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Chloride-based accelerators are widely used to accelerate cement hydration; however, there is no focus on the effect of the interaction between Cl− and SO42− on cement hydration. Hence, the interaction effect between initial gypsum and sodium chloride (NaCl) in the cement hydration process was investigated. Isothermal calorimetry, scanning electron microscopy, thermogravimetric analysis, X-ray diffraction and inductively coupled plasma spectroscopy were used to evaluate the hydration process of cement paste. Moreover, a thermodynamic model and boundary nucleation and a growth model were applied to calculate the hydration products and describe the hydration process, respectively. It is clear that sodium chloride can accelerate cement hydration, but as the incorporated sodium chloride increases, the acceleration effect is weakened. The incorporation of chloride salts will promote the dissolution of minerals and increase the growth rate. In the early stage of hydration, the formation of ettringite precedes formation of Friedel's salt, owing to the fact that tricalcium aluminate (C3A) favours binding with SO42−, which can be demonstrated by the change in ion concentrations and the evolution of hydration products. The formation of Kuzel's salt depends not only on the chloride concentration but also on the hydration time.

Thermosensitive genic male sterile (TGMS) wheat lines are the core of two-line hybrid systems. Understanding the mechanism that regulates male sterility in TGMS wheat lines is helpful for promoting wheat breeding. Several studies have obtained information regarding the mechanisms associated with male sterility at the transcriptional level, but it is not clear how the post-transcriptional process of alternative splicing might contribute to controlling male sterility. In this study, we performed genome-wide analyses of alternative splicing during the meiosis stage in TGMS line BS366 using PacBio and RNA-Seq hybrid sequencing. Cytological observations indicated that cytoskeleton assembly in pollen cells, calcium deposition in pollen and tapetal cells, and vesicle transport in tapetal cells were deficient in BS366. According to our cytological findings, 49 differentially spliced genes were isolated. Moreover, 25 long non-coding RNA targets and three bHLH transcription factors were identified. Weighted gene co-expression network analysis detected four candidate differentially spliced genes that had strong co-relation with the seed setting percentage, which is the direct representation of male sterility in BS366. In this study, we obtained comprehensive data regarding the alternative splicing-mediated regulation of male sterility in TGMS wheat. The candidates identified may provide the molecular basis for an improved understanding of male sterility.

Our study aims to assess whether asiaticoside promotes the recovery of SINOFH by inhibiting bone marrow stem cells (BMSCs) differentiation into osteoclasts (OC). BMMs were induced to form OC system by dexamethasone in vitro and ELISA detected the expression of OC-related genes formation by asiaticoside. BMSCs were cultured followed by analysis of BMSCs morphology under microscope, gene expression by qRT-PCR. TRACP and c-Src level by western blot, RANKL, OPG and TRACP5b level by ELISA. Asiaticoside inhibited the expression of OC formation in SIONFH. The expression of OC-related genes increased with the induction days. With the increasing of induction days, asiaticoside level in culture fluid was decreased. While after asiaticoside interference, OCrelated genes and proteins levels were significantly down-regulated. Aasiaticoside can significantly increase the RANKL signaling protein expression. In conclusion, asiaticoside promotes the recovery of SINOFH by inhibiting BMSCs differentiation into OC.

Purpose High-ductility cementitious composites (HDCC) have an excellent crack controlled capacity and corrosion resistance capacity, which has a promising application in structure engineering under harsh environment. The purpose of this study is to explore the corrosion mechanism of steel bar in HDCC. Design/methodology/approach Intact and the pre-cracked HDCC specimens under the coupled action of different dry–wet cycles and chloride attack were designed, and intact normal concrete (NC) was also considered for comparison. Corrosion behavior of a steel bar embedded in HDCC was analyzed by an electrochemical method, a chloride permeability test and X-ray computed tomography. Findings Steel corrosion probability is related to the chloride permeability of the HDCC cover, and the chloride permeability resistance of HDCC is better than that of NC. Besides, crack is the key factor affecting the corrosion of steel bars, and the HDCC with narrower cracks have a lower corrosion rate. Slight pitting occurs at the crack tips. In addition, the self-healing products and corrosion products fill up the cracks in HDCC, preventing the external aggressive ions from entering and thereby decreasing the steel corrosion rate. Originality/value HDCC has a superior corrosion resistance than that of NC, effects of variable crack width on corrosion behavior of steel bar in HDCC under the coupled actions of different dry–wet cycles and chloride attack are investigated, which can provide the guide for the design application of HDCC material in structure engineering exposed to marine environment.

The coordinated utilization of nitrogen (N) and phosphorus (P) is vital for plants to maintain nutrient balance and achieve optimal growth. Previously, we revealed a mechanism by which nitrate induces genes for phosphate utilization; this mechanism depends on NRT1.1B-facilitated degradation of cytoplasmic SPX4, which in turn promotes cytoplasmic-nuclear shuttling of PHR2, the central transcription factor of phosphate signaling, and triggers the nitrate-induced phosphate response (NIPR) and N-P coordinated utilization in rice. In this study, we unveiled a fine-tuning mechanism of NIPR in the nucleus regulated by Highly Induced by Nitrate Gene 1 (HINGE1, also known as RLI1), a MYB-transcription factor closely related to PHR2. RLI1/HINGE1, which is transcriptionally activated by PHR2 under nitrate induction, can directly activate the expression of phosphate starvation-induced genes. More importantly, RLI1/HINGE1 competes with PHR2 for binding to its repressor proteins in the nucleus (SPX proteins), and consequently releases PHR2 to further enhance phosphate response. Therefore, RLI1/HINGE1 amplifies the phosphate response in the nucleus downstream of the cytoplasmic SPX4-PHR2 cascade, thereby enabling fine-tuning of N-P balance when nitrate supply is sufficient.

Background Immunotherapies such as PD-L1 inhibitors have shown promising efficiency in breast cancer (BC) patients. However, treatment responses for immunotherapies are diverse since the immunogenicity of breast cancer is heterogeneous. Specific subtypes such as hormone receptor (HR)-positive, human EGF receptor 2 (HER2)-positive, and triple-negative breast cancer (TNBC) have shown heterogeneity in immunogenicity. Therefore, precisely identification of patients potentially benefit from immunotherapy is important. Previous studies have proved PD-L1 expression and tumor mutational burden (TMB) as predictive biomarkers for immunotherapy. Here, we report the PD-L1 expression and TMB status in Chinese BC patients with different subtypes. Using comprehensive molecular analysis, we also characterized the genomic features related to these biomarkers. Methods Tumor samples from 112 Chinese patients with BC were collected and subjected to next-generation sequencing (NGS) and immunohistochemical (IHC) analysis. NGS were performed in a laboratory accredited by College of American Pathologists (CAP) and certified by Clinical Laboratory Improvement Amendments (CLIA) using validated panel targeting 450 cancer genes. Genomic alterations, included including single base substitution, short and long insertions/deletion (Indel), copy number variation, gene fusion, and rearrangement, were assessed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. Tumor tissues were analyzed for PD-L1 expression by IHC with 22C3 or 28-8 antibodies, respectively. Results The 112 Chinese BC patients consisted of 87 HR+ (77.7%), 19 TNBC (17.0%) and 6 HR-/ HER2 + (5.3%), with a median age of 47.5 years old (range 24-81). Of all patients, 42.0% were positive for PD-L1 expression (CPS≥1), including 30.4% PD-L1 (1≥CPS>10) and 11.6% PD-L1 (CPS≥10). PD-L1 expression were observed in HR+ BCs (41.4%) as well as in TNBC (47.4%) and HR-/ HER2+ (33.3%) subtypes, no significant difference were observed among the three subtypes. 8.9% patients were TMB-High (≥10 muts/Mb) with median TMB of 3.4 muts/Mb (range 0-80.8). TMB was slightly correlated with PD-L1 expression (Kendall tau = 0.241; P =0.01). 17.0% of PD-L1 positive patients and 3.1% of PD-L1 negative patients were TMB-High (p=0.016). Patients with PD-L1 CPS≥10 had significantly higher median TMB (7.1 vs. 3.1 muts/Mb, p Conclusion Our data shows that the PD-L1 expression has no significant difference among HR+, TNBC and HR-/ HER2+ subtypes. These data provide the hypothesis that PD-L1 expression positive in different subtype breast cancers may benefit from immune treatment, including HER2 and Luminal subtypes. Otherwise, there was a correlation between PD-L1 expression and TMB, High TMB was also observed in PD-L1 negative patients, which may enrich the subgroup of patients who could benefit from immunotherapy. The verification of integrated predictive biomarkers for immunotherapy in BC is further needed. Citation Format: Ning Liao, Cao Li, Jundong Wu, Bo Chen, Guochun Zhang, Xueri Li, Liping Guo, Guangnan Wei, Jiali Lin, Yingzi Li, Yuchen Zhang, Hsiaopei Mok, Chongyang Ren, Yulei Wang, Kai Li, Cheukfai Li, Lingzhu Wen, Minghan Jia, Tengjiao Lin, Chunyan Cheng. Pd-l1 expression among different subtypes of chinese breast cancer patients [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-44.

Background: T cell hyporesponsiveness is crucial for the functional immune system and prevents the damage induced by alloreactive T cells in autoimmune pathology and transplantation. Methods: We detected the phenotype of PRDM1 overexpressed human primary T cells. To investigate the molecular mechanisms of PRDM1 regulating T cells, we performed RNA-seq, MethylationEPIC BeadChip array, CUT&Tag and ATAC-seq in PRDM1 overexpressed human primary T cells. Findings: Overexpression of PRDM1 in primary T cells expanded Treg cell subsets and increased the secretion of IL-4, while decreased expression had the opposite effects. Integrated multiomics analysis showed that PRDM1 directly upregulated T cell inhibitory genes such as CD244, KLF2 and KLRD1 and downregulated the T cell activation gene IL2, indicating that PRDM1 could promote a tolerant transcriptional profile in primary T cells. Binding motifs of key T cell function regulators, such as FOS, JUN and AP-1, were enriched in PRDM1 binding sites and that PRDM1 altered the chromatin accessibility of these regions. Furthermore, the PRDM1 expression level in allografts was negatively related to acute graft-versus-host disease (aGVHD) occurrence after hematopoietic stem cell transplantation (HSCT). Interpretation: Our systematic multiomics analysis found that the transcription factor (TF) PRDM1 acts as a pioneer TF and master regulator during T cell hyporesponsiveness in human primary T cells. These results demonstrated that PRDM1 is sufficient for inducing T cell hyporesponsiveness and could be a predictive biomarker for HSCT prognosis. Funding: This work was partly supported by grants from the National Key Research and Development Program of China (2017YFA0104500), Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001), Key Program of the National Natural Science Foundation of China (No.81530046, 81930004), Beijing Municipal Natural Science Foundation (Grant No. 7204319). Declaration of Interest: None to declare. Ethical Approval: The study has been approved by the Ethics Committee of Peking University People's Hospital, and written informed consent from all subjects was obtained

To correlate contrast-enhanced ultrasound (CEUS) features with pathological prognostic factors of breast invasive ductal carcinomas (IDCs). 169 patients who were admitted to our hospital with confirmed IDCs diagnosed between August 2017 and June 2019 were selected. CEUS indicators included the time of contrast agent entered the lesion, the degree of enhancement, the boundary of the lesion, whether there was perfusion defect and nourishing blood vessels, and etc. These parameters correlated with traditional prognostic factors (tumour size, histological grade, axillary lymph node status) and immunohistochemical biomarkers (ER, PR, c-erbB-2, Ki-67, and TOPO-II). Perfusion defects after enhancement were predictive factors of PR negative expression (r = − 0.318, OR = 0.239) and TOPO-II overexpression (r = 0.284, OR = 3.577). Centripetal enhancement was negatively correlated with ER expression (r = − 0.350, OR = 0.246). The lesions with a larger range after enhancement than the conventional ultrasound had a higher histological grade (r = 0.215). Perfusion defects were positively correlated with lymph node metastasis (r = 0.221) and negatively correlated with the expression of ER and PR (r = − 0.342, r = − 0.318). Contrast-enhanced ultrasound features of IDCs have a certain correlation with pathological prognostic factors, which is conducive in assessing the prognosis of these patients.

Background TP53 is a crucial tumor suppressor gene. However, the mutation pattern of TP53 in Chinese patients with breast cancer has not yet been determined. Methods A total of 411 untreated patients with invasive breast cancer diagnosed at Guangdong Provincial People's Hospital (GDPH) between June 2017 to September 2018 were recruited into the study. Mutational alterations in TP53 were detected and correlations between TP53 mutations and clinicopathological features analyzed. Comparative analysis of the data in the GDPH cohort with those in the METABRIC cohort were carried out. Results A significantly higher rate of TP53 mutations was detected in the GDPH cohort (51.3%) compared with the METABRIC cohort (34.4%) (P = 25%, HR‐ and Her2+ in breast cancer had higher mutation probability of TP53 (P

The cross-linked network of DUT-67/tubular polypyrrole (T-PPY) composites was first synthesized by in-situ growth zirconium - based metal-organic frameworks (DUT-67) with T-PPY. The introduction of T-PPY effectively increases conductivity of DUT-67/T-PPY composites, weakens accumulation of the DUT-67, and exposes more active sites of DUT-67. DUT-67/T-PPY/GCE manifests increased electrocatalytic activity toward reduction of nitrofurazone and ornidazole compared with DTU-67. A novel electrochemical sensor based on DUT-67/T-PPY was established to effectively detect two anti-infective drugs, respectively. Under optimized experimental conditions, the proposed sensor shows a wider linear range for nitrofurazone that is composed by two line segments (9.08–354.08 μM and 354.08–1004.04 μM). Meanwhile, the sensor also displays a linear response to ornidazole in the range of (0.7–100.5 μM and 100.5–250.4 μM) as well as a low LOD as 0.25 μM (S/N = 3). The proposed sensor was used for the detection of nitrofurazone and ornidazole in actual samples, and the satisfactory results were acquired. This research provides an efficient strategy for fabricating novel electrochemical sensor based on cross-linked network structure of T-PPY and MOFs.

In this study, sows were fed 200 (LD), 800 (ND) and 3200 (HD) IU of vitamin D3/kg basal diet during pregnancy (from 41 d to birth), respectively. All their offspring pigs were fed the same vitamin D3 replete die. At 150 days of age, a total of 18 offspring pigs (six offspring pigs per maternal diet group, sex balance) were weighed and slaughtered to investigate effects of maternal vitamin D3 during pregnancy on fatty acids synthase (FASN) and hormone-sensitive lipase (LIPE) expression in offspring pigs. The results showed that LD offspring pigs had higher FASN mRNA expression and the ratio of FASN/LIPE mRNA expression in subcutaneous adipose tissue, as well as higher LIPE mRNA expression of longissimus dorsal muscle, whereas, had lower the ratio of FASN/LIPE mRNA expression in longissimus dorsal muscle compared with ND or HD offspring pigs, respectively. Meanwhile, LD offspring pigs had higher carcass fat, average backfat thickness (ABFT), serum insulin and leptin levels, lower intramuscular fat (IMF), serum free fatty acid and triglycerol levels compared with ND or HD offspring pigs. In addition, the ratio of FASN/LIPE mRNA expression was negatively correlated with IMF content, and positively correlated to carcass fat content and ABFT in offspring pigs. Meanwhile, FASN mRNA expression was positively correlated with carcass fat content, while negatively correlated with ABFT in offspring pigs. These results suggested that maternal vitamin D3 affected fat accumulation and meat quality by regulating FASN and LIPE mRNA expression in offspring pigs.

The co‐evolving tumour cells and the systemic immune environment are mutually dysregulated. Tumours affect the immune response in a complex manner. For example, although lymphocytes are mobilized in response to tumours, their function is impaired by tumour progression. This study aimed to explore how the baseline and dynamic renal cell carcinoma (RCC) tumour burdens affect the T‐cell repertoire, and whether the baseline T‐cell receptor β‐chain (TCRB) diversity predicts prognosis. To characterise the TCRB repertoire, the baseline and follow‐up peripheral TCRB repertoires of 45 patients with RCC and 2 patients with benign renal disease patients were examined using high‐throughput TCRB sequencing. To explain the significance of TCRB diversity, 56 peripheral leukocyte samples from 28 patients before and after surgery were subjected to transcriptome sequencing. To validate the results, an advanced RCC patient's sample was subjected to single‐cell RNA sequencing (scRNA, 10x Genomics). Higher TCRB diversity was found to be correlated with a higher lymphocyte‐to‐neutrophil ratio, especially indicating more naïve T cells. High‐baseline TCRB diversity predicted a better prognosis for stage IV patients, and different tumour burdens exerted distinct effects on the immune status. The pre‐operative TCRB diversity was significantly higher in benign and stage I (low tumour burden) RCC patients than in stage IV (high tumour burden) patients. After the tumour burden of advanced patients was mostly relieved, we observed that the TCRB diversity was restored, T‐cell exhaustion was reduced, and naïve T‐cells were mobilized. It was demonstrated that the circulating TCRB repertoire could reflect the immune status and predict prognosis, and to some extent that cytoreductive nephrectomy (CN) reduces the burden of the immune system in advanced patients, which might provide a good opportunity for immunotherapy. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR− HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

Vitamin D has been discovered centuries ago, and current studies have focused on the biological effects of vitamin D on adipogenesis. Besides its role in calcium homeostasis and energy metabolism, vitamin D is also involved in the regulation of development and process of metabolic disorders. Adipose tissue is a major storage depot of vitamin D. This review summarized studies on the relationship between vitamin D and adipogenesis and furthermore focuses on adipose metabolic disorders. We reviewed the biological roles and functionalities of vitamin D, the correlation between vitamin D and adipose tissue, the effect of vitamin D on adipogenesis, and adipose metabolic diseases. Vitamin D is associated with adipogenesis, and vitamin D supplements can reduce the burden caused by metabolic diseases. The review provides new insights and basis for medical therapy on adipose metabolic diseases.

Background: Next generation sequencing (NGS) and the according target-based precision therapy has shown promising efficacy in many tumors. Here we report the genomic characteristics of Chinese breast cancer to support the development of more precise treatment strategy. Methods: Formalin fixed, paraffin embedded (FFPE) tumor samples and matched peripheral blood samples of 220 Chinese cancer patients including 218 females and 2 males were collected for NGS-based 450-genes panel assay. Pathological subtypes included 104 HR+/HER2-, 30 HR-/HER2+, 44 HR+/HER2+ and 42 triple negative breast cancers (TNBC). Assessed genomic alterations included single base substitution, short and long insertions/deletion, copy number variation, gene fusion and rearrangement. MSK breast cancer data was obtained from cBioPortal for comparing the difference between Chinese and Western patients. Results: The top mutated genes were TP53 (88.1%), PIK3CA (26.2%) and PTEN (21.4%) in TNBC; ERBB2 (86.7%), TP53 (86.7%), CDK12 (80.0%) and PIK3CA (23.3%) in HR-/HER2+ patients; ERBB2 (75%), TP53 (61.4%), CDK12 (54.5%) and PIK3CA (45.5%) in HR+/HER2+ patients. In HR+/HER2- patients, the most frequently mutated genes was PIK3CA (49.0%), followed by TP53 (30.8%) and GATA3 (27.9%), whereas the frequency of PIK3CA and GATA3 mutation were lower (41.6% and 19%, respectively) in Western patients. Although Alpelisib was approved by FDA in PIK3CA mutated HR+/HER2- patients, we observed PIK3CA mutation frequency had no difference among four subtypes. In this cohort, patients with PIK3CA mutation were significantly elder than patient without PIK3CA mutation (50 vs 47 years old, p=0.006). The hotspot mutations of PIK3CA (E542X, E545X and H1047X) accounted for 79.8% of PIK3CA mutations (71/89). Gene fusion/rearrangement was observed in 26% patients, in which 4 patients had gene fusions. Gene variations in homologous recombination pathway were found in 27.7% of patients. Among the 11.4% of patients with BRCA1/2 mutations, 11 patients harbored germline mutations and 19 patients had somatic mutations. Rearrangement accounted for 35% in somatic BRCA1/2 mutations. In the patients with germline BRCA1/2 mutation, 6 were HR+/HER2- patients who have been approved to use Olaparib. Based on the usage of CDK4/6 inhibitor in HR+/HER2- patients, this 450-genes panel enabled us to find that 41.3% HR+/HER2- patients had genes variations are related to CDK4/6 inhibitor resistance (CCND1, 18.3%; FGFR1 17.3%; NF1, 7.7%; MDM2, 6.7%; ESR1, 6.7% and RB1, 1.9%). The median TMB was 4.3 Muts/Mb in the whole cohort and patients with KMT2C mutations had significantly higher TMB (5.5 vs 3.8 Muts/Mb, p=0.004). In addition, Chinese breast cancer patients had a significantly higher frequency of KMT2C mutations compared to western patients (11.4% vs 1.4%, p Citation Format: Ning Liao, Guochun Zhang, Bo Chen, Yulei Wang, Kai Li, Chongyang Ren, Hsiaopei Mok, Li Cao, Lingzhu Wen, Minghan Jia, Cheukfai Li, Liping Guo, Guangnan Wei, Jiali Lin, Jiangguo Lai, Honglin Guo, Wenjing Wang, Shiyue Zhang, Zhijian Song, Jian Wang, Hui Chen, Jinwei Hu, Weifeng Wang, Weiwei Shi, Kai Wang. Comprehensive genomic analysis of Chinese breast cancer and clinical application [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-07-03.

Background MYC is frequently amplified and its amplification is associated with poor prognosis in breast cancer patients. This study aimed to determine the prevalence of MYC alterations from Chinese patients, the correlations between MYC amplification and clinicopathological characteristics, as well as its impacts on patient outcomes in breast cancer patients. Methods We analyzed 412 cases of breast cancer specimens in Guangdong Provincial People's Hospital (GDPH) for MYC alterations from June 1, 2017 to September 27, 2018, using next generation sequencing. The associations between MYC amplification and clinicopathological characteristics were determined using chi square. We further compared the our results with those from The Cancer Genome Atlas (TCGA) cohort (n=1079). Kaplan-Meier curves were drawn to determine the impacts of MYC amplification on patient outcomes. Results MYC was amplified in 12.44% (51/410) in GDPH cohort and the mean copy number of our cohort was 4.42 (2.84-11.27), while the frequency of MYC amplification in TCGA cohort was much higher (21.22%, 229/1079). Except that, we also found two fusions. Among these, one was RTFDC1-MYC fusion (AF=1.62%) and the other was PVT1-MYC fusion (AF=3.33%). The case with PVT1-MYC fusion was also found to have PVT1-MYC co-amplification concurrently. In TCGA cohort, we found MYC amplification to be associated with age (P=0.047), tumor type (P=0.000), ER status (P=0.000), PR status (P=0.000), HER2 status (P=0.008) and molecular subtype (P=0.000). Whereas, except for molecular subtype (P=0.028), we only found MYC amplification to be associated with tumor size (P=0.023) and Ki-67 (P=0.031) in GDPH cohort. According to the survival information from TCGA, patients with MYC amplification had significantly inferior overall survival (OS) in both triple negative breast cancer (TNBC) (P=0.02) and HR+/HER2+ breast cancer patients (P=0.03). Conclusions This study evaluated the differences of MYC mutations in Chinese and and TCGA cohort breast cancer patients. Except for MYC amplification, we found two rare fusions. Results showed MYC amplified less frequently in Chinese patients and was associated with inferior OS in both TNBC and HR+/HER2+ breast cancer patients. We suggest further research with expand the sample size is necessary to draw the ethnical differences of MYC mutations. Citation Format: Li Cao, Guochun Zhang, Yulei Wang, Bo Chen, Chongyang Ren, Lingzhu Wen, Liping Guo, Kai Li, Minghan Jia, Ning Liao. Associations between MYC alterations and clinical pathological characteristics in Chinese patients and TCGA cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-22.

Purpose: Somatic alterations of PIK3CA gene is an important therapeutic target in breast cancer (BC). The PI3Kα-specific inhibitor alpelisib was remarkably active against PIK3CA-mutated, HR-positive/HER2-negative BC in the SOLAR-1 trial. We hypothesized that PIK3CA alterations in Chinese BC patients across different molecular subtypes might differ from other ethnic groups and this information would be useful for selecting anti-PI3K therapy. Methods: The molecular profile of the PIK3CA gene was analyzed in 412 Chinese untreated invasive BC patients with ER/HER2 molecular subtypes, using a 540 gene next-generation sequencing panel. The results were compared to the molecular profile of Caucasian breast cancer patients in The Cancer Genome Atlas(TCGA-white). Results: Compared to wild type, PIK3CA alterations were more frequent in the ER+ subtype (49.3%, p=0.024), and tumors with low ki67 proliferation (58.3%, p=0.007) and low histological grade (grade I/II/III 80%, 53.4%, 35.9%, p Citation Format: Minghan Jia, Ning Liao, Bo Chen, Guochun Zhang, Yulei Wang, Xiaoqing Chen, Liping Guo, Li Cao, Hsiaopei Mok, Chongyang Ren, Kai Li, Cheukfai Li, Lingzhu Wen, Jiali Lin, Guangnan Wei, Zhou Zhang, Charles M Balch. PIK3CA somatic alterations in 412 chinese invasive breast cancers: Higher frequency of mutant H1047R detected by next generation sequencing compared to breast cancer in caucasians [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-11.

Background Around the world, lung cancer is the leading cause of cancer-related death. Lung adenocarcinomas are among the most common diagnosed forms of lung cancer, whose overall survival has not improved significantly, which makes finding an effective therapeutic target vital. Transcobalamin (TCN1) is a vitamin B12-binding protein which regulates cobalamin homeostasis. In tumor tissues, TCN1 is expressed highly, and its expression is correlated with cancer aggressiveness and poor prognosis according to recent studies and bioinformatic analyses. However, its effect on lung adenocarcinoma (LUAD) is unknown. Methods We evaluated whether TCN1 shows diagnostic and prognostic value in LUAD using bioinformatic analysis. In particular, various databases and analysis tools were used to determine TCN1’s relationship with LUAD, including TCGA, GTEx, GEO, STRING, and TISIDB. Results As compared to normal lung tissue, the level of TCN1 expression in LUAD tissues was significantly higher (P < 0.001). TCN1 also had a good ability to distinguish lung adenocarcinoma from non-lung adenocarcinoma samples [area under the curve (AUC) = 0.788]. According to univariate Cox statistics, high expression levels of TCN1 correlate with poor overall survival (OS) in LUAD (P < 0.001). Moreover, based on a multivariate Cox analysis, TCN1 expression was independently correlated with OS (P = 0.011). GO/KEGG and GSEA indicated enrichment in epidermal cell differentiation (P < 0.0005), keratinocyte differentiation (P < 0.0005), neuroactive ligand–receptor interaction (P < 0.0005), epithelial–mesenchymal transition (P = 0.029, FDR = 0.023) and TNFA signaling via NFKB (P = 0.029, FDR = 0.023). Furthermore, TCN1 is associated with immune infiltration based on an analysis of immune cell infiltration. Conclusions In summary, TCN1 could be used as a prognostic and diagnostic biomarker and provide deeper perspectives for the development of therapies and prognostic markers in LUAD.

Elucidation the kinetics of neutralizing antibody response in the coronavirus disease 2019 (COVID-19) convalescents is crucial for the future control of the COVID-19 pandemic and vaccination strategies. Here we tested 411 sequential plasma samples collected up to 480 days post symptoms onset (d.a.o) from 214 convalescents of COVID-19 across clinical spectrum without re-exposure history after recovery and vaccination of SARS-CoV-2, using authentic SARS-CoV-2 microneutralization (MN) assays. COVID-19 convalescents free of re-exposure and vaccination could maintain relatively stable anti-RBD IgG and MN titers during 400∼480 d.a.o after the peak at around 120 d.a.o and the subsequent decrease. Undetectable neutralizing activity started to occur in mild and asymptomatic infections during 330 to 480 d.a.o with an overall rate of 14.29% and up to 50% for the asymptomatic infections. Significant decline in MN titers was found in 91.67% COVID-19 convalescents with ≥ 50% decrease in MN titers when comparing the available peak and current MN titers (≥ 300 d.a.o). Antibody-dependent immunity could also provide protection against most of circulating variants after one year, while significantly decreased neutralizing activities against the Beta, Delta and Lambda variants were found in most of individuals. In summary, our results indicated that neutralizing antibody responses could last at least 480 days in most COVID-19 convalescents despite of the obvious decline of neutralizing activity, while the up to 50% undetectable neutralizing activity in the asymptomatic infections is of great concern.

Simple Summary Subcutaneous fat is an important factor affecting the meat quality and feed conversion rate of waterfowl. The current study compared the transcriptome data of Muscovy duck subcutaneous fat among three developmental stages, aiming at exploring the key regulatory genes for subcutaneous fat deposition. The results generated abundant candidate genes and pathways involving in subcutaneous fat deposition in Muscovy duck. This study provides an important reference for revealing the developmental mechanisms of subcutaneous fat in duck. Abstract Subcutaneous fat is a crucial trait for waterfowl, largely associated with meat quality and feed conversion rate. In this study, RNA-seq was used to identify differentially expressed genes of subcutaneous adipose tissue among three developmental stages (12, 35, and 66 weeks) in Muscovy duck. A total of 138 and 129 differentially expressed genes (DEGs) were identified between 35 and 12 weeks (wk), and 66 and 35 wk, respectively. Compared with 12 wk, subcutaneous fat tissue at 35 wk upregulated several genes related to cholesterol biosynthesis and fatty acid biosynthesis, including HSD17B7 and MSMO1, while it downregulated fatty acid beta-oxidation related genes, including ACOX1 and ACSL1. Notably, most of the DEGs (92.2%) were downregulated in 66 wk compared with 35 wk, consistent with the slower metabolism of aging duck. Protein network interaction and function analyses revealed GC, AHSG, FGG, and FGA were the key genes for duck subcutaneous fat from adult to old age. Additionally, the PPAR signaling pathway, commonly enriched between the two comparisons, might be the key pathway contributing to subcutaneous fat metabolism among differential developmental stages in Muscovy duck. These results provide several candidate genes and pathways potentially involved in duck subcutaneous fat deposition, expanding our understanding of the molecular mechanisms underlying subcutaneous fat deposition during development.

Background Previous study had demonstrated that sestrin2 (Sesn2) expression was increased in human failing heart. Although, the circulating Sesn2 concentrations in patients with chronic heart failure (CHF) remains unknown. This study investigated plasma Sesn2 concentrations in patients with CHF and the role between Sesn2 and the occurrence of major adverse cardiac events. Methods A total of 80 control subjects and 220 CHF patients were enrolled and the Sesn2 concentrations of each sample were measured. Additionally, the occurrence of major adverse cardiac events in each CHF patient were followed prospectively for 36 months. Results Increased plasma Sesn2 concentrations were found in CHF patients and gradually increased from New York Heart Association (NYHA) functional class II to IV. The Sesn2 concentrations were positively correlated with N-terminal B-type natriuretic peptide (NT-pro BNP) but negatively correlated with left ventricular ejection fraction (LVEF) in CHF patients. The ROC curve suggested that Sesn2 had a certain value in predicting major adverse cardiac events during CHF patients, although, the predictive role of Sesn2 is not as good as NT-pro BNP. In addition, the multivariate Cox hazard analysis was performed after the CHF patients were divided into 3 groups (low, middle, and high) base on the plasma Sesn2 concentrations category, and the results showed that both high and middle Sesn2 concentrations increased the incidence of major adverse cardiac events when compared with low Sesn2 group. Furthermore, CHF patients with major adverse cardiac events showed higher Sesn2 concentrations when compared with CHF without major adverse cardiac events. The Kaplan-Meier analysis was performed after the CHF patients were divided into 2 groups according to the median Sesn2 concentrations and the results revealed that patients with high Sesn2 concentrations had a higher risk of major adverse cardiac events compared with those with low Sesn2. Conclusions Plasma Sesn2 concentrations were increased in CHF patients and positively correlated with the severity of CHF. Increased Sesn2 concentrations significantly increased the occurrence of major adverse cardiac events and suggested poor outcome in CHF patients.

Purpose Breast cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast cancer subtype stratification. Methods We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database. Results The samples were gathered into three clusters following implementation of the t-SNE and DBSCAN algorithms and were categorized as ‘hallmark-tsne’ subtypes. Here, we identified a high-risk luminal A dominant breast cancer subtype (C3) that displayed increased motility, cancer stem cell-like features, a higher expression of hormone/luminal-related genes, a lower expression of proliferation-related genes and immune dysfunction. With regard to immune dysfunction, we observed that the motility-increased C3 subtype exhibited high granulocyte colony stimulating factor (G-CSF) expression accompanied by neutrophil aggregation. Cancer cells that produce high levels of G-CSF can stimulate neutrophils to form neutrophil extracellular traps, which promote cancer cell migration. This finding sheds light on one potential explanation for why the C3 subtype correlates with poor prognosis. Conclusions The hallmark-tsne subtypes confirmed again that even the luminal A subtype is heterogeneous and can be further subdivided. The biological processes and immune heterogeneity of breast cancer must be understood to facilitate the improvement of clinical treatments. Electronic supplementary material The online version of this article (10.1007/s10549-019-05135-w) contains supplementary material, which is available to authorized users.

The deterioration of cement based materials in marine and salts lakes environment is complicated problem, due to the presence of chlorides and sulfate simultaneously. The influence of sulfate on the chloride diffusion mechanism was evaluated by scanning electron microscopy (SEM-EDS), mercury intrusion porosimetry (MIP) and X-ray diffraction (XRD). The total chloride profile was also used to illustrate the influence of chloride and sulfate salts concentrations on chloride diffusion. The results show that the chloride binding and formation of Friedel’s salt are inhibited by the presence of sulfate. The presence of sulfate increases chloride diffusion in the short term, while it inhibits the chloride diffusion from a long-term perspective. The aggressive ions penetrate into the mortar causing mortar’s porosity decrease, especially the pore

BACKGROUND Depression is one of the most common and specific symptoms among menopausal women, leading to significant personal, family, and economic burdens. Some studies have shown that phytoestrogens can help relieve symptoms of depression. OBJECTIVES This systematic review and meta-analysis aim to assess the efficacy and safety of phytoestrogens in treating depression among menopausal women. METHODS A comprehensive search for relevant studies published until November 25, 2020, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database, Web of Science, and EMBASE. Statistical analyses were performed with R 4.0.3.and Review Manager 5.4. RESULTS 2183 studies were identified and 10 studies with 15 independent reports were included, involving 1248 participants. The quality of the four studies was assessed as high risk, six studies were assessed as unclear. The analyses conducted according random effects model indicated the significant positive effect on depressive symptoms for postmenopausal women compared with the placebo (SMD = -0.62; 95% CI = -1.13 to -0.12; Q = 45.62, df = 14, P 100 mg/d) and ultralow dose (0

BackgroundThe relationship between body mass index (BMI) and the prognosis or treatment response in patients with breast cancer has been demonstrated in previous studies, but the somatic mutation profiles in breast cancer patients with different BMIs have not been explored.MethodsIn the present study, the somatic mutation profiles in 421 female breast cancer patients who were stratified into three subgroups based on BMI (normal weight, overweight/obese, and underweight) were investigated. Capture-based targeted sequencing was performed using a panel comprising 520 cancer-related genes.ResultsA total of 3547 mutations were detected in 390 genes. In breast cancer patients with different BMI statuses, the tumors exhibited high mutation frequency and burden. TP53 was the most common gene in the three groups, followed by PIK3CA, ERBB2, and CDK12. Meanwhile, the mutation hotspots in TP53 and PIK3CA were the same in the three BMI groups. More JAK1 mutations were identified in underweight patients than those in normal patients. Except for JAK1, differentially mutated genes in postmenopausal patients were completely different from those in premenopausal patients. The distribution of mutation types was significantly different among BMI groups in the postmenopausal group. Underweight patients in the postmenopausal group harbored more TP53 mutations, more amplifications, and more mutations in genes involved in the WNT signaling pathway.ConclusionsOur next-generation sequencing (NGS)-based gene panel analysis revealed the gene expression profiles of breast cancer patients with different BMI statuses. Although genes with high mutation frequency and burden were found in different BMI groups, some subtle differences could not be ignored. JAK1 mutations might play a vital role in the progression of breast cancer in underweight patients, and this needs further analysis. Postmenopausal underweight patients with breast cancer have more aggressive characteristics, such as TP53 mutations, more amplifications, and more mutations in genes involved in the WNT signaling pathway. This study provides new evidence for understanding the characteristics of breast cancer patients with different BMIs.

The gut–liver axis has been increasingly recognized as a major autoimmunity modulator. However, the implications of intestinal barrier in the pathogenesis of autoimmune hepatitis (AIH) remain elusive. Here, we investigated the functional role of gut barrier and intestinal microbiota for hepatic innate immune response in AIH patients and murine models. In this study, we found that AIH patients displayed increased intestinal permeability and pronounced RIP3 activation of liver macrophages. In mice models, intestinal barrier dysfunction increased intestinal bacterial translocation, thus amplifying the hepatic RIP3-mediated innate immune response. Furthermore, GSK872 dampened RIP3 activation and ameliorated the activation and accumulation of liver macrophages in vitro and in vivo experiments. Strikingly, broad-spectrum antibiotic ablation significantly alleviated RIP3 activation and liver injury, highlighting the causal role of intestinal microbiota for disease progression. Our results provided a potentially novel mechanism of immune tolerance breakage in the liver via the gut-liver axis. In addition, we also explored the therapeutic and research potentials of regulating the intestinal microbiota for the therapy of AIH.

Education actively helps us develop our well-being and health, but postgraduate students are at high risk of depression. The prevalence of depression symptoms varies from 6.2% to 84.7% among them, and its changes throughout the years remains unclear. The present study aimed to estimate the real prevalence of depression symptoms among postgraduate students and the changes from 1980 to 2020. Thirty-seven primary studies with 41 independent reports were included in the meta-analysis (none reports were in high-quality, three were medium-to-high quality, 20 were low-to-medium quality, and 18 were low-quality), involving 27,717 postgraduate students. The pooled prevalence of overall, mild, moderate, and severe depression symptoms was 34% (95% CI: 28-40, I2 = 98.6%), 27% (95% CI: 22-32, I2 = 85.8%), 13% (95% CI: 8-21, I2 = 97.3%), and 8% (95% CI: 6-11, I2 = 81.0%), respectively. Overall, the prevalence of depression symptoms remained relatively constant through the years following 1980 (overall: β = -0.12, 95% CI: [-0.39, 0.15], p = 0.39; mild: β = 0.24, 95% CI: [-0.02, 0.51], p = 0.07; moderate: β = -0.24, 95% CI: [-0.75, 0.26], p = 0.34; severe: β = 0.13, 95% CI: [-0.25, 0.51], p = 0.50). Doctoral students experienced more depressive symptoms than did master's students (43% vs. 27%; Q = 2.23, df = 1, p = 0.13), and studies utilising non-random sampling methods reported a higher prevalence of mild depression and lower moderate depression symptoms than those that used random sampling (overall: 34% vs. 29%; Q = 0.45, df = 1, p = 0.50; mild: 29% vs. 21%; Q = 1.69, df = 1, p = 0.19; moderate: 16% vs. 25%; Q = 1.79, df = 1, p = 0.18; severe: 8% vs. 9%; Q = 0.13, df = 1, p = 0.72) despite these differences was not statistically significant. The prevalence of depression symptoms was moderated by the measurements and the quality of primary studies. More than one-third of postgraduates reported depression symptoms, which indicates the susceptibility to mental health risk among postgraduates. School administrators, teachers, and students should take joint actions to prevent mental disorders of postgraduates from increasing in severity.

BACKGROUND Disease awareness is an important aspect of psychological adjustment in cancer patients; however, there is limited evidence that acceptance and commitment therapy (ACT) is recommended for the treatment of mental illness in cancer patients. PURPOSE To assess the effectiveness of ACT for cancer patients with mental illness. METHODS Ten databases were searched for publications up to July 25, 2020, using combinations of search terms related to mental health, cancer, and randomised controlled trials (RCTs). Two researchers independently screened the literature, extracted data, and assessed the quality of the study. RESULTS Seventeen RCTs (877 cancer patients) were mainly of low quality, compared with control group, ACT was associated with improved outcomes after treatment completion and at 1-3 months and at 3-6 months of follow-up for depression (Standardised mean difference [SMD] = -0.93, 95% CI, -1.36 to -0.51, P

In the present study, the synergetic effect and mechanism of ultrasound (US) and slightly acidic electrolyzed water (SAEW) on the inactivation of Escherichia coli (E. coli) were evaluated. The results showed that US combined with SAEW treatment showed higher sanitizing efficacy for reducing E. coli than US and SAEW alone treatment. US and US combined with SAEW treatments resulted in smaller particle size of E. coli compared to the control and SAEW treatment. In addition, US combined with SAEW treatment induced the highest potassium leakage. However, the highest protein leakage was recorded in US treatment. Moreover, scanning and transmission electron microscopy analysis revealed that the greatest damage of the appearance and ultrastructure of E. coli was achieved after US combined with SAEW treatment. The synergetic effect was also confirmed by CLSM analysis. Fluorescence spectroscopy suggested that treatments of US, SAEW, and US combined with SAEW changed protein conformation of E. coli. Overall, the present study demonstrated that the sterilization mechanism of US combined with SAEW treatment was decreasing the particle size and disrupting the permeability of cell membrane and the cytoplasmic ultrastructure as well as changing protein conformation of E. coli.

Prostate cancer is one of the most common male genitourinary cancers worldwide. The incidence of prostate cancer varies widely around the world, with the highest region at 150/100,000 and the lowest region at 1/100,000 [1–7]. Of the most common cancers occurred in men, the prostate cancer accounted for almost 1 in 5 new diagnoses [2]. Epidemiologic studies show that prostate cancer is multifactorial and may be related to age, race, genetic background, geographical location, and dietary constituents. Of those, age and family history are the main risk factors, 13% to 26% of prostate cancer patients with positive family history (Table 10.1). Histological study of autopsy showed that approximately 33% of 40–60 years males have prostate cancer [8]. The incidence increases with age and reaches up to 75% in males >85 years [9]. In addition, the incidence in Europe-American males is higher than Asian males, especially, the African American with the highest incident rate. The risk of prostate cancer in Asian males increases when they migrate to Western regions [1, 4].

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause. Accumulating evidence shows that gut microbiota and intestinal barrier play significant roles in AIH thus the gut–liver axis has important clinical significance as a potential therapeutic target. In the present study, we found that Bifidobacterium animalis ssp. lactis 420 (B420) significantly alleviated S100-induced experimental autoimmune hepatitis (EAH) and modulated the gut microbiota composition. While the analysis of clinical specimens revealed that the fecal SCFA quantities were decreased in AIH patients, and B420 increased the cecal SCFA quantities in EAH mice. Remarkably, B420 application improved intestinal barrier function through upregulation of tight junction proteins in both vitro and vivo experiments. Moreover, B420 decreased the serum endotoxin level and suppressed the RIP3 signaling pathway of liver macrophages in EAH mice thus regulated the proliferation of Th17 cells. Nevertheless, the inhibition effect of B420 on RIP3 signaling pathway was blunted in vitro studies. Together, our results showed that early intervention with B420 contributed to improve the liver immune homeostasis and liver injury in EAH mice, which might be partly due to the protection of intestinal barrier. Our study suggested the potential efficacy of probiotics application against AIH and the promising therapeutic strategies targeting gut–liver axis for AIH.

Background: Fat deposition affected meat quality and the suitable amount of intramuscular fat (IMF) can significantly improve the taste of meat, palatability, juicy, tenderness and flavor, thereby enhancing the meat quality in animals. Although, calpastatin (CAST) and peroxisome proliferator-activated receptor-ã (PPARã) could regulate meat quality by altering meat tenderness or IMF content in animals, reports concerning the relationship between CAST, PPARã expression and pork quality is unclear.Methods: A total of twenty 28-day-old purebred weaned Jinhua and Landrace piglets (10 piglets per breed) were divided into two groups according to breed for the feeding trials lasting for 120 days. At the 148 days of age, 3 pigs of each breed were selected to slaughter. Total RNA was extracted from longissimus dorsi and biceps femoris muscle to investigate the differential expression of PPARã and CAST in muscle tissues of different breed pigs by RT-PCR methods, as well as their relationship with IMF and carcass lean content.Result: These results suggested that PPARã is an important effector for regulating fat deposition in pigs, which was correlated with IMF and carcass lean content of pigs. This data would provide a scientific basis for the regulation of pork quality.