Publications by authors named "Ling Yang"

1,648 Publications

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Comparison of case-based learning combined with Rain Classroom teaching and traditional method in complete denture course for undergraduate interns.

BMC Med Educ 2022 Aug 9;22(1):610. Epub 2022 Aug 9.

Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-Sen University, 56 Lingyuan Road West, Guangzhou, 510055, Guangdong, China.

Background: Complete denture, as an important restoration method for edentulism, is difficult to study for beginners, especially in linking the theory with clinical practice.

Objective: This study was aimed to compare the teaching effects between case-based learning combined with Rain Classroom teaching and traditional lecture method in the clinical course of complete denture prosthesis for undergraduate interns.

Methods: In a course called "Problems and treatment strategies of complete denture after wearing", interns were divided into two groups: one for traditional lecture-based teaching with PowerPoint slideshow (the control group, n = 28); and the other for case-based learning combined with Rain Classroom teaching, which published information before class, discussed specific clinic cases in class and got real-time interns' feedback via WeChat (the test group, n = 22). Both groups received the same exam and questionnaire survey after class. The Q&A participation of interns in class, theoretical test scores and questionnaire survey responses were used to evaluate the teaching effects. An independent sample t-test and the chi-square test or Fisher's exact test were used for statistical analysis in this study.

Results: The Q&A participation of interns in the test group was much better than that of the control group. The average score on the theoretical test after class in the test group (72.14 ± 12.24) was significantly higher than that in the control group (61.29 ± 20.12) (P < 0.05). In the test group, 94.54% (21/22) of the interns preferred the new teaching mode.

Conclusion: Case-based learning combined with Rain Classroom teaching is helpful to enliven the classroom atmosphere, inspire studying enthusiasm, and achieve a good learning effect in both theory and clinical practice related to complete denture prosthesis.
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http://dx.doi.org/10.1186/s12909-022-03678-zDOI Listing
August 2022

Exploring Patient Perspectives of Body Image Conversations in Primary Care: Understandings, Experiences, and Expectations.

J Patient Exp 2022 1;9:23743735221117366. Epub 2022 Aug 1.

Department of Family Medicine, McMaster University, Hamilton, ON, Canada.

Primary care physicians (PCPs) and patients identified body image conversations to be difficult but necessary. As first points of contact in the healthcare system, PCPs are ideal candidates for addressing body image concerns. Through latent thematic analysis of 12 interviews, this paper explores patient preferences with body image conversations in primary care. We identified challenges that patients faced in sharing body image concerns, expectations they hold for physicians, and suggested potential areas of future research and ways to improve care.
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http://dx.doi.org/10.1177/23743735221117366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346258PMC
August 2022

Diagnostic Value of Prostate-Specific Antigen Combined with Plasma miRNA-149 Expression in Patients with Prostate Cancer Based on Experimental Data and Bioinformatics.

Contrast Media Mol Imaging 2022 22;2022:6094409. Epub 2022 Jul 22.

Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China.

Purpose: The aim of this study is to explore the diagnostic value of prostate-specific antigen (PSA) combined with serum miRNA-149 expression in prostate cancer (PCa) by conducting experiments and bioinformatics analysis. . 50 PCa patients were enrolled on the experimental group from January 2020 to December 2021. 56 patients with benign prostatic hyperplasia (BPH) were selected as the control group at the same time. Real-time fluorescent quantitative PCR was applied to investigate the miRNA-149 expression. PSA was detected by using a chemiluminescence meter using Abbott i4000. Applying bioinformatics analysis, we explored the expression of hsa-miR-149 in PCa in The Cancer Genome Atlas (TCGA) database. Kaplan-Meier analyses were used to evaluate the prognostic value, and the ROC curve was applied.

Results: The expression level of miRNA-149 in the PCa group was significantly higher than that in the BPH group ( < 0.05). The PSA level in the PCa group was also significantly higher than that in the BPH group ( < 0.05). TCGA data analysis revealed that PCa tissues had significantly increased hsa-miR-149 expression. The results of survival analysis showed that patients with high expression of hsa-miR-149 had better prognosis. Additionally, the pathological N stage of PCa correlates with the hsa-miR-149 expression level ( = 0.002). According to ROC curve analysis, the region under the curve was 0.653, 95% CI: 0.576-0.730.

Conclusion: High expression of serum miRNA-149 is associated with PCa patients. Although combined PSA did not improve the diagnostic efficacy, miRNA-149 has high specificity in the diagnosis of PCa. miRNA-149 might be a novel marker for early diagnosis and prognosis assessment for PCa.
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http://dx.doi.org/10.1155/2022/6094409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337946PMC
August 2022

Association of anxiety with cardiovascular disease in a Chinese cohort of 0.5 million adults.

J Affect Disord 2022 Aug 4. Epub 2022 Aug 4.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing 100191, China.

Background: Anxiety might be a potentially modifiable risk factor of cardiovascular diseases (CVDs). Evidence relating anxiety symptoms and generalized anxiety disorder (GAD) to CVDs from prospective cohort study was still lacking in China.

Methods: Participants aged 30 to 79 years old from 10 areas across China were recruited during 2004-2008 and were followed up until 2017. 487,209 participants without CVDs at baseline remained for analyses. Anxiety symptoms (panic attacks and continuous anxiety) during the past 12 months were identified in a face-to-face interview. Participants with continuous anxiety were further assessed for GAD using Composite International Diagnostic Interview-Short Form. The primary outcomes were incident CVD, ischaemic heart disease (IHD), haemorrhagic stroke (HS), and ischaemic stroke (IS).

Results: During 4.7 million person-years of follow-up, we documented 140,365 incident cases of CVD. For panic attacks, the multivariable-adjusted HRs (95 % CI) were 1.08 (1.04-1.13), 1.10 (1.02-1.19), 1.20 (1.05-1.38) and 1.20 (1.11-1.30) for CVD, IHD, HS and IS, respectively. Continuous anxiety was positively associated with incident CVD and IHD, and the corresponding HRs were 1.12 (1.04-1.20) and 1.21 (1.07-1.37).

Limitations: Anxiety symptoms were examined according to self-reported questionnaires, which could constitute key study limitations.

Conclusions: Among the Chinese adults, those with anxiety symptoms or GAD might be important at-risk population of CVD.
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http://dx.doi.org/10.1016/j.jad.2022.08.008DOI Listing
August 2022

Airway acidification impaired host defense against infection by promoting type 1 interferon β response.

Emerg Microbes Infect 2022 Aug 5:1-37. Epub 2022 Aug 5.

Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200092, China.

Airway microenvironment played an important role in the progression of chronic respiratory disease. Here we showed that standardized pondus hydrogenii (pH) of exhaled breath condensate (EBC) of bronchiectasis patients was significantly lower than that of controls and was significantly correlated with bronchiectasis severity index (BSI) scores and disease prognosis. EBC pH was lower in severe patients than that in mild and moderate patients. Besides, acidic microenvironment deteriorated pulmonary infection in mice models. Mechanistically, acidic microenvironment increased outer membrane vesicles (PA_OMVs) release and boosted it induced the activation of interferon regulatory factor3 (IRF3)-interferonβ (IFN-β) signaling pathway, ultimately compromised the anti-bacteria immunity. Targeted knockout of IRF3 or type 1 interferon receptor (IFNAR1) alleviated lung damage and lethality of mice after infection that aggravated by acidic microenvironment. Together, these findings identified airway acidification impaired host resistance to infection by enhancing its induced the activation of IRF3-IFN-β signaling pathway. Standardized EBC pH may be a useful biomarker of disease severity and a potential therapeutic target for the refractory infection. The study also provided one more reference parameter for drug selection and new drug discovery for bronchiectasis.
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http://dx.doi.org/10.1080/22221751.2022.2110524DOI Listing
August 2022

Healthy lifestyle and life expectancy at age 30 years in the Chinese population: an observational study.

Lancet Public Health 2022 Aug 1. Epub 2022 Aug 1.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China; Peking University Center for Public Health and Epidemic Preparedness & Response, Beijing, China.

Background: The improvement of life expectancy is one of the aims of the Healthy China 2030 blueprint. We aimed to investigate the extent to which healthy lifestyles are associated with life expectancy in Chinese adults.

Methods: We used the prospective China Kadoorie Biobank (CKB) study to examine the relative risk of mortality associated with individual and combined lifestyle factors (never smoking or quitting not for illness, no excessive alcohol use, being physically active, healthy eating habits, and healthy body shape). Participants with coronary heart disease, stroke, cancer, or missing values for body-mass index were excluded. For analysis of chronic respiratory diseases, participants with chronic obstructive pulmonary disease or asthma were excluded. We estimated the national prevalence of lifestyle factors using data from the China Nutrition and Health Surveillance (CNHS; 2015) and derived mortality rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (2015). All three data sources were combined to estimate the life expectancy of individuals at age 30 years following different levels of lifestyle factors by using the life table method. The cause-specific decomposition of the life expectancy differences was analysed using Arriaga's method.

Findings: After the exclusion of CKB participants with coronary heart disease, stroke, cancer, or missing BMI data at baseline, 487 209 were included in the primary analysis. Participants with COPD or asthma at baseline were additionally excluded for chronic respiratory disease-related analysis, leaving 451 233 participants with data available for analysis. Data from 171 127 adults aged 30-84 years from the CNHS 2015 were used to estimate the sex-specific and age-specific prevalence of lifestyle-related factors. There were 42 496 deaths documented over a median follow-up of 11·1 years (IQR 10·2-12·1) in CKB. The adjusted hazard ratios (aHRs) of participants adopting five versus 0-1 low-risk factors was 0·38 (95% CI 0·34-0·43) for all-cause mortality, aHR 0·37 (0·30-0·46) for cardiovascular disease mortality, aHR 0·47 (0·39-0·56) for cancer mortality, and aHR 0·30 (0·14-0·64) for chronic respiratory disease mortality. The life expectancy at age 30 years for individuals with 0-1 low-risk factors was on average 41·7 years (95% CI 41·5-42·0) for men and 47·3 years (46·6-48·0) for women. For individuals with all five low-risk factors, the life expectancy at age 30 was 50·5 years (95% CI 48·5-52·4) for men and 55·4 years (53·5-57·4) for women; meaning a difference of 8·8 years (95% CI 6·8-10·7) for men and 8·1 years (6·5-9·9) for women. The estimated extended life expectancy for men and women was mainly attributable to reduced death from cardiovascular disease (2·4 years [27% of the total extended life expectancy] for men and 3·7 years [46%] for women), cancer (2·6 years [30%] for men and 0·9 years [11%] for women), and chronic respiratory disease (0·6 years [7%] for men and 1·2 years [15%] for women).

Interpretation: Our findings suggest that increasing the adoption of these five healthy lifestyle factors through public health interventions could be associated with substantial gains in life expectancy in the Chinese population.

Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Kadoorie Charitable Foundation, UK Wellcome Trust.
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http://dx.doi.org/10.1016/S2468-2667(22)00110-4DOI Listing
August 2022

Doxycycline Suppresses Vasculogenic Mimicry in Human Pterygium Fibroblasts.

Curr Eye Res 2022 Aug 3:1-8. Epub 2022 Aug 3.

Eye Institute, Affiliated Hospital of Nantong University, Nantong, China.

Purpose: To explore the effect of doxycycline on vasculogenic mimicry (VM) formation and the potential mechanism in human pterygium fibroblasts in order to find novel targets for pterygium therapy.

Methods: First, we demonstrate the existence of VM in 73 pterygium specimens by CD31 and periodic acid Schiff (PAS) dual staining. Then we used cell counting kit-8, clone formation assay and flow cytometry to prove the inhibitory effect of doxycycline on cell proliferation and apoptosis. The VM formation was evaluated through wound healing assay, cell transwell assay and three-dimensional cell culture combined with PAS staining. Finally, we used Western blot to testify the correlation of the VM and the factors in protein level preliminarily.

Results: Our results showed that VM existed in human pterygium specimens exactly. Otherwise, in human pterygium fibroblasts, doxycycline induced a dose-dependent inhibitory effect on cell proliferation and apoptosis induction. Besides, doxycycline significantly suppressed vasculogenic mimicry tube formation, cell migration and invasion. Furthermore, doxycycline impaired the expression of MMP-9, MMP-2 and VEGF which may related to pterygium VM formation.

Conclusions: Doxycycline decelerated pterygium progression might be through inhibiting VM formation according to the downregulation of MMP-9, MMP-2 and VEGF, which may provide the basis of further studies involving doxycycline for pterygium treatment.
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http://dx.doi.org/10.1080/02713683.2022.2108455DOI Listing
August 2022

Alteration of peripheral cortisol and autism spectrum disorder: A meta-analysis.

Front Psychiatry 2022 15;13:928188. Epub 2022 Jul 15.

Department of Military Cognitive Psychology, School of Psychology, Army Medical University, Chongqing, China.

Cortisol is the main HPA axis hormone secreted by the adrenal cortex, and influences metabolism, cognition, and behavior. Recently, a plethora of studies have tried to confirm the correlation between peripheral cortisol and autism spectrum disorder (ASD). However, the results were controversial. We assessed the effects of peripheral cortisol on ASD in this study. The included studies were identified according to the inclusion and exclusion criteria. The pooled Hedges' g and its 95% confidence interval were selected to evaluate the association between peripheral cortisol and ASD. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also undertaken based on the obtained information. There were a total of twelve studies with 375 ASD patients and 335 controls included in our meta-analysis. Obvious heterogeneity across studies was found in the overall analysis. Peripheral cortisol levels were significantly elevated in ASD patients compared with controls in the absence of obvious heterogeneity. A single study did not influence the overall comparison results. Meta-regression analyses revealed that age and gender of the included subjects, sample size, and publication year did not moderate effects on the present results. These findings may provide us some targeted strategies to the diagnosis and treatment of ASD.
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http://dx.doi.org/10.3389/fpsyt.2022.928188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334910PMC
July 2022

MTERF3 contributes to MPP+-induced mitochondrial dysfunction in SH-SY5Y cells.

Acta Biochim Biophys Sin (Shanghai) 2022 Jul 25. Epub 2022 Jul 25.

Parkinson's disease (PD) is a neurodegenerative disorder causing severe social and economic burdens. The origin of PD has been usually attributed to mitochondrial dysfunction. To this end, mitochondrial transcription regulators become attractive subjects for understanding PD pathogenesis. Previously, we found that the expression of mitochondrial transcription termination factor 3 (MTERF3) was reduced in MPP+-induced mice model of PD. In the present study, we probe the function of MTERF3 and its role in MPP+-induced cellular model of PD. Initially, we observe that MTERF3 expression is also reduced in MPP+-induced cellular model of PD, which can be mainly attributed to the increase of MTERF3 degradation. Next, we examine the effect of MTERF3 knockdown and overexpression on the replication, transcription, and translation of mitochondrial DNA (mtDNA). We show that knockdown and overexpression of MTERF3 have opposite effects on mtDNA transcript level but similar effects on mtDNA expression level, in line with MTERF3's dual roles in mtDNA transcription and translation. In addition, we examine the effect of MTERF3 knockdown and overexpression on mitochondrial function with and without MPP+ treatment, and find that MTERF3 seems to play a generally protective role in MPP+-induced mitochondrial dysfunction. Together, this work suggests a regulatory role of MTERF3 in MPP+-induced cellular model of PD and may provide clues in designing novel therapeutics against PD.
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http://dx.doi.org/10.3724/abbs.2022098DOI Listing
July 2022

Short-term prognostic value of clinical data in hospitalized patients with intermediate-risk acute pulmonary embolism.

BMC Cardiovasc Disord 2022 07 28;22(1):335. Epub 2022 Jul 28.

Department of Cardiology, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, Anhui, People's Republic of China.

Background: Intermediate-risk acute pulmonary embolism (APE) patients are usually defined as hemodynamically stable, comprehending a great therapeutic dilemma. Although anticoagulation therapy is sufficient for most intermediate-risk APE patients, some patients can deteriorate and eventually require a systemic fibrinolytic agent or thrombectomy. Hence, this study aimed to evaluate the predictive value of differences in clinical data for the short-term prognosis of intermediate-risk APE patients.

Methods: A retrospective cohort of 74 intermediate-risk APE patients confirmed by computed tomography pulmonary angiography was analyzed in the present study. Adverse clinical event outcomes included PE-related in-hospital deaths, critical systolic blood pressure consistently under 90 mmHg, refractory to volume loading and vasopressor infusion requirements, mechanical ventilation, and cardiopulmonary resuscitation. The APE patients were stratified into two groups: adverse outcome (n = 25) and control (n = 49) groups. Then, the clinical data of the two groups were compared. Receiver operating characteristic (ROC) curves were used to explore the predictive value of white blood cell (WBC) counts and the right to left ventricular short-axis (RV/LV) ratio. Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit statistic.

Results: The brain natriuretic peptide, WBC count, and the RV/LV ratio were higher in patients with adverse outcomes compared to controls. The APE patients with adverse outcomes presented significantly higher rates of syncope, Negative T waves (NTW) in V1-V3, intermediate-high risk, thrombolytic therapy, and low arterial oxygen saturation (SaO) compared to controls. In the multivariate logistic regression analysis, the SaO < 90%, [odds ratio (OR) 5.343, 95% confidence interval (CI) 1.241-23.008; p = 0.024], RV/LV ratio (OR 7.429, 95% CI 1.145-48.209; p = 0.036), Syncope (OR 12.309, 95% CI 1.702-89.032; p = 0.013), NTW in V1-V3 (OR 5.617, 95% CI 1.228-25.683; p = 0.026), and WBC count (OR 1.212, 95% CI 1.035-1.419; p = 0.017) were independent predictors of in-hospital adverse outcomes among APE patients. The ROC curve analysis indicated that the RV/LV ratio can be used to predict adverse outcomes (AUC = 0.748, p < 0.01) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.070). Moreover, an RV/LV ratio > 1.165 was predictive of adverse outcomes with sensitivity and specificity of 88.00 and 59.20%, respectively. The WBC counts were also able to predict adverse outcomes (AUC = 0.752, p < 0.01) and calibration (Hosmer-Lemeshow goodness of fit test, p = 0.251). A WBC count > 9.05 was predictive of adverse outcomes with sensitivity and specificity of 68.00 and 73.50%, respectively.

Conclusion: Overall, a SaO < 90%, RV/LV ratio, Syncope, NTW in V1-V3, and WBC counts could independently predict adverse outcomes in hospitalized intermediate-risk APE patients.
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http://dx.doi.org/10.1186/s12872-022-02783-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331586PMC
July 2022

Spin engineering of triangulenes and application for nano nonlinear optical materials design.

Phys Chem Chem Phys 2022 Aug 10;24(31):18529-18542. Epub 2022 Aug 10.

Wenzhou Institute, University of Chinese Academy of Sciences, 1 Jinlian Street, Wenzhou 325001, China.

The recently synthesized triangulenes with non-bonding edge states could have broad potential applications in magnetics, spintronics and electro-optics if they have appropriate electronic structure modulation. In the present work, strategies based on molecular orbital theory through heteroatom doping are proposed to redistribute, reduce or eliminate the spin of triangulenes for novel functional materials design, and the role of B, N, NBN, and BNB in such intended electronic structure manipulation is scrutinized. π-Extended triangulenes with tunable electronic properties could be potential nonlinear optical (NLO) materials with appropriate inhibition of their polyradical nature. The elimination of spin is achieved by B, N, NBN, and BNB doping with the intended geometric arrangement for enhanced polarity. Intended doping of BNB results in an optimal structure with large static first hyperpolarizability (〈〉) as well as strong Hyper-Rayleigh scattering (HRS) (-2; , ) ( = 1064.0 nm), TG7-BNB-ba with a large 〈〉 (18.85 × 10 esu per heavy atom) and (1.15 × 10 esu per heavy atom) much larger than that of a synthesized triangular molecule (1.12 × 10 esu of 〈〉 per heavy atom and 5.04 × 10 esu of per heavy atom). The strong second order NLO responses in the near-infrared and visible regions, particularly the strong sum frequency generation, make these B or (and) N doped triangulenes promising candidates for the fabrication of novel carbon-based optoelectronic devices and micro-NLO devices.
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http://dx.doi.org/10.1039/d2cp02915dDOI Listing
August 2022

The Gut Microbiota: A Novel Player in Autoimmune Hepatitis.

Front Cell Infect Microbiol 2022 11;12:947382. Epub 2022 Jul 11.

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Autoimmune hepatitis (AIH) is a chronic immune-mediated liver disease distributed globally in all ethnicities with increasing prevalence. If left untreated, the disease will lead to cirrhosis, liver failure, or death. The intestinal microbiota is a complex ecosystem located in the human intestine, which extensively affects the human physiological and pathological processes. With more and more in-depth understandings of intestinal microbiota, a substantial body of studies have verified that the intestinal microbiota plays a crucial role in a variety of digestive system diseases, including alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). However, only a few studies have paid attention to evaluate the relationship between AIH and the intestinal microbiota. While AIH pathogenesis is not fully elucidated yet, some studies have indicated that intestinal microbiota putatively made significant contributions to the occurrence and the development of AIH by triggering several specific signaling pathways, altering the metabolism of intestinal microbiota, as well as modulating the immune response in the intestine and liver. By collecting the latest related literatures, this review summarized the increasing trend of the aerobic bacteria abundance in both AIH patients and AIH mice models. Moreover, the combination of specific bacteria species was found distinct to AIH patients, which could be a promising tool for diagnosing AIH. In addition, there were alterations of luminal metabolites and immune responses, including decreased short-chain fatty acids (SCFAs), increased pathogen associated molecular patterns (PAMPs), imbalanced regulatory T (Treg)/Th17 cells, follicular regulatory T (TFR)/follicular helper T (TFH) cells, and activated natural killer T (NKT) cells. These alterations participate in the onset and the progression of AIH multiple mechanisms. Therefore, some therapeutic methods based on restoration of intestinal microbiota composition, including probiotics and fecal microbiota transplantation (FMT), as well as targeted intestinal microbiota-associated signaling pathways, confer novel insights into the treatment for AIH patients.
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http://dx.doi.org/10.3389/fcimb.2022.947382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310656PMC
July 2022

Morphological and Physiological Indicators for Screening Cell Lines with High Potential for Somatic Embryo Maturation at an Early Stage of Somatic Embryogenesis in Pinus Koraiensis.

Plants (Basel) 2022 Jul 18;11(14). Epub 2022 Jul 18.

State Key Laboratory of Tree Genetics and Breeding, School of Forestry, Northeast Forestry University, Harbin 150040, China.

Many cell lines in the embryogenic callus cannot produce somatic embryos (SEs) even if they meet the optimal SE maturation culture conditions during conifer somatic embryogenesis. This phenomenon hinders the progress of the industrial-scale reproduction of conifers. Therefore, there is an urgent need to obtain morphological and physiological markers to screen embryogenic calli in response to SE maturation conditions. To detect cell lines with high somatic embryogenesis potential during the proliferation process, we counted the number of pro-embryos and early SEs (ESEs) in different cell lines and storage substances, endogenous hormones, and polyamine contents. The results showed that the yield of SEs was heavily dependent on genotype ( = 0.001). There were high levels of PE III (pro-embryo III) number, ESE number, and soluble protein content, in the response cell lines (R cell lines), which were 1.6-, 3-, and 1.1-fold those of the obstructive cell lines (B cell lines), respectively. The B cell line had high levels of starch, auxin (IAA), Put, Spd, and putrescine: spermine (Put: Spm) compared to the R cell line. In addition, the numbers of PE III, ESEs, and soluble protein content were significantly positively correlated with SE yield. In contrast, the contents of starch, abscisic acid (ABA), Put, Spm, and Spd were significantly negatively correlated with SE yield. To ensure the accuracy of the results, we used nine cell lines to test the results. The PE III and ESE numbers and the Spm and Spd contents were positively correlated with SE yield, while the levels of starch, ABA, IAA, Put: Spd, and Put: Spm were negatively correlated with SE yield. Thus, we recommend using high PE III and ESEs as morphological indicators and low levels of starch, IAA, ABA, and Put: Spm as physiological markers to screen cell lines with a high somatic embryogenesis potential. In addition, we also found that the relationship between Spd, Spm, and SE yield was opposite in the two experimental results. Therefore, we speculate that the differences in Spd and Spm content are mainly affected by genotype. In conclusion, this study obtained the morphological and physiological markers of some high-somatic embryogenic cell lines by comparing the differences between nine somatic embryogenic cell lines. Our results can guide the improvement of conifer somatic embryogenesis technology and can provide a theoretical basis for accelerating the application of biotechnology in large-scale artificial breeding.
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http://dx.doi.org/10.3390/plants11141867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316463PMC
July 2022

TP53 and LRP1B Co-Wild Predicts Improved Survival for Patients with LUSC Receiving Anti-PD-L1 Immunotherapy.

Cancers (Basel) 2022 Jul 12;14(14). Epub 2022 Jul 12.

Department of Medical Oncology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China.

Immunotherapy brought long-term benefits for partial patients with lung squamous cell carcinoma (LUSC). The predictor of anti-PD-L1 therapy was controversial and limited in LUSC. We aimed to explore novel biomarker for LUSC immunotherapy and the potential mechanism. Five hundred and twenty-five Chinese patients (Geneplus cohort) with LUSC underwent targeted sequencing and were involved to explore the genomic profiling. and were the most frequently recurrent genes and correlated to higher tumor mutational burden (TMB). We observed that LUSC patients with and co-wild (co-wild type) were associated with better survival of anti-PD-L1 therapy compared with mutant or mutant (mutant type) in POPAR/OAK cohort. Copy-number variation (CNV) and whole genome doubling (WGD) data from TCGA LUSC cohort were obtained to assess the CNV events. There were fewer CNV alterations and lower chromosome instability in patients with / co-wild compared with those with / mutant. RNA expression data from the TCGA LUSC cohort were collected to explore the differences in RNA expression and tumor immune microenvironment (TIME) between mutant and co-wild groups. The / co-wild type had a significantly increased proportion of multiple tumor-infiltrating lymphocytes (TILs), including activated CD8 T cell, activated dendritic cell (DC), and effector memory CD8 T cell. Immune-related gene sets including checkpoint, chemokine, immunostimulatory, MHC and receptors were enriched in the co-wild type. In conclusion, / co-wild LUSC conferred an elevated response rate in anti-PD-L1 therapy and improved survival, which was associated with a chromosome-stable phenotype and an activated immune microenvironment.
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http://dx.doi.org/10.3390/cancers14143382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320428PMC
July 2022

Occurrence of Carrying and in Southern China: New Insights in the Evolution of Megaplasmid IMP-26.

Antibiotics (Basel) 2022 Jun 28;11(7). Epub 2022 Jun 28.

Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.

The spread of multidrug-resistant enterobacteria strains has posed a significant concern in public health, especially when the strain harbors metallo-beta-lactamase (MBL)-encoding and mobilized colistin resistance () genes as such genetic components potentially mediate multidrug resistance. Here we report an IncHI2/2A plasmid carrying and in multidrug-resistant human isolates YL4. Antimicrobial susceptibility testing was performed by the broth microdilution method. According to the results, YL4 was resistant to several antimicrobials, including β-lactams, fluorquinolones, sulfanilamide, glycylcycline, and aminoglycosides, except for amikacin. To investigate the plasmid further, we conducted whole-genome sequencing and sequence analysis. As shown, YL4 possessed a circular chromosome with 5,171,477 bp length and two plasmids, pYL4.1 (321,744 bp) and pYL4.2 (46,771 bp). Importantly, sharing high similarity with plasmids pZHZJ1 and pIMP-26, pYL4.1 has an IncHI2/2A backbone holding a variable region containing , , and two copies of . After comprehensively comparing relevant plasmids, we proposed an evolutionary pathway originating from ancestor pZHZJ1. Then, via an acquisition of the element and a few recombination events, this plasmid eventually evolved into pYL4.1 and pIMP-26 through two different pathways. In addition, the phage-like plasmid pYL4.2 also carried a gene. Remarkably, this study first identified a multidrug-resistant strain co-harboring and on a megaplasmid pYL4.1 and also included a proposed evolutionary pathway of epidemic megaplasmids carrying .
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http://dx.doi.org/10.3390/antibiotics11070869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312351PMC
June 2022

Risks of Stroke and Heart Disease Following Hysterectomy and Oophorectomy in Chinese Premenopausal Women.

Stroke 2022 Jul 13:STROKEAHA121037305. Epub 2022 Jul 13.

Clinical Trial Service Unit and Epidemiological Studies Unit (M.H.F.P., P.Y., Y.C., Z.C., R.C., L.Y.).

Background: Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO.

Methods: A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies.

Results: Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06-1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12-1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery.

Conclusions: Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.
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http://dx.doi.org/10.1161/STROKEAHA.121.037305DOI Listing
July 2022

The Neutrophil-to-Lymphocyte Ratio is Associated with the Requirement and the Duration of Invasive Mechanical Ventilation in Acute Respiratory Distress Syndrome Patients: A Retrospective Study.

Can Respir J 2022 16;2022:1581038. Epub 2022 Jul 16.

Department of Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality and most ARDS patients require ventilatory support. Applying appropriate ventilation strategies based on patients' individual situations has a direct impact upon patients' outcome. The neutrophil-to-lymphocyte ratio (NLR) has been shown to predict the early requirement of invasive mechanical ventilation (IMV) in patients with coronavirus disease 2019 (COVID-19). Our study aimed to investigate the relationship between baseline NLR and IMV in ARDS.

Methods: A retrospective study was performed on patients who were diagnosed with ARDS using the Berlin definition and admitted to the First Affiliated Hospital of Soochow University from 2017 to 2022. Clinical data within 24 h after the ARDS diagnosis were collected from the medical record system. Based on the ventilation strategies during hospitalization, patients were divided into three groups and their clinical characteristics were compared. Furthermore, logistic regression analysis was used to screen the independent risk factors for IMV. STROBE checklist was used for this manuscript.

Results: 520 ARDS patients were included and the median NLR value in IMV group was significantly higher than that of other groups ( < 0.001). NLR was significantly associated with the requirement of IMV in ARDS patients (OR, 1.042; 95% CI, 1.025-1.060; < 0.001), other independent risk factors included PaO/FiO, Hb, lactate, and use of vasoactive drugs (all < 0.05). Moreover, we found that the duration of IMV was longer in patients with high NLR (8[IQR, 3-13], 10[IQR, 6-16], respectively, =0.025).

Conclusions: Our results revealed that high baseline NLR level was significantly correlated with an increased risk of IMV in patients with ARDS. Furthermore, higher NLR was associated with prolonged duration of IMV in patients with ARDS.
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http://dx.doi.org/10.1155/2022/1581038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287782PMC
July 2022

Sevoflurane Inhibits lncRNA HOTAIR-Modulated Stability of HK2 mRNA in a m6A-Dependent Manner to Dampen Aerobic Glycolysis and Proliferation in Lung Cancer.

Biomed Res Int 2022 6;2022:4668774. Epub 2022 Jul 6.

Hemodialysis Room, The Second People's Hospital of Three Gorges University (Yichang Second People's Hospital), Yichang, 443000 Hubei Province, China.

Previous studies have shown that sevoflurane has an inhibitory effect on tumor cells. So far, the effect of sevoflurane on hepatocellular carcinoma needs to be confirmed by more studies. HOX transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA (lncRNA), has been shown to enhance cancer cell proliferation and medication resistance. The inherent importance and biological function of HOTAIR in the course of lung cancer (LC) is, however, poorly unclear. HOTAIR was shown to be highly elevated in LC cells in this investigation. Impairment of function trials with sevoflurane indicated that it has anticancer effects on LC cell growth, apoptosis, and aerobic glycolysis. In a mechanistic manner, HOTAIR was related to HK2 mRNA and promoted expression and constancy. Additional research revealed that HOTAIR coupled with hexokinase 2 (HK2) mRNA and favorably controlled its stabilization in a traditional-component way. By HK2, the LC enhancement role was mediated. In summary, our data show that HOTAIR promotes the synthesis and proliferation of LC glycogen by increasing the transcription of HK2, and HOTAIR is likely to be a potential treatment for LC patients.
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http://dx.doi.org/10.1155/2022/4668774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279057PMC
July 2022

Conventional and genetic risk factors for chronic Hepatitis B virus infection in a community-based study of 0.5 million Chinese adults.

Sci Rep 2022 Jul 15;12(1):12075. Epub 2022 Jul 15.

Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, BDI Building, Old Road Campus, University of Oxford, Oxford, OX3 7LF, UK.

Despite universal vaccination of newborns, the prevalence of chronic hepatitis virus B (HBV) infection and the associated disease burden remain high among adults in China. We investigated risk factors for chronic HBV infection in a community-based study of 512,726 individuals aged 30-79 years recruited from ten diverse areas during 2004-2008. Multivariable logistic regression was used to estimate odds ratios (ORs) of hepatitis B surface antigen (HBsAg) positivity recorded at baseline by sociodemographic and lifestyle factors, and medical history. In a random subset (n = 69,898) we further assessed the association of 18 single nucleotide polymorphisms (SNPs) previously shown to be associated with HBsAg positivity and development of chronic liver disease (CLD) (1600 cases). Several factors showed strong associations with HBsAg positivity, particularly younger age (< 40 vs. ≥ 60 years: OR 1.48, 95% CI 1.32-1.66), male sex (1.40, 1.34-1.46) and urban residency (1.55, 1.47-1.62). Of the 18 SNPs selected, 17 were associated with HBsAg positivity, and 14 with CLD, with SNPs near HLA-DPB1 were most strongly associated with both outcomes. In Chinese adults a range of genetic and non-genetic factors were associated with chronic HBV infection and CLD, which can inform targeted screening to help prevent disease progression.
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http://dx.doi.org/10.1038/s41598-022-16360-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9287541PMC
July 2022

Associations of muscle mass, strength, and quality with all-cause mortality in China: a population-based cohort study.

Chin Med J (Engl) 2022 Jul 15. Epub 2022 Jul 15.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.

Background: It remains unclear about the association of muscle mass, strength, and quality with death in the general Chinese population of diverse economical and geographical backgrounds. The present study aimed to comprehensively examine such associations across different regions in China.

Methods: Based on the China Kadoorie Biobank study, the present study included 23,290 participants who were aged 38 to 88 years and had no prevalent cardiovascular diseases or cancer. Muscle mass and grip strength were measured using calibrated instruments. Arm muscle quality was defined as the ratio of grip strength to arm muscle mass. Low muscle mass, grip strength, and arm muscle quality were defined as the sex-specific lowest quintiles of muscle mass index, grip strength, and arm muscle quality, respectively. Cox proportional hazards models yielded hazard ratios (HRs) and 95% confidence intervals (CIs) for risks of all-cause mortality in relation to muscle mass, strength, and quality.

Results: During a median follow-up of 3.98 years, 739 participants died. The HR (95% CI) of all-cause mortality risk was 1.28 (1.08-1.51) for low appendicular muscle mass index, 1.38 (1.16-1.62) for low total muscle mass index, 1.68 (1.41-2.00) for low grip strength, and 1.41 (1.20-1.66) for low arm muscle quality in models adjusted for sociodemographic characteristics, lifestyle factors, and medical histories.

Conclusion: Low muscle mass, grip strength, and arm muscle quality are all associated with short-term increased risks of mortality, indicating the importance of maintaining normal muscle mass, strength, and quality for general Chinese adults.
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http://dx.doi.org/10.1097/CM9.0000000000002193DOI Listing
July 2022

Radiomic Machine Learning and External Validation Based on 3.0 T mpMRI for Prediction of Intraductal Carcinoma of Prostate With Different Proportion.

Front Oncol 2022 28;12:934291. Epub 2022 Jun 28.

Department of Radiology, West China Hospital of Sichuan University, Chengdu, China.

Purpose: To assess the association of radiomics features based on multiparametric MRI (mpMRI) with the proportion of intraductal carcinoma of prostate (IDC-P) and validate the predictive models.

Materials And Methods: We retrospectively included pre-treatment MR images of prostate cancer (PCa) with IDC components of high proportion (≥10%, hpIDC-P), low proportion (<10%, lpIDC-P), and pure acinar adenocarcinoma (PAC) from our institution for training and internal validation and cooperated cohort for external validation. Normalized images of T2WI, diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) map, and dynamic contrast enhanced (DCE) sequences were used for radiomics modeling. The clinical model was built based on serum total prostate specific antigen (tPSA) and Gleason score (GS), and the integrated model was the combination of Rad-score and clinicopathological data. The discrimination ability was assessed by area under the receiver operating characteristic curve (ROC-AUC) in the internal and external validation sets and compared by DeLong test.

Results: Overall, 97 patients with hpIDC-P, 87 lpIDC-P, and 78 PAC were included for training and internal validation, and 11, 16, and 19 patients for external validation. The integrated model for predicting hpIDC-P got the best ROC-AUC of 0.88 (95%CI = 0.83-0.93) in internal and 0.86 (95%CI = 0.72-1.0) in external validation, which both outperformed clinical models (AUC=0.78, 95% CI = 0.72-0.85, AUC=0.69, 95% CI = 0.5-0.85, respectively) based solely on GS, and the radiomics model (AUC=0.85, 95% CI = 0.79-0.91) was slightly inferior to the integrated model and better than the clinical model in internal dataset. The integrated model for predicting lpIDC-P outperformed both radiomics and clinical models in the internal dataset, while slightly inferior to the integrated model for predicting hpIDC-P.

Conclusions: Radiomics signature improved differentiation of both hpIDC-P and lpIDC-P versus PAC when compared with the clinical model based on Gleason score, and was validated in an external cohort.
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http://dx.doi.org/10.3389/fonc.2022.934291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9274129PMC
June 2022

Expression of nuclear factor kappa B in ovine maternal inguinal lymph nodes during early pregnancy.

BMC Vet Res 2022 Jul 11;18(1):266. Epub 2022 Jul 11.

Department of Animal Science, School of Life Sciences and Food Engineering, Hebei University of Engineering, No. 19 Taiji Road, Handan, 056038, China.

Background: Pregnancy-induced immunological changes contribute to the maternal immune tolerance. Nuclear factor kappa B (NF-κB) pathway participates in regulating both innate and adaptive immunities, and lymph nodes play key roles in adaptive immune reaction. However, it is unclear whether early pregnancy changes the expression of NF-κB family in maternal lymph node in sheep.

Methods: In this study, the samples of inguinal lymph nodes were collected from ewes on day 16 of the estrous cycle, and on days 13, 16 and 25 of pregnancy, and expression of NF-κB family, including NF-κB p105 (NFKB1), NF-κB p100 (NFKB2), p65 (RELA), RelB (RELB) and c-Rel (REL), were analyzed through real-time quantitative PCR, Western blot and immunohistochemical analysis.

Results: The expression levels of NF-κB p105 and c-Rel downregulated, but NF-κB p100 upregulated on day 25 of pregnancy. The expression levels of p65, RelB and c-Rel peaked at day 13 of pregnancy, and expression level of RelB was higher during early pregnancy comparing to day 16 of the estrous cycle. In addition, p65 protein was located in the subcapsular sinus and lymph sinuses.

Conclusion: This paper reported for the first time that early pregnancy has effects on the expression of NF-κB family, which may contribute to the maternal immunoregulation through blood circulation and lymph circulation during early pregnancy in sheep.
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http://dx.doi.org/10.1186/s12917-022-03373-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275262PMC
July 2022

The Effects of Fenugreek Extract on Growth Performance, Serum Biochemical Indexes, Immunity and NF-κB Signaling Pathway in Broiler.

Front Vet Sci 2022 23;9:882754. Epub 2022 Jun 23.

College of Animal Science and Technology, Hunan Agricultural University, Changsha, China.

In order to study the regulation of Fenugreek seed extract (FSE) on the immunity of broilers, and explore the appropriate amount of FSE in broilers' production, 1-day-old yellow feather broilers with a total of 420 birds were randomly allocated into seven treatments. Each treatment had six replicates, with 10 birds per replicate. The two control groups were the basic fodder group fed with basal diet and the bacitracin zinc group added 30 mg/kg bacitracin zinc to the basal diet. Experimental groups included five levels of FSE (50, 100, 200, 400, and 800 mg/kg FSE to the basal diet, respectively). The pre-test period was 7 days and the formal test lasted for 56 days. The results showed that the average daily gain (ADG) of 50 and 800 mg/kg FSE groups was significantly increased ( < 0.01), and the feed to gain ratio (F/G) of FSE groups was significantly decreased ( < 0.01) compared with the basic fodder and the bacitracin zinc groups. Compared with the basic fodder group, the serum total cholesterol (TC) content in the FSE groups was significantly decreased ( < 0.05), the serum low density lipoprotein cholesterol (LDL-C) content of 50, 100, and 800 mg/kg FSE groups was significantly lower than that of the basic fodder group ( < 0.05). Compared with the basic fodder and bacitracin zinc groups, the serum immunoglobulins (IgG, IgM, IgA) content of 100 and 200 mg/kg FSE groups were significantly increased ( < 0.05). Compared with the bacitracin zinc group, the serum interleukins (IL-1, IL-10) content of 400 mg/kg FSE group were significantly increased ( ≤ 0.05), and the serum interferon-γ (IFN-γ) content of 100 and 200 mg/kg FSE groups was significantly increased ( < 0.05). Compared with the basic fodder group, the lower doses (0-400 mg/kg) of FSE had no significant effect on the mRNA expression of toll-like receptors 4/ myeloid differentiation factor 88/ nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathways ( > 0.05). The 800 mg/kg FSE treatment group significantly increased the expression levels of nuclear factor-κB (NF-κB) mRNA in the spleen of broilers ( < 0.05). The zinc bacitracin group significantly increased the expression levels of myeloid differentiation factor 88 (MyD88) and nuclear factor-κB (NF-κB) mRNA ( ≤ 0.05). The results showed that FSE could promote the secretion of immunoglobulins, regulate the body's cytokines, and have a positive effect on immunity in broilers. Furthermore, the recommended supplement of FSE is 100 mg/kg in the broiler diet.
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http://dx.doi.org/10.3389/fvets.2022.882754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260050PMC
June 2022

Association between intestinal microbiota and inflammatory bowel disease.

Animal Model Exp Med 2022 Jul 8. Epub 2022 Jul 8.

State Key Laboratory of Animal Nutrition, Department of Animal Nutrition and Feed Science, China Agricultural University, Beijing, China.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), has emerged as a global disease with high incidence, long duration, devastating clinical symptoms, and low curability (relapsing immune response and barrier function defects). Mounting studies have been performed to investigate its pathogenesis to provide an ever-expanding arsenal of therapeutic options, while the precise etiology of IBD is not completely understood yet. Recent advances in high-throughput sequencing methods and animal models have provided new insights into the association between intestinal microbiota and IBD. In general, dysbiosis characterized by an imbalanced microbiota has been widely recognized as a pathology of IBD. However, intestinal microbiota alterations represent the cause or result of IBD process remains unclear. Therefore, more evidences are needed to identify the precise role of intestinal microbiota in the pathogenesis of IBD. Herein, this review aims to outline the current knowledge of commonly used, chemically induced, and infectious mouse models, gut microbiota alteration and how it contributes to IBD, and dysregulated metabolite production links to IBD pathogenesis.
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http://dx.doi.org/10.1002/ame2.12255DOI Listing
July 2022

An archetype of the electron-unobstructed core-shell composite with inherent selectivity: conductive metal-organic frameworks encapsulated with metal nanoparticles.

Nanoscale 2022 Jul 14;14(27):9655-9660. Epub 2022 Jul 14.

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

The acquisition of monodisperse metal nanoparticles covered by conductive metal-organic frameworks (cMOFs) is an archetype of an electron-unobstructed core-shell composite, valued for its potential electrocatalytic ability and selectivity enhancement. In this work, [email protected] composites with direct interfaces showed better performance in the oxygen reduction reaction than composites with indirect interfaces or with lower electroconductivity shells. This composite was proved to exhibit the ability to expedite electron transfer with different thicknesses of electrode materials. The detailed mechanism was studied by exploring the conductivity of shell materials, interfaces between cores and shells, and the surface electronic structure of the nanoparticles. We also report reaction selectivity from the inherent porous shells in the selective reduction of cinnamyl alcohol.
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http://dx.doi.org/10.1039/d2nr02681cDOI Listing
July 2022

Single-cell sequencing reveals CD133CD44-originating evolution and novel stemness related variants in human colorectal cancer.

EBioMedicine 2022 Jul 1;82:104125. Epub 2022 Jul 1.

Department of Radiotherapy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Electronic address:

Background: Tumor heterogeneity of human colorectal cancer (CRC)-initiating cells (CRCICs) in cancer tissues often represents aggressive features of cancer progression. For high-resolution examination of CRCICs, we performed single-cell whole-exome sequencing (scWES) and bulk cell targeted exome sequencing (TES) of CRCICs to investigate stemness-specific somatic alterations or clonal evolution.

Methods: Single cells of three subpopulations of CRCICs (CD133CD44, CD133CD44, and CD133CD44 cells), CRC cells (CRCCs), and control cells from one CRC tissue were sorted for scWES. Then, we set up a mutation panel from scWES data and TES was used to validate mutation distribution and clonal evolution in additional 96 samples (20 patients) those were also sorted into the same three groups of CRCICs and CRCCs. The knock-down experiments were used to analyze stemness-related mutant genes. Neoantigens of these mutant genes and their MHC binding affinity were also analyzed.

Findings: Clonal evolution analysis of scWES and TES showed that the CD133CD44 CRCICs were the likely origin of CRC before evolving into other groups of CRCICs/CRCCs. We revealed that AHNAK2, PLIN4, HLA-B, ALK, CCDC92 and ALMS1 genes were specifically mutated in CRCICs followed by the validation of their functions. Furthermore, four predicted neoantigens of AHNAK2 were identified and validated, which might have applications in immunotherapy for CRC patients.

Interpretation: All the integrative analyses above revealed clonal evolution of CRC and new markers for CRCICs and demonstrate the important roles of CRCICs in tumorigenesis and progression of CRCs.

Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.
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http://dx.doi.org/10.1016/j.ebiom.2022.104125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254347PMC
July 2022

Comparison of Reproductive Function Between Normal and Hyperandrogenemia Conditions in Female Mice With Deletion of Hepatic Androgen Receptor.

Front Endocrinol (Lausanne) 2022 9;13:868572. Epub 2022 Jun 9.

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Obesity, altered glucose homeostasis, hyperinsulinism, and reproductive dysfunction develops in female humans and mammals with hyperandrogenism. We previously reported that low dose dihydrotestosterone (DHT) administration results in metabolic and reproductive dysfunction in the absence of obesity in female mice, and conditional knock-out of the androgen receptor (Ar) in the liver (LivARKO) protects female mice from DHT-induced glucose intolerance and hyperinsulinemia. Since altered metabolic function will regulate reproduction, and liver plays a pivotal role in the reversible regulation of reproductive function, we sought to determine the reproductive phenotype of LivARKO mice under normal and hyperandrogenemic conditions. Using Cre/Lox technology, we deleted the in the liver, and we observed LivARKO female mice have normal puberty timing, cyclicity and reproductive function. After DHT treatment, like control mice, LivARKO experience altered estrous cycling, reduced numbers of corpus lutea, and infertility. Liver Ar is not involved in hyperandrogenemia-induced reproductive dysfunction. The reproductive dysfunction in the DHT-treated LivARKO lean females with normal glucose homeostasis indicates that androgen-induced reproductive dysfunction is independent from metabolic dysfunction.
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http://dx.doi.org/10.3389/fendo.2022.868572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218244PMC
June 2022

Nitrogen-Doped Carbon-Encapsulated Ordered Mesoporous SiO as Anode for High-Performance Lithium-Ion Batteries.

Chem Asian J 2022 Jun 24:e202200440. Epub 2022 Jun 24.

School of Environmental and Chemical Engineering, Shanghai University, 200444, Shanghai, P. R. China.

June 2022

A giant desmoid-type fibromatosis of the abdominal cavity.

Asian J Surg 2022 Jun 21. Epub 2022 Jun 21.

Biobank of Pathology Department, Suining Central Hospital, Suining, Sichuan, China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.06.026DOI Listing
June 2022

Targeting the SOX2/PARP1 complex to intervene in the growth of esophageal squamous cell carcinoma.

Biomed Pharmacother 2022 Jun 20;153:113309. Epub 2022 Jun 20.

Central Laboratory, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China; School of Medicine, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:

Elevated SOX2 protein levels are closely correlated with the increased incidence of esophageal squamous cell carcinoma (ESCC). However, establishing effective target measures for ESCC treatments continue to be researched. It has been previously proposed that SOX2 represents a potential therapeutic target for ESCC. Here, we found that the enzyme Poly(ADP-Ribose) polymerase 1 (PARP1) enriched in ESCCs interact with SOX2. Inhibition of PARP1 with 3-aminobenzamide (3-ABA) or shRNA knockdown reduced the proliferation of ESCCs, accompanied by decreased protein levels of SOX2. RNA sequencing demonstrated that PARP1 inhibition affected multiple signaling pathways involved in cancer cell proliferation. Additionally, 3-ABA synergistically suppressed the growth of ESCC cells when combined with cisplatin, and metformin potentiated the suppressive effect of 3-ABA on ESCC cell growth. Together these findings suggest that targeting SOX2 binding partner PARP1 provides a possible avenue to treat patients with high levels of SOX2.
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http://dx.doi.org/10.1016/j.biopha.2022.113309DOI Listing
June 2022
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