Publications by authors named "Jiaxin Yang"

172 Publications

High Mobility Organic Lasing Semiconductor with Crystallization-Enhanced Emission for Light-Emitting Transistors.

Angew Chem Int Ed Engl 2021 Jul 18. Epub 2021 Jul 18.

Tianjin University, Department of Chemistry, zhongguancun, 100190, Beijing, CHINA.

The development of high mobility organic laser semiconductors with strong emission is of great scientific and technical importance, but challenging. Herein, we present a high mobility organic laser semiconductor, 2,7-diphenyl-9H-fluorene (LD-1) showing unique crystallization-enhanced emission guided by elaborately modulating its crystal growth process. The obtained one-dimensional nanowires of LD-1 show outstanding integrated properties including: high absolute photoluminescence quantum yield (PLQY) approaching 80%, high charge carrier mobility of 0.08 cm 2 V -1 s -1 , Fabry-Perot lasing characters with a low threshold of 86 uJ cm -2 and a high-quality factor of ~ 2400. Furthermore, electrically induced emission was obtained from an individual LD-1 crystal nanowire-based light-emitting transistor due to the recombination of holes and electrons simultaneously injected into the nanowire, which provides a good platform for the study of electrically pumped organic lasers and other related ultrasmall integrated electrical-driven photonic devices.
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http://dx.doi.org/10.1002/anie.202108224DOI Listing
July 2021

A deep learning algorithm based on 1D CNN-LSTM for automatic sleep staging.

Technol Health Care 2021 Jun 25. Epub 2021 Jun 25.

College of Bioengineering, Chongqing University, Chongqing, China.

Background: Sleep staging is an important part of sleep research. Traditional automatic sleep staging based on machine learning requires extensive feature extraction and selection.

Objective: This paper proposed a deep learning algorithm without feature extraction based on one-dimensional convolutional neural network and long short-term memory.

Methods: The algorithm can automatically divide sleep into 5 phases including awake period, non-rapid eye movement sleep period (N1 ∼ N3) and rapid eye movement using the electroencephalogram signals. The raw signal was processed by the wavelet transform. Then, the processed signal was directly input into the deep learning algorithm to obtain the staging result.

Results: The accuracy of staging is 93.47% using the Fpz-Cz electroencephalogram signal. When using the Fpz-Cz and electroencephalogram signal, the algorithm can obtain the highest accuracy of 94.15%.

Conclusion: These results show that this algorithm is suitable for different physiological signals and can realize end-to-end automatic sleep staging without any manual feature extraction.
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http://dx.doi.org/10.3233/THC-212847DOI Listing
June 2021

Analysis of the genomic landscape of yolk sac tumors reveals mechanisms of evolution and chemoresistance.

Nat Commun 2021 06 11;12(1):3579. Epub 2021 Jun 11.

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

Yolk sac tumors (YSTs) are a major histological subtype of malignant ovarian germ cell tumors with a relatively poor prognosis. The molecular basis of this disease has not been thoroughly characterized at the genomic level. Here we perform whole-exome and RNA sequencing on 41 clinical tumor samples from 30 YST patients, with distinct responses to cisplatin-based chemotherapy. We show that microsatellite instability status and mutational signatures are informative of chemoresistance. We identify somatic driver candidates, including significantly mutated genes KRAS and KIT and copy-number alteration drivers, including deleted ARID1A and PARK2, and amplified ZNF217, CDKN1B, and KRAS. YSTs have very infrequent TP53 mutations, whereas the tumors from patients with abnormal gonadal development contain both KRAS and TP53 mutations. We further reveal a role of OVOL2 overexpression in YST resistance to cisplatin. This study lays a critical foundation for understanding key molecular aberrations in YSTs and developing related therapeutic strategies.
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http://dx.doi.org/10.1038/s41467-021-23681-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196104PMC
June 2021

Luminescent detection of pesticides by color changeable flexible coumarin-3-carboxylic acid/GdF:Sm composite film.

Spectrochim Acta A Mol Biomol Spectrosc 2021 Nov 26;261:120002. Epub 2021 May 26.

School of Physics & The Key Laboratory of Weak Light Nonlinear Photonics, Ministry of Education, Nankai University, Tianjin 300071, PR China; Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan 030006, PR China. Electronic address:

The utilization and residue of pesticides exist multifaceted non-restrictive effects on food safety and ecological protection. Exploitation of rapid and sensitive pesticide detection technology is imperative and will be helpful to better control the detriment of pesticides. Here, a novel flexible film has been prepared based on organic-inorganic composite materials (coumarin-3-carboxylic acid and GdF:Sm), which exhibits good optical performance and can well realize the timely and maneuverable detection for different pesticides. The spectra and luminescence properties of each composition in the composite have been analyzed systematically, and the coordinated fluorescence emission of Sm and coumarin-3-carboxylic acid is revealed at an excitation wavelength of 373 nm. Besides, the energy transfer mechanism is also researched by both experiment and theoretical calculation. The actual detection of different pesticides reveals differential fluorescence influence degree. Meanwhile, the flexible film still possesses sensitive recognition in the presence of micro concentration of pesticides. Results indicate that the flexible film with good optical performance can produce visual detection ability and provide a promising strategy for wider detection applications.
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http://dx.doi.org/10.1016/j.saa.2021.120002DOI Listing
November 2021

Tumor Volume Predicts High-Risk Patients and Guides Initial Chemoradiotherapy for Early Cervical Cancer.

Front Oncol 2021 27;11:640846. Epub 2021 Apr 27.

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

We evaluated the relationship between the minimum tumor-free margin, tumor volume, and adverse pathological risk factors in early cervical cancer and explored the predictive value of these parameters for different types of risk patients to guide individualized therapeutic strategies. Patients who received the initial treatment of radical operation of cervical cancer and their postoperative pathological reports in our hospital from July 1, 2017, to June 30, 2019, were reviewed. Their minimum tumor-free margin and tumor volume were measured on preoperative magnetic resonance imaging. Student's t-test and the receiver operating characteristic curve analysis were used for data analysis. A total of 240 patients were included. Adverse pathological risk factors were as follows: deep cervical infiltration, 95 (39.6%) cases; lymph vascular space invasion, 91 (37.9%); lymph node metastasis, 20 (8.3%); parametrial infiltration, 8 (3.3%); tumor diameter ≥4 cm, 7 (2.9%); and positive surgical margin, 1 (0.4%). According to the adverse pathological factors, there were 20 (8.3%) high-risk patients, 50 (20.8%) medium-risk patients, and 170 (70.8%) low-risk patients. The ranges of the minimum tumor-free margin and tumor volume were 0.01-13.5 mm and 105-27,990 mm, respectively. The minimum tumor-free margin with lymph node metastasis was significantly smaller than that without (P <0.05). The tumor volume with parametrial infiltration, deep cervical infiltration, or lymph vascular space invasion was significantly greater than that without (P < 0.05). The tumor volume was significantly different among low-, medium-, and high-risk patients (P <0.05). Tumor volume was of predictive value for high-risk patients (P < 0.05). With 3,505 mm as the cutoff value, the sensitivity and specificity for the prediction of high-risk patients were 88.9% and 84.8%, respectively. Tumor volume can be used as a great predictor of high-risk patients (cutoff value, 3,505 mm), which could be an indication of initial chemoradiotherapy for early cervical cancer.
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http://dx.doi.org/10.3389/fonc.2021.640846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111085PMC
April 2021

The blue light receptor CRY1 interacts with GID1 and DELLA proteins to repress GA signaling during photomorphogenesis in Arabidopsis.

Mol Plant 2021 May 7. Epub 2021 May 7.

College of Biology, Hunan Province Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan Hybrid Rape Engineering and Technology Research Center, Hunan University, Changsha 410082, China; Shenzhen Institute, Hunan University, Shenzhen 518057, China. Electronic address:

Light is a critical environmental cue that regulates a variety of diverse plant developmental processes. Cryptochrome 1 (CRY1) is the major photoreceptor that mediates blue light-dependent photomorphogenic responses such as the inhibition of hypocotyl elongation. Gibberellin (GA) participates in the repression of photomorphogenesis and promotes hypocotyl elongation. However, the antagonistic interaction between blue light and GA is not well understood. Here, we report that blue light represses GA-induced degradation of the DELLA proteins (DELLAs), which are key negative regulators in the GA signaling pathway, via CRY1, thereby inhibiting the GA response during hypocotyl elongation. Both in vitro and in vivo biochemical analyses demonstrated that CRY1 physically interacts with GA receptors-GA-INSENSITIVE DWARF 1 proteins (GID1s)-and DELLAs in a blue light-dependent manner. Furthermore, we showed that CRY1 inhibits the association between GID1s and DELLAs. Genetically, CRY1 antagonizes the function of GID1s to repress the expression of cell elongation-related genes and thus hypocotyl elongation. Taken together, our findings demonstrate that CRY1 coordinates blue light and GA signaling for plant photomorphogenesis by stabilizing DELLAs through the binding and inactivation of GID1s, providing new insights into the mechanism by which blue light antagonizes the function of GA in photomorphogenesis.
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http://dx.doi.org/10.1016/j.molp.2021.05.011DOI Listing
May 2021

Molecular Weight Engineering in High-Performance Ambipolar Emissive Mesopolymers.

Angew Chem Int Ed Engl 2021 Jun 1;60(27):14902-14908. Epub 2021 Jun 1.

Tianjin Key Laboratory of Molecular Optoelectronic Sciences, Department of Chemistry, School of Science, Tianjin University, Tianjin, 300072, China.

Mesopolymers with high solubility, free of structural defects, and negligible batch-to-batch variation open a new avenue for organic optoelectronics. Organic light emitting transistors that combine the functions of organic light-emitting diodes and organic field-effect transistors. However, charge transport ability and light emitting strength are contradictory within one conjugated polymer. Herein, three low-molecular-weight mesopolymers with thienopyrroledione-benzothiadiazole repeating units (meso-TBTF) were obtained. The mesopolymers show strong solid-state emission and high ambipolar carrier mobility. The molecular weights of meso-TBTF can be tuned by polymerization temperature. The mesopolymers have photoluminescence quantum yields (PLQY) of about 50 % in solution and 10 % in solid state. Polymer light emitting diodes of this material are fabricated to explore its potential use in optoelectronic devices.
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http://dx.doi.org/10.1002/anie.202105036DOI Listing
June 2021

Oxytocinergic Modulation of Threat-Specific Amygdala Sensitization in Humans Is Critically Mediated by Serotonergic Mechanisms.

Biol Psychiatry Cogn Neurosci Neuroimaging 2021 Apr 21. Epub 2021 Apr 21.

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

Background: Overarching conceptualizations propose that the complex social-emotional effects of oxytocin (OXT) in humans are partly mediated by interactions with other neurotransmitter systems. Recent animal models suggest that the anxiolytic effects of OXT are critically mediated by the serotonin (5-HT) system, yet direct evidence in humans is lacking.

Methods: To determine the role of 5-HT in OXT-induced attenuation of amygdala threat reactivity and sensitization/desensitization, we conducted a parallel-group, randomized, placebo-controlled, double-blind experiment during which 121 healthy subjects underwent a transient decrease in 5-HT signaling via acute tryptophan depletion or the corresponding placebo-control protocol before the administration of intranasal OXT or placebo intranasal spray, respectively. Mean and repetition-dependent changes in threat-specific amygdala reactivity toward threatening stimuli (angry faces) as assessed by functional magnetic resonance imaging served as the primary outcome.

Results: No main or interaction effects of treatment on amygdala threat reactivity were observed, yet OXT switched bilateral amygdala threat sensitization to desensitization, and this effect was significantly attenuated during decreased central 5-HT signaling via pretreatment with acute tryptophan depletion.

Conclusions: The present findings provide the first evidence for a role of OXT in threat-specific amygdala desensitization in humans and suggest that these effects are critically mediated by the 5-HT system. OXT may have a therapeutic potential to facilitate amygdala desensitization, and adjunct upregulation of 5-HT neurotransmission may facilitate OXT's anxiolytic potential.
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http://dx.doi.org/10.1016/j.bpsc.2021.04.009DOI Listing
April 2021

The Broad Autism Phenotype Questionnaire (BAPQ): Strengths, weaknesses and future improvements in Chinese version.

Asian J Psychiatr 2021 Jun 6;60:102655. Epub 2021 Apr 6.

National Clinical Research Center for Mental Disorders, Department of Psychiatry, The Second Xiangya Hospital, Central South University, Hunan Medical Center for Mental Health, Changsha, Hunan, China. Electronic address:

Broad Autism Phenotype (BAP) refers to a set of symptoms or personality traits which similar but not meet the diagnostic criteria for autism in relatives of individuals with Autism Spetrum Disorders (ASD).The Broad Autism Phenotype Questionnaire (BAPQ) is one of the new and widely used assessment tools to measure BAP.It has been translated into 8 different languages and some versions were investigated the psychometric properties but not including Chinese version (BAPQ-C).This study aimed to analyze the reliability and validity of the BAPQ-C and explore its applicability in the Chinese population. 1,618 families were included in the study consisting of 890 ASD children and 728 typically developed(TD)children. Our results did not find a well-fitting three-factor(Aloof,Rigid,Pragmatic language) structure which is consistent with previous studies.But we formed a model that only included Aloof and Pragmatic language dimensions.The parameter after removing the rigid dimension was significantly better.This study indicated that the short version of Aloof and Pragmatic language sub-scales has good reliability and validity and can be used to study BAP in the Chinese population. Nevertheless, more studies are still needed to improve the psychometric properties of the BAPQ-C.
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http://dx.doi.org/10.1016/j.ajp.2021.102655DOI Listing
June 2021

Interneuron development and dysfunction.

FEBS J 2021 Apr 12. Epub 2021 Apr 12.

Precise Genome Engineering Center, School of Life Sciences, Guangzhou University, China.

Understanding excitation and inhibition balance in the brain begins with the tale of two basic types of neurons, glutamatergic projection neurons and GABAergic interneurons. The diversity of cortical interneurons is contributed by multiple origins in the ventral forebrain, various tangential migration routes, and complicated regulations of intrinsic factors, extrinsic signals, and activities. Abnormalities of interneuron development lead to dysfunction of interneurons and inhibitory circuits, which are highly associated with neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and intellectual disability. In this review, we mainly discuss recent findings on the development of cortical interneuron and on neurodevelopmental disorders related to interneuron dysfunction.
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http://dx.doi.org/10.1111/febs.15872DOI Listing
April 2021

Evaluation of Cervical High-Grade Squamous Intraepithelial Lesions-Correlated Markers as Triage Strategy for Colposcopy After Co-Testing.

Onco Targets Ther 2021 19;14:2075-2084. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People's Republic of China.

Background: Colposcopy was referred in cases with severe abnormalities in co-testing. Although p16/Ki67 dual staining reduced the referral rate, its sensitivity and specificity need to be enhanced.

Methods: The expressions of p16, Ki-67, SMAD3, YAP1, RELA were evaluated in the colposcopy referral population. The inclusion criteria included 30-60 years and diagnosed with HPV16/18-positive, other HR-HPV-positive with ASCUS, LSIL, AGC (atypical glandular cell) in co-testing. Colposcopies, endocervical curettages of cervical biopsies were also collected. Cases were excluded if there were no biopsies, if the interval between a cervical screening test and biopsies was more than 6 months, or if insufficient tissue was available as a formalin-fixed paraffin-embedded block. The pathology was independently reviewed by two pathologists. Discrepant interpretations were adjudicated by a third pathologist.

Results: In total, 1194 of 1273 cases who were referred to colposcopy were evaluated in the present study. The sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 62.1% and 89.5%, respectively. p16+ combined with YAP1+ and/or RELA+ provided a sensitivity and specificity of 70.9% and 89.5%, respectively, while 72.8% and 86.4% were achieved by p16+ combined with YAP1+ and/or SMAD3+ and/or RELA+. In HPV16/18+ and LSIL subgroups, the sensitivity and specificity of p16+ combined with Ki-67+ for predicting CIN2+ were 67.7% and 87.6%, respectively, for the former group and 58.6%, 88.8%, respectively, for the latter group. p16+, YAP1+/RELA+ showed a better performance for predicting CIN2+ with a better sensitivity and considerable specificity in the other HPV+ combined with ASCUS group than were achieved by p16+ combined with Ki-67+. RELA+ and the combination of p16 and RELA/YAP1 also provided the Max AUC area.

Conclusion: Our study shows that RELA and the combination of p16 and RELA/YAP1 achieved better sensitivity and specificity for detecting morphologically CIN2+ lesions.
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http://dx.doi.org/10.2147/OTT.S300269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989978PMC
March 2021

Oncological and Reproductive Outcomes of Cystectomy Compared with Unilateral Salpingo-Oophorectomy as Fertility-Sparing Surgery in Patients with Apparent Early Stage Pure Immature Ovarian Teratomas.

Ann Surg Oncol 2021 Mar 26. Epub 2021 Mar 26.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

Purpose: To compare the oncological and reproductive outcomes of patients with apparent early stage pure ovarian immature teratomas (IMTs) treated with unilateral salpingo-oophorectomy (USO) or cystectomy.

Patients And Methods: We retrospectively reviewed the medical records of patients with apparent early stage pure ovarian IMTs who received fertility-sparing surgery (FSS) between 1984 and 2019. FSS was defined as preservation of the uterus and at least one adnexa. Recurrence rates were compared between patients receiving USO and cystectomy. Reproductive outcomes and menstrual histories were assessed by telephone interview.

Results: A total of 124 patients were included, of whom 83 underwent USO and 41 underwent cystectomy. After a median follow-up of 70.6 months (range: 6.2-410.6 months), eight patients suffered recurrences (5 in the USO group and 3 in the cystectomy group). The median times to recurrence were 5.0 and 5.1 months in the USO and cystectomy groups, respectively (P = 0.764). All patients with recurrence were successfully salvaged by surgery, except for one death. Univariate analysis showed no difference in disease-free survival and overall survival between the groups (P = 0.781, 0.155). Of the 111 patients contacted by telephone, 97 resumed menstruation following the surgery. Of the 31 patients desiring pregnancy, 26 achieved 28 pregnancies. USO (83.3%), like cystectomy (85.7%), resulted in excellent pregnancy rates.

Conclusions: A USO is the standard treatment for women with early stage pure IMTs who want to preserve fertility. However, a cystectomy with adjuvant chemotherapy may be a suitable fertility-sparing therapy when a cystectomy is the only surgical option.
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http://dx.doi.org/10.1245/s10434-021-09719-zDOI Listing
March 2021

Alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC): a retrospective study of 27 cases.

Arch Gynecol Obstet 2021 Mar 9. Epub 2021 Mar 9.

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

Objective: The aim of the study was to investigate the relative risk factors associated with the prognosis and effective treatments of alpha-fetoprotein (AFP)-producing epithelial ovarian carcinoma (EOC).

Method: We presented three cases of AFP-producing EOC and performed a brief review to summarize the clinicopathological features and prognostic factors of 24 cases that have been previously reported. We evaluated the correlations among prognostic and clinical parameters, such as stage, pathology and chemotherapy regimens. In addition, a retrospective review of these 27 cases was conducted, and survival curves were estimated using the Kaplan-Meier method.

Results: The patients were aged between 23 and 77 years. The median overall survival was 10 months, and ten (37.04%) patients died within 18 months. We compared the overall mean survival times of all patients in different stages, and the results suggest that the postoperative pathological staging is hardly correlated with prognosis (P = 0.76). There was a correlation between pathology and prognosis (P = 0.0018). The mean survival time was longer for patients who had undergone chemotherapy than for those without chemotherapy (14.88 vs 0.65 months) (P < 0.0001). Moreover, although patients had a good response to the regimens for PEB and TC (P = 0.004), there was no significant difference between PEB and TC (P = 0.386).

Conclusions: AFP-producing EOC is uncommon and regarded as an extremely malignant type of tumor. Patients with chemotherapy may have a longer survival time; additionally, PEB and TC may be an optimal selection for this kind of tumor. Further large-scale studies are needed to confirm our findings.
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http://dx.doi.org/10.1007/s00404-021-06017-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942666PMC
March 2021

Chem-inspired hollow ceria nanozymes with lysosome-targeting for tumor synergistic phototherapy.

J Mater Chem B 2021 03;9(10):2515-2523

Research Center of Pharmaceutical Preparations and Nanomedicine, College of Pharmacy, Chongqing Medical University, Chongqing 400016, China.

The precise operation of the hypoxic tumor microenvironment presents a promising way to improve treatment efficacy, in particular in tumor synergistic phototherapy. This work reports an innovative approach to build adenosine triphosphate-modified hollow ceria nanozymes ([email protected]) that manipulate tumor hypoxia to effectively achieve drug delivery. Hollow ceria nanoparticles (HCNPs) exhibit a controllable hollow structure through varying nitric acid concentrations in the nanocomposites. Specifically, ATP modification makes HCNPs exceptionally biocompatible and stable and acts as a regulator of HCNP enzymatic activity. In the stage of drug loading, newly prepared [email protected] serves as an in situ oxygen-generating agent because of its ability to simulate catalase. Therefore, [email protected] has adjustable enzymatic properties that act like a "switch" to selectively supply oxygen in response to high levels of hydrogen peroxide expression and the slightly acidic lysosomal environment of the tumor to enhance lysosome-targeted photodynamic therapy. Moreover, the obvious anticancer effects of [email protected] are demonstrated in vitro and in vivo. Overall, a simple and rapid self-assembly strategy to form and modify multifunctional HCNPs is reported, which may further propel their application in the field of precision tumor treatment.
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http://dx.doi.org/10.1039/d0tb02837aDOI Listing
March 2021

Identification of a Six-Gene Signature for Predicting the Overall Survival of Cervical Cancer Patients.

Onco Targets Ther 2021 5;14:809-822. Epub 2021 Feb 5.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Background: Although the incidence of cervical cancer has decreased in recent decades with the development of human papillomavirus vaccines and cancer screening, cervical cancer remains one of the leading causes of cancer-related death worldwide. Identifying potential biomarkers for cervical cancer treatment and prognosis prediction is necessary.

Methods: Samples with mRNA sequencing, copy number variant, single nucleotide polymorphism and clinical follow-up data were downloaded from The Cancer Genome Atlas database and randomly divided into a training dataset (N=146) and a test dataset (N=147). We selected and identified a prognostic gene set and mutated gene set and then integrated the two gene sets with the random survival forest algorithm and constructed a prognostic signature. External validation and immunohistochemical staining were also performed.

Results: We obtained 1416 differentially expressed prognosis-related genes, 624 genes with copy number amplification, 1038 genes with copy number deletion, and 163 significantly mutated genes. A total of 75 candidate genes were obtained after overlapping the differentially expressed genes and the genes with genomic variations. Subsequently, we obtained six characteristic genes through the random survival forest algorithm. The results showed that high expression of , and and low expression of and were associated with a poor prognosis in cervical cancer patients. We constructed a six-gene signature that can separate cervical cancer patients according to their different overall survival rates, and it showed robust performance for predicting survival (training set: ˂ 0.001, AUC = 0.82; testing set: ˂ 0.01, AUC = 0.59).

Conclusion: Our study identified a novel six-gene signature and nomogram for predicting the overall survival of cervical cancer patients, which may be beneficial for clinical decision-making for individualized treatment.
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http://dx.doi.org/10.2147/OTT.S276553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873033PMC
February 2021

Providing a view for toxicity mechanism of tetracycline by analysis of the connections between metabolites and biologic endpoints of wheat.

Ecotoxicol Environ Saf 2021 Apr 2;212:111998. Epub 2021 Feb 2.

School of Horticulture and Landscape Architecture, Henan Institute of Science and Technology, Xinxiang 453003, China; Henan Province Engineering Research Center of Horticultural Plant Resource Utilization and Germplasm Enhancement, Xinxiang 453003, China.

Metabolomics is an implement for testing the toxicity of antibiotics, and provides a comprehensive view of the overall response to stress; however, the connections between metabolites and biologic endpoints keep unclear in response to antibiotics. In this study, wheat seeds were exposed to tetracycline for 5 days. The results proved that tetracycline restrained growth, reduced chlorophyl and carotinoid contents and cell permeability, and increased reactive oxygen species (ROS) levels and malondialdehyde (MDA) content. Orthogonal partial least squares (OPLS) was used to analyze the connections between metabolites and biologic endpoints, which discovered that 11 metabolic pathways were significantly affected by tetracycline, and amino acid metabolism could largely apply to root growth and ROS accumulation, while carbohydrate metabolism could have a ruling effect on tetracycline-induced cell permeability. 13 metabolites all played active roles in mediating tetracycline's effects on root length, root fresh weight and cell permeability but had no significant effects on ROS levels. The majority of metabolites with passive effects on root length, root fresh weight and cell permeability had active effects on ROS levels. These results offer a view about stress reaction of wheat to tetracycline.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111998DOI Listing
April 2021

Heterogeneous ozonation of ofloxacin using MnO -CeO /γ-Al O as a catalyst: Performances, degradation kinetics and possible degradation pathways.

Water Environ Res 2021 Feb 1. Epub 2021 Feb 1.

College of Chemical Engineering, Beijing University of Chemical Technology, Beijing, China.

In this study, the performance of ofloxacin (OFX) degradation in synthetic wastewater using synthesized MnO -CeO /γ-Al O as a heterogeneous ozonation catalyst was evaluated. The removal rates of OFX and chemical oxygen demand (COD) during 15-day continuous-flow experiments were 98.2% and 76.7% on average, respectively. An ozone index (mgCOD/mgO ) of 1.09 with a high ozone utilization efficiency of 91.39% was achieved. The pseudo-first-order rate constant of ofloxacin degradation reached 15.216 × 10  min , which was five times that (3.085 × 10  min ) without catalysts. The results of gas chromatography-mass spectrometry (GC-MS) demonstrated that a variety of small-molecule organics occurred in the final oxidation products, such as 4-hydroxyl-4-methyl-2-pentanone and 2-oxoadipic acid in addition to homologs of OFX. The results of this study suggested that hydroxyl radicals played critical roles in the degradation and mineralization of OFX via four main pathways: (a) electrophilic addition of nitrogen; (b) breakdown of carbon-carbon double bonds; (c) hydrolysis of ether rings; and (d) halodecarboxylation of carboxyl groups. The biodegradability (BOD /COD) of OFX after catalytic ozonation reached 0.54. PRACTITIONER POINTS: Ofloxacin wastewater was treated using catalytic ozonation in a 15-day continuous experiment with MnO -CeO /γ-Al O as a catalyst. The ozone index reached 1.09 mgCOD/mgO during ozonation of ofloxacin. The presence of the catalyst increased the reaction rate constant by a factor of five. 4-hydroxy-4-methyl-2-pentanone was the primary ofloxacin oxidation product.
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http://dx.doi.org/10.1002/wer.1524DOI Listing
February 2021

Heterogeneous ozonation of ofloxacin using MnO -CeO /γ-Al O as a catalyst: Performances, degradation kinetics and possible degradation pathways.

Water Environ Res 2021 Feb 1. Epub 2021 Feb 1.

College of Chemical Engineering, Beijing University of Chemical Technology, Beijing, China.

In this study, the performance of ofloxacin (OFX) degradation in synthetic wastewater using synthesized MnO -CeO /γ-Al O as a heterogeneous ozonation catalyst was evaluated. The removal rates of OFX and chemical oxygen demand (COD) during 15-day continuous-flow experiments were 98.2% and 76.7% on average, respectively. An ozone index (mgCOD/mgO ) of 1.09 with a high ozone utilization efficiency of 91.39% was achieved. The pseudo-first-order rate constant of ofloxacin degradation reached 15.216 × 10  min , which was five times that (3.085 × 10  min ) without catalysts. The results of gas chromatography-mass spectrometry (GC-MS) demonstrated that a variety of small-molecule organics occurred in the final oxidation products, such as 4-hydroxyl-4-methyl-2-pentanone and 2-oxoadipic acid in addition to homologs of OFX. The results of this study suggested that hydroxyl radicals played critical roles in the degradation and mineralization of OFX via four main pathways: (a) electrophilic addition of nitrogen; (b) breakdown of carbon-carbon double bonds; (c) hydrolysis of ether rings; and (d) halodecarboxylation of carboxyl groups. The biodegradability (BOD /COD) of OFX after catalytic ozonation reached 0.54. PRACTITIONER POINTS: Ofloxacin wastewater was treated using catalytic ozonation in a 15-day continuous experiment with MnO -CeO /γ-Al O as a catalyst. The ozone index reached 1.09 mgCOD/mgO during ozonation of ofloxacin. The presence of the catalyst increased the reaction rate constant by a factor of five. 4-hydroxy-4-methyl-2-pentanone was the primary ofloxacin oxidation product.
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http://dx.doi.org/10.1002/wer.1524DOI Listing
February 2021

Could Adjuvant Chemotherapy Improve Prognosis for Cervical Cancer Patients with Elevated Pretreatment Serum Squamous-Cell Carcinoma Antigen?

Risk Manag Healthc Policy 2021 11;14:109-116. Epub 2021 Jan 11.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Objective: The aim of this study was to explore whether adjuvant chemotherapy could improve prognosis for cervical cancer patients with elevated pretreatment serum squamous-cell carcinoma antigen (SCC-Ag).

Methods: Propensity-score matching and inverse probability of treatment weighting (IPTW) were used to ensure balanced groups for patients with (arm A) and without adjuvant chemotherapy (arm B). All patients were treated between January 2012 and December 2014 at a single center. Study outcomes were disease-free survival (DFS) and overall survival (OS).

Results: In total, 81 patients were included in this study. By propensity-score matching, 35 patients were included in each group (arm A and arm B). Median follow-up was 60 months in arm A and 66 months in arm B. Overall, 85.7% of patients in arm A and 71.4% of those in arm B received adjuvant radiotherapy. DFS and OS curves were similar between arms A and B (=0.971 and 0.633, respectively). With IPTW, arm A was not associated with prognosis in terms of DFS (HR 0.946, 95% CI 0.237-3.784; =0.938) or OS (HR 1.020, 95%CI 0.357-2.913; =0.970).

Conclusion: For patients with elevated pretreatment SCC-Ag, adjuvant chemotherapy was not found to improve prognosis. Also, a considerable proportion of these patients had postoperative indications for adjuvant radiotherapy. For these cervical cancer patients with elevated pretreatment SCC-Ag, the choice of radical hysterectomy and adjuvant chemotherapy should be prudent.
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http://dx.doi.org/10.2147/RMHP.S273848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810669PMC
January 2021

Nitric oxide-donating and reactive oxygen species-responsive prochelators based on 8-hydroxyquinoline as anticancer agents.

Eur J Med Chem 2021 Feb 5;212:113153. Epub 2021 Jan 5.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China. Electronic address:

Metal ion chelators based on 8-hydroxyquinoline (8-HQ) have been widely explored for the treatment of many diseases. When aimed at being developed into potent anticancer agent, a largely unmet issue is how to avoid nonspecific chelation of metal ions by 8-HQ in normal cells or tissues. In the current work, a two-step strategy was employed to both enhance the anticancer activity of 8-HQ and improve its cancer cell specificity. Considering the well-known anticancer activity of nitric oxide (NO), NO donor furoxan was first connected to 8-HQ to construct HQ-NO conjugates. These conjugates were screened for their cytotoxicity, metal-binding ability, and NO-releasing efficiency. Selected conjugates were further modified with a ROS-responsive moiety to afford prochelators. Among all the target compounds, prodrug HQ-NO-11 was found to potently inhibit the proliferation of many cancer cells but not normal cells. The abilities of metal chelation and NO generation by HQ-NO-11 were confirmed by various methods and were demonstrated to be essential for the anticancer activity of HQ-NO-11. In vivo studies revealed that HQ-NO-11 inhibited the growth of SW1990 xenograft to a larger extent than 8-HQ. Our results showcase a general method for designing novel 8-HQ derivatives and shed light on obtaining more controllable metal chelators.
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http://dx.doi.org/10.1016/j.ejmech.2021.113153DOI Listing
February 2021

Identification of Somatic Mutations in Papanicolaou Smear DNA and Plasma Circulating Cell-Free DNA for Detection of Endometrial and Epithelial Ovarian Cancers: A Pilot Study.

Front Oncol 2020 14;10:582546. Epub 2020 Dec 14.

Berry Oncology Corporation, Beijing, China.

Objectives: The aim of this study was to identify tumor-derived DNA from Papanicolaou (Pap) smear and plasma specimens collected from patients with endometrial cancer or atypical hyperplasia (EC/AH) or epithelial ovarian cancer (OC).

Methods: Tumor tissues, peripheral blood, and Pap smear samples were collected from patients with EC/AH and patients with epithelial OC. Somatic mutations of tumor specimens in EC/AH and OC were examined by whole-exome sequencing using a 127-driver gene panel from The Cancer Genome Atlas (TCGA). A nine-gene EC/AH panel and an eight-gene OC panel were established based on the identified significantly mutated genes in the EC/AH and OC tumor specimens. Circulating single-molecule amplification and resequencing technology (cSMART) was applied to evaluate somatic mutations in Pap smear DNA and plasma circulating cell-free DNA (ccfDNA) using the EC/AH and OC gene panels.

Results: In EC/AH group, there existed 22 tumors and 14 of the 22 tumors contributed hot spot mutations for the EC/AH nine-gene panel. In the Pap smear subgroup, all 21 Pap smears tested positive. Nine out of 11 (81.8%) identified the same gene mutations with their matched tumors and the remaining 10 Pap smears all tested positive. In the plasma subgroup, 10 out of 26 (38.5%) plasmas tested positive. One out of 13 (7.7%) identified the same gene mutation with its matched tumor and 5 out of the remaining 13 plasmas (38.5%) tested positive. In OC group, there existed 17 tumors and 16 of the 17 tumors contributed hot spot mutations for the OC eight-gene panel. In the Pap smear subgroup, all 11 Pap smears tested positive. Five out of 10 (50.0%) identified the same gene mutations with their matched tumors and the remaining one Pap smear also tested positive. In the plasma subgroup, all 22 plasmas tested positive. Ten out of 14 (71.4%) identified the same gene mutation with their matched tumors and the remaining 4 plasmas all tested positive.

Conclusions: Tumor-derived DNA can be detected in Pap smears and plasmas from patients with EC/AH or epithelial OC. Using a small gene-panel, early detection of EC/AH and OC might be promising. However, the value of plasma ccfDNA for EC/AH requires further investigation.
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http://dx.doi.org/10.3389/fonc.2020.582546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768029PMC
December 2020

Nrf2 Activators as Dietary Phytochemicals Against Oxidative Stress, Inflammation, and Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review.

Front Psychiatry 2020 20;11:561998. Epub 2020 Nov 20.

Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China.

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with limited available treatments and diverse causes. In ASD patients, numerous researches demonstrated various alterations in inflammation/immune, oxidative stress, and mitochondrial dysfunction, and these alterations could be regulated by Nrf2. Hence, we aimed to systematically review the current evidence about the effects of Nrf2 activator supplementation on ASD objects from studies, animal studies, and clinical studies. Relevant articles were retrieved through searching for the Cochrane Library, PubMed, Web of Science, Scope, Embase, and CNKI databases (through September 23, 2020). Ultimately, we identified 22 preclinical studies, one cell culture study, and seven clinical studies, covering a total of five Nrf2 activators. For each Nrf2 activator, we focused on its definition, potential therapeutic mechanisms, latest research progress, research limitations, and future development directions. Our systematic review provided suggestive evidence that Nrf2 activators have a potentially beneficial role in improving autism-like behaviors and abnormal molecular alterations through oxidant stress, inflammation, and mitochondrial dysfunction. These dietary phytochemicals are considered to be relatively safer and effective for ASD treatment. However, there are few clinical studies to support the Nrf2 activators as dietary phytochemicals in ASD, even though several preclinical studies. Therefore, caution should be warranted in attempting to extrapolate their effects in human studies, and better design and more rigorous research are required before they can be determined as a therapeutic option.
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http://dx.doi.org/10.3389/fpsyt.2020.561998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714765PMC
November 2020

Glycoconjugates for glucose transporter-mediated cancer-specific targeting and treatment.

Carbohydr Res 2020 Dec 12;498:108195. Epub 2020 Nov 12.

Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China. Electronic address:

First observed in 1920s, the Warburg effects have inspired scientists to harness the unique glucose metabolism of cancer cells for targeted therapy for a century. Carbohydrate-drug conjugates are explicitly designed for selective uptake by cancer cells overexpressing glucose transporters. We summarize the progress in developing glycoconjugates for cancer-specific targeting and treatment over the past decade (2010-2020) and point to some future directions in this field.
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http://dx.doi.org/10.1016/j.carres.2020.108195DOI Listing
December 2020

Effects of gut microbial-based treatments on gut microbiota, behavioral symptoms, and gastrointestinal symptoms in children with autism spectrum disorder: A systematic review.

Psychiatry Res 2020 11 26;293:113471. Epub 2020 Sep 26.

Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University Changsha, Hunan, China. Electronic address:

Many studies have identified some abnormalities in gastrointestinal (GI) physiology (e.g., increased intestinal permeability, overall microbiota alterations, and gut infection) in children with autism spectrum disorder (ASD). Furthermore, changes in the intestinal flora may be related to GI and ASD symptom severity. Thus, we decided to systematically review the effects of gut microbial-based interventions on gut microbiota, behavioral symptoms, and GI symptoms in children with ASD. We reviewed current evidence from the Cochrane Library, EBSCO PsycARTICLES, PubMed, Web of Science, and Scope databases up to July 12, 2020. Experimental studies that used gut microbial-based treatments among children with ASD were included. Independent data extraction and quality assessment of studies were conducted according to the PRISMA statement. Finally, we identified 16 articles and found that some interventions (i.e., prebiotic, probiotic, vitamin A supplementation, antibiotics, and fecal microbiota transplantation) could alter the gut microbiota and improve behavioral symptoms and GI symptoms among ASD patients. Our findings highlight that the gut microbiota could be a novel target for ASD patients in the future. However, we only provided suggestive but not conclusive evidence regarding the efficacy of interventions on GI and behavioral symptoms among ASD patients. Additional rigorous trials are needed to evaluate the effects of gut microbial-based treatments and explore potential mechanisms.
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http://dx.doi.org/10.1016/j.psychres.2020.113471DOI Listing
November 2020

CYP27B1 Downregulation: A New Molecular Mechanism Regulating EZH2 in Ovarian Cancer Tumorigenicity.

Front Cell Dev Biol 2020 14;8:561804. Epub 2020 Oct 14.

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

Background: Ovarian cancer has the highest mortality rate among gynecologic cancers, and most patients are diagnosed in advanced stages. Enhancer of zeste homolog 2 (EZH2) is a major tumor marker and an effective therapeutic target for ovarian cancer, but the underlying molecular mechanism remains unclear. The present study investigated the biological effects of EZH2 knockout in SKOV3 cells and and explored the molecular mechanism by integrated analysis of messenger RNA sequencing (mRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) data.

Methods: The CRISPR/Cas9 system was used to establish EZH2 knockout SKOV3 cells. Protein expression was evaluated by Western blotting. The effect of EZH2 on ovarian cancer was evaluated with MTT, wound healing, Transwell, and apoptosis assays and with a xenograft model. mRNA-seq and ChIP-seq were performed to explore the molecular mechanism underlying the biological function of EZH2. Immunohistochemical staining (IHC) of tissue arrays was used to analyze the correlations among EZH2 and CYP27B1 expressions and prognosis.

Results: We obtained three EZH2 knockout subclones. EZH2 knockout SKOV3 cells exhibited significantly suppressed proliferation, migration, and invasion and a significantly increased apoptosis rate. The subcutaneous tumor formation rate decreased from 100 to 0% in the EZH2 knockout group. Integrated analysis of the mRNA-seq and ChIP-seq data identified 1,455 significantly upregulated genes with matching downregulated trimethylation of histone H3 lysine 27 (H3K27me3) methylation binding sites in 1b11H cells compared to SKOV3 cells. The set of downregulated genes in EZH2 knockout cells was highly enriched in genes regulating the activation of steroid biosynthesis; the top-ranked hub gene was CYP27B1. The EZH2 and CYP27B1 expression levels showed a statistically significant inverse correlation, which was also associated with unfavorable prognosis. The experiment demonstrated that CYP27B1 can suppress the proliferation, migration, and invasion of ovarian cancer cells. Moreover, the levels of AKT and p-AKT were significantly increased, whereas STAT3 was downregulated, in 1b11H cells compared to SKOV3 cells. Moreover, STAT3 and AKT overexpression was observed in 1b11H siRNA for CYP27B1 (siCYP27B1) cells.

Conclusion: EZH2 plays an important role in promoting cell proliferation, migration, and invasion in ovarian cancer by regulating the core steroid biosynthesis gene H3K27me3 methylation. Moreover, CYP27B1, the steroid biosynthesis hub gene, might be a novel therapeutic target for ovarian cancer.
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http://dx.doi.org/10.3389/fcell.2020.561804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591459PMC
October 2020

Discover novel disease-associated genes based on regulatory networks of long-range chromatin interactions.

Methods 2021 05 21;189:22-33. Epub 2020 Oct 21.

Department of Computational Mathematics, Science and Engineering, Michigan State University, 428 S. Shaw Ln., East Lansing, MI 48824, USA. Electronic address:

Identifying genes and non-coding genetic variants that are genetically associated with complex diseases and the underlying mechanisms is one of the most important questions in functional genomics. Due to the limited statistical power and the lack of mechanistic modeling, traditional genome-wide association studies (GWAS) is restricted to fully address this question. Based on multi-omics data integration, cell-type specific regulatory networks can be built to improve GWAS analysis. In this study, we developed a new computational infrastructure, APRIL, to incorporate 3D chromatin interactions into regulatory network construction, which can extend the networks to include long-range cis-regulatory links between non-coding GWAS SNPs and target genes. Combinatorial transcription factors that co-regulate groups of genes are also inferred to further expand the networks with trans-regulation. A suite of machine learning predictions and statistical tests are incorporated in APRIL to predict novel disease-associated genes based on the expanded regulatory networks. Important features of non-coding regulatory elements and genetic variants are prioritized in network-based predictions, providing systems-level insights on the mechanisms of transcriptional dysregulation associated with complex diseases.
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http://dx.doi.org/10.1016/j.ymeth.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026483PMC
May 2021

Characterization of a LuxR repressor for 3,17β-HSD in Comamonas testosteroni ATCC11996.

Chem Biol Interact 2021 Feb 28;336:109271. Epub 2020 Sep 28.

Changchun University of Science and Technology, 7989 Weixing Road, 130022, Changchun, PR China. Electronic address:

3,17β-Hydroxysteroid dehydrogenase in Comamonas testosteroni (C. testosteroni) is a key enzyme involved in the degradation of steroid compounds. Recently, we found that LuxR is a negative regulator in the expression of the 3,17β-HSD gene. In the present work, we cultured wild-type and LuxR knock-out mutants of C. testosteroni with inducers such as testosterone, estradiol, progesterone or estrone. HPLC analysis showed that the degradation activities towards testosterone, estradiol, progesterone, and estrone by C.T.-LuxR-KO1 were increased by 7.1%, 9.7%, 11.9% and 3.1%, respectively compared to the wild-type strain. Protein conformation of LuxR was predicted by Phyre 2 Server software, where the N-terminal 86(Ile), 116(Ile), 118(Met) and 149(Phe) residues form a testosterone binding hydrophobic pore, while the C-terminus forms the DNA binding site (HTH). Further, luxr point mutant plasmids were prepared by PCR and co-transformed with pUC3.2-4 into E. coli HB101. ELISA was used to determine 3,17β-HSD expression after testosterone induction. Compared to wild-type luxr, 3,17β-HSD expression in mutants of I86T, I116T, M118T and F149S were decreased. The result indicates that testosterone lost its capability to bind to LuxR after the four amino acid residues had been exchanged. No significant changes of 3,17β-HSD expression were found in K354I and Y356 N mutants compared to wild-type luxr, which indicates that these two amino acid residues in LuxR might relate to DNA binding. Native LuxR protein was prepared from inclusion bodies using sodium lauroylsarcosinate. Molecular interaction experiments showed that LuxR protein binds to a nucleotide sequence which locates 87 bp upstream of the βhsd promoter. Our results revealed that steroid induction of 3,17β-HSD in C. testosteroni in fact appears to be a de-repression, where testosterone prevents the LuxR regulator protein binding to the 3,17β-HSD promoter domain.
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http://dx.doi.org/10.1016/j.cbi.2020.109271DOI Listing
February 2021

Comprehensive profiling of immune-related genes in soft tissue sarcoma patients.

J Transl Med 2020 09 1;18(1):337. Epub 2020 Sep 1.

Department of Orthopedic, Affiliated Hospital of Chengde Medical University, Hebei, China.

Background: Immune-related genes (IRGs) have been confirmed to have an important role in tumorigenesis and tumor microenvironment formation. Nevertheless, a systematic analysis of IRGs and their clinical significance in soft tissue sarcoma (STS) patients is lacking.

Methods: Gene expression files from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx) were used to select differentially expressed genes (DEGs). Differentially expressed immune-related genes (DEIRGs) were determined by matching the DEG and ImmPort gene sets, which were evaluated by functional enrichment analysis. Unsupervised clustering of the identified DEIRGs was conducted, and associations with prognosis, the tumor microenvironment (TME), immune checkpoints, and immune cells were analyzed simultaneously. Two prognostic signatures, one for overall survival (OS) and one for progression free survival (PFS), were established and validated in an independent set. Finally, two transcription factor (TF)-IRG regulatory networks were constructed, and a crucial regulatory axis was validated.

Results: In total, 364 DEIRGs and four clusters were identified. OS, TME scores, five immune checkpoints, and 12 types of immune cells were found to be significantly different among the four clusters. The two prognostic signatures incorporating 20 DEIRGs showed favorable discrimination and were successfully validated. Two nomograms combining signature and clinical variables were generated. The C-indexes were 0.879 (95%CI 0.832 ~ 0.926) and 0.825 (95%CI 0.776 ~ 0.874) for the OS and PFS signatures, respectively. Finally, TF-IRG regulatory networks were established, and the MYH11-ADM regulatory axis was verified in three independent datasets.

Conclusion: This comprehensive analysis of the IRG landscape in soft tissue sarcoma revealed novel IRGs related to carcinogenesis and the immune microenvironment. These findings have implications for prognosis and therapeutic responses, which reveal novel potential prognostic biomarkers, promote precision medicine, and provide potential novel targets for immunotherapy.
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http://dx.doi.org/10.1186/s12967-020-02512-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465445PMC
September 2020

Microglia mediated neuroinflammation in autism spectrum disorder.

J Psychiatr Res 2020 11 29;130:167-176. Epub 2020 Jul 29.

Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Background: Although the precise pathophysiologies underlying autism spectrum disorder (ASD) has not yet been fully clarified, growing evidence supports the involvement of neuroinflammation in the pathogenesis of this disorder, with microglia being particular relevance in the pathophysiologic processes.

Objective: The present review aimed to systematically characterize existing literature regarding the role of microglia mediated neuroinflammation in the etiology of ASD.

Methods: A systematic search was conducted for records indexed within Pubmed, EMBASE, or Web of Science to identify potentially eligible publications. Study selection and data extraction were performed by two authors, and the discrepancies in each step were settled through discussions.

Results: A total of 14 studies comprising 1007 subjects met the eligibility criteria for this review, including 8 immunohistochemistry (IHC) studies, 5 genetic analysis studies, and 1 positron emission tomography (PET) studies. Although small in quantity, the included studies collectively pointed to a role of microglia mediated neuroinflammation in the pathogenesis of ASD.

Conclusion: Findings generated from this review consistently supported the involvement of neuroinflammation in the development of ASD, confirmed by the activation of microglia in different brain regions, involving increased cell number or cell density, morphological alterations, and phenotypic shifts.
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http://dx.doi.org/10.1016/j.jpsychires.2020.07.013DOI Listing
November 2020

Leverage Large-Scale Biological Networks to Decipher the Genetic Basis of Human Diseases Using Machine Learning.

Methods Mol Biol 2021 ;2190:229-248

Department of Computational Mathematics, Science and Engineering, Michigan State University, East Lansing, MI, USA.

A fundamental question in precision medicine is to quantitatively decode the genetic basis of complex human diseases, which will enable the development of predictive models of disease risks based on personal genome sequences. To account for the complex systems within different cellular contexts, large-scale regulatory networks are critical components to be integrated into the analysis. Based on the fast accumulation of multiomics and disease genetics data, advanced machine learning algorithms and efficient computational tools are becoming the driving force in predicting phenotypes from genotypes, identifying potential causal genetic variants, and revealing disease mechanisms. Here, we review the state-of-the-art methods for this topic and describe a computational pipeline that assembles a series of algorithms together to achieve improved disease genetics prediction through the delineation of regulatory circuitry step by step.
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http://dx.doi.org/10.1007/978-1-0716-0826-5_11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433890PMC
March 2021
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