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Antimony selenide (Sb2Se3) is a promising light absorber material for solar cells because of its superior photovoltaic properties. However, the current performance of the Sb2Se3 solar cell is much lower than its theoretical value (∼32%) due to its low open-circuit voltage (VOC). In this paper, we have demonstrated inorganic vanadium oxides (VOx) as a hole transport layer (HTL) for Sb2Se3 solar cells to enhance efficiency through the VOC improvement. Here, a solution-processed VOx through the decomposition of the triisopropoxyvanadium (V) oxide is deposited on the Sb2Se3 absorber layer prepared by close-spaced sublimation (CSS). With VOx HTL, the built-in voltage (Vbi) is significantly increased, leading to improved VOC for the Sb2Se3 solar cell devices. As a result, the efficiency of the device increases from an average efficiency of 5.5% to 6.3% with the VOx.

Although perovskite solar cells (PSCs) have made revolutionary progress in terms of power conversion efficiency (PCE), to achieve long-term stability and low-cost device manufacturing for commercialization of the devices, selection of proper hole transport layer (HTL) and affordable back contact are still crucial to realize the upscale manufacturing. However, the carbon-based perovskite still faces great challenges to further improve the device performance due to the low quality of the carbon/perovskite interface. Inorganic NiOx is a superior HTL candidate due to its favorable energy band alignment, superior chemical stability, high hole mobility, and low-cost manufacturing. To address the poor interface quality of the carbon-based PSCs, we report electrospun NiOx fibers as an effective HTL, resulting in highly efficient device performance of PCEs up to 13.73% when deployed in our carbon-based PSCs. NiOx has been introduced as an interfacial layer between the perovskite and the carbon counter electrode to study its impact on interfacial modification and device performance.

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.

Sb2Se3 is a promising absorber material for thin-film solar cells owing to its earth-abundant and non-toxic constituents, superior optoelectronic properties, and unique one-dimensional crystal structure. To further increase the power conversion efficiency of the Sb2Se3, we fabricated an n-i-p structure by integrating a solution-processed NiOx hole-transport layer (HTL) into Sb2Se3 solar cells to enhance the carrier collection. In this study, we systematically screen the thickness of NiOx HTL and demonstrate an improved average power conversion efficiency from 6.12% to 7.15% with a 50 nm NiOx HTL. The mechanism associated with the improved device performance was characterized through the microstructure of the material, device physics, and interface electronic behaviors. It is also shown that the low-cost and scalable solution-processed NiOx HTL can improve device stability under an accelerated stress test. Thus, this work paves a way to further improve the performance of antimony chalcogenides-based solar cells via tailoring the inorganic HTL.

Flexible rockfall barriers are commonly constructed on steep hillsides to mitigate rockfall. The evaluation of the dynamic response of proprietary flexible rockfall barriers is conventionally performed using full-scale field tests by dropping a block onto the barriers in accordance with the European test standard ETAG 027. The block typically has a spherical or polyhedral shape and cannot reproduce more complex rockfall scenarios encountered in the field. Little attention has been paid to the effects of the block shape on the impact force and structural response. This paper aims to quantitatively reveal the influence of the block shape on the dynamic response of flexible rockfall barriers. First, an ellipsoidal model is established to approximately simulate the block, and the sphericity is employed as the representative index of the block’s shape. A full-scale test on a typical flexible barrier system is carried out and then used to calibrate an advanced three-dimensional finite element model. Finally, the dynamic responses of flexible rockfall barriers are analyzed and discussed, focusing on the effects of the block’s shape. The numerical results show that the sphericity will obviously influence the maximum elongation of flexible barriers, the peak impact force, the peak force of the upslope anchor cable, the peak force of the lower main support cable, the axial peak force of the post, and the peak shear force at the post foundation. The assumption of spherical or polyhedral blocks in the test standard could lead to the defensive failure of flexible rockfall barriers in some impact scenarios.

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.

This review is focused on the rapidly developing area of organocatalysed cyclic carbonate synthesis. It starts with an introduction to carbon capture and utilisation in general, which introduces the importance of cyclic carbonates. The various mechanisms for cyclic carbonate synthesis are next discussed with a focus on the relative and absolute stereochemical consequences of each mechanism and how this combined with other physical organic chemistry techniques can be used to distinguish between three main mechanistic classes: epoxide activation; carbon dioxide activation and dual activation. Section 2 of the review then discusses recently reported homogeneous organocatalysed systems whilst section 3 surveys recently reported heterogeneous catalyst systems. For each catalyst system, the mechanism of action is discussed with reference to the mechanisms introduced at the start of the review and key parameters such as the optimal temperature, pressure and catalyst loading are given combined with information on substrate scope and yields. This allows the various catalysts to be critically compared on the basis of whichever parameter(s) are of most significance to the reader. A Final Thoughts/Perspective section focusses on the limitations of the use of turnover frequency and turnover number to compare catalysts in this reaction and makes the case for authors to use of a wider range of green metrics when reporting new catalysts. Finally, the Conclusions section focuses on future challenges such as the use of biomass derived epoxides, use of impure carbon dioxide and the need to develop new and existing highly active catalysts out of the laboratory and into real world applications.

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.

In this essay, we provide an overview of a social worker-led, interdisciplinary practice model designed to combine essential online psycho-social support and local community self-governance for COVID-19 patients with minor symptoms in quarantine field hospitals in the city of Wuhan from February to May 2020. The interdisciplinary bridging response teams (IBRTs) model was designed for congregating settings to bridge offline community mobilization and online interdisciplinary professional services. We discuss the two-tier structure and organization of the practice model, the professionals’ roles and main tasks, and the key features that ensured the success of the model.

Phase diagram is a powerful tool to guide the exploitation of thermal energy materials. Heat storage technology of phase-change material (PCM) was widely used to solve major energy utilization problems on large energy consumption and low utilization efficiency. In this work, a novel solid-liquid phase diagram of the binary system octadecanoic acid (C18-acid) + octadecanol (C18-OH) was investigated using the differential scanning calorimeter (DSC). The phase-change temperature and phase-change enthalpies against the composition of C18-acid and C18-OH were determined experimentally, and then the binary phase diagram of T–X (X expresses the mass fraction of C18-OH in the two components of C18-acid and C18-OH) was established for the first time. The phase diagram belongs to a binary simple system with one eutectic point, and the content of C18-OH at eutectic point is 0.4 in mass fraction. Neither solid solution nor copolymer was formed. The thermal chemical properties on the phase-change latent heat (Q), phase-change temperature (Tp), and the thermal conductivity (λ) for the composition at the eutectic point of the binary system are 198.7 J·g−1, 44.2°C, and 0.2352 W·m−1·K−1, respectively. This result indicates that the material at eutectic point has a great potential to be used as energy storage material for supply of heat and scouring bath.

Robust single spin color centers in solid state systems with telecom wavelength emission are vital to quantum photonics and quantum networks. The nitrogen vacancy (NV) centers in silicon carbide (S...

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 intrinsic hydrophobicity, deficient light absorption of solar energy, and the energy loss from the radiation relaxation of charges that decreases the solar–thermal conversion efficiency, have s...

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.

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.

The TiSe2 nanosheets were prepared by means of ultrasound-assisted liquid phase exfoliation (LPE) and the nonlinear saturable absorption properties were experimentally investigated. The modulation depth, saturation intensity and nonsaturable absorbance of the prepared 1T-TiSe2 SA were 15.7%, 1.28 MW/cm2 and 8.2%, respectively. Taking advantage of the saturable absorption properties of TiSe2-based SA, a passively Q-switched erbium-doped fiber (EDF) laser was systematically demonstrated. The pulse repetition rates varied from 24.50 kHz up to 73.79 kHz with the increasing pump power. The obtained shortest pulse width was 1.31 μs with pulse energy of 79.28 nJ. The system presented merits of low-cost SA preparation, system compactness, superb stability and high competition.

Electricity retailer is the most critical player in the restructured electricity market. Retailer's electricity procurement problem is a big challenge for them. Electricity retailer can purchase their energy from various options such as pool market, forward contracts, and etc. A relatively new way with a lesser investigation is the demand response exchange market. In this paper, the risk-constrained stochastic power procurement problem of electricity retailers is formulated by modeling the uncertainty of pool-market price and consumers' electricity demand. The Downside risk constraints (DRC) risk-evaluation method is used to obtain risk-based power procurement scheduling of electricity retailers. By using the proposed method, conservative electricity retailer can experience a scenario-independent strategy over the stochastic optimization. In other words, the proposed risk strategy is such that impose more cost for electricity retailer while having an equal cost in all scenarios. Based on the obtained results, the operation cost of electricity retailers in all scenarios is closed to about $4827570, which is a relatively zero-risk strategy due to equality overall scenarios. Besides, results are compared in two cases to demonstrate the advantages of the proposed risk-evaluation method. Also, the Pareto front between risk-in-cost and expected cost can introduce an optimal risk-strategy for electricity retailers in the presence of uncertainties. Finally, the risk-averse strategy of electricity retailer is proposed to obtain the retailer's optimal conservative schedule during power procurement in the presence of uncertainties.

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.

Renewable energy sources such as solar and wind provide an effective solution for reducing dependency on conventional power generation and increasing the reliability and quality of power systems. Presented in this paper are design and implementation of a laboratory scale solar microgrid cyber-physical system (CPS) with wireless data monitoring as a teaching tool in the engineering technology curriculum. In the system, the solar panel, battery, charge controller, and loads form the physical layer, while the sensors, communication networks, supervisory control and data acquisition systems (SCADA) and control systems form the cyber layer. The physical layer was seamlessly integrated with the cyber layer consisting of control and communication. The objective was to create a robust CPS platform and to use the system to promote interest in and knowledge of renewable energy among university students. Experimental results showed that the maximum power point tracking (MPPT) charge controller provided the loads with power from the solar panel and used additional power to charge the rechargeable battery. Through the system, students learned and mastered key concepts and knowledge of multi-disciplinary areas including data sampling and acquisition, analog to digital conversion, solar power, battery charging, control, embedded systems and software programing. It is a valuable teaching resource for students to study renewable energy in CPS.

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

Quasi-one-dimensional van der Waals Sb2Se3 compound is a promising absorber material with desired optical properties and has theoretical potential to achieve high power conversion efficiency (PCE) of ∼30%. Here, we report a new window layer, i.e., sputtered CdSe, which can enhance the Sb2Se3 device stability during light soaking and improve the photocurrent collection. Compared to the widely used CdS window layer, CdSe can suppress the interfacial diffusion between the window layer and the Sb2Se3 film, thereby reducing interfacial recombination sites. The dominant degradation mechanism in the CdS/Sb2Se3 devices is found to be the S diffusion instead of the Cd diffusion, as CdSe/Sb2Se3 devices did not show degradation during the 85 °C 120 h 1-Sun light soaking with similar Cd diffusion. Meanwhile, the enhanced photocurrent and reduced series resistivity in the CdSe/Sb2Se3 solar cells lead to an improved PCE of 4.5% with a glass/FTO/CdSe/Sb2Se3/graphite cell architecture. The obtained results suggest that CdSe can be employed as a window layer in the thin-film solar cells made of stable and efficient Sb2Se3-like quasi-one-dimensional van der Waals materials, providing a cost-effective way to integrate into the traditional thin-film solar cell manufacturing process.

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.

Defects in silicon carbide have been explored as promising spin systems in quantum technologies. However, for practical quantum metrology and quantum communication, it is critical to achieve on-dem...

Color centers in silicon carbide have recently attracted broad interest as high bright single photon sources and defect spins with long coherence time at room temperature. There have been several methods to generate silicon vacancy defects with excellent spin properties in silicon carbide, such as electron irradiation and ion implantation. However, little is known about the depth distribution and nanoscale depth control of the shallow defects. Here, a method is presented to precisely control the depths of the ion implantation induced shallow silicon vacancy defects in silicon carbide by using reactive ion etching with little surface damage. After optimizing the major etching parameters, a slow and stable etching rate of about 5.5 ± 0.5 nm min-1 can be obtained. By successive nanoscale plasma etching, the shallow defects are brought close to the surface step by step. The photoluminescence spectrum and optically detected magnetic resonance spectra are measured, which confirm that there were no plasma-induced optical and spin property changes of the defects. By tracing the mean counts of the remaining defects after each etching process, the depth distribution of the defects can be obtained for various implantation conditions. Moreover, the spin coherence time T2* of the generated VSi defects is detected at different etch depths, which greatly decreases when the depth is less than 25 nm. The method of nanoscale depth control of silicon vacancies would pave the way for investigating the surface spin properties and the applications in nanoscale sensing and quantum photonics.

Large-scale Electric Vehicles connected to the distribution network will increase the peak-to-valley difference of the distribution network, resulting in a peak-to-peak situation, which will cause serious impacts on the distribution network including network-loss increase and safety decline. Therefore, Electric Vehicles orderly guidance plays a significant role concerning this area. Based on the user's consideration of economic benefits and enthusiasm, a real-time electricity price model for electric vehicle response is established. In addition, an orderly charging strategy is proposed under this basis. Three goals are expected to be achieved in this study: minimize he peak-valley load difference of the distribution network, minimize user costs, maximize the profits of charging station operators, and establish a multi-objective charging optimization model. The real-time weight adjustment factor is added in front of the user, which can adjust the corresponding weights according to different electricity prices in order to deal with different situations. Besides the quantum particle swarm optimization algorithm is added to the chaotic map for optimization. Finally, an example is used to simulate a certain distribution network system, whose results prove the effectiveness of real-time electricity price guidance and the practicability of the improved model.

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: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. Methods: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. Results: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p 80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. Conclusion: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.

There is an increasing number of studies focusing on extreme weather all over the world, but global trends and research topics related to extreme weather are still unclear. This study aimed to explore the current situation, research themes, and future trends in the field of extreme weather. Publications published from 1980 to 2019 were identified and retrieved from the Web of Science Core Collection databases by using keywords on May 5, 2020. Excel 2019, VOSviewer, R, and CiteSpace were used for scientific analysis. The results showed that (1) the number of publications on extreme weather research has rapidly increased and expanded continually, shifting from core disciplines to interdisciplinary fields; (2) the International Journal of Climatology was the most productive journal, and climate and environment were the most popular subject categories. Most studies were carried out in the USA, China, Germany, and other nations, and the Chinese Academy of Sciences was the most productive institution; (3) the main research topics were summarized as (a) climate change; (b) variability; (c) trends; (d) rainfall; (e) temperature; and (f) maximum. At the same time, (4) keyword bursts analysis showed that the domain focused on changes to atmospheric rivers, the impacts of global nitrogen content on extreme weather, and the relationship between water quality, soil moisture content, and extreme weather. Based on the in-depth analysis of extreme weather research, this paper developed a further understanding of the developments in this field over the past 39 years and also provided a reference for future research.

BACKGROUND The purpose of this study was to investigate factors influencing bleeding in patients with acute coronary syndrome (ACS) who are on aspirin and ticagrelor as dual antiplatelet therapy. MATERIAL AND METHODS This retrospective case-control study included 50 patients with ACS (25 with reported bleeding events and 25 without) on aspirin and ticagrelor. Adenosine diphosphate (ADP)- and arachidonic acid (ACA)-induced platelet aggregation rates were measured using light transmission aggregometry. Single-nucleotide polymorphisms (SNPs) in PEAR1, GP1BA, and GSTP1 were genotyped. RESULTS ACA-induced platelet aggregation rates were obviously lower in patients with bleeding events than in those without (13.28±8.46% vs. 24.93±9.89%, P0.001). No significant differences in ADP-induced platelet aggregation rates were observed between the 2 groups (16.17±9.74% vs. 16.88±12.69%, P0.05). Among those with bleeding events and among controls, 70% and 80% had an ACA-induced platelet aggregation rate of 0-18% and 18-50%, respectively. Mutation rates of rs6065 in GP1BA and rs1695, rs4891, and rs8191439 in GSTP1 also differed significantly between the 2 groups. CONCLUSIONS Lower ACA-induced platelet aggregation rates are associated with increased risk of bleeding in patients with ACS who are on aspirin and ticagrelor. An ACA-induced platelet aggregation rate of 18% may be considered the cutoff point for identifying high risk of aspirin-associated bleeding events in patients with ACS. SNP genotyping may also help predict the risk of bleeding in patients with ACS.

Purpose Despite the therapeutic success of existing HER2-targeted therapies, tumors respond quite differently to them. This study aimed at figuring out genetic mutation profile of Chinese HER2-positive patients and investigating predictive factors of neoadjuvant anti-HER2 responses. Methods We employed two cohorts. The first cohort was comprised of 181 HER2-positive patients treated at Guangdong Provincial People’s Hospital from 2012 to 2018. The second cohort included 40 patients from the first cohort who underwent HER2-targeted neoadjuvant chemotherapy. Genetic mutations were characterized using next-generation sequencing. We employed the most commonly used definition of pathological complete response (pCR)-eradication of tumor from both breast and lymph nodes (ypT0/is ypN0). Results In Chinese HER2-positive breast cancer patients, TP53 (74.6%), CDK12 (64.6%) and PIK3CA (46.4%) have the highest mutation frequencies. In cohort 2, significant differences were found between pCR and non-pCR groups in terms of the initial Ki67 status, TP53 missense mutations, TP53 LOF mutations, PIK3CA mutations and ROS1 mutations (p = 0.028, 0.019, 0.005, 0.013, 0.049, respectively). Furthermore, TP53 LOF mutations and initial Ki67 status (OR 7.086, 95% CI 1.366–36.749, p = 0.020 and OR 6.007, 95% CI 1.120–32.210, p = 0.036, respectively) were found to be predictive of pCR status. Conclusion TP53 LOF mutations and initial Ki67 status in HER2-positive breast cancer are predictive of pCR status after HER2-targeted NACT.

Ecological high ductility cementitious composites (ECO-HDCC) produced with recycled crumb rubber (RCR) and recycled asphalt concrete (RAC) were developed for the purpose of achieving highly ductile materials with effective engineering cost and environmental burden. Mechanical performance factors such as tensile, compressive, flexural behaviors and fracture toughness of ECO-HDCC were investigated. In addition, fiber dispersion, scanning electron microscopy and X-ray computed tomography tests were performed to reveal the mechanical performances of ECO-HDCC. Results indicate that the contributions of limited contents for RCR as well as RAC to fiber dispersion are beneficial. Adverse effects on mechanical performances of ECO-HDCC are observed as RCR or RAC content increases. The tensile ductility, flexural deflection and ductility indexes of ECO-HDCC increase as RCR or RAC content increases. Strength loss of ECO-HDCC can be attributed to recycled aggregates with low stiffness, which results in high porosity of ECO-HDCC. In addition, low matrix strength can positively affect the fiber bridging capacity, resulting in higher tensile ductility, flexural strength and fracture toughness.

Currently, the conventional atmospheric pressure-based and vacuum-based tumbling processes have a limited improvement on the chicken characteristic attributes during the marination process. In view of this, through a breathing (pressure change) tumbling strategy, ultrasonication (40 kHz, 140 W) was applied to improve tenderness, taste, and microstructure of chicken by a redesigned tumbler. The results showed that the tumbling with the breathing action and ultrasonication significantly enhanced the marinating absorptivity, tenderness and taste, and accelerated the degradation of myosin light chain. Free peptides (from 1465.9 ± 34.6 to 4725.7 ± 43.2 μg/mL) and amino acids (from 1.503 ± 0.096 to 2.593 ± 0.109 mg/mL) rose evidently for the control and the breathing tumbling treatment assisted by ultrasound respectively. Raman analysis revealed that strength of disulfide bonds declined from 0.731 ± 0.006 to 0.607 ± 0.011 a.u. and the conversion from α-helix (decreased by 67.23%) into β-fold (increased by 1573%) conformation occurred. Low field NMR analysis indicated that the content of immobilized water increased from 77385 ± 14 to 137011 ± 106 au·ms by integral calculus. Scanning and transmission electron microscopies clearly showed a prospective rupture of myofibers, myofibrils, and lysosomes. Overall, as a potential alternative, the breathing ultrasonic tumbling means improved the marinating efficiency and characteristics of marinated chicken breast.

T cell hyporesponsiveness is crucial for functional immune system and prevent the damage induced by alloreactive T cells in autoimmune pathology and transplantation. As one of the most important regulators during B cell development, PRDM1 (also known as BLIMP-1) has been demonstrated its essential role for maintaining T cell hyporesponsiveness and homeostasis, evidenced by Prdm1 deficient mice accumulating activated T cells and developing multiorgan inflammatory disease. However, the mechanism of PRDM1 regulating T cell hyporesponsiveness is still ambiguous. In this study, we took advantage of multiomics technologies and systemic report the central role of PRDM1 in inducing human primary T cell hyporesponsiveness. Firstly, we overexpressed PRDM1 in human primary T cells and found increased ratio of CD4 +CD25 +FOXP3 + Treg cell subsets and increased IL-4 secretion. In parallel, inhibited PRDM1 expression level in human T cells decreased ratio of Treg cells and secretion of IL-4. Meanwhile, transcriptome analyses revealed that overexpressed PRDM1 enriched negative regulation of cell proliferation signaling pathway and resulted in a global reduction in IL-2 and inflammatory response signaling pathways. Furthermore, overexpressed PRDM1 in primary T cells upregulated several negative regulators of T cell function like EOMES, KLF2, LILRB1, KLRB1 and CD244, indicating a pioneer role of PRDM1 in inducing T cell hyporesponsive. To further investigate the regulation role of T cell hyporesponsiveness of PRDM1, we performed CUT&Tag and ATAC-seq in PRDM1 overexpressed primary T cells. CUT&Tag analysis showed PRDM1 could directly upregulated T cell hyporesponsiveness related gene such as KLF2, CD244 and KLRD1. Importantly, we observed consistent changes of IL-2, central regulator of T cell activation, in PRDM1 overexpressed T cell from ATAC-seq, CUT&Tag and RNA-seq data. We found PRDM1 could binding to IL-2 locus and decreased the chromatin accessibility of IL-2, consequently downregulated the expression level of IL-2 in human primary T cells. Moreover, altered open chromatin regions (OCRs) in PRDM1 overexpressed T cells enriched the similar transcription factors (TFs) with PRDM1 binding sites, indicating PRDM1 might be a pioneer TF in T cell hyporesponsiveness. These results demonstrated PRDM1 is sufficient for inducing T cell hyporesponsiveness in human primary T cells. To further validate the coexpression relationship between PRDM1 and Treg cell central TF FOXP3, we upregulated PRDM1 expression level on Jurkat T cells lines. The results also showed that elevated FOXP3 both in mRNA and protein level accompanied with upregulated PRDM1 expression level. To analyze the mechanism of PRDM1 regulating FOXP3 expression level, CUT&Tag data analyses showed that PRDM1 might upregulated FOXP3 by directly binding to the enhancer region of upstream of FOXP3 locus. Meanwhile, PRDM1 indirectly upregulated FOXP3 by upregulated KLF2, evidenced by inhibiting KLF2 in PRDM1 overexpressed primary T cells downregulated FOXP3 expression level. To further investigate the clinical implication of PRDM1 inducing T cell hyporesponsiveness, we detected the relationship of PRDM1 expression level and acute graft-versus-host disease(aGVHD) occurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our results showed that patients with aGVHD (n=7) exhibited lower PRDM1 expression level than those without aGVHD in the same period after HSCT (n=7). Furthermore, we detected the expression level of PRDM1 in CD4 + T cell and CD8 + T cells from bone marrow allografts (BM) or peripheral blood allografts (PB) and followed up the occurrence of GVHD after HSCT for 2 years (n=18). There are low expression levels of PRDM1 in CD4 + T cells both from BM or PB grafts corelated with aGVHD occurrence in patients after allo-HSCT compared with those without aGVHD occurrence. In conclusion, our study provides the global regulatory model of PRDM1 in human primary T cell. We introduced PRDM1 as a sufficient regulator in T cell hyporesponsiveness induction, which is altering the chromatin accessibility and directly upregulated T cell inhibitory signals and downregulated T cell activated signals. The negative relationship between PRDM1 expression level with GVHD occurrence indicated it might be a potential biomarker for indicating HSCT prognosis. Disclosures No relevant conflicts of interest to declare.

Aims To demonstrate a nonempirical workflow to select host-specific probiotics for aquaculture industry. Methods and Results Using both culture-dependent and culture-independent methods, we have systematically investigated, for the first time, the gut microbiota of twelve subtropical aquatic animal species. We found that the diversity, abundance and distribution of gut micro-organisms of these animals were host-specific and that lactic acid bacteria (LAB) were predominant among the indigenous probiotic microbes. Using culturing method, we isolated and characterized ninety-eight LAB strains; however, only a few strains was representative of the dominant LAB OTUs recovered by culture-independent analysis. Conclusions Two cultured LAB strains, Enterococcus faecalis LS1-2 and Enterococcus faecium Z1-2, capturing the major LAB OTUs in the sequencing data set of the most animal samples and showing significant antimicrobial activities against shrimp pathogens, were suggested to be the candidates of shrimp probiotics. Significance and Impact of Study Disease outbreak and the consequential abuse of antibiotics have been the constraints to the aquaculture industry. However, the selection of probiotic bacteria is currently still an empirical process due to our limited knowledge on the gastrointestinal microbiota of aquatic organisms. Our study points to a nonempirical selection process by which host-specific probiotics can be developed.

Background We reviewed Burkholderia cepacia infections in a hospital from 2013-2016 to report a suspicious outbreak that occurred in a surgical intensive care unit in 2015, and to outline the infection control measures adopted thereafter. Methods Review of the health care–associated infection data regarding B cepacia via the surveillance system, hospital information system, electronic medical records, and laboratory information system together with the outbreak investigation was managed by the health care–associated infection control team. Results During June 1-14, 2015, 4 cases of ventilator-associated pneumonia (VAP) were identified; B cepacia was isolated from endotracheal aspirate samples. On June 16, 120 environmental samples were collected and analyzed for microbiologic differentiation. Thirteen strains of B cepacia were prominently found in the expiratory blocks of ventilators, revealing the biocontamination source. After chemical disinfection without damaging ventilator components, repeat microbiologic testing of random ventilator samples yielded negative results until July 30, 2015. Retrospective data showed that isolation rates of B cepacia strains had increased since 2014. Although the resistance phenotype of these strains varied slightly, they exhibited similar patterns of antibiotic susceptibility . Conclusions Routine cleaning and disinfection of ventilators, in addition to an intervention bundle, should form part of an integrated VAP prevention and management approach.

The dc-dc converters at the Advanced Photon Source (APS) at the Argonne National Laboratory, Illinois, are more than 15 years old. An upgrade to a digital control system is being evaluated to resolve aging and obsolescence issues. These converters supply power to electromagnets used to guide high-energy beams, so a highly accurate control system is required for the dc?dc converters. This article describes the design and evaluation of a digital control system to regulate the output current and resolve aging and obsolescence issues.

Myocardial remodeling serves an important role in the pathophysiology of coronary heart disease. The angiotensin-converting enzyme (ACE)2-angiotensin-(1-7) [Ang (1‑7)]‑Mas receptor (MasR) axis is a key regulator in myocardial remodeling and development of heart failure. To investigate how ACE2‑Ang‑(1‑7)‑MasR axis function on myocardial remodeling and cardiac fibrosis in post‑myocardial infarction (MI), male Sprague‑Dawley rats (weight, 200±20 g) were used to establish the model of myocardial infarction by ligating the left coronary artery. The present study suggests that telmisartan (Tel) and olmesartan (Olm) (5 mg/kg/d) can inhibit myocardial remodeling of post‑myocardial infarction through the ACE2‑Ang (1‑7)‑MasR pathway. Administration of Tel or Olm was demonstrated to significantly inhibit collagen deposition using Masson staining. In addition, telmisartan and olmesartan was indicated to antagonize angiotensin II (Ang II) and upregulate ACE2, MasR, Ang (1‑7) expression in myocardial tissue using immunoassay and ELISA test, and the effect of Olm was more marked than that of Tel at the same dosage. Simultaneously, compared with the MI or Sham group, the mRNA and protein expression of ACE2, Ang II and MasR in myocardial tissue demonstrated a remarkable increase in the Olm group, when compared with the Tel group. Taken together, our data demonstrated that ACE2‑Ang (1‑7)‑MasR axis may present a potential protective role in the development of myocardial remodeling and may provide a new target for drug development of cardiac fibrosis. In conclusion, Olm is superior to Tel in inhibiting myocardial local Ang II level reducing myocardial collagen deposition and improving myocardial remodeling by upregulating the expression of ACE2, Ang (1‑7) and MasR.