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Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancer is the most prevalent type of breast cancer, in which endocrine therapy resistance and distant relapse remain unmet challenges. Accurate molecular classification is urgently required for guiding precision treatment. We established a large-scale multi-omics cohort of 579 patients with HR+/HER2−breast cancer and identified the following four molecular subtypes: canonical luminal, immunogenic, proliferative and receptor tyrosine kinase (RTK)-driven. Tumors of these four subtypes showed distinct biological and clinical features, suggesting subtype-specific therapeutic strategies. The RTK-driven subtype was characterized by the activation of the RTK pathways and associated with poor outcomes. The immunogenic subtype had enriched immune cells and could benefit from immune checkpoint therapy. In addition, we developed convolutional neural network models to discriminate these subtypes based on digital pathology for potential clinical translation. The molecular classification provides insights into molecular heterogeneity and highlights the potential for precision treatment of HR+/HER2−breast cancer.

Arginine kinase (AK) was identified as an allergen in Crassostrea angulata. However, little information is available about its epitopes. In this study, AK from C. angulatawas registered to the World Health Organization/International Union of Immunological Societies allergen nomenclature committee to be named as Cra a 2. The immunoglobulin G/immunoglobulin E-binding capacity of Cra a 2 was significantly reduced after chemical denaturation treatment. Further, eight linear mimotopes and five conformational mimotopes of Cra a 2 were obtained using phage panning. In addition to six linear epitopes that have been identified, two linear epitopes were verified by a synthetic peptide, of which L-Cra a 2-2 was conserved in shellfish. Four conformational epitopes were verified by site-directed mutation, among which mutation of C-Cra a 2-1 affected the structure and reduced the immunoreactivity of Cra a 2 most significantly. Overall, the identified epitopes may lay a foundation for the development of hypoallergenic oyster products through food processing.

Sarcoplasmic calcium-binding protein is a stable allergen in Scylla paramamosainand named Scy p 4. To explore the importance of linear epitopes in the immunoglobulin G (IgG)/immunoglobulin E (IgE)-binding capacity of Scy p 4, chemical denaturants were used to destroy the structure. Scy p 4 was reduced with dithiothreitol and subsequently alkylated with iodoacetamide (IAA). Furthermore, the structural analysis indicated that IAA–Scy p 4 was an unstructured protein. The inhibition enzyme-linked immunosorbent assay showed that IAA–Scy p 4 could inhibit the binding of Scy p 4 to sensitize serum, with inhibition rates reached 55%. Moreover, the linear mimotopes of Scy p 4 were predicted in silico. Three linear epitopes were verified by serological tests and named L-Scy p 4-1 (AA76–91), L-Scy p 4-2 (AA111–125), and L-Scy p 4-3 (AA137–146). Overall, these data provide an understanding of the relationship between the structure and allergenicity about Scy p 4, and the identified linear epitopes can be used for diagnosis and food processing of shellfish allergy.

In order to reduce the immunoreactivity of sarcoplasmic calcium-binding protein (SCP), site-directed mutations were used to replace key amino acids in the conformational epitopes and calcium-binding sites. The mutant SCPs (mSCPs) were expressed in Escherichia coli, and their immunoreactivities were analyzed using iELISA and basophil activation assays. Furthermore, the structural changes of mSCPs were determined from the circular dichroism spectra. The iELISA results showed that mSCPs could effectively inhibit the binding of wild-type SCP (wtSCP) to sensitive serum, with inhibition rates that reached 90%. Moreover, mSCPs could downregulate the expression levels of CD63 and CD203c on the basophil surface. Compared with wtSCP, the peak values were significantly changed, and the calcium binding ability was impaired, which explained the decline in immunoreactivities of the mSCPs. All of the data confirmed that this approach was effective in reducing the immunoreactivity of SCP and could be applied to other shellfish allergens.

Oysters are an important shellfish group known to cause food allergy; however, knowledge of their sensitization components and cross-reactivity is limited. This study aimed to identify a novel allergen in Crassostrea angulataand investigate its cross-reactivity. To this end, a 20 kDa protein was purified from oyster and confirmed to be a sarcoplasmic-calcium-binding protein (SCP) by LC-MS/MS. A 537 bp open reading frame was obtained from oyster SCP total RNA, which encoded 179 amino acids, and was expressed in Escherichia coli. According to the circular dichroism results, digestion assay, and inhibition ELISA, the recombinant SCP (rSCP) exhibited similar physicochemical properties and IgG-binding activity to native SCP. rSCP displayed stronger IgE-binding activity by immunological method. Moreover, a different intensity of cross-reactivity and sequence homology were demonstrated between shellfish species. Collectively, these findings provide novel insight into shellfish allergens, which can be used to aid in the in vitrodiagnosis of oyster-sensitized patients.

Mud crab (Scylla paramamosain) is a commonly consumed seafood as a result of its high nutritional value; however, it is associated with food allergy. The current understanding of crab allergens remains insufficient. In the present study, an 18 kDa protein was purified from crab muscle and confirmed to be myosin light chain 1 (MLC1) by matrix-assisted laser desorption/ionization–tandem time-of-flight mass spectrometry. Total RNA was isolated and amplified to obtain a MLC1 open reading frame of 462 bp, encoding 154 amino acids. A structural analysis revealed that recombinant MLC1 (rMLC1) expressed in Escherichia colicontained α-helix and random coil. Moreover, rMLC1 displayed strong immunoactivity by dot blot and a basophil activation test. Furthermore, seven allergenic epitopes of MLC1 were predicted, and five critical epitope regions were identified by an inhibition enzyme-linked immunosorbent assay and human mast cell degranulation assay. This comprehensive research of an allergen helps to conduct component-resolved diagnoses and immunotherapies related to crab allergies.

A solid buoyancy material (SBM) for deep sea was prepared with a new unsaturated polyester as the base resin, the hollow glass microspheres (HGM) as filler and some other additives. The new kind of unsaturated polyester resin (IPP-UP) was prepared with itaconic acid, isophthalic acid and propylene glycol as the raw materials, on the main chain of which the unsaturated double bonds exist as pendant groups. The hollow glass microspheres are purchased from 3M Company, USA, with the density of 0.42g/cm3 and compressive strength 55.2MPa. By adjust the amount of the hollow glass microspheres, samples of SBM for deep sea with different densities, water absorptions and compressive strengths were made. Studies have shown that, when the filling amount of HGM reaches 60% of the base resin system mass, the buoyant material exhibits excellent low density, low water absorption and high compressive strength which are 0.62g/cm3, 0.59% at 20°C for 24 hours and 67.5MPa.

AbstractThis article pertains to experimental validation of the study presented in a previous paper by the same authors , in which the transverse vibration characteristics of piezoceramic circular plates with V-notches were investigated theoretically using Ritz’s method incorporating defined equivalent constants. For experimental measurement, two optical methods – amplitude-fluctuation electronic speckle pattern interferometry (AF-ESPI) and laser Doppler vibrometry (LDV) – were employed to conceptualize the analytical results. The AF-ESPI method demonstrates the advantages of combining high fringe sensitivity and noise reduction, which are achieved using the time-averaged and subtraction electronic speckle pattern interferometry methods, respectively. Both vibration mode shapes and resonant frequencies of V-notched piezoceramic plates were obtained using the AF-ESPI method; in addition, the resonant frequencies were also determined quickly using the LDV method. By varying the corner angles and notch–depth ratios, various types of piezoceramic plate (V-notched, sectorial, semicircular, segmented, and sharp-notched) were used for experimental measurements. Numerical calculations were performed using the finite element method, and the results were compared with the experimental measurements and theoretical predictions. It was shown that the resonant frequencies and mode shapes obtained using the two experimental methods agreed fairly closely with the theoretical and numerical results.

In this paper, we study the group decision making (GDM) problem with two-tuple linguistic information .we propose a way to calculate the comprehensive assessment information. Then average preference degree of one alternative over all the other alternatives is calculated. Thus, the ranking of alternatives is obtained by the comparison of linguistic two-tuple information.

In this paper, the self-curable unsaturated polyester was put forward as a new solution to air pollution problems caused by the cross-linking monomer’s volatilization in unsaturated polyesters (UP) industry. Two kinds of unsaturated polyesters with the vinyl double bonds at the side chain were synthesized with Itaconic acid (IA) or Itaconic anhydride (ITA) as raw materials. The first one was prepared with IA, isophthalic acid and propylene glycol (IPP-UP), and the second one was synthesized with glycidol (GL) and ITA (IG-UP). Investigation demonstrates that the latter UP resin could be self-cured through the nucleophilic addition reaction of hydroxyl groups with double bonds or the free-radical homopolymerization of double bonds when they were heated without cross-linking monomers. However, the former couldn’t. Factors on self-crosslinking activity and crosslinking mechamism of pendant vinyl bonds from IA or ITA were explored.1H-NMR and FT-IR were used to characterize.

Game theory predicts that as the operational sex ratio (OSR; the ratio of sexually active males to fertilizable females) increases, reproductive males may adopt alternative reproductive behaviors. Empirical studies indicated that alternative behaviors may differ for different species. In the present study, we investigated the influence of different male-biased OSRs on male reproductive behaviors shown by a freshwater fish, the rose bitterling Rhodeus ocellatus. Six levels of the OSR (1:1, 2:1, 3:1, 5:1, 7:1, and 9:1) were established, and male leading, aggression, and preoviposition ejaculation behaviors were recorded. Our experiments showed that at low OSRs, the leading behavior of male rose bitterling increased with an increasing OSR, reaching a maximum at an OSR of 3:1, and then decreased as the OSR further increased. In contrast, aggression and preoviposition ejaculation behavior continually increased with an increasing OSR. Notably, males possibly lost their territorial position to other males and became sneakers when facing more rivals. These observations suggest that at lower OSRs, male rose bitterling mainly rely on leading behavior, while at higher OSRs, they increasingly adopt aggression and preoviposition ejaculation. Therefore, for the rose bitterling, (1) decreased leading behavior and (2) increased aggression and preoviposition ejaculation are two alternative responses in the face of an increasing OSR, which is a more straightforward strategy for facing an increased risk of sperm competition than that adopted by its congener, the European bitterling.

Self curable unsaturated polyesters with pendant hydroxyl groups on main chain were synthesized through the polycondensation of maleic anhydride and glycidol at different raw material ratios. The preparation process and self-curing properties were studied. Investigation demonstrated that the unsaturated polyester resin could be self cured through the addition reaction of pendant hydroxyl groups with the double bonds on main chain when it was heated above 150°C without additional cross-linking monomer. This research may contribute to improve air pollution caused by volatile of cross-linking monomers. H-nuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR) were used to characterize.

Alpha‐fetoprotein is a well‐known tumor marker in the screening and follow‐up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha‐fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45‐year‐old man who was found to have an alpha‐fetoprotein‐producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha‐fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha‐fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha‐fetoprotein. Serum alpha‐fetoprotein declined transiently after esophagectomy and fluctuation of alpha‐fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha‐fetoprotein‐producing adenocarcinoma. Monitoring of serum alpha‐fetoprotein may be useful in the evaluation and follow‐up of esophageal alpha‐fetoprotein‐producing adenocarcinoma.

Alpha-fetoprotein is a well-known tumor marker in the screening and follow-up of hepatocellular carcinoma. In Taiwanese society, a high prevalence of hepatitis and hepatoma and elevation of alpha-fetoprotein associated with liver function impairment usually suggested clinics undertake further examination for liver or genital tumor. We report the case of 45-year-old man who was found to have an alpha-fetoprotein-producing esophageal adenocarcinoma with an initial presentation of liver function impairment and rapid elevation of alpha-fetoprotein. Esophageal cancer was diagnosed via endoscope and a biopsy proved the presence of adenocarcinoma. A small endoscopic biopsy specimen failed to identify the alpha-fetoprotein positive tumor cell. Esophagectomy was performed and histopathological study of surgical specimen revealed grade II adenocarcinoma with regional metastatic lymphadenopathy. Immunohistochemical study was focal positive for alpha-fetoprotein. Serum alpha-fetoprotein declined transiently after esophagectomy and fluctuation of alpha-fetoprotein level was noted during the treatment with adjuvant chemotherapy. Finally, 19 months after the operation, the patient died due to multiple organ metastases with multiple organ failure. Thus, a small specimen for upper endoscopy may not be sufficient in the presence of alpha-fetoprotein-producing adenocarcinoma. Monitoring of serum alpha-fetoprotein may be useful in the evaluation and follow-up of esophageal alpha-fetoprotein-producing adenocarcinoma.

A series of novel terpyridyl Zn(II))-based metallo-polymers, including metallo-homopolymers and metallo-alt-copolymer, containing carbazole pendants attached to the C-9 position of fluorene by long alkyl spacers were constructed by self-assembled reaction. The integrated ratios of 1H NMR reveal a facile result to distinguish the differences between metallo-homopolymers and copolymers. To further investigate these polymers, UV-vis and PL spectral titration experiments were also carried out by varying the molar ratios of zinc(II) ions to monomers. The photophysical properties of these polymers exhibited blue PL emissions (around 420 nm) with quantum yields of 11-23% (in DMF) and the PL results revealed that the formation of excimers were suppressed by the incorporation of carbazole pendant groups. In addition, the EL results showed green EL emissions (around 550 nm) with turn-on voltages of 6.0-6.5 V, maximum efficiencies of 0.85-1.1 cd A-1(at 100 mA cm-2), and maximum luminances of 1704-2819 cd/m2(around 15 V), correspondingly.

This study reports an integrated microfluidic chip for polymerase chain reaction (PCR) applications utilizing digital microfluidic chip (DMC) technology. Several crucial procedures including sample transportation, mixing, and DNA amplification were performed on the integrated chip using electro-wetting-on-dielectric (EWOD) effect. An innovative concept of hydrophobic/hydrophilic structure has been successfully demonstrated to integrate the DMC chip with the on-chip PCR device. Sample droplets were generated, transported and mixed by the EWOD-actuation. Then the mixture droplets were transported to a PCR chamber by utilizing the hydrophilic/hydrophobic interface to generate required surface tension gradient. A micro temperature sensor and two micro heaters inside the PCR chamber along with a controller were used to form a micro temperature control module, which could perform precise PCR thermal cycling for DNA amplification. In order to demonstrate the performance of the integrated DMC/PCR chips, a detection gene for Dengue II virus was successfully amplified and detected. The new integrated DMC/PCR chips only required an operation voltage of 12VRMSat a frequency of 3 KHz for digital microfluidic actuation and 9VDCfor thermal cycling. When compared to its large-scale counterparts for DNA amplification, the developed system consumed less sample and reagent and could reduce the detection time. The developed chips successfully demonstrated the feasibility of Lab-On-a-Chip (LOC) by utilizing EWOD-based digital microfluidics.This study reports an integrated microfluidic chip for polymerase chain reaction (PCR) applications utilizing digital microfluidic chip (DMC) technology. Several crucial procedures including sample transportation, mixing, and DNA amplification were performed on the integrated chip using electro-wetting-on-dielectric (EWOD) effect. An innovative concept of hydrophobic/hydrophilic structure has been successfully demonstrated to integrate the DMC chip with the on-chip PCR device. Sample droplets were generated, transported and mixed by the EWOD-actuation. Then the mixture droplets were transported to a PCR chamber by utilizing the hydrophilic/hydrophobic interface to generate required surface tension gradient. A micro temperature sensor and two micro heaters inside the PCR chamber along with a controller were used to form a micro temperature control module, which could perform precise PCR thermal cycling for DNA amplification. In order to demonstrate the performance of the integrated DMC/PCR chips, a detection gene for Dengue II virus was successfully amplified and detected. The new integrated DMC/PCR chips only required an operation voltage of 12VRMSat a frequency of 3 KHz for digital microfluidic actuation and 9VDCfor thermal cycling. When compared to its large-scale counterparts for DNA amplification, the developed system consumed less sample and reagent and could reduce the detection time. The developed chips successfully demonstrated the feasibility of Lab-On-a-Chip (LOC) by utilizing EWOD-based digital microfluidics.

The effect of substrate surface roughness on the wettability of Sn-Bi solders is investigated by the eutectic Sn-Bi alloy on Cu/Al2O3substrates at 190 °C. To engineer the surface with different roughnesses, the Cu-side of the substrates is polished with sandpaper with abrasive number 100, 240, 400, 600, 800, 1200, and 1 μm alumina powder, respectively. Both dynamic and static contact angles of the solder drops are studied by the real-time image in a dynamic contact angle analyzer system (FTA200). During dynamic wetting, the wetting velocity of the solder drop decreases for the rougher surface. However, the time to reach the static contact angle seems to be identical with different substrate surface roughness. The wetting tip of the solder cap exhibits a waveform on the rough surface, indicating that the liquid drop tends to flow along the valley. As the solder drops reach a static state, the static contact angle increases with the substrate surface roughness. This demonstrates that the wettability of solders degrades as the substrates become rough.