Publications by authors named "Wentao Yang"

238 Publications

qRT-PCR-based DNA homologous recombination-associated 4-gene score predicts pathologic complete response to platinum-based neoadjuvant chemotherapy in triple-negative breast cancer.

Breast Cancer Res Treat 2021 Nov 19. Epub 2021 Nov 19.

Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Rd., Shanghai, 200032, China.

Purpose: Cumulative evidence suggests that the addition of platinum agents as neoadjuvant chemotherapy (NACT) could improve the pathologic complete response (pCR) rate in triple-negative breast cancer (TNBC). We aimed to develop a DNA homologous recombination (HR)-associated gene expression score to predict tumor sensitivity to platinum-based NACT in TNBC.

Methods: A retrospective cohort of 127 patients who were diagnosed with TNBC and received platinum-based NACT in Fudan University Shanghai Cancer Center from 2012 to 2017 was included in this study. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the expression levels of eight HR-associated genes were analyzed from formalin-fixed paraffin-embedded core-needle biopsy samples obtained before NACT. A random forest model was built to estimate the weight of each gene expression level and clinicopathological factors. The training set was used to modulate parameters and select the best model. The performance of the final model was evaluated in the validation set.

Results: A 4-gene (BRCA1, XRCC5, PARP1, and RAD51) scoring system was developed. TNBC patients with a higher score had a nearly fourfold likelihood of achieving pCR to platinum-based NACT compared with patients with a lower score [odds ratio (OR) = 3.878; P < 0.001]. At the cutoff value of - 2.644, the 4-gene scoring system showed high sensitivity in predicting pCR in the breast (93.0%) and pCR in the breast/axilla (91.8%), while at the cutoff value of - 1.969, the 4-gene score showed high specificity for pCR in the breast (85.7%) and pCR in the breast/axilla (80.8%).

Conclusion: The qRT-PCR-based 4-gene score has the potential to predict pCR to platinum-based NACT in TNBC.
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http://dx.doi.org/10.1007/s10549-021-06442-xDOI Listing
November 2021

The prognostic significance of left atrial appendage peak flow velocity in the recurrence of persistent atrial fibrillation following first radiofrequency catheter ablation.

J Thorac Dis 2021 Oct;13(10):5954-5963

College of Medicine, Nankai University, Tianjin, China.

Background: Atrial fibrillation (AF) relapse following radiofrequency catheter ablation (RFCA) for persistent atrial fibrillation (PeAF) continues to be a concern. This study establishes a connection between left atrial appendage peak flow velocity (LAAV) and recurrence of AF in individuals having PeAF following first RFCA.

Methods: We retrospectively studied 164 successive PeAF patients who had first RFCA between January 2018 and December 2019. Before the ablation, the LAAV was recorded using transesophageal echocardiography (TEE). The demographic and clinical data of the individuals were gathered. Participants were monitored at regular intervals to monitor for recurrence of AF. We employed Cox proportional hazards regression to determine if LAAV, as well as other clinical indicators, were predictive of AF recurrence in follow-up.

Results: In this study, AF relapse was seen in 43 patients (26.2%) following a median follow-up of 15 [interquartile range (IQR): 12-18] months. It was shown that the LAAV was decreased in individuals who had recurrences of AF (0.36±0.05 0.45±0.17 m/s, P=0.004). Using Kaplan-Meier analysis, it was discovered that the low LAAV (0.37 m/s) group had a poorer event-free survival rate compared to the high LAAV (>0.37 m/s) group (17.6 21.2 months, log-rank P=0.002) group. Based on the results of the multivariate Cox regression analysis, a LAAV of fewer than 0.37 m/s [hazard ratio (HR): 2.32; 95% confidence interval (CI): 1.177-4.227; P=0.014] was shown to be an independent predictor of AF recurrence following RFCA.

Conclusions: A low LAAV is associated with AF relapse, and it is a predictor of AF relapse following the first RFCA for PeAF. This discovery may be useful in the optimization of treatment strategies and the care of patients with PeAF.
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http://dx.doi.org/10.21037/jtd-21-1363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575843PMC
October 2021

FOXC1.

Arch Pathol Lab Med 2021 Nov 16. Epub 2021 Nov 16.

From the Department of Pathology, Fudan University Shanghai Cancer Center.

Context.—: Few studies have investigated the features of FOXC1 protein expression in invasive breast cancer subtypes as defined by immunohistochemistry (IHC)-based surrogate molecular classification.

Objective.—: To investigate the diagnostic utility of the IHC-based FOXC1 test in breast cancer subtyping and to evaluate the correlation between FOXC1 expression and clinicopathologic parameters in triple-negative breast cancer (TNBC).

Design.—: FOXC1 expression was evaluated with IHC in a large cohort of 2443 patients with breast cancer. Receiver operating characteristic (ROC) curves were used to assess the diagnostic ability of FOXC1 expression to predict the triple-negative phenotype and to identify the best cutoff value. FOXC1 expression was correlated with the clinicopathologic parameters of TNBC.

Results.—: The expression rate of FOXC1 in TNBC was significantly higher than in other subtypes. The area under the ROC curve confirmed the high diagnostic value of FOXC1 for the prediction of the triple-negative phenotype. The cutoff value of 1% showed a maximized sum of sensitivity and specificity. In TNBC, FOXC1 expression was significantly associated with aggressive tumor phenotypes. Furthermore, FOXC1 expression was primarily observed in invasive breast carcinoma of no special type and metaplastic carcinoma but rarely in invasive carcinoma with apocrine differentiation. Correspondingly, FOXC1 expression was significantly associated with the expression of basal markers but was negatively correlated with apocrine-related markers in TNBC.

Conclusions.—: In conclusion, FOXC1 is a highly specific marker for the triple-negative phenotype. Moreover, immunohistochemical detection of FOXC1 expression can be used as an additional diagnostic tool for the triple-negative phenotype and subclassification in TNBC.
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http://dx.doi.org/10.5858/arpa.2021-0039-OADOI Listing
November 2021

Tumoral Morphologic Features From Cervical Biopsies That Are Predictive of a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual-type Cervical Adenocarcinomas: A Multi-institutional Study.

Am J Surg Pathol 2021 Nov 11. Epub 2021 Nov 11.

Department of Obstetrics and Gynecology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital Department of Pathology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan Province Departments of Pathology Gynecologic Oncology, Sun Yat-Sen University Cancer Center Department of Pathology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province Department of Pathology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai Department of Pathology, Women's Hospital, School of Medicine Zhejiang University, Hangzhou, Zhejiang Province Department of Pathology, Sheng Jing Hospital of China Medical University, Shenyang, Liaoning Province Department of Pathology, Shandong University School of Basic Medical Sciences Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University School of Medicine, Jinan, Shandong Province Department of Pathology, The Seventh Medical Center of Chinese PLA General Hospital Department of Pathology, The First Medical Center of Chinese PLA General Hospital, Beijing, China Departments of Pathology Obstetrics and Gynecology Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX Department of Pathology, Women & Infants Hospital & Alpert Medical School of Brown University, Providence, RI Department of Pathology, University of California San Diego, La Jolla, CA Archway Health, Boston, MA.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.
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http://dx.doi.org/10.1097/PAS.0000000000001833DOI Listing
November 2021

African swine fever virus MGF505-11R inhibits type I interferon production by negatively regulating the cGAS-STING-mediated signaling pathway.

Vet Microbiol 2021 Oct 21;263:109265. Epub 2021 Oct 21.

College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China. Electronic address:

African swine fever (ASF) is an acute, hemorrhagic, and highly contact infectious disease caused by African swine fever virus (ASFV) infecting domestic pigs or wild boars, the mortality rate up to 100 %. Evasion of host innate immunity plays a vital role in the pathogenesis of ASFV. Studies have showed that the MGF505 genes involve in regulating the IFN-I response, but its mechanism of action remains poorly understood. In our present study, ASFV MGF505-11R inhibited IFN-β and ISRE activation induced by cGAS, IRF7, IRF3-5D, STING, IKKε and TBK1 accompanied by decreases of IFN-β, ISG15 and ISG56 mRNA transcription. ASFV MGF505-11R interacted with STING, degrading STING expression by the lysosomal, ubiquitin-proteasome and autophagy pathways. Moreover, ASFV MGF505-11R could inhibit the phosphorylation of TBK1 and IRF3 stimulated by cGAS/STING overexpression. Finally, the truncation mutation analysis indicated that the 1-191 aa and 182-360 aa of ASFV MGF505-11R could inhibit cGAS-STING-mediated activation of IFN-β promoters. In short, these results demonstrated that ASFV MGF505-11R involved in regulating the IFN-I response by negatively regulating the cGAS signaling pathway. In summary, this study preliminarily clarified the molecular mechanism of ASFV MGF505-11R gene antagonizing IFN-I-mediated antiviral, which will helpfully provide new strategies for treatment and prevention of ASF.
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http://dx.doi.org/10.1016/j.vetmic.2021.109265DOI Listing
October 2021

NUDT15 variants confer high incidence of second malignancies in children with acute lymphoblastic leukemia.

Blood Adv 2021 Oct 18. Epub 2021 Oct 18.

Chiba Children's Hospital, Chiba, Japan.

The effect of genetic variation on second malignant neoplasms (SMNs) remains unclear. First, we identified the pathogenic germline variants in cancer-predisposing genes among 15 children with SMNs after childhood leukemia/lymphoma using whole-exome sequencing. As the prevalence was low, we focused on the association between SMNs and NUDT15 in primary acute lymphoblastic leukemia (ALL) cases. NUDT15 is one of the 6-mercaptopurine (6-MP) metabolic genes, and its variants are common in East Asian individuals. The prevalence of NUDT15 hypomorphic variants was higher in patients with SMN (n = 14, 42.9%) than general population in gnomAD database (19.7%) (p = 0.042). In the validation study with a cohort of 438 unselected patients with ALL, the cumulative incidence of SMN was significantly higher among cases with NUDT15 variant (3.0%, 95% CI, 0.6%-9.4%) than those without (0.3%, 95% CI, 0.0-1.5%) (p = 0.045). The 6-MP dose of SMN patients with a NUDT15 variant was higher than that of those without SMN (p = 0.045). The 6-MP related mutational signature was observed in SMN specimens after 6-MP exposure. In cells under 6-MP exposure, a higher level of 6-MP-induced DNA damage in NUDT15 knockdown iPS cells. Our study indicates that NUDT15 variants may confer a risk of SMN after treatment with 6-MP among patients with ALL.
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http://dx.doi.org/10.1182/bloodadvances.2021005507DOI Listing
October 2021

Circular RNA promotes development of glioblastoma by regulating the miR-361-3p/miR-324-5p/ signaling pathway.

Mol Ther Oncolytics 2021 Sep 29;22:483-494. Epub 2021 Jul 29.

Department of Neurosurgery, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, Shanghai 200032, P.R. China.

Circular RNA (circRNA) is a new type of long-sequence RNA formed by a noncanonical form of alternative splicing called back-splicing. Emerging evidence has revealed that circRNAs are involved in cancer progression, regulating cancer-related genes through sponging microRNAs (miRNAs). In our study, we identified a novel upregulated circRNA, , through analyzing circRNAs microarray data of glioblastoma from GEO datasets (GSE146463). Quantitative real-time PCR was used to further confirm the upregulation of in glioblastoma cell lines and tissues. Silencing inhibits glioblastoma proliferation and through cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry analysis, and western blot analysis and xenograft tumor model. Mechanistically, could directly sponge miR-324-5p and miR-361-3p. , known as a novel anti-apoptosis gene, is a target gene both of miR-324-5p and miR-361-3p. Thus, promotes expression through sponging miR-324-5p and miR-361-3p. In conclusion, our study revealed the biological function and mechanism of in glioblastoma progression and that could be a potential therapeutic target for glioblastoma.
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http://dx.doi.org/10.1016/j.omto.2021.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433060PMC
September 2021

In Vivo Production of HN Protein Increases the Protection Rates of a Minicircle DNA Vaccine against Genotype VII Newcastle Disease Virus.

Vaccines (Basel) 2021 Jul 2;9(7). Epub 2021 Jul 2.

College of Animal Medicine, Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Lab of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.

The Cre-recombinase mediated in vivo minicircle DNA vaccine platform (CRIM) provided a novel option to replace a traditional DNA vaccine. To further improve the immune response of our CRIM vaccine, we designed a dual promoter expression plasmid named pYL87 which could synthesize short HN protein under a prokaryotic in vivo promoter P and full length HN protein of genotype VII Newcastle disease virus (NDV) under the previous eukaryotic CMV promoter at the same time. Making use of the self-lysed strain as a delivery vesicle, chickens immunized with the pYL87 construction showed an increased serum haemagglutination inhibition antibody response, as well as an increased cell proliferation level and cellular IL-4 and IL-18 cytokines, compared with the previous CRIM vector pYL47. After the virus challenge, the pYL87 vector could provide 80% protection compared to 50% protection against genotype VII NDV in pYL47 immunized chickens, indicating a promising dual promoter strategy used in vaccine design.
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http://dx.doi.org/10.3390/vaccines9070723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310180PMC
July 2021

Epithelioid leiomyosarcoma of broad ligament harboring PGR-NR4A3 and UBR5-PGR gene fusions: a unique case report.

Virchows Arch 2021 Aug 5. Epub 2021 Aug 5.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China.

A novel molecular subset of epithelioid leiomyosarcomas with rhabdoid features harboring PGR gene rearrangements has recently been documented. Herein, we present a unique case of PGR-rearranged smooth muscle tumor with both PGR-NR4A3 and UBR5-PGR gene fusions reported in a 30-year-old woman who had a mass in the broad ligament. The histological examination showed a round/polygonal to spindle cell tumor with abundant myxoid matrix and focal hyalinization, resulting in an epithelioid pattern. Immunohistochemical examination revealed that the tumor had variable staining for desmin, SMA, and h-caldesmon and diffuse nuclear staining of ER, PR, and WT1. Furthermore, targeted RNA sequencing analysis revealed PGR-NR4A3 and UBR5-PGR gene fusions. Our case in addition with the reported cases suggest that myxoid matrix with two types of tumor cells (round/polygonal epithelioid cells and spindle cells) may be significant for the diagnosis of PGR-NR4A3 fusion-positive leiomyosarcoma. UBR5-PGR gene fusion is a novel finding in epithelioid leiomyosarcoma.
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http://dx.doi.org/10.1007/s00428-021-03169-4DOI Listing
August 2021

Germline and tumor BRCA1/2 pathogenic variants in Chinese triple-negative breast carcinomas.

J Cancer Res Clin Oncol 2021 Oct 13;147(10):2935-2944. Epub 2021 Jul 13.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.

Purpose: BRCA1/2 screening for all triple-negative breast cancer (TNBC) patients younger than 60 years may still be an economic burden in China. Further evidences that include incidence and outcome of BRCA1/2 pathogenic variants (PV) screened based on younger age or family history (FH) are worth discussing for improving the cost-effectiveness of BRCA1/2 testing in Chinese TNBC. We aimed to investigate the prevalence of germline and tumor BRCA1/2 PV based on age screening in Chinese TNBC patients.

Methods: Paired blood and tumor DNA from 124 unselected Chinese TNBC patients with less than or equal to 55 years were collected and analyzed for BRCA1/2 PV. Clinicopathological characteristics including age at diagnosis, FH and follow-up data were collected for further analysis.

Results: The entire frequency of germline and tumor BRCA1/2 PV was 21.0 and 25%, respectively. Among them, 20 (16.1%) germline and 5 (4.0%) somatic BRCA1/2 single-nucleotide variant/insertion/deletions were found by NGS testing, 6 (4.8%) BRCA1 large genomic rearrangements were detected in blood DNA by MPLA. There was significant correlation between FH of HBOC and germline BRCA1/2 PVs among these patients. Patients with tumor BRCA1/2 PVs had significant improvements than non-carriers in PFS (p = 0.047). No significant impacts were found between various mutation status in OS outcomes. No significant differences were found between BRCA1 or BRCA2 and non-carriers in PFS or OS.

Conclusion: There is a high incidence of germline and tumor BRCA1/2 PVs in Chinese TNBC patients with less than or equal to 55 years old. Tumor BRCA1/2 PV carriers showed an improved survival outcome. Our results suggest that BRCA1/2 PVs testing addressed within each specific clinical scenario could be more cost-effective for patients.
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http://dx.doi.org/10.1007/s00432-021-03696-2DOI Listing
October 2021

Clinicopathological significance of WT1 expression in invasive breast carcinoma with >90% mucinous component.

J Clin Pathol 2021 Jul 8. Epub 2021 Jul 8.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

Aims: This study was aimed to investigate the clinicopathological significance of immunohistochemical (IHC) Wilm's tumour 1 (WT1) expression in invasive breast carcinoma with >90% mucinous components.

Methods: One hundred specimens of invasive breast carcinoma with >90% mucinous component were collected. All H&E-stained slides were reviewed, and the clinicopathological data, including sex, age, tumour size, nuclear grade, histological grade, growth pattern and lymph node (LN) status, were collected. IHC staining of WT1, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki-67 was performed. Fluorescence in situ hybridisation was used to verify the amplification of the HER2 gene. The relationship between WT1 expression and clinicopathological features was analysed statistically.

Results: WT1 expression was detected in 67% (67/100) of invasive breast carcinoma with >90% mucinous components. WT1 expression was significantly associated with low-to-intermediate nuclear grade/histological grade, ER and PR positivity, HER2 negativity, Ki-67 proliferation index <30% and noLN metastasis (all p<0.001). Micropapillary architecture was observed in 80% of cases. WT1 expression was not significantly correlated with different percentage of micropapillary components (p=0.422). None of the histological grade 3 tumours, tumours with HER2 overexpression/amplification and triple-negative specimens showed WT1 expression.

Conclusions: WT1 expression was significantly related with low-intermediate nuclear/histological grade, ER positivity, HER2 negativity, a lower Ki-67 proliferation index and no LN metastasis in invasive breast carcinoma with >90% mucinous component. The micropapillary growth pattern in this type of tumour did not show a specific relationship with WT1 expression.
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http://dx.doi.org/10.1136/jclinpath-2021-207464DOI Listing
July 2021

Effects of Organic Fertilizers on Cd Activity in Soil and Cd Accumulation in Rice in Three Paddy Soils from Guizhou Province.

Bull Environ Contam Toxicol 2021 Dec 9;107(6):1161-1166. Epub 2021 Jul 9.

College of Resource and Environmental Engineering, Guizhou University, Guiyang, 550025, China.

A greenhouse pot experiment was conducted to investigate the effects of organic fertilizer application on Cd activity in soil and Cd accumulation in rice in paddy soils with different levels of contamination from varying Cd sources in Guizhou Province (the soil types are NJ, which is a soil with a high geological background of Cd; and QX and JZ, which are anthropogenic Cd-polluted soils). The application of organic fertilizer increased the content of organic matter in the soil and reduced the concentration of acetic acid-extractable Cd in QX and JZ paddy soils. Organic fertilizer increased rice yields and significantly decreased the Cd concentration in brown rice. In the QX and JZ soils, however, the concentration of Cd in brown rice exceeded the allowable maximum levels (MLs) of Cd in China. In contrast, the concentration of Cd in brown rice in NJ soil met the MLs of Cd. Additionally, the average daily dose and the health risk index of Cd in NJ soil were much lower than those in QX and JZ soils. The results indicate that organic fertilizer application is a promising and economic means to control Cd pollution in paddy soil. Moreover, risk assessment shows that the risk of exposure to Cd in the high geological background soil (NJ) was much lower than that in anthropogenically polluted soils (QX and JZ).
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http://dx.doi.org/10.1007/s00128-021-03326-0DOI Listing
December 2021

Dual Antiplatelet Therapy vs. Single Antiplatelet Therapy After Transcatheter Aortic Valve Replacement: An Updated Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2021 21;8:679703. Epub 2021 Jun 21.

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Although mainstream guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in patients following transcatheter aortic valve replacement (TAVR), it is not evidence-based. We aim to investigate the safety and efficacy of DAPT vs. single antiplatelet therapy (SAPT) after TAVR, and review updated evidence. We systematically searched PubMed, Embase, and Cochrane for studies comparing DAPT to SAPT after TAVR from inception to November 30, 2020. The primary outcome was major adverse cardiac and cerebrovascular events, including all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and major or life-threatening bleeding (LTB). Subgroup analysis was performed according to study type (randomized control trials vs. observational studies) using a fixed-effects model. The quality of evidence was assessed by two scoring systems and GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Twelve studies of 20,766 patients were included in our meta-analysis. Compared with SAPT, DAPT was associated with an increased risk for combined life threatening and major bleeding [OR 1.73 (1.19-2.51), = 0.004] after TAVR. Such a difference was largely driven by major bleeding [OR 2.29 (1.68-3.11), < 0.001]. There were no significant differences on major adverse cardiovascular events (MACE) [OR 1.19 (0.99-1.44), = 0.07], cardiovascular mortality [OR 1.46 (0.93-2.30), = 0.10], and stroke [OR 0.97 (0.80-1.16), = 0.71]. Compared with SAPT, post-TAVR DAPT was associated with increased risks of major or life-threatening bleeding without additional benefits of reducing thrombotic events. Future guidelines for post-TAVR antiplatelet strategy are expected to be updated as new high-quality evidence emerges. PROSPERO, Identifier: CRD42021230075.
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http://dx.doi.org/10.3389/fcvm.2021.679703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255616PMC
June 2021

Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia.

J Clin Invest 2021 Jun 24. Epub 2021 Jun 24.

Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, United States of America.

Genetic alterations in the RUNX1 gene are associated with benign and malignant blood disorders, particularly of megakaryocyte and myeloid lineages. The role of RUNX1 in acute lymphoblastic leukemia (ALL) is less clear, particularly how germline genetic variation influences the predisposition to this type of leukemia. Sequencing 4,836 children with B-ALL and 1,354 cases of T-ALL, we identified 31 and 18 germline RUNX1 variants, respectively. RUNX1 variants in B-ALL consistently showed minimal damaging effects. By contrast, 6 T-ALL-related variants result in drastic loss of RUNX1 activity as a transcription activator in vitro. Ectopic expression of dominant-negative RUNX1 variants in human CD34+ cells repressed differentiation into erythroid, megakaryocytes, and T cells, while promoting myeloid cell development. Chromatin immunoprecipitation sequencing of T-ALL models showed distinctive patterns of RUNX1 binding by variant proteins. Further whole genome sequencing identified JAK3 mutation as the most frequent somatic genomic abnormality in T-ALL with germline RUNX1 variants. Co-introduction of RUNX1 variant and JAK3 mutation in hematopoietic stem and progenitor cells in mice gave rise to T-ALL with early T-cell precursor phenotype. Taken together, these results indicated that RUNX1 is an important predisposition gene for T-ALL and pointed to novel biology of RUNX1-mediated leukemogenesis in the lymphoid lineages.
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http://dx.doi.org/10.1172/JCI147898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409579PMC
June 2021

Network-based systems pharmacology reveals heterogeneity in LCK and BCL2 signaling and therapeutic sensitivity of T-cell acute lymphoblastic leukemia.

Nat Cancer 2021 Mar 21;2(3):284-299. Epub 2021 Jan 21.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy, and novel therapeutics are much needed. Profiling patient leukemia' drug sensitivities , we discovered that 44.4% of childhood and 16.7% of adult T-ALL cases exquisitely respond to dasatinib. Applying network-based systems pharmacology analyses to examine signal circuitry, we identified preTCR-LCK activation as the driver of dasatinib sensitivity, and T-ALL-specific LCK dependency was confirmed in genome-wide CRISPR-Cas9 screens. Dasatinib-sensitive T-ALLs exhibited high BCL-XL and low BCL2 activity and venetoclax resistance. Discordant sensitivity of T-ALL to dasatinib and venetoclax is strongly correlated with T-cell differentiation, particularly with the dynamic shift in LCK vs. BCL2 activation. Finally, single-cell analysis identified leukemia heterogeneity in LCK and BCL2 signaling and T-cell maturation stage, consistent with dasatinib response. In conclusion, our results indicate that developmental arrest in T-ALL drives differential activation of preTCR-LCK and BCL2 signaling in this leukemia, providing unique opportunities for targeted therapy.
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http://dx.doi.org/10.1038/s43018-020-00167-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208590PMC
March 2021

Adjuvant effects of bacterium-like particles in the intranasal vaccination of chickens against Newcastle disease.

Vet Microbiol 2021 Aug 4;259:109144. Epub 2021 Jun 4.

College of Veterinary Medicine, Jilin Agricultural University, Changchun, China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, China; Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, China. Electronic address:

Given that the respiratory mucosa is an important site for the initial replication of Newcastle disease virus (NDV), developing intranasal vaccines for chickens is an effective strategy to protect against this disease. The low immunogenicity of inactivated NDV administered by the mucosal route motivated us to identify a safe and potent adjuvant. Previous studies have shown that bacterium-like particles (BLPs), which serve as mucosal adjuvants, induce effective local and systemic immune responses through TLR2 signaling in both mammals and humans. Here, we report that BLPs could activate the innate immune system of chickens in a manner that was dependent on the combination of chicken TLR2 type 1 (chTLR2t1) and chicken TLR1 type 1 (chTLR1t1). The chicken macrophage-like HD11 cell line was stimulated with BLPs, resulting in the production of nitric oxide and the expression of the proinflammatory cytokines IFN-γ, IL-1β and IL-6. Chickens intranasally immunized with inactivated NDV vaccines mixed with BLP adjuvants exhibited significantly increased levels of local SIgA in their tracheal lavage fluid and as well as hemagglutination-inhibiting antibodies in serum samples. The strong systemic and local immune responses induced by BLP-adjuvanted vaccines provided 100 % protection against intranasal challenge with a lethal dose of virulent NDV without showing any signs of disease. These results indicate that BLPs should be considered for use as a potential mucosal adjuvant for inactivated NDV vaccines and other vaccines for poultry.
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http://dx.doi.org/10.1016/j.vetmic.2021.109144DOI Listing
August 2021

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Cancers (Basel) 2021 May 8;13(9). Epub 2021 May 8.

Russian Association of Oncological Mammology, Department of Breast Tumours of Federal State Budgetary Institution "Petrov Research Institute of Oncology", 197758 Saint Petersburg, Russia.

: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. : A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. : These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.
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http://dx.doi.org/10.3390/cancers13092262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125909PMC
May 2021

The effects of nested miRNAs and their host genes on immune defense against Bacillus thuringiensis infection in Caenorhabditis elegans.

Dev Comp Immunol 2021 10 27;123:104144. Epub 2021 May 27.

Department of Evolutionary Ecology and Genetics, Christian-Albrechts-Universität zu Kiel, Am Botanischen Garten 1-9, 24118, Kiel, Germany; Max Planck Institute for Evolutionary Biology, 24306, Ploen, Germany. Electronic address:

microRNAs (miRNAs) are small non-coding RNA-molecules that influence translation by binding to the target gene mRNA. Many miRNAs are found in nested arrangements within larger protein-coding host genes. miRNAs and host genes in a nested arrangement are often transcribed simultaneously, which may indicate that both have similar functions. miRNAs have been implicated in regulating defense responses against pathogen infection in C. elegans and in mammals. Here, we asked if miRNAs in nested arrangements and their host genes are involved in the C. elegans response against infection with Bacillus thuringiensis (Bt). We performed miRNA sequencing and subsequently focused on four nested miRNA-host gene arrangements for a functional genetic analysis. We identified mir-58.1 and mir-2 as negative regulators of C. elegans resistance to Bt infection. However, we did not find any miRNA/host gene pair in which both contribute to defense against Bt.
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http://dx.doi.org/10.1016/j.dci.2021.104144DOI Listing
October 2021

M2 macrophage-derived exosomal long non-coding RNA AGAP2-AS1 enhances radiotherapy immunity in lung cancer by reducing microRNA-296 and elevating NOTCH2.

Cell Death Dis 2021 05 10;12(5):467. Epub 2021 May 10.

Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human diseases. We aimed to identify the effect of the lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1)/miR-296/notch homolog protein 2 (NOTCH2) axis on the progression and radioresistance of lung cancer. Expression of AGAP2-AS1, miR-296, and NOTCH2 in lung cancer cells and tissues from radiosensitive and radioresistant patients was determined, and the predictive role of AGAP2-AS1 in the prognosis of patients was identified. THP-1 cells were induced and exosomes were extracted, and the lung cancer cells were respectively treated with silenced AGAP2-AS1, exosomes, and exosomes upregulating AGAP2-AS1 or downregulating miR-296. The cells were radiated under different doses, and the biological processes of cells were assessed. Moreover, the natural killing cell-mediated cytotoxicity on lung cancer cells was determined. The relationships between AGAP2-AS1 and miR-296, and between miR-296 and NOTCH2 were verified. AGAP2-AS1 and NOTCH2 increased while miR-296 decreased in radioresistant patients and lung cancer cells. The malignant behaviors of radioresistant cells were promoted compared with the parent cells. Inhibited AGAP2-AS1, macrophage-derived exosomes, and exosomes overexpressing AGAP2-AS1 or inhibiting miR-296 facilitated the malignant phenotypes of radioresistant lung cancer cells. Furthermore, AGAP2-AS1 negatively regulated miR-296, and NOTCH2 was targeted by miR-296. M2 macrophage-derived exosomal AGAP2-AS1 enhances radiotherapy immunity in lung cancer by reducing miR-296 and elevating NOTCH2. This study may be helpful for the investigation of radiotherapy of lung cancer.
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http://dx.doi.org/10.1038/s41419-021-03700-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110970PMC
May 2021

Recombinant Lactobacillus plantarum NC8 strain expressing porcine rotavirus VP7 induces specific antibodies in BALB/c mice.

Acta Biochim Biophys Sin (Shanghai) 2021 May;53(6):707-718

College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun 130118, China.

The major etiologic agent that causes acute gastroenteritis worldwide in young animals and children is Group A rotavirus. Currently, commercially available vaccines do not often prevent porcine rotavirus (PRV) infection. In this study, we evaluated the efficacy of oral recombinant Lactobacillus vaccine against PRV in a mouse model. Lactobacillus plantarum NC8 was used as the host strain, and bacterial vectors were constructed, because the NC8 isolated has shown the capability to survive gastric transit and to colonize the intestinal tract of humans and other mammals. To explore the immunological mechanisms, lactic acid bacterial vectors were used to express VP7 antigen from PRV. We constructed an L. plantarum strain with surface-displayed VP7, named NC8-pSIP409-pgsA-VP7-DCpep. The expressed recombinant protein had a molecular weight of ∼37 kDa. The strain was used to immunize BALB/c mice to evaluate their immunomodulatory characteristics. Mice were orally immunized with recombinant L. plantarum NC8-pSIP409-pgsA-VP7-DCpep at a dose of 2 × 109 colony forming units/200 µl. The results showed that NC8-pSIP409-pgsA-VP7-DCpep significantly stimulated the differentiation of dendritic cells (DCs) in Peyer's patches (PPs) and increased the serum levels of IL-4 and IFN-γ, as measured by enzyme-linked immunosorbent assay in mice treated with NC8-pSIP409-pgsA-VP7-DCpep. Compared to the empty vector group, NC8-pSIP409-pgsA-VP7-DCpep significantly increased the production of B220+ B cells in mesenteric lymph nodes (MLNs) and PPs and also increased the titer levels of the VP7-specific antibodies, including IgG and sIgA. The administration of NC8-pSIP409-pgsA-VP7-DCpep mediated relatively broad cellular responses. This study reveals that clear alternatives exist for PRV control strategies and provides information on PRV infection.
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http://dx.doi.org/10.1093/abbs/gmab050DOI Listing
May 2021

Prognostic value of extranodal extension in axillary lymph node-positive breast cancer.

Sci Rep 2021 05 5;11(1):9534. Epub 2021 May 5.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.

Several studies have demonstrated that extranodal extension (ENE) is associated with prognosis in breast cancer. Whether this association should be described in pathological reports warrants further investigation. In this research, we evaluated the predictive value of ENE in axillary lymph nodes (ALNs) in invasive breast cancer and explored the feasibility of employing ENE to predict clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) in clinical practice. In addition, the cutoff values of perpendicular diameter ENE (PD-ENE) and circumferential diameter ENE (CD-ENE) of ENE were investigated. A total of 402 cases of primary invasive breast cancer were extracted from Fudan University Shanghai Cancer Center; these patients underwent axillary lymph node dissection (ALND) between 2010 and 2015. ENE in the ALN was defined as the tumor cells breaking through the lymph node capsule into peripheral adipose tissue and causing connective tissue reactions. Relationships between ENE and clinicopathological features, nodal burden, disease recurrence-free survival (DRFS) and overall survival (OS) were analyzed. PD-ENE was defined by measuring from the point where tumor tissue broke the node capsule to the highest point of the tumor cells in the perinodal adipose tissue.K The average PD-ENE was 1.8 mm; therefore, we divided ENE-positive patients into two groups: PD-ENE no greater than 2 mm and PD-ENE greater than 2 mm. CD-ENE was defined as measuring along the nodal capsule as the distance between peripheral edges of the ENE area. According to the average circumferential diameter (CD-ENE), we classified ENE-positive patients into two groups: CD-ENE no greater than 3 mm and CD-ENE greater than 3 mm. Correlations between ENE cutoffs and prognosis were analyzed. In this cohort of patients, 158 (39.3%) cases were positive for ENE in ALN.98 (24.4%) cases had PD-ENE no larger than 2 mm, and 60 (14.9%) cases had PD-ENE larger than 2 mm. Also, 112 (27.9%) cases had CD-ENE no larger than 3 mm, and 46 (11.4%) cases had CD-ENE larger than 3 mm. Statistical analysis indicated that histological grade, N stage, and HER2 overexpression subtype were associated with ENE. The presence of ENE had significant statistical correlations with nodal burden, including N stage, median metastatic tumor diameter and peri-lymph node vascular invasion (p < 0.001, p < 0.001, p = 0.001, respectively). Cox regression analysis demonstrated that patients with ENE exhibited significantly reduced DRFS in both univariable analysis (HR 2.126, 95% CI 1.453-3.112, p < 0.001) and multivariable analysis (HR 1.745, 95% CI 1.152-2.642, p = 0.009) compared with patients without ENE. For overall survival (OS), patients with ENE were associated with OS in univariable analysis (HR 2.505, 95% CI 1.337-4.693, p = 0.004) but not in multivariable analysis (HR 1.639, 95% CI 0.824-3.260, p = 0.159). Kaplan-Meier curves and log-rank test showed that patients with ENE in ALN had lower DRFS and OS (for DRFS: p < 0.0001; and for OS: p = 0.002, respectively). However, neither the PD-ENE group (divided by 2 mm) nor the CD-ENE group (divided by 3 mm) exhibited significant differences regarding nodal burden and prognosis. Our study indicated that ENE in the ALN was a predictor of prognosis in breast cancer. ENE was an independent prognostic factor for DRFS and was associated with OS. ENE in the ALN was associated with a higher nodal burden. The size of ENE, which was classified by a 3-mm (CD-ENE) or 2-mm (PD-ENE) cutoff value, had no significant prognostic value in this study. Based on our findings, the presence of ENE should be included in routine pathological reports of breast cancers. However, the cutoff values of ENE warrant further investigation.
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http://dx.doi.org/10.1038/s41598-021-88716-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099896PMC
May 2021

High frequency of and promoter mutations in fibromatosis-like spindle cell carcinomas.

J Clin Pathol 2021 May 5. Epub 2021 May 5.

Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China

Aims: Fibromatosis-like spindle cell carcinomas (FLSCCs) are rare metaplastic breast cancers (MBCs) that are characterised by bland spindle cells in a collagenous stroma. Although some MBCs are highly malignant, FLSCCs have indolent behaviour with low potential for lymph node or distant metastasis. Owing to their rarity, there are limited genomic data on FLSCCs. In this study, we analysed the clinicopathological features and molecular characteristics of four FLSCCs to elucidate the pathogenesis of these rare tumours.

Methods And Results: Four pure FLSCCs were sequenced by DIAN (Hangzhou Lab) using a 324-gene platform (FoundationOne CDx) with licensed technologies. The results showed that most FLSCCs harboured the pathogenic H1047R mutation in (3/4, 75%) and the -124C>T mutation in the telomerase reverse transcriptase () promoter (3/4, 75%). No copy number variations were observed in any cases in our study.

Conclusions: Our study showed that and promoter mutations were common genetic features of FLSCCs. These findings contribute to our understanding of FLSCCs biology.
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http://dx.doi.org/10.1136/jclinpath-2020-207071DOI Listing
May 2021

Simultaneous Vascular Reconstruction and Cervical Anastomosis in McKeown Esophagectomy.

Front Surg 2021 8;8:646811. Epub 2021 Apr 8.

Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.

A stomach was considered ineligible to be an ideal conduit conventionally if its right gastroepiploic artery (RGEA) were injured. However, both sufficient blood flow and good venous return are crucial to the success of reconstruction. And there lacks robust evidence regarding the surgical techniques of reconstructing RGEA and right gastroepiploic vein (RGEV) and performing cervical anastomosis with gastric conduit simultaneously. Herein, we summarized the key surgical techniques for simultaneous vascular reconstruction and gastric conduit anastomosis in McKeown esophagectomy.
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http://dx.doi.org/10.3389/fsurg.2021.646811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060638PMC
April 2021

A strategy for complete telomere-to-telomere assembly of ciliate macronuclear genome using ultra-high coverage Nanopore data.

Comput Struct Biotechnol J 2021 9;19:1928-1932. Epub 2021 Apr 9.

Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, China.

Ciliates contain two kinds of nuclei: the germline micronucleus (MIC) and the somatic macronucleus (MAC) in a single cell. The MAC usually have fragmented chromosomes. These fragmented chromosomes, capped with telomeres at both ends, could be gene size to several megabases in length among different ciliate species. So far, no telomere-to-telomere assembly of entire MAC genome in ciliate species has been finished. Development of the third generation sequencing technologies allows to generate sequencing reads up to megabases in length that could possibly span an entire MAC chromosome. Taking advantage of the ultra-long Nanopore reads, we established a simple strategy for the complete assembly of ciliate MAC genomes. Using this strategy, we assembled the complete MAC genomes of two ciliate species and , composed of 181 and 214 chromosomes telomere-to-telomere respectively. The established strategy as well as the high-quality genome data will provide a useful approach for ciliate genome assembly, and a valuable community resource for further biological, evolutionary and population genomic studies.
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http://dx.doi.org/10.1016/j.csbj.2021.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060514PMC
April 2021

Homologous recombination repair gene mutations show no survival benefits in Chinese high-grade serous ovarian cancer patients.

Ann Transl Med 2021 Mar;9(5):364

Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: The purpose of our study was to identify germline and somatic homologous recombination repair (HRR) pathway gene mutations and their clinical-prognostic impact in Chinese high-grade serous ovarian cancer (HGSC) patients.

Methods: We applied next-generation sequencing (NGS) in consecutive patients who underwent primary surgery for HGSC in November and December 2015 at our institution. Paired peripheral blood (or para-carcinoma tissue) samples and tumor samples from 42 Chinese women were tested to identify both germline and somatic deleterious mutations through all exons in and 22 other core HRR genes. Clinic-pathological data were collected until February, 2020. Associations between HRR gene mutations and clinical characters and outcomes were also evaluated.

Results: Deleterious germline HRR mutations were identified in 16.7% (7/42) of the HGSC patients. One patient had both germline and mutations. Six patients had only somatic mutations, increasing the HRR mutation rate to 31.0% (13/42). Neither germline nor somatic HRR gene mutations were related with residual disease (P=0.233) nor platinum sensitivity (P=0.851). In the univariate and multivariate analyses, germline HRR gene mutation status was not associated with progression-free survival (PFS) or overall survival (OS). In addition, no prognostic differences between somatic HRR mutated patients and wild-type patients were found.

Conclusions: Our results suggest that the HRR gene defect was not associated with improved survival in our Chinese HGSC patient cohort.
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http://dx.doi.org/10.21037/atm-20-5136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033363PMC
March 2021

Observation of Distinct Spatial Distributions of the Zero and Nonzero Energy Vortex Modes in (Li_{0.84}Fe_{0.16})OHFeSe.

Phys Rev Lett 2021 Mar;126(12):127001

Hefei National Laboratory for Physical Science at Microscale and Department of Physics, University of Science and Technology of China, Hefei, Anhui 230026, China.

The energy and spatial distributions of vortex bound state in superconductors carry important information about superconducting pairing and the electronic structure. Although discrete vortex states, and sometimes a zero energy mode, had been observed in several iron-based superconductors, their spatial properties are rarely explored. In this study, we used low-temperature scanning tunneling microscopy to measure the vortex state of (Li,Fe)OHFeSe with high spatial resolution. We found that the nonzero energy states display clear spatial oscillations with a period corresponding to bulk Fermi wavelength; while in contrast, the zero energy mode does not show such oscillation, which suggests its distinct electronic origin. Furthermore, the oscillations of positive and negative energy states near E_{F} are found to be clearly out of phase. Based on a two-band model calculation, we show that our observation is more consistent with an s_{++} wave pairing in the bulk of (Li, Fe)OHFeSe, and superconducting topological states on the surface.
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http://dx.doi.org/10.1103/PhysRevLett.126.127001DOI Listing
March 2021

Effector and regulator: Diverse functions of C. elegans C-type lectin-like domain proteins.

PLoS Pathog 2021 04 1;17(4):e1009454. Epub 2021 Apr 1.

Department of Evolutionary Ecology and Genetics, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.

In C. elegans, 283 clec genes encode a highly diverse family of C-type lectin-like domain (CTLD) proteins. Since vertebrate CTLD proteins have characterized functions in defense responses against pathogens and since expression of C. elegans clec genes is pathogen-dependent, it is generally assumed that clec genes function in C. elegans immune defenses. However, little is known about the relative contribution and exact function of CLEC proteins in C. elegans immunity. Here, we focused on the C. elegans clec gene clec-4, whose expression is highly upregulated by pathogen infection, and its paralogs clec-41 and clec-42. We found that, while mutation of clec-4 resulted in enhanced resistance to the Gram-positive pathogen Bacillus thuringiensis MYBt18247 (Bt247), inactivation of clec-41 and clec-42 by RNAi enhanced susceptibility to Bt247. Further analyses revealed that enhanced resistance of clec-4 mutants to Bt247 was due to an increase in feeding cessation on the pathogen and consequently a decrease in pathogen load. Moreover, clec-4 mutants exhibited feeding deficits also on non-pathogenic bacteria that were in part reflected in the clec-4 gene expression profile, which overlapped with gene sets affected by starvation or mutation in nutrient sensing pathways. However, loss of CLEC-4 function only mildly affected life-history traits such as fertility, indicating that clec-4 mutants are not subjected to dietary restriction. While CLEC-4 function appears to be associated with the regulation of feeding behavior, we show that CLEC-41 and CLEC-42 proteins likely function as bona fide immune effector proteins that have bacterial binding and antimicrobial capacities. Together, our results exemplify functional diversification within clec gene paralogs.
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http://dx.doi.org/10.1371/journal.ppat.1009454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051790PMC
April 2021

Chronic Secondary Cardiorenal Syndrome: The Sixth Innovative Subtype.

Front Cardiovasc Med 2021 9;8:639959. Epub 2021 Mar 9.

Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

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http://dx.doi.org/10.3389/fcvm.2021.639959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985164PMC
March 2021

Phytol derived from chlorophyll hydrolysis in plants is metabolized via phytenal.

J Biol Chem 2021 Jan-Jun;296:100530. Epub 2021 Mar 11.

Institute of Molecular Physiology and Biotechnology of Plants (IMBIO), University of Bonn, Bonn, Germany. Electronic address:

Phytol is the isoprenoid alcohol bound in ester linkage to chlorophyll, the most abundant photosynthetic pigment in plants. During leaf senescence, large amounts of phytol are released by chlorophyll degradation. However, the pathway of phytol catabolism in plants is unknown. We hypothesized that phytol degradation in plants might involve its oxidation into the long-chain aldehyde phytenal. Using GC-MS for aldehyde quantification after derivatization with methylhydroxylamine, phytenal was identified in leaves, whereas other long-chain aldehydes (phytanal and pristanal) were barely detectable. We found that phytenal accumulates during chlorotic stresses, for example, salt stress, dark-induced senescence, and nitrogen deprivation. The increase in the phytenal content is mediated at least in part independently of enzyme activities, and it is independent of light. Characterization of phytenal accumulation in the pao1 mutant affected in chlorophyll degradation revealed that phytenal is an authentic phytol metabolite derived from chlorophyll breakdown. The increase in phytenal was even stronger in mutants affected in the production of other phytol metabolites including vte5-2 (tocopherol deficient) and pes1 pes2 (fatty acid phytyl ester deficient). Therefore, phytenal accumulation is controlled by competing, alternative pathways of phosphorylation (leading to tocopherol production) or esterification (fatty acid phytyl ester production). As a consequence, the content of phytenal is maintained at low levels, presumably to minimize its toxic effects caused by its highly reactive aldehyde group that can form covalent bonds with and inactivate the amino groups of proteins.
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http://dx.doi.org/10.1016/j.jbc.2021.100530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054155PMC
August 2021
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