Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non‐BRCA1/2 gene. Major mutant non‐BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non‐BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER‐2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐BRCA1/2 genes, while TP53 and PALB2 had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐BRCA1/2 genes when treated as a whole.
Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency ...of germline mutations in 40 cancer predisposition genes, including
BRCA1
and
BRCA2
, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next‐generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in
BRCA1/2
, 61 in 15 other BC susceptibility genes and 3 in both
BRCA1/2
and non‐
BRCA1/2
gene. Major mutant non‐
BRCA1/2
genes were
TP53
(n = 18),
PALB2
(n = 11),
CHEK2
(n = 6),
ATM
(n = 6) and
BARD1
(n = 5). No factors predicted pathologic mutations in non‐
BRCA1/2
genes when treated as a whole.
TP53
mutations were associated with HER‐2 positive BC and younger age at diagnosis; and
CHEK2
and
PALB2
mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non‐
BRCA1/2
genes.
TP53
and
PALB2
had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non‐
BRCA1/2
genes, some clinical features were associated with mutations of several particular genes.
What's new?
The prevalence of mutations in breast cancer predisposition genesare not well investigated in Asia. We assessed germline mutations of 40 cancer susceptibility genes in 937 consecutive selected breast cancer patients from 26 centers of China, and discovered 23.8% of participates carried the pathogenic mutation, including 6.8% with mutations in non‐
BRCA1/2
genes, while
TP53
and
PALB2
had a relatively high mutation rates (1.9% and 1.2%).There was no factors predicted for detrimental mutations in non‐
BRCA1/2
genes when treated as a whole.
AIM: Real-time and rapid identification of the malignant tissue can be performed during or before surgical operation.Here we aimed to detect in vivoand in situcolorectal cancer by using Fourier ...transform infrared (FTIR) spectroscopy and fiber-optic technology.METHODS: A total of five patients with large intestine cancer were detected in vivo and in situ. Of them, three cases of colon cancer and one case of cecum cancer were detected intraoperatively and in vivo by using a FTIR spectrometer during surgical operation, and one case of rectum cancer was explored non-invasively and in vivo before the surgical operation. Normal and malignant colorectal tissues were detected in vivo and in situ using FTIR spectroscopy on the basis of fundamental studies.RESULTS: There were significant differences between FTIR spectra of normal and malignant colorectal tissues detected in vivo and in situ. Experimental results revealed that the spectral characteristics of normal and malignant tissues found in vivo and in situ were similar to those obtained from in vitro measurement in our previous fundamental research.CONCLUSION: FTIR fiber-optic attenuated total reflectance (ATR) spectroscopy can identify in situ and in vivo colorectal cancer. FTIR spectroscopic method with fiber optics is a non-invasive, rapid, accurate and in vivo cancer detection technique in clinical diagnosis.
AIM: To determine if Fourier-transform infrared (FT-IR) spectroscopy of endoscopic biopsies could accurately diagnose gastritis and malignancy. METHODS: A total of 123 gastroscopic samples, including ...11 cases of cancerous tissues, 63 cases of chronic atrophic gastritis tissues, 47 cases of chronic superficial gastritis tissues and 2 cases of normal tissues, were obtained from the First Hospital of Xi'an Jiaotong University, China, A modified attenuated total reflectance (ATR) accessory was linked to a WQD-500 FT-IR spectrometer for spectral measurement followed by submission of the samples for pathologic analysis. The spectral characteristics for different types of gastroscopic tissues were summarized and correlated with the corresponding pathologic results. RESULTS: Distinct differences were observed in the FT-IR spectra of normal, atrophic gastritis, superficial gastritis and malignant gastric tissues. The sensitivity of FT-IR for detection of gastric cancer, chronic atrophic gastritis and superficial gastritis was 90.9%, 82.5%, 91.5%, and specificity was 97.3%, 91.7%, 89.5% respectively. CONCLUSION: FT-IR spectroscopy can distinguish gastric inflammation from malignancy.
The Tarim River Basin (TRB) is an extremely arid area in China, suffering from dry climate and intense human activities, which have brought about significant changes in ecological processes and then, ...led to serious ecological vulnerability (EV). This study proposes an assessment framework to evaluate EV and analyze its dynamic change in the TRB during 2005–2015. An integrated method is developed with the Fuzzy Analytic Hierarchy Process (FAHP) and the Pressure-State-Response (PSR) framework, which highlights impacts of nature and anthropogenic interference on the ecology. Specific management strategies are put forward based on the spatial recognition of ecologically vulnerable areas in the TRB. The EV is divided into four vulnerability levels including Light I, Medium II, Heavy III and Very heavy IV. Results show that the average EV is at Heavy III vulnerability level in the TRB in the last 2005–2015, and there has been an increasing trend in EV, which even has come up to the Very heavy IV vulnerability level in the year 2013–2015. As a whole, the EV displays a high-to-low gradient from east to west during the study period. Heavy III and Very heavy IV vulnerability levels, distributed in the East, mainly in the mainstream areas with characterization of frequent human interferences, tend to increase persistently. In contrast, Light I vulnerability level, mainly in the west source areas, shows a significant decline after 2010. Based on the results, some suggestions targeted at different vulnerable areas were proposed to help restore ecological environments by integrating legal managements with public efforts. The proposed methodology, reflecting the nature and human interaction on the EV is of practical use for the ecological restorations in the TRB.
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•An integrated indicator system for specially assessment of ecological vulnerability (EV) is established.•The EV was largely aggravated in the Tarim River Basin (TRB) during 2005–2015.•The Heavy III level dominates throughout the TRB with a low-to-high spatial distribution from west to east.•Ecological restorations with different use control for different partitions are proposed.
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•CS–SA as an eco-friendly corrosion inhibitor for mild steel in HCl media.•CS–SA is a mixed-type inhibitor which mainly restrained the cathodic process.•Surface morphology analysis ...confirmed the inhibitive character of CS–SA.•CS–SA adsorbed on steel substrate through donor-acceptor interaction mechanism.
The development of effective and environment-friendly corrosion inhibitors is of great significance for the protection of mild steel in hydrochloric acid media. Accordingly, a natural polysaccharide mixture inhibitor composed of chondroitin sulfate derived from pig cartilage (CS-PC) and sodium alginate (SA) is developed here, and the synergistic effect of the two polysaccharides towards adsorption on mild steel in 1 M HCl is studied. The inhibition performance has been studied using weight loss test, electrochemical investigations, SEM, SECM and UV methods. The results indicate that the mixtures of CS-PC and SA strongly inhibit the corrosion of mild steel compared to individual inhibitors (i.e., 95.18 % versus 72.78 %), and show a synergistic inhibition effect. The structure-activity relationship between the molecular structure of the CS-PC + SA mixture and its corrosion inhibition performance has been discussed by using the quantum chemistry calculation and molecular dynamics simulations. It is believed that these results have certain guiding significance for the rational design of efficient corrosion inhibitor.
With large-scale developments, the Manas River Basin (MRB) is in an extreme imbalance especially in land use, thus causing a series of ecological problems. A reliable dynamic ecological risk ...assessment is expected to provide useful information for the economic development. Through coupling spatial Cellular Automaton-Markov (CA-Markov) model and Landsat satellite images in 2000, 2008 and 2016, we forecasted the land use maps in 2024 and 2032. Based on the ecological risk model, we evaluated the ecological risk at landscape level from 2000 to 2032. More importantly, an improved evaluation of ecological risk was proposed based on terrain gradients and the correlation between terrain niche index (TNI) and future ecological risk was analyzed. The results showed that the artificial oases and urban are expanding, while the natural grassland is shrinking. Corresponding to the rapid development stage and stable consolidation stage, farmland will be followed by a slower increase (2016–2032) after a rapid increase (2000–2016), and water decreases first but then is projected to recover. As the overall spatial diversity increasing, the ecological risk in the whole basin is growing, especially in grassland. Compared with the stable critical state in artificial landscape, the future ecological risks in natural landscape tend to increase due to the cumulative effects of human activities. Also, we found that the great ecological risk mainly happens in “high altitude and complex terrain” or “low altitude and flat terrain” areas. The future ecological risk in medium terrain niche index (TNI) gradient will increase, while it will decrease in the lowest. Above all, the proposed framework can do well in forecasting ecological risk at landscape level, and can help simply infer the changes of ecological risk based on terrain.
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•Land use evaluation and projection with CA-Markov•Artificial oases and urban are expanding, the natural grassland is shrinking.•Overall ecological risk has risen with increasing spatial diversity.•Future ecological risk will increase in the medium terrains, but decrease in the low.
Extreme multi-label text classification (XMTC) aims at tagging a document with most relevant labels from an extremely large-scale label set. It is a challenging problem especially for the tail labels ...because there are only few training documents to build classifier. This paper is motivated to better explore the semantic relationship between each document and extreme labels by taking advantage of both document content and label correlation. Our objective is to establish an explicit
l
abel-
a
ware representation for each document with a
h
ybrid
a
ttention deep neural network model(
LAHA
).
LAHA
consists of three parts. The first part adopts a multi-label self-attention mechanism to detect the contribution of each word to labels. The second part exploits the label structure and document content to determine the semantic connection between words and labels in a same latent space. An adaptive fusion strategy is designed in the third part to obtain the final label-aware document representation so that the essence of previous two parts can be sufficiently integrated. Extensive experiments have been conducted on six benchmark datasets by comparing with the state-of-the-art methods. The results show the superiority of our proposed
LAHA
method, especially on the tail labels.
Solar powered local interface evaporation has high conversion efficiency, water purification, seawater desalination, power generation and other potentials. However, the ineffective integration and ...expensive materials of hybrid solar thermal devices undermine the widespread development and practical outdoor use of solar energy. This article proposes a low-cost and sustainable 3D carbonated sucrose evaporator that achieves broadband light absorption, thermal insulation, and high hydrophilicity for high-performance water evaporation and self-desalination. The dome array structure not only effectively reduces the diffuse reflection of light, but also significantly increases the solar evaporation rate with excellent salt resistance and long-term stability. A high evaporation rate of 3.54 kg m
−2
h
−1
and an efficiency of 95.86% were achieved under one sun illumination, and the evaporation rate was 3.48 kg m
−2
h
−1
h even in high-salinity brine (15 wt% NaCl solution). In addition, the synergistic coupling of solar-steam and solar-electricity technologies can simultaneously achieve a high evaporation rate of 3.43 kg m
−2
h
−1
and an output power of 0.48 W m
−2
, providing great hope for people in developing regions to cope with freshwater and electricity shortages.
The synergistic coupling of solar-steam and solar-electricity technologies can achieve a high evaporation of 3.43 kg m
−2
h
−1
and an output power of 0.48 W m
−2
, providing hope for people in developing regions to cope with freshwater and shortages.
Macroautophagy/autophagy is a host natural defense response. Viruses have developed various strategies to subvert autophagy during their life cycle. Recently, we revealed that autophagy was activated ...by binding of Avibirnavirus to cells. In the present study, we report the inhibition of autophagy initiated by PIK3C3/VPS34 via the PDPK1-dependent AKT-MTOR pathway. Autophagy detection revealed that viral protein VP3 triggered inhibition of autophagy at the early stage of Avibirnavirus replication. Subsequent interaction analysis showed that the CC1 domain of VP3 disassociated PIK3C3-BECN1 complex by direct interaction with BECN1 and blocked autophagosome formation, while the CC3 domain of VP3 disrupted PIK3C3-PDPK1 complex via directly binding to PIK3C3 and inhibited both formation and maturation of autophagosome. Furthermore, we found that PDPK1 activated AKT-MTOR pathway for suppressing autophagy via binding to AKT. Finally, we proved that CC3 domain was critical for role of VP3 in regulating replication of Avibirnavirus through autophagy. Taken together, our study identified that Avibirnavirus VP3 links PIK3C3-PDPK1 complex to AKT-MTOR pathway and inhibits autophagy, a critical step for controlling virus replication.
ATG14/Barkor: autophagy related 14; BECN1: beclin 1; CC: coiled-coil; ER: endoplasmic reticulum; hpi: hours post-infection; IBDV: infectious bursal disease virus; IP: co-immunoprecipitation; mAb: monoclonal antibody; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MTOR: mechanistic target of rapamycin kinase; PDPK1: 3-phosphoinositid-dependent protein kinase-1; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns3K: phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; SQSTM1: sequestosome 1; vBCL2: viral BCL2 apoptosis regulator.
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