptor (TR) gene that is crucial for larvae to acquire "competence" for the metamorphic transition in the mussel Mytilus courscus (Mc). The mechanisms of thyroid signaling in bivalves are still largely unknown. In the present study, we molecularly characterized the full-length of two iodothyronine deiodinase genes (McDx and McDy). Phylogenetic analysis revealed that deiodinases of molluscs (McDy, CgDx and CgDy) and vertebrates (D2 and D3) shared a node representing an immediate common ancestor, which resembled vertebrates D1 and might suggest that McDy acquired specialized function from vertebrates D1. Anti-thyroid compounds, methimazole (MMI) and propylthiouracil (PTU), were used to investigate their effects on larval metamorphosis and juvenile development in M. coruscus. Both MMI and PTU significantly reduced larval metamorphosis in response to the metamorphosis inducer epinephrine. MMI led to shell growth retardation in a concentration-dependent manner in juveniles of M. coruscus after 4 weeks of exposure, whereas PTU had no effect on juvenile growth. It is hypothesized that exposure to MMI and PTU reduced the ability of pediveliger larvae for the metamorphic transition to respond to the inducer. The effect of MMI and PTU on larval metamorphosis and development is most likely through a hormonal signal in the mussel M. coruscus, with the implications for exploring the origins and evolution of metamorphosis.
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http://dx.doi.org/10.1038/s41598-021-98930-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481496PMC
September 2021

Skeletal muscle mass indexes and nonalcoholic fatty liver disease in Chinese elders.

Asia Pac J Clin Nutr 2021 Sep;30(3):446-456

Institute of Nutrition & Health, Qingdao University, Qingdao, China. Email:

Background And Objectives: As an endocrine organ, the mass of skeletal muscle is closely related to human health. The present study aimed to investigate the relationship between regional skeletal muscle and nonalcoholic fatty liver disease (NAFLD) in Chinese elders.

Methods And Study Design: A total of 1,328 participants (579 males and 749 females), aged 65 to 96 years were recruited between March to November 2020 in Qingdao, China. Of these, 400 cases and 400 healthy controls, matched by gender and age (±3 years), were included in the study. Skeletal muscle mass was measured by bioelectrical impedance analysis, and body weight was adopted to standardize skeletal muscle mass to obtain skeletal muscle mass indexes.

Results: Inverse associations were observed for trunk muscle mass index (TMI) (OR=0.42; 95% CI: 0.19, 0.93; p for trend=0.083) and leg skeletal muscle mass index (LMI) (OR=0.41; 95% CI: 0.18, 0.97; p for trend=0.012) with NAFLD risk after adjustment for age, body mass index, glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, dietary intakes of energy, carbohydrate, protein and fat, smoking, alcohol drinking, education and physical activity. Dose-response analysis indicated that per standard deviation increment of LMI was associated with 23% (95%CI: 0.63, 0.95) reduction of NAFLD risk.

Conclusions: The present study demonstrates that higher TMI and LMI are associated with a lower NAFLD risk.
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http://dx.doi.org/10.6133/apjcn.202109_30(3).0011DOI Listing
September 2021

Prediction of hyperbolic exciton-polaritons in monolayer black phosphorus.

Nat Commun 2021 Sep 24;12(1):5628. Epub 2021 Sep 24.

State Key Laboratory of Surface Physics, Key Laboratory of Micro and Nano-Photonic Structures (Ministry of Education), and Department of Physics, Fudan University, Shanghai, 200433, China.

Hyperbolic polaritons exhibit large photonic density of states and can be collimated in certain propagation directions. The majority of hyperbolic polaritons are sustained in man-made metamaterials. However, natural-occurring hyperbolic materials also exist. Particularly, natural in-plane hyperbolic polaritons in layered materials have been demonstrated in MoO and WTe, which are based on phonon and plasmon resonances respectively. Here, by determining the anisotropic optical conductivity (dielectric function) through optical spectroscopy, we predict that monolayer black phosphorus naturally hosts hyperbolic exciton-polaritons due to the pronounced in-plane anisotropy and strong exciton resonances. We simultaneously observe a strong and sharp ground state exciton peak and weaker excited states in high quality monolayer samples in the reflection spectrum, which enables us to determine the exciton binding energy of ~452 meV. Our work provides another appealing platform for the in-plane natural hyperbolic polaritons, which is based on excitons rather than phonons or plasmons.
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http://dx.doi.org/10.1038/s41467-021-25941-5DOI Listing
September 2021

Inhibition of viral suppressor of RNAi proteins by designer peptides protects from enteroviral infection in vivo.

Immunity 2021 Oct 22;54(10):2231-2244.e6. Epub 2021 Sep 22.

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences (CAS), Wuhan 430071, China. Electronic address:

RNA interference (RNAi) is the major antiviral mechanism in plants and invertebrates, but the absence of detectable viral (v)siRNAs in mammalian cells upon viral infection has questioned the functional relevance of this pathway in mammalian immunity. We designed a series of peptides specifically targeting enterovirus A71 (EV-A71)-encoded protein 3A, a viral suppressor of RNAi (VSR). These peptides abrogated the VSR function of EV-A71 in infected cells and resulted in the accumulation of vsiRNAs and reduced viral replication. These vsiRNAs were functional, as evidenced by RISC-loading and silencing of target RNAs. The effects of VSR-targeting peptides (VTPs) on infection with EV-A71 as well as another enterovirus, Coxsackievirus-A16, were ablated upon deletion of Dicer1 or AGO2, core components of the RNAi pathway. In vivo, VTP treatment protected mice against lethal EV-A71 challenge, with detectable vsiRNAs. Our findings provide evidence for the functional relevance of RNAi in mammalian immunity and present a therapeutic strategy for infectious disease.
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http://dx.doi.org/10.1016/j.immuni.2021.08.027DOI Listing
October 2021

Downregulation of GNA15 Inhibits Cell Proliferation P38 MAPK Pathway and Correlates with Prognosis of Adult Acute Myeloid Leukemia With Normal Karyotype.

Front Oncol 2021 6;11:724435. Epub 2021 Sep 6.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Background: The prognosis of acute myeloid leukemia (AML) with a normal karyotype is highly heterogonous, and the current risk stratification is still insufficient to differentiate patients from high-risk to standard-risk. Changes in some genetic profiles may contribute to the poor prognosis of AML. Although the prognostic value of G protein subunit alpha 15 () in AML has been reported based on the GEO (Gene Expression Omnibus) database, the prognostic significance of has not been verified in clinical samples. The biological functions of in AML development remain open to investigation. This study explored the clinical significance, biological effects and molecular mechanism of in AML.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA expression level of in blasts of bone marrow specimens from 154 newly diagnosed adult AML patients and 26 healthy volunteers. AML cell lines, Kasumi-1 and SKNO-1, were used for lentiviral transfection. Cell Counting Kit-8 (CCK8) and colony formation assays were used to determine cell proliferation. Cell cycle and apoptosis were analyzed by flow cytometry. The relevant signaling pathways were evaluated by Western blot. The Log-Rank test and Kaplan-Meier were used to evaluate survival rate, and the Cox regression model was used to analyze multivariate analysis. Xenograft tumor mouse model was used for experiments.

Results: The expression of in adult AML was significantly higher than that in healthy individuals. Subjects with high expression showed lower overall survival and relapse-free survival in adult AML with normal karyotype. High expression was independently correlated with a worse prognosis in multivariate analysis. Knockdown of inhibited cell proliferation and cell cycle progression, and induced cell apoptosis in AML cells. -knockdown induced down-regulation of p-P38 MAPK and its downstream p-MAPKAPK2 and p-CREB. Rescue assays confirmed that P38 MAPK signaling pathway was involved in the inhibition of proliferation mediated by GNA15 knockdown.

Conclusions: In summary, was highly expressed in adult AML, and high expression was independently correlated with a worse prognosis in adult AML with normal karyotype. Knockdown of inhibited the proliferation of AML regulated by the P38 MAPK signaling pathway. Therefore, may serve as a potential prognostic marker and a therapeutic target for AML in the future.
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http://dx.doi.org/10.3389/fonc.2021.724435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451478PMC
September 2021

Neonatal Piglets Are Protected from Clostridioides difficile Infection by Age-Dependent Increase in Intestinal Microbial Diversity.

Microbiol Spectr 2021 Sep 22:e0124321. Epub 2021 Sep 22.

Department of Veterinary Microbiology and Preventative Medicine, Iowa State Universitygrid.34421.30, Ames, Iowa, USA.

While Clostridioides difficile is recognized as an important human pathogen, it is also a significant cause of gastroenteritis and associated diarrhea in neonatal pigs. Since clinical disease is rarely diagnosed in piglets older than 1 week of age, it is hypothesized that natural resistance is associated with the increased complexity of the intestinal microbiota as the animals age. To test this, piglets were challenged with C. difficile (ribotype 078/toxinotype V) at times ranging from 2 to 14 days of age, and the severity of disease and microbial diversity of the cecal microbiota were assessed. Half of the piglets that were challenged with C. difficile at 2 and 4 days of age developed clinical signs of disease. The incidence of disease decreased rapidly as the piglets aged, to a point where none of the animals challenged after 10 days of age showed clinical signs. The cecal microbial community compositions of the piglets also clustered by age, with those of animals 2 to 4 days old showing closer relationships to one another than to those of older piglets (8 to 14 days). This clustering occurred across litters from 4 different sows, providing further evidence that the resistance to C. difficile disease in piglets greater than 1 week old is directly related to the diversity and complexity of the intestinal microbiota. C. difficile is an important bacterial pathogen that is the most common cause of infections associated with health care in the United States. It also causes significant morbidity and mortality in neonatal pigs, and currently there are no preventative treatments available to livestock producers. This study determined the age-related susceptibility of piglets to C. difficile over the first 2 weeks of life, along with documenting the natural age-related changes that occurred in the intestinal microbiota over the same time period in a controlled environment. We observed that the populations of intestinal bacteria within individual animals of the same age, regardless of litter, showed the highest degree of similarity. Identifying bacterial species associated with the acquisition of natural resistance observed in older pigs could lead to the development of new strategies to prevent and or treat disease caused by C. difficile infection.
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http://dx.doi.org/10.1128/Spectrum.01243-21DOI Listing
September 2021

A Bayesian latent class mixture model with censoring for correlation analysis in antimicrobial resistance across populations.

BMC Med Res Methodol 2021 09 20;21(1):186. Epub 2021 Sep 20.

Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, United States of America.

Background: The emergence of antimicrobial resistance across populations is a global threat to public health. Surveillance programs often monitor human and animal populations to evaluate trends of emergence in these populations. Many national level antibiotic resistance surveillance programs quantify the proportion of resistant bacteria as a means of monitoring emergence and control measures. The reason for monitoring these different populations are many, including interest in similar changes in resistance which might provide insight into emergence and control options.

Methods: In this research, we developed a method to quantify the correlation in antimicrobial resistance across populations, for the conventionally unnoticed mean shift of the susceptible bacteria. With the proposed Bayesian latent class mixture model with censoring and multivariate normal hierarchy, we address several challenges associated with analyzing the minimum inhibitory concentration data.

Results: Application of this approach to the surveillance data from National Antimicrobial Resistance Monitoring System led to a detection of positive correlation in the central tendency of azithromycin resistance of the susceptible populations from Salmonella serotype Typhimurium across food animal and human populations.

Conclusions: Our proposed approach has been shown to be accurate and superior to the commonly used naïve estimation by simulation studies. Further implementation of this Bayesian model could serve as a useful tool to indicate the co-existence of antimicrobial resistance, and potentially a need of clinical intervention.
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http://dx.doi.org/10.1186/s12874-021-01384-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454148PMC
September 2021

Circ_0022382 ameliorated intervertebral disc degeneration by regulating TGF-β3 expression through sponge adsorption of miR-4726-5p.

Bone 2021 Sep 16;154:116185. Epub 2021 Sep 16.

Yijishan Hospital of Wannan Medical College Wuhu, Anhui, China. Electronic address:

Circular RNAs (circRNAs) participate in the progression of many diseases, but knowledge on the role of circRNAs in intervertebral disc degeneration (IDD) is limited. In this study, we discovered the characteristics of a new circRNA (circ_0022382) in human endplate chondrocytes. Currently, real-time quantitative polymerase chain reaction (RT-qPCR) showed that the relative expression level of circ_0022382 was significantly lower under intermittent cyclic tension stimulation than in the control group. circ_0022382, miR-4726-5p and Transforming growth factor 3 (TGF-β3) were evaluated by RT-qPCR, Western Blot and immunofluorescence assay. Additionally, the role and mechanism of circ_0022382 in vivo were also consistent in the rat model. Furthermore, Intermittent cyclic mechanical tension can cause degeneration of endplate chondrocytes. The tension-sensitive circRNA_0022382 was decreased, and we found that circRNA_0022382 promoted morphology of endplate chondrocytes by sponge-binding miR-4726-5p down-regulation of target gene the TGF-β3 expression, thereby alleviating IDD. In a rat model of acupuncture, intervertebral disc injection of circ_0022382 relieved the progression of IDD in vivo. In conclusion, the circ_0022382/miR-4726-5p/TGF-β3 axis plays a key role in the anabolism and catabolism of the endplate chondrocyte extracellular matrix (ECM). It is suggested that circ_0022382 may provide a new approach for the prevention and treatment of IDD.
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http://dx.doi.org/10.1016/j.bone.2021.116185DOI Listing
September 2021

Corrigendum: 7-Ethyl-10-Hydroxycamptothecin, A DNA Topoisomerase I Inhibitor, Performs BRD4 Inhibitory Activity and Inhibits Human Leukemic Cell Growth.

Front Pharmacol 2021 30;12:757060. Epub 2021 Aug 30.

Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

[This corrects the article DOI: 10.3389/fphar.2021.664176.].
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http://dx.doi.org/10.3389/fphar.2021.757060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435846PMC
August 2021

Sequential cleavage and blastocyst embryo transfer and IVF outcomes: a systematic review.

Reprod Biol Endocrinol 2021 Sep 14;19(1):142. Epub 2021 Sep 14.

Reproductive Endocrinology Center, Hangzhou Women's Hospital (Hangzhou Maternity and Child Health Care Hospital), Hangzhou, 310000, China.

Background: Sequential embryo transfer has been proposed as a way to improve embryo implantation in women for in vitro fertilization (IVF), but the effect on pregnancy outcomes remains ambiguous. This systematic review was conducted to investigate the efficacy of sequential embryo transfer on IVF outcomes.

Methods: A literature search was performed in the PubMed, Web of Science, Cochrane Library, ScienceDirect and Wanfang databases. Data were pooled using a random- or fixed-effects model according to study heterogeneity. The results are expressed as relative risks (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated by the I statistic. The study protocol was registered prospectively on INPLASY, ID: INPLASY202180019.

Results: Ten eligible studies with 2658 participants compared sequential embryo transfer and cleavage transfer, while four studies with 513 participants compared sequential embryo transfer and blastocyst transfer. The synthesis results showed that the clinical pregnancy rate was higher in the sequential embryo transfer group than in the cleavage embryo transfer group (RR 1.42, 95% CI 1.26-1.60, P< 0.01) for both women who did experience repeated implantation failure (RIF) (RR 1.58, 95% CI 1.17-2.13, P< 0.01) and did not experience RIF (Non-RIF) (RR 1.44, 95% CI 1.20-1.66, P< 0.01). However, sequential embryo transfer showed no significant benefit over blastocyst embryo transfer.

Conclusion: The current systematic review demonstrates that sequential cleavage and blastocyst embryo transfer improve the clinical pregnancy rate over conventional cleavage embryo transfer. For women with adequate embryos, sequential transfer could be attempted following careful consideration. More high-grade evidence from prospective randomized studies is warranted.
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http://dx.doi.org/10.1186/s12958-021-00824-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439041PMC
September 2021

A sensitive aptasensor based on rolling circle amplification and G-rich ssDNA/terbium (III) luminescence enhancement for ofloxacin detection in food.

Talanta 2021 Dec 4;235:122783. Epub 2021 Aug 4.

School of Food and Biological Engineering, Xihua University, Chengdu, 610039, China; Key Laboratory of Food Non Thermal Processing, Engineering Technology Research Center of Food Non Thermal Processing, Yibin Xihua University Research Institute, Yibin, Sichuan, 644004, China. Electronic address:

As the light-harvesting "antenna", G-rich oligonucleotides (such as the G-quadruplex) can interact with lanthanide (III) to bring a luminescent enhancement response. In this study, phenomenon of luminescent enhancement of G-triplex/terbium (III) (G3/Tb) and interaction between G3 and Tb were first reported and characterized. Based on G3/Tb luminescence, a label-free aptasensor for the detection of ofloxacin (OFL) residues in the food was developed. The OFL triggered the action of rolling circle amplification (RCA) allowed for the amplification product of G3-forming sequences in the single-stranded DNA, which promoted the conformational transition of the G3/Tb complexes once the addition of Tb. Under the optimal conditions, the logarithmic correlation between the G3/Tb luminescence intensity and the concentration of OFL was found to be linear in the range of 5-1000 pmol L (R = 0.9949). The limit of detection was 0.18 pmol L (3σ/slope). Additionally, the good recoveries of 90.19-108.89 % and the relative standard deviations values of 0.59-5.87 % were obtained in the application of the aptasensor detecting OFL in the practical samples. These results confirmed that the present aptasensor has a good analytical performance and bright prospect for detecting ofloxacin residues in food.
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http://dx.doi.org/10.1016/j.talanta.2021.122783DOI Listing
December 2021

Degraded polysaccharides from Porphyra haitanensis: purification, physico-chemical properties, antioxidant and immunomodulatory activities.

Glycoconj J 2021 Oct 13;38(5):573-583. Epub 2021 Sep 13.

School of Food Science and Biotechnology, Zhejiang Gongshang University, Xiasha, Hangzhou, Zhejiang, 310018, People's Republic of China.

To explore effect of the structural properties of porphyra haitanensis polysaccharide on its biological activity, degraded porphyra polysaccharides were separated and purified by Cellulose DEAE-52 and Sephadex G-100 chromatography, obtaining three purified components (P1, P2 and P3). All the three components were sulfate polysaccharides containing the repeating units of → 3) β-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →, and → 3) β-D-galactose (1 → 4) α-L-galactose-6-S (1 →, and → 3) 6-O-methyl-β-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →. The molecular weight of the three fractions was measured to be 300.3, 130.4 and 115.1 kDa, respectively. Their antioxidant activity was investigated by the determination of the free radical scavenging effect and ferric reducing power. It was found that P1, P2 and P3 possessed marked antioxidant activity. It was also found that they appreciably enhanced the proliferation, phagocytic ability and nitric oxide secretion in RAW264.7 cells. Lower molecular weight and higher sulfate content were beneficial to bioactivities of P. haitanensis polysaccharides. Overall, P2 and P3 possess superior immuno-modulatory activity to that of P1 and PHP. Thus, the current work will provide the basis for the better utilization of P. haitanensis to develop the related functional foods.
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http://dx.doi.org/10.1007/s10719-021-10009-9DOI Listing
October 2021

SARS-CoV-2 Membrane Glycoprotein M Triggers Apoptosis With the Assistance of Nucleocapsid Protein N in Cells.

Front Cell Infect Microbiol 2021 25;11:706252. Epub 2021 Aug 25.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences (CAS), Wuhan, China.

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don't know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.
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http://dx.doi.org/10.3389/fcimb.2021.706252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425412PMC
September 2021

Pathogenesis of a novel porcine parainfluenza virus type 1 isolate in conventional and colostrum deprived/caesarean derived pigs.

Virology 2021 Nov 3;563:88-97. Epub 2021 Sep 3.

Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, 1850 Christensen Drive, Ames, IA 50011, USA. Electronic address:

Two experimental challenge studies were conducted to evaluate the pathogenesis of a porcine parainfluenza virus type 1 (PPIV-1) isolate. Four-week-old conventional (CON) pigs were challenged in Study 1 and six-week-old caesarean derived/colostrum deprived (CDCD) pigs were challenged in Study 2. Results indicate that PPIV-1 shedding and replication occur in the upper and lower respiratory tracts of CON and CDCD pigs as detected by RT-qPCR and immunohistochemistry. Mild macroscopic lung lesions were observed in CON pigs but not in CDCD pigs. Microscopic lung lesions were mild and consisted of peribronchiolar lymphocytic cuffing and epithelial proliferation in CON and CDCD pigs. Serum neutralizing antibodies were detected in the CON and CDCD pigs by 14 and 7 days post inoculation, respectively. This study provides evidence that in spite of PPIV-1 infection and replication in challenged swine, significant clinical respiratory disease was not observed.
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http://dx.doi.org/10.1016/j.virol.2021.08.015DOI Listing
November 2021

Pulmonary Benefits of Intervention with Air Cleaner among Schoolchildren in Beijing: A Randomized Double-Blind Crossover Study.

Environ Sci Technol 2021 Sep 7. Epub 2021 Sep 7.

Key Laboratory of Environment and Human Health, National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, China.

We conducted a crossover study employing air cleaner intervention among 125 schoolchildren aged 9-12 years in a boarding school in Beijing, China. The PM concentrations were monitored, and 27 biomarkers were analyzed. We used the linear mixed-effects model to evaluate the association of intervention/time-weighted PM concentrations with biomarkers. The outcomes showed that air cleaner intervention was associated with FeNO, exhaled breath condensate (EBC) IL-1β, and IL-6, which decreased by 12.57%, 10.83%, and 4.33%, respectively. Similar results were observed in the associations with PMs. Lag 1 day PMs had the strongest relationship with biomarkers, and significant changes were observed in biomarkers such as FEV, FeNO, EBC 8-iso, and MCP-1. Boys showed higher percentage changes than girls, and the related biomarkers were FeNO, EBC 4-HNE, IL-1β, IL-6, and MCP-1. The results showed that biomarkers such as FeNO, EBC IL-6, MCP-1, and 4-HNE could sensitively reflect the early abnormal response of the respiratory system under short-term PM exposure among healthy schoolchildren and indicated that (1) air cleaners exert a protective effect on children's respiratory system. (2) PM had lag and cumulative effect, lag 1 day had the greatest effect. (3) The boys were more sensitive than the girls.
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http://dx.doi.org/10.1021/acs.est.1c03146DOI Listing
September 2021

Motor Circuit and Superior Temporal Sulcus Activities Linked to Individual Differences in Multisensory Speech Perception.

Brain Topogr 2021 Sep 4. Epub 2021 Sep 4.

The Clinical Hospital of Chengdu Brain Science Institute, High-Field Magnetic Resonance Brain Imaging Key Laboratory of Sichuan Province, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 611731, People's Republic of China.

Integrating multimodal information into a unified perception is a fundamental human capacity. McGurk effect is a remarkable multisensory illusion that demonstrates a percept different from incongruent auditory and visual syllables. However, not all listeners perceive the McGurk illusion to the same degree. The neural basis for individual differences in modulation of multisensory integration and syllabic perception remains largely unclear. To probe the possible involvement of specific neural circuits in individual differences in multisensory speech perception, we first implemented a behavioral experiment to examine the McGurk susceptibility. Then, functional magnetic resonance imaging was performed in 63 participants to measure the brain activity in response to non-McGurk audiovisual syllables. We revealed significant individual variability in McGurk illusion perception. Moreover, we found significant differential activations of the auditory and visual regions and the left Superior temporal sulcus (STS), as well as multiple motor areas between strong and weak McGurk perceivers. Importantly, the individual engagement of the STS and motor areas could specifically predict the behavioral McGurk susceptibility, contrary to the sensory regions. These findings suggest that the distinct multimodal integration in STS as well as coordinated phonemic modulatory processes in motor circuits may serve as a neural substrate for interindividual differences in multisensory speech perception.
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http://dx.doi.org/10.1007/s10548-021-00869-7DOI Listing
September 2021

A neural decoding algorithm that generates language from visual activity evoked by natural images.

Neural Netw 2021 Aug 12;144:90-100. Epub 2021 Aug 12.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, 610054, China. Electronic address:

Transforming neural activities into language is revolutionary for human-computer interaction as well as functional restoration of aphasia. Present rapid development of artificial intelligence makes it feasible to decode the neural signals of human visual activities. In this paper, a novel Progressive Transfer Language Decoding Model (PT-LDM) is proposed to decode visual fMRI signals into phrases or sentences when natural images are being watched. The PT-LDM consists of an image-encoder, a fMRI encoder and a language-decoder. The results showed that phrases and sentences were successfully generated from visual activities. Similarity analysis showed that three often-used evaluation indexes BLEU, ROUGE and CIDEr reached 0.182, 0.197 and 0.680 averagely between the generated texts and the corresponding annotated texts in the testing set respectively, significantly higher than the baseline. Moreover, we found that higher visual areas usually had better performance than lower visual areas and the contribution curve of visual response patterns in language decoding varied at successively different time points. Our findings demonstrate that the neural representations elicited in visual cortices when scenes are being viewed have already contained semantic information that can be utilized to generate human language. Our study shows potential application of language-based brain-machine interfaces in the future, especially for assisting aphasics in communicating more efficiently with fMRI signals.
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http://dx.doi.org/10.1016/j.neunet.2021.08.006DOI Listing
August 2021

Flavonoid subclasses and CHD risk: a meta-analysis of prospective cohort studies.

Br J Nutr 2021 Sep 2:1-11. Epub 2021 Sep 2.

Institute of Nutrition & Health, Qingdao University, Qingdao, People's Republic of China.

Epidemiological studies have shown that higher intake of flavonoid is inversely associated with CHD risk. However, which flavonoid subclass could reduce CHD risk has remained controversial. The present meta-analysis of prospective cohort studies aimed to quantitatively assess the associations between flavonoid subclasses and CHD risk. A systematic literature search was implemented from PubMed and Web of Science databases up to March 2021, and eligible studies were identified. Multivariate-adjust relative risks (RR) with corresponding 95 % CI were pooled by using a random-effects model. A restricted cubic spline regression model was performed for non-linear dose-response analysis. A total of 19 independent prospective cohort studies with 894 471 participants and 34 707 events were included. The results showed that dietary intakes of anthocyanins (RR = 0·90; 95 % CI: 0·83, 0·98), proanthocyanidins (RR = 0·78; 95 % CI: 0·65, 0·94), flavonols (RR = 0·88; 95 % CI: 0·79, 0·98), flavones (RR = 0·94; 95 % CI: 0·89, 0·99) and isoflavones (RR = 0·90; 95 % CI: 0·83, 0·98) were negatively associated with CHD risk. Dose-response analysis showed that increment of 50 mg/d anthocyanins, 100 mg/d proanthocyanidins, 25 mg/d flavonols, 5 mg/d flavones and 0·5 mg/d isoflavones were associated with 5 % reduction in CHD risk, respectively. Sensitivity and subgroup analyses were used to further support these associations. The present results indicate that dietary intakes of fruits and vegetables abundant five flavonoid subclasses, namely anthocyanins, proanthocyanidins, flavonols, flavones and isoflavones, are associated with a lower risk of CHD.
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http://dx.doi.org/10.1017/S0007114521003391DOI Listing
September 2021

Tumour-stroma ratio is a valuable prognostic factor for oral tongue squamous cell carcinoma.

Oral Dis 2021 Aug 29. Epub 2021 Aug 29.

Department of Oral and Maxillofacial-Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Beijing, China.

Objective: The objectives of this study were to estimate the prognostic value of the tumour-stroma ratio (TSR) and tumour budding (TB) in oral tongue squamous cell carcinoma (OTSCC) and to establish a reliable model to predict the outcome of OTSCC patients.

Methods: A total of 103 patients surgically treated at our hospital were enrolled in this study. Chi-square tests, Kaplan-Meier analyses and Cox proportional hazards regression models were performed for statistical analysis.

Results: Fifty-six patients were categorized as stroma-rich, and 47 patients were categorized as stroma-poor. Only pathological grade was associated with the TSR (p = 0.017). Kaplan-Meier analysis showed that stroma-rich, high-intensity budding and high risk groups were associated with worse prognosis. The Cox regression model showed that the TSR was an independent risk factor for OTSCC patients prognosis, and the high risk group was also related to poor prognosis (p < 0.05). TB was significantly associated with poor prognosis but was not an independent risk factor.

Conclusions: We found that patients in the stroma-rich group had a worse long-term prognosis. The TSR is an independent risk factor for OTSCC patients' outcome. In addition, a risk model that combined the TSR and TB proved to be valuable for predicting OTSCC patients' outcome.
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http://dx.doi.org/10.1111/odi.14013DOI Listing
August 2021

Observation of Giant Optical Linear Dichroism in a Zigzag Antiferromagnet FePS.

Nano Lett 2021 Aug 16;21(16):6938-6945. Epub 2021 Aug 16.

Department of Physics, University of Washington, Seattle, Washington 98195, United States.

Direct optical probing of the antiferromagnetic order parameter in atomically thin samples is challenging, for example, via magneto-optical spectroscopy, due to the lack of net magnetization. Here, we report zigzag-antiferromagnetism (AFM) induced optical linear dichroism (LD) in layered transition-metal thiophosphate FePS down to the monolayer limit. The observed LD is giant despite having the optical wave vector parallel to the Néel vector. The LD is at least one order of magnitude larger than those reported in other antiferromagnetic systems, where the optical wave vector is orthogonal to the Néel vector. The large LD enables the probe of 60° orientated zigzag-AFM domains. The optical anisotropy in FePS originates from an electronic anisotropy associated with the zigzag direction of the AFM order and is independent of the spin-pointing direction. Our findings point to a new optical approach for the investigation and control of zigzag or stripe magnetic order in strongly correlated systems.
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http://dx.doi.org/10.1021/acs.nanolett.1c02188DOI Listing
August 2021

Rhamnolipid Enhances the Nitrogen Fixation Activity of by Influencing Lysine Succinylation.

Front Microbiol 2021 30;12:697963. Epub 2021 Jul 30.

College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, China.

The enhancement of nitrogen fixation activity of diazotrophs is essential for safe crop production. Lysine succinylation (K) is widely present in eukaryotes and prokaryotes and regulates various biological process. However, knowledge of the extent of K in nitrogen fixation of is scarce. In this study, we found that 250 mg/l of rhamnolipid (RL) significantly increased the nitrogen fixation activity of by 39%, as compared with the control. Real-time quantitative reverse transcription PCR (qRT-PCR) confirmed that RL could remarkably increase the transcript levels of and genes. In addition, a global K of was profiled using a 4D label-free quantitative proteomic approach. In total, 5,008 K sites were identified on 1,376 succinylated proteins. Bioinformatics analysis showed that the addition of RL influence on the K level, and the succinylated proteins were involved in various metabolic processes, particularly enriched in oxidative phosphorylation, tricarboxylic acid cycle (TCA) cycle, and nitrogen metabolism. Meanwhile, multiple succinylation sites on MoFe protein (NifDK) may influence nitrogenase activity. These results would provide an experimental basis for the regulation of biological nitrogen fixation with K and shed new light on the mechanistic study of nitrogen fixation.
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http://dx.doi.org/10.3389/fmicb.2021.697963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360865PMC
July 2021

ASO Author Reflections: A Simple Method to Predict Risk Factors of Complications After Pneumonectomy.

Ann Surg Oncol 2021 Aug 11. Epub 2021 Aug 11.

Minimally Invasive Treatment Center, Beijing Chest Hospital, Beijing, China.

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http://dx.doi.org/10.1245/s10434-021-10629-3DOI Listing
August 2021

Identification and Validation of PIK3CA as a Marker Associated with Prognosis and Immune Infiltration in Renal Clear Cell Carcinoma.

J Oncol 2021 27;2021:3632576. Epub 2021 Jul 27.

Department of Urology, Central South University, Changsha 410013, China.

Background: Kidney renal clear cell carcinoma (KIRC) is the most prevalent renal malignancy. The therapeutic strategies for advanced KIRC are very few, with only sunitinib being widely approved. Mutations in the PIK3CA gene can affect tumor cell proliferation, metastasis, and patients' survival.

Methods: Bioinformatics analysis was performed to explore the expression and clinical significance of PIK3CA in KIRC. Moreover, qRT-PCR was conducted to verify the result.

Results: Subgroup analyses of KIRC tissue based on gender, tumor grade, and cancer stage indicated downregulation of PIK3CA mRNA expression. The KIRC patients with high PIK3CA expression indicated a better overall survival, progression-free survival, and disease-free survival. A predictive nomogram was constructed and demonstrated that the calibration plots for the 3-year and 5-year OS rates were predicted relatively well compared with an ideal model in the TCGA KIRC cohort. The validation study revealed that downregulation of PIK3CA in KIRC tissues and low PIK3CA expression had a poor overall survival with an AUC of 0.775 in the ROC curve. Moreover, Cox regression analysis revealed that PIK3CA expression and clinical stage were independent factors affecting the prognosis of KIRC patients. PIK3CA expression was found to be significantly associated with the abundance of immune cells and immune biomarker sets. PIK3CA and associated genes were found to be mainly associated with immune response and the JAK-STAT signaling pathway.

Conclusion: We identified PIK3CA as a potential biomarker for prognosis correlated with immune infiltrates in KIRC. Further studies should focus on the functions of PIK3CA in KIRC carcinogenesis.
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http://dx.doi.org/10.1155/2021/3632576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337125PMC
July 2021
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