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Summary: Background: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. Methods: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. Findings: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. Interpretation: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. Funding: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

ABSTRACTEnterotoxigenic Escherichia coli (ETEC) is one of the major pathogens contributing to piglet diarrhea, with significant implications for both piglet health and the economic aspects of the livestock industry. SW207 is an isolate of Bacillus halotolerans isolated from the cold- and disease-resistant Leixiang pigs in Northeastern China. We have discovered that SW207 can survive in the pig’s gastrointestinal fluid and under conditions of high bile salt concentration, displaying potent antagonistic activity against ETEC. In this study, we established a weaned piglet diarrhea model infected with ETEC to investigate the role of SW207 in preventing diarrhea and improving intestinal health. Results indicate that SW207 upregulates the expression of tight junction proteins, including claudin-1, occludin, and zonula occludens-1, at both the transcriptional and translational levels. Furthermore, SW207 reduces serum endotoxin, D-lactic acid, and various oxidative stress markers while enhancing piglet mechanical barrier function. In terms of immune barrier, SW207 suppressed the activation of the TLR4/MyD88/NF-κB pathway, reducing the expression of various inflammatory factors and upregulating the expression of small intestine mucosal sIgA. Concerning the biological barrier, SW207 significantly reduces the content of E. coli in the intestines and promotes the abundance of beneficial bacteria, thereby mitigating the microbiota imbalance caused by ETEC. In summary, SW207 has the potential to prevent weaned piglet diarrhea caused by ETEC, alleviate intestinal inflammation and epithelial damage, and facilitate potential beneficial changes in the intestinal microbiota. This contributes to elucidating the potential mechanisms of host-microbe interactions in preventing pathogen infections.IMPORTANCEEnterotoxigenic Escherichia coli (ETEC) has consistently been one of the significant pathogens causing mortality in weaned piglets in pig farming. The industry has traditionally relied on antibiotic administration to control ETEC-induced diarrhea. However, the overuse of antibiotics has led to the emergence of drug-resistant zoonotic bacterial pathogens, posing a threat to public health. Therefore, there is an urgent need to identify alternatives to control pathogens and reduce antibiotic usage. In this study, we assessed the protective effect of a novel probiotic in a weaned piglet model infected with ETEC and analyzed its mechanisms both in vivo and in vitro. The study results provide theoretical support and reference for implementing interventions in the gut microbiota to alleviate early weaned piglet diarrhea and improve intestinal health.

Olfactory dysfunction (OD) is one of the important and difficult-to-treat symptoms of eosinophilic chronic rhinosinusitis (CRS), which is typically associated with type 2 inflammation where eosinophils (EOSs) function as both effectors and initiators. Eosinophilic infiltration in the olfactory mucosa (OM) is associated with severe OD, mucosal erosion, and more loss of olfactory sensory neurons (OSNs). Active EOS-derived cytokines, chemokines, and eosinophil granule proteins may lead to aggravation of inflammation, tissue damage, and impairment of the survival and regeneration of OSNs. Recent studies show that EOSs can lead to apoptosis of OSNs through axonal and neural body damage, turnover disorder of OSNs through the loss of immature OSNs and globose basal cells (GBCs), changed proliferative activity of horizontal basal cells (HBCs), and dysfunction of OSNs through the breakdown of neuroepithelial integrity and alteration of ion concentration in OSNs and mucin. In this review, we outline the current progress on the role of EOSs on OD in patients with eosinophilic CRS and the mechanism of EOS-associated injury of the OM and OSNs in experimental animal models with sinonasal inflammation. Further investigations on the molecular mechanisms of tissue eosinophilia-induced injury of OSNs are warranted to obtain new therapeutic targets and achieve better restoration of olfactory function.

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) is a novel alternative to perfluorooctane sulfonate (PFOS), with environmental health risks largely unknown. The present study aims to unravel the adipogenesis effects and underlying molecular initiating events of OBS, which are crucial for understanding and predicting its adverse outcome. In undifferentiated human mesenchymal stem cells (hMSCs), exposure to 1–100 nM of OBS for 7 days stimulated reactive oxygen species production. In the subsequent multipotent differentiation, hMSCs favored adipogenesis and repressed osteogenesis. The point of departure (PoD) for cellular responses of OBS was 38.85 nM, higher than PFOS (0.39 nM). Notably, OBS/PFOS co-exposure inhibited osteogenesis and synergistically promoted adipogenesis. Consistently, the expression of adipogenic marker genes was up-regulated, while that of osteogenic marker genes was down-regulated. The decreased adiponectin and elevated tumor necrosis factor α (TNFα) secretion were observed in differentiated cells exposed to the mixture of OBS and PFOS. The co-treatment of a peroxisome proliferator-activated receptor γ (PPARγ) antagonist alleviated the adipogenic effects of PFOS and its combination with OBS. Moreover, OBS/PFOS co-exposure induced peroxisome PPARγ activation in reporter gene assays, and increased formation of PPARγ - retinoid X receptor α (RXRα) heterodimers measured by co-immunoprecipitation assays. Molecular docking showed interaction energy of OBS (-20.7 kcal/mol) with intact PPARγ-RXRα complex was lower than that of PFOS (-25.9 kcal/mol). Overall, single OBS exhibited lower potency in inducing adipogenesis but is comparable to PFOS in repressing osteogenesis, whereas OBS/PFOS co-exposure increases interaction with PPARγ-RXRα heterodimers, resulting in the synergistic activation of PPARγ, ultimately enhancing adipogenesis at the expense of osteogenic differentiation. The results indicate the potential health risks of increased obesity and decreased bone density caused by OBS and its co-exposure with PFOS, as well as other perfluorinated alkylated substances mixtures.

AbstractPre-trained language models have been successful in many knowledge-intensive NLP tasks. However, recent work has shown that models such as BERT are not “structurally ready” to aggregate textual information into a [CLS] vector for dense passage retrieval (DPR). This “lack of readiness” results from the gap between language model pre-training and DPR fine-tuning. Previous solutions call for computationally expensive techniques such as hard negative mining, cross-encoder distillation, and further pre-training to learn a robust DPR model. In this work, we instead propose to fully exploit knowledge in a pre-trained language model for DPR by aggregating the contextualized token embeddings into a dense vector, which we call agg★. By concatenating vectors from the [CLS] token and agg★, our Aggretriever model substantially improves the effectiveness of dense retrieval models on both in-domain and zero-shot evaluations without introducing substantial training overhead. Code is available at https://github.com/castorini/dhr.

The advent of 5G technology presented new challenges regarding the high-frequency characteristics of electrical signals and their impact on the cover glass properties of electronic devices. This study aimed to analyze the effect of the Li/Na molar ratio on the dielectric and mechanical properties, as well as the structural characteristics, of lithium aluminosilicate glass-ceramics. Using the melting method, we prepared lithium aluminosilicate base glasses and subsequently crystallized them by adjusting the molar ratio. XRD and TEM analyses were employed to investigate the resultant structures and crystal formation in the five base glasses. It was observed that Li2Si2O5 and LiAlSi4O10 crystals precipitated, exhibiting varying degrees of crystallinity and crystal ratios. Through a comparison of dielectric properties before and after crystallization, it was found that the dielectric constants of the glass-ceramics were consistently reduced. This decrease can be attributed to the lower dielectric constants exhibited by both crystalline phases compared to the parent lithium aluminosilicate glasses. Furthermore, the presence of glass crystals effectively immobilized the alkali metal ions within the glass phase, impeding their movement under an electric field. Consequently, the dielectric loss value of the glass-ceramics decreased with the increasing amount of precipitated crystals. By carefully adjusting the composition and optimizing the crystallization process, we successfully produced lithium aluminosilicate glass-ceramics, demonstrating excellent mechanical and optical properties, coupled with low dielectric properties.

While genetic factors were associated with over 30% of colorectal cancer (CRC) patients, mutations in CRC-susceptibility genes were identified in only 5% to 10% of these patients. Besides, previous studies on hereditary CRC were largely designed to analyze germline mutations in patients with single genetic high-risk factor, which limited understanding of the association between genotype and phenotypes. From January 2015 to December 2018, we retrospectively enrolled 2,181 patients from 8,270 consecutive CRC cases, covering 5 categories of genetic high-risk factors. Leukocyte genomic DNA was analyzed for germline mutations in cancer predisposition genes. The germline mutations under each category were detected and analyzed in association with CRC susceptibility, clinical phenotypes, and prognoses. A total of 462 pathogenic variants were detected in 19.3% of enrolled CRC patients. Mismatch repair gene mutation was identified in 9.1% of patients, most prevalent across all high-risk groups. Homologous recombination (HR) gene mutations were detected in 6.5% of cases, penetrated in early-onset and extra-colonic cancer risk groups. Mutations in HR genes, including BARD1, RAD50, and ATM, were found to increase CRC risk with odds ratios of 2.8-, 3.1-, and 3.1-fold, respectively. CRC patients with distinct germline mutations manifested heterogeneous phenotypes in clinicopathology and long-term prognoses. Thus, germline mutation screenings should be performed for CRC patients with any of those genetic risk factors. This study also reveals that HR gene mutations may be another major driver for increased CRC risk.

C4 olefin is an important feedstock for the chemical industry. Designing an effective and stable industrial process for preparing C4 olefin from renewable ethanol is crucial for further sustainable chemical production. In this study, a comprehensive evaluation system of an experimental scheme was constructed based on the Analytic Hierarchy Process/Entropy Weight Method-Technique for Order Preference by Similarity to Ideal Solution (AHP/EWM-TOPSIS) and Chemical production indicators. Using this evaluation system, a Back Propagation Neural Network (BPNN) based on a Genetic Algorithm (GA) was constructed after simulating C4 olefin production conditions using the Improved Mixed Congruential method. Subsequently, the production scheme with the highest evaluation score was determined when the temperature was not limited and when the temperature was lower than 350°C through a series of mathematical models. Overall, our mathematical models provide guidance for the commercial production of ethanol to butene and effectively reduce the risk of scaling up the chemical process to pilot or industrial scale.

As the primary molecular target, there is still a gap between the peroxisome proliferator-activated receptors (PPARs) regulation and the adverse health effects caused by per- and polyfluoroalkyl substances (PFASs). The effects of PFASs on cellular differentiation regulated by PPARs is likely significant given the association of PFASs exposure with obesity and decreased bone density. Human mesenchymal stem cells (hMSCs) were used as an in vitro model to assess the roles of PPAR subtypes in the multipotent differentiation of hMSCs affected by perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA) and their replacement compounds. PFASs increased the expression of three PPAR subtypes in proliferating and differentiating hMSCs. Meanwhile, PFOS and PFOA decreased osteogenesis, enhanced adipogenesis, and increased bone turnover in hMSCs. Similarly, PFOA alternatives, hexafluoropropylene oxide dimer acid (HFPO-DA) and hexafluoropropylene oxide trimer acid (HFPO-TA), exhibited similar or even higher potency in affecting stem cell differentiation compared with PFOA. Perfluorohexanesulfonate (PFHxS) inhibited osteogenesis with comparable potency to PFOS. In contrast, 6:2 chlorinated poly-fluoroalkyl ether sulfonate (6:2Cl-PFESA) enhanced osteogenesis. PPARβ expression is significantly positively correlated with osteogenesis and osteoprotegerin (OPG) secretion in 6:2Cl-PFESA treated cells. shRNA knockdown of PPARβ remarkably reversed the osteogenic effects of 6:2Cl-PFESA and enhanced the adipogenic effects of the six chemicals. The results suggested that the adverse effects and relative potency of PFASs on the multipotent differentiation of hMSCs were dependent on the integrated action of the three PPAR subtypes, which facilitates a better understanding of the molecular initiating events of PFASs. The present study may well explain the mechanism of the decreased bone density and increased obesity incidence among those exposed to legacy PFASs, and indicates the necessity of further health risk assessment for the alternatives.

Abstract Purpose To study whether retinal pigment epithelium (RPE) disruption and choroidal hyper-transmission on spectral-domain optical coherence tomography (SD-OCT) are signs of inflammatory neovascularization (CNV) in punctate inner choroidopathy (PIC). Methods This is a prospective cohort study. Seventeen patients (18 eyes) were diagnosed as PIC without CNV at baseline. Changes of morphological characteristics including choroidal hyper-transmission, hypo-transmission, RPE disruption, and ellipsoid zone (EZ) damage on SD-OCT were observed and recorded at baseline, 4, 8 and 12 weeks, respectively. The occurrence of CNV was detected by OCTA at each visit. Fisher’s exact test was used to compare the relationship with each morphological sign and evaluate the predictable capability of secondary CNV in PIC (PIC+CNV) based on the structure changes on OCT. Results Among the 18 eyes, a total of 5 eyes (27.8%) developed PIC+CNV subsequently within 4 weeks follow-up. At 4, 8 and 12 weeks of follow-up, RPE disruption and choroidal hyper-transmission were found in all 5 PIC+CNV eyes. The incidence of RPE disruption was significant higher in PIC+CNV eyes compared with PIC eyes (P=0.001). PIC eyes with hyper-transmission had a higher risk for developing CNV compared with those without hyper-transmission (P=1.17×10-3). 2 out of 5 PIC+CNV eyes had a choroidal hypo-transmission component adjacent to hyper-transmission zone at 4 weeks of follow-up, and hypo-transmission could be observed in all 5 PIC+CNV eyes at 8 weeks of follow-up. The incidence of choroidal hypo-transmission was significant higher in PIC+CNV eyes than PIC eyes after 8 weeks. EZ damage began to recover at 4 weeks of follow-up and had no significant difference in the PIC eyes and PIC+CNV eyes (P=0.150, 0.196, 0.353). Conclusion The presence of choroidal hyper-transmission and RPE disruption on SD-OCT is associated with the PIC+CNV. SD-OCT imaging facilitates the differentiation and track of the progression of inflammatory lesions and secondary CNV in PIC.

Si-B-C-N/diamond-like carbon (DLC) gradient films with different layers were prepared on a glass substrate by radio frequency magnetron sputtering, and the structure and surface morphology of the resulting films were analyzed by scanning electron microscopy, Raman spectrometry, and X-ray photoelectron spectroscopy. The mechanical and optical properties of the films were studied using a multifunctional material mechanical testing system, UV-Vis spectrophotometer, and micro-Vickers hardness tester. The gradient structure promotes the formation of sp3 bonds and improves the hardness and optical transmittance of the resulting films. Among the prepared films, the single-layer Si-B-C-N/DLC gradient film shows the highest optical transmittance (97%). Film–substrate adherence is strengthened by the introduction of the gradient structure. The best adhesion was obtained with a double-layer Si-B-C-N/DLC gradient film. Suitable anti-wear properties were exhibited in both dry (0.18) and wet (0.07) conditions. In this paper, evaluation of the microstructural, optical, and mechanical properties of the films could provide new insights into improvements in the bonding force of glass-based DLC films and enrich the experimental data of DLC multilayer film systems.

In this study, for the first time, a cluster-plus-glue-atom model was used to optimize the composition of lithium aluminosilicate glass-ceramics. Basic glass in glass-ceramics was considered to be a 16-unit combination of three-valence {M2O3} and one-valence {Li2O} units. By adjusting the ratio of {M2O3} and {Li2O}, the composition of basic glass could be optimized. After optimization, the average cation valence of the base glass was increased to 2.875. After heat treatment of the optimized base glass, it is found that the crystal size, proportion, and crystallinity changed obviously compared with that before optimization. The main crystalline phases of all the lithium aluminosilicate glass-ceramics prepared in this work were Li2Si2O5 and LiAlSi4O10. All optimized glass-ceramics had an obvious improvement in the crystallinity, with one of the largest having a crystallinity of over 90%. Furthermore, its bending strength was 159 MPa, the microhardness was 967 Hv, and the visible light transmission rate exceeded 90%. Compared with the widely used touch panel cover glass, the optical properties were close, and the mechanical properties were greatly improved. Due to its excellent performance, it could be used in microelectronics, aerospace, deep-sea exploration, and other fields.

In this paper, we used differential scanning calorimetry (DSC), high-temperature X-ray diffraction (HT-XRD), and confocal scanning laser microscopy (CSLM) to investigate the Li2O–Al2O3–SiO2 glass crystallization process. At 943 K, lithium disilicate (Li2Si2O5) phase crystals began to precipitate in the Li2O–Al2O3–SiO2 glass with a crystal size of 50–70 nm. At the temperature of 1009 K, petalite (LiAlSi4O10) crystals began to precipitate in the vitreous phase, forming composite spherical crystals of LiAlSi4O10 and Li2Si2O5 with size in the range of 90–130 nm. Furthermore, the Kissinger method and KAS method of the JMAK model were used to calculate the crystallization activation energy and the Avrami index “n”. It was found that the precipitation mechanism of the two kinds of crystals is whole crystallization; accordingly, the selection of crystallization heat treatment system was guided to determine the nucleation and crystallization temperature.

The manifold microchannel (MMC) heat sink is characterized by high heat transfer efficiency, high compactness, and low flow resistance. It can be an effective method for the high-flux removal of high-power electronic components. To further enhance the performance of the MMC, a double-layer pin–fin MMC structure was designed. The thermodynamic properties, including the flow and heat transfer characteristics, were numerically investigated using ANSYS Fluent with deionized water as the working liquid. Compared with the single-layer MMC, the temperature uniformity is better, the pressure drop is lower, and the comprehensive performance is improved at the cost of slightly larger thermal resistance for the double-layer MMC. The geometric effects on the thermodynamic performance were also analyzed. The results show that among the pin–fin structures with round, diamond-shaped, and rectangular cross-sections, the round pin–fins demonstrate the best comprehensive performance and the minimal thermal resistance. Under the same inlet velocity, the thermal resistance is decreased, and the comprehensive performance is first increased and then decreased as the pin–fin size increases. In addition, it is recommended to adopt a larger height ratio for low inlet velocity and a smaller height ratio for high inlet velocity.

With the number of objectives increasing, the traditional multi-objective evolutionary algorithms (MOEAs) will lead to a reduction of convergence pressure. Specifically, the number of non-dominated solutions in many-objective optimization problems (MaOPs) accounts for the majority of the population. Generational distance (GD) is originally designed to calculate the sum of adjacent distances of solution sets obtained by different algorithms and thus GD is a credible indicator to measure the convergence of many-objective evolutionary algorithms (MaOEAs). In this paper, a GD indicator-based evolutionary algorithm is proposed to solve many-objective optimization problems. First, for the same rank of non-dominated solutions, their adjacent distances are introduced to be the indicator for the selection of the potentially appropriate individuals. Second, in order to maintain good diversity at the same time, an improved niching method based on the angles of candidate solutions is proposed. One solution can only compare the adjacent distance with the solutions in its niche. Solutions are assigned new ranks according to the niching method. Third, in order to eliminate the influence of the order of comparison and assign a higher rank to the solutions with good diversity, a new comparison method is proposed to solve the problem. Finally, the simulation results show that compared with the state of the art algorithms, the proposed algorithm is effective.

Real-world optimization tasks often have more than three objectives, hence are Many-objective Optimization Problems (MaOPs). MaOPs are challenging because of the difficulties in obtaining the true Pareto front of high dimensionality. The number of objectives can be reduced. However, existing objective reduction methods are computationally expensive as they need to identify non-dominant solutions by running multi-objective evolutionary algorithms (MOEAs). In this paper, we propose an efficient yet effective objective reduction method, named Objective Reduction using Sampling and Affinity Propagation (ORSAP). First, a sampling method is used to collect points that can represent objectives by calculating objectives' improvements. Second, affinity propagation is adopted to cluster the objectives, so redundant objectives may group together. Then, only the centroid objectives are kept as non-redundant objectives. The experiments on a range of benchmark MaOP instances show that ORSAP can successfully retain non-redundant objectives and remove redundant ones with low computational cost. It is highly competitive compared to the state-of-the-art objective reduction methods. In addition, ORSAP can significantly improve optimization performance when integrating with MOEAs.

Aims: To report potential vaccine-induced ocular adverse events following inactivated COVID-19 vaccination (Sinopharm and Sinovac). Methods: This case series took place at a tertiary referral center in the southeast of China (Xiamen Eye Center in Fujian Province) from February 2021 to July 2021. Patients who received the first dose of inactivated COVID-19 vaccine and developed vaccine-related ocular adverse events within 10 days were included. The diagnosis of vaccine-related ocular adverse events was guided by the World Health Organization causality assessment and the Naranjo criteria. Results: Ten eyes of seven patients (two male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30–55 years). The mean time of ocular adverse event manifestations was 4.9 days (range, 1–10 days). Three patients were diagnosed with Vogt–Koyanagi–Harada (VKH)-like uveitis, one with multifocal choroiditis, one with episcleritis, one with iritis, and one with acute idiopathic maculopathy. Two patients received the second dose of vaccine. One patient had exacerbation of VKH, and one patient had no symptoms. An aqueous humor analysis in three patients revealed elevated proinflammatory cytokines and negative virus copy. All the patients had transient ocular disturbance and responded well to steroids. No recurrence was noted during 6 months of follow-up. Conclusions: Potential ocular adverse events should be reported to increase the awareness of the health community for timely detection and proper treatment.

A 48-year-old woman had an acute blurred vision in the right eye immediately after drainage of liver abscess. Her best corrected visual acuity (BCVA) was 8/400; fundus photography suggested the diagnosis of endogenous endophthalmitis with chorioretinitis and vitritis. Due to the bad systemic condition, a systemic antibiotic combined with periocular triamcinolone (TA) was carried out first. Inflammatory cells in the vitreous cavity were decreased after treatment; however, fundus fluorescein angiography (FFA) showed abnormal dilation and leakage of the capillaries and retinal-choroidal anastomose, supporting that there was retinal angiomatous proliferation (RAP). Vitreous interleukin-6 (IL-6) was only slightly elevated; the ratio of interleukin-10 (IL-10) and IL-6 was less than 1, and the etiological test was negative. After receiving intravitreal vancomycin injection combined with periocular TA injection, the patient’s BCVA was improved from 16/400 to 20/400 with a reduction in vitreous inflammatory cells. However, the patient’s RAP was progressed and her BCVA was dramatically decreased to count finger/30 cm. After intravitreal injection of ranibizumab, the patient’s BCVA was 5/400 with a significant shrink in lesions and absorption of hemorrhage, exudation, and fluid. Thus, we suggest that early anti-inflammatory treatment in conjunction with anti-VEGF may achieve a better prognosis in patients with inflammatory retinal angiomatous proliferation (RAP).

Ba0.6Sr0.4TiO3 (BST) ceramic materials have been widely used in the field of multilayer ceramic capacitors. Surface modification through the surface coating to form a heterogeneous layer could effectively improve the dielectric properties. In this work, BST powders were prepared by a co-precipitation method. The effects of reaction conditions on the microstructure of the BST powder were investigated. The reaction temperatures significantly affected the morphology of BST powder, and the rhombic-type particles were obtained with the reaction temperature around 80 °C. Meanwhile, the BST@Fe2O3 was prepared by the chemical precipitation method using BST powders with rhombic-type microstructure as “core”, and the so-called “core-shell” microstructure was confirmed in the BST@Fe2O3 powder. Then, BST@x wt%Fe2O3 (x = 2.5, 5, 7.5, and 10, denoting the different content of Fe2O3) ceramics were further prepared, and the influence of “core-shell” structure on the phase structure, microstructure, and dielectric properties was investigated. With the increasing of Fe2O3 content, the ferroelectric–paraelectric phase transition temperature shifts toward lower temperatures, and dielectric peaks gradually become broad and frequency-dependent, which may be due to inconsistent chemical composition from core to shell.

Air is usually compressed adiabatically in the compressor. As the operating speed of compressors can be several thousand rpm, heat generated during compression cannot be sufficiently transmitted to the environment in such a short time. It is for this reason that compressor efficiency is limited. Isothermal compression could be an alternative choice applied on industrial compressor and compressed air energy storage (CAES). This paper proposed a new kind of piston to perform isothermal compression. Surface area of such isothermal piston structure is larger. A certain amount of fluid at the chamber bottom absorbs the heat from the isothermal piston. Heat transfer between piston and fluid during compression is investigated. Air pressure is measured to validate the effectiveness of this proposed piston structure in heat transfer. Compression work of the proposed isothermal piston and conventional one is compared. One issue of this comparison is that air-liquid dissolution can affect the pressure and compression work. The influence of dissolution is quantified with Henry’s Law. Quantitative analysis is performed to determine that heat transfer is the dominant factor affecting the pressure and compression work. Some simple experiments are described in this paper, which shed light on that heat transfer could be significantly improved adopting this proposed isothermal piston.

Purpose. To investigate the iTRAQ-based proteomic changes of visual cycle-associated proteins in RPE of rd12 mice before and after RPE65 gene delivery. Mehtods. The right eyes of rd12 mice underwent RPE65 gene delivery by subretinal injection at P14, leaving the left eyes as control. C57BL/6J mice were served as a wide-type control group. ERGs were recorded at P42, and RPE-choroid-sclera complex was collected to evaluate the proteomic changes in visual cycle-associated proteins by iTRAQ-based analysis. Western blot was used to confirm the changes in the differentially expressed proteins of interest. Results. ERG parameters improved dramatically at P42 after RPE65 delivery. The proteomics analysis identified a total 536 proteins with a global false discovery rate of 0.21%, out of which 7 were visual cycle-associated proteins. RALBP-1, RBP-1, and IRBP were reduced in the untreated rd12 eyes and the former two were improved after gene therapy, confirmed by Western blot analysis. Conclusions. RPE65 gene delivery restored retinal function at P42 and modified the expression of other functional proteins implicated in the visual cycle. The level of RALBP-1 was still below the normal level after gene therapy in rd12 mice, which may explain the delayed dark adaption in LCA patients undergoing similar therapy.

Stargardt Disease (STGD) is the commonest genetic form of juvenile or early adult onset macular degeneration, which is a genetically heterogeneous disease. Molecular diagnosis of STGD remains a challenge in a significant proportion of cases. To address this, seven patients from five putative STGD families were recruited. We performed capture next generation sequencing (CNGS) of the probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Seven disease-causing mutations in ABCA4 and two in PROM1 were identified by CNGS, which provides a confident genetic diagnosis in these five families. We also provided a genetic basis to explain the differences among putative STGD due to various mutations in different genes. Meanwhile, we show for the first time that compound heterozygous mutations in PROM1 gene could cause cone-rod dystrophy. Our findings support the enormous potential of CNGS in putative STGD molecular diagnosis.