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Ling Gui Zhu Gan decoction (LGZGD) is a traditional Chinese medicine (TCM) prescription that is widely used in cardiovascular disease clinical prevention and treatment with high efficacy. Recent studies have shown that LGZGD can also be used in hyperlipidemia (HL) intervention, but its pharmacodynamic material basis and its mechanisms remains unclear. This study aimed to reveal the protective effects of LGZGD on HL, elucidate the pharmacodynamic material basis. The hamster HL model was established by high-fat diet. Thereafter, non-targeted metabolomics and quantitative lipidomics were established for screening differential metabolites and pathways. Finally, the mechanisms were elucidated based on network pharmacology to screen for shared targets, which were computational selected by molecular docking. After four weeks of LGZGD administration, the TC, TG, and liver index levels decreased notably and hepatocyte injury was obviously reduced. The Multi-omics identified 62 differential metabolites and 144 differential lipids, respectively. The network pharmacology study predicted 343, 85, and 974 relevant targets from LGZGD components, HL, differential metabolites and lipids, respectively. Eventually, seven core targets were selected by molecular docking. Six key components in LGZGD, including genistein and naringenin, could play a therapeutic role in HL by regulating seven pathways, including HMGCR and PPARA. This comprehensive strategy provides a promising example and approach for further research on TCM for the treatment of lipid metabolic diseases.

Yttrium aluminum garnet (YAG)-based optical fiber is one of the research hotspots in the field of fiber lasers due to its combined advantages of a wide doping range of rare earth ions and the high mechanical strength of YAG material, as well as the flexibility and small size of the fiber structure. YAG-based optical fibers and related laser devices can be used in communication, sensing, medicine, etc. A comprehensive review of YAG-based optical fibers is provided in this paper. Firstly, the fabrication processes of YAG-based optical fibers are summarized and the structure and properties of fibers are classified and compared. Secondly, according to the optical wavelength regions, rare earth-doped YAG-based optical fibers for the applications of single-frequency and mode-locked fiber lasers are summarized. Lastly, the development challenges in both the fabrication and applications of YAG-based optical fibers are discussed.

【Objective】 The objective of this study is to investigate the water and salt movement during freeze-thaw period under partial autumn watering conditions in the Hetao Irrigation District. Specifically, the study focuses on comparing the water and salt dynamics between autumn irrigated farmland and non-autumn irrigated farmland (spring irrigated the following year). 【Method】 Field sampling observations and laboratory experiments were conducted to analyze the variations in soil temperature, soil moisture, and soil salinity during the freeze-thaw period under autumn watering and non-autumn watering conditions. 【Result】 After partial autumn irrigation, the temperature gradually decreased from the surface to the deeper layers in autumn irrigated farmland, while it decreased gradually in spring irrigated farmland. During the freezing process, the soil temperature in the 0~60 cm layer of autumn irrigated farmland dropped below 0 ℃ 30 days earlier than in spring irrigated farmland. In the melting process, the temperature in the 0~60 cm layer of autumn irrigated farmland rose above 0 ℃ 10 days later than in spring irrigated farmland. The desalination of the 0~100 cm soil layer in autumn irrigated farmland occurred mainly after autumn watering and during the freezing period, resulting in a desalting percentage of 47.38%. However, spring irrigated fields experienced salt accumulation of 35.68% and 16.87% during the freezing and melting stages, respectively. Throughout the freeze-thaw period, the net salt flux in each layer of both autumn irrigated and spring irrigated fields was negative, but it increased with soil depth. However, in spring irrigated farmland, the net salt flux initially increased and then decreased with increasing soil depth. 【Conclusion】 The water and salt migration patterns during the freeze-thaw period were influenced by the water level differences between autumn irrigated and spring irrigated fields. The time difference between the freezing and melting processes led to salt accumulation in spring irrigated fields before the next year’s spring irrigation. These findings provide valuable insights into the water and salt migration dynamics in irrigated and non-irrigated farmland, as well as the optimal development of autumn irrigation and spring irrigation practices under local autumn watering conditions.

Inadequate information sharing and difficult information diffusion are the main factors that cause upstream and downstream enterprises to default on supply chain finance. Blockchain technology, which exploits distributed storage and a consensus mechanism, can provide effective solutions to overcome these problems such as information sharing. When blockchain technology is adopted by the enterprises that comprise the supply chain finance business, this technology shows a diffusion trend. As a result, the decision pertaining to the application of novel technologies is affected. Therefore, to investigate the diffusion mechanism pertaining to the blockchain technology that is applied in supply chain finance, the study exploited the idea of a class of SEIR infectious disease models, and built a blockchain model that considers the supply chain financial system. Besides, the study verifies the stability of the model by constructing a Lyapunov function. The results indicate that the basic reproduction number determines the proliferation of the blockchain technology. When the basic reproduction number is less than 1, the proliferation of the blockchain technology that is applied in supply chain finance system would terminate. By contrast, when the basic reproduction number is greater than 1, during the average infection period, the number of non-adopting enterprises that accept the blockchain technology becomes greater than 1, which can maintain a continuous impact on supply chain finance system. Over time, the number of enterprises that accept blockchain technology tends to be stable. Through numerical simulations that consider the influencing parameters pertaining to the basic regeneration number, which has important effect on blockchain technology diffusion, we enlarge the diffusion efficiency and increase the transfer rate of potential on-chain enterprises or decrease the default exit rate. As a result, we facilitate the diffusion of blockchain technology in the system.

The mineralization of octacalcium phosphate (OCP) crystals in gel media was studied in the presence of a magnetic field. OCP crystal growth was found to be dependent on mineralization temperature, mineralization time, and the magnetic field. Higher temperatures significantly reduced the mineralization time, which is crucial for directional growth of OCP crystals. The growth of OCP crystals was accelerated by the applied magnetic field, while OCP crystals generated in the presence of a magnetic field exhibited increased length and width of oriented growth. This study provides valuable insights into the influence of mineralization factors in bioprocessing-inspired manufacturing processes.

Optical temperature sensors, which can accurately detect temperature in biological systems, are crucial to the development of healthcare monitoring. To challenge the state-of-art technology, it is necessary to design single luminescence center doped materials with multi-wavelength emission for optical temperature sensors with more modes and higher resolution. Here, an Er3+ single-doped KYF4 nanocrystals glass ceramic with an obvious thermochromic phenomenon is reported for the first time, which shows a different temperature-dependent green, red, and near-infrared luminescence behavior based on thermal disturbance model. In addition, Er3+ single-doped GC fiber was drawn and fabricated into multi-mode optical fiber temperature sensor, which has superior measured temperature resolution (＜0.5 ​°C), excellent detection limit (0.077 ​°C), and high correlation coefficient (R2) of 0.99997. More importantly, this sensor can monitor temperature in different scenarios with great environmental interference resistance and repeatability. These results indicate that our sensor shows great promise as a technology for environmental and healthcare monitoring, and it provides a route for the design of optical fiber temperature sensors with multi-mode and high resolution.

Cyanotis arachnoidea C. B. Clarke is a traditional Chinese medicinal herb that has a limited clinical use in the treatment of diabetes mellitus (DM) in minority areas of Guizhou in China. However, few prior reports are available on the quality control of Cyanotis arachnoidea, and its quality markers and hypoglycemic mechanism are still unclear. The purpose of this study is to explore the quality markers (Q-markers) of Cyanotis arachnoidea and predict its hypoglycemic mechanism. In this study, ultra-high-performance liquid chromatography (UHPLC) fingerprint combined with chemical pattern recognition were performed, and four differential components were screened out as quality markers, including 20-Hydroxyecdysone, 3-O-acetyl-20-hydroxyecdysone, Ajugasterone C, and 2-O-acetyl-20-hydroxyecdysone. Network pharmacology analysis revealed 107 therapeutic target genes of Cyanotis arachnoidea in DM treatment, and the key targets were Akt1, TNF, IL-6, MAPK3, and JUN. The hypoglycemic mode of action of Cyanotis arachnoidea may be mediated by tumor necrosis factor (TNF) signaling, cancer, insulin resistance, and JAK-STAT pathways. Molecular docking analysis disclosed that the foregoing quality markers effectively bound their key target genes. An in vitro experiment conducted on pancreatic islet β-cells indicated that the forenamed active components of Cyanotis arachnoidea had hypoglycemic efficacy by promoting PI3K/Akt and inhibiting MAPK signaling. UHPLC also accurately quantified the quality markers. The identification and analysis of quality markers for Cyanotis arachnoidea is expected to provide references for the establishment of a quality control evaluation system and clarify the material basis and hypoglycemic mechanisms of this traditional Chinese medicine (TCM).

Tripterygium glycosides tablets (TGT) are the commonly used preparation for rheumatoid arthritis (RA). However, the changes in TGT on RA are still unclear at the metabolic level. This study aimed to reveal the biological processes of TGT in collagen-induced arthritis (CIA) rats through integrated metabolomics and network analysis. First, the CIA model in rats was established, and the CIA rats were given three doses of TGT. Then, the endogenous metabolites in the serum from normal rats, CIA rats, and CIA rats treated with varying doses of TGT were detected by UHPLC-QTOF-MS/MS. Next, univariate and multivariate statistical analyses were performed to find the differential metabolites. Finally, differential metabolites, metabolic pathways, and hub genes were analyzed integrally to reveal the biological processes of TGT in CIA rats. The paw diameter, arthritis score, immunoglobulin G (IgG) concentration, CT image, and histological assay showed that TGT had evident therapeutic effects on CIA rats. Untargeted metabolomics revealed that TGT could ameliorate the down-regulation of lipid levels in CIA rats. Four key differential metabolites were found including LysoP(18:0), LysoPA(20:4), LysoPA(18:2), and PS(O-20:0/17:1). The glycerophospholipid metabolic pathway was perturbed in treating CIA with TGT. A total of 24 genes, including PLD1, LPCAT4, AGPAT1, and PLA2G4A, were found to be the hub genes of TGT in CIA rats. In conclusion, the integrated analysis provided a novel and holistic perspective on the biological processes of TGT in CIA rats, which could give helpful guidance for further TGT on RA. Future studies based on human samples are necessary.

Odorant-binding proteins (OBPs) play important roles in the insect olfactory system since they bind external odor molecules to trigger insect olfactory responses. Previous studies have identified some plant-derived volatiles that attract the pervasive insect pest Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), such as phenylacetaldehyde, benzyl acetate, 1-heptanol, and hexanal. To characterize the roles of CmedOBPs in the recognition of these four volatiles, we analyzed the binding abilities of selected CmedOBPs to each of the four compounds, as well as the expression patterns of CmedOBPs in different developmental stages of C. medinalis adult. Antennaes of C. medinalis adults were sensitive to the studied plant volatile combinations. Expression levels of multiple CmedOBPs were significantly increased in the antennae of 2-day-old adults after exposure to volatiles. CmedOBP1, CmedOBP6, CmedPBP1, CmedPBP2, and CmedGOBP2 were significantly up-regulated in the antennae of volatile-stimulated female and male adults when compared to untreated controls. Fluorescence competition assays confirmed that CmedOBP1 could strongly bind 1-heptanol, hexanal, and phenylacetaldehyde; CmedOBP15 strongly bound benzyl acetate and phenylacetaldehyde; and CmedOBP26 could weakly bind 1-heptanol. This study lays a theoretical foundation for further analysis of the mechanisms by which plant volatiles can attract C. medinalis. It also provides a technical basis for the future development of efficient plant volatile attractants of C. medinalis.

Plants and insects are engaged in a tight relationship, with phytophagous insects often utilizing volatile organic substances released by host plants to find food and egg-laying sites. Using plant volatiles as attractants for integrated pest management is vital due to its high efficacy and low environmental toxicity. Using naturally occurring plant volatiles combined with insect olfactory mechanisms to select volatile molecules for screening has proved an effective method for developing plant volatile-based attractant technologies. However, the widespread adoption of this technique is still limited by the lack of a complete understanding of molecular insect olfactory pathways. This paper first describes the nature of plant volatiles and the mechanisms of plant volatile perception by insects. Then, the attraction mechanism of plant volatiles to insects is introduced with the example of Cnaphalocrocis medinalis. Next, the progress of the development and utilization of plant volatiles to manage pests is presented. Finally, the functions played by the olfactory system of insects in recognizing plant volatiles and the application prospects of utilizing volatiles for green pest control are discussed. Understanding the sensing mechanism of insects to plant volatiles and its utilization will be critical for pest management in agriculture.

Epoxy thermal conductive adhesives with high thermal conductivity and dynamic mechanical properties are important thermally conductive materials for fabricating highly integrated electronic devices. In this paper, micro-Al2O3 is used as a thermally conductive filler for the epoxy resin composite and investigated the effect of micron-sized alumina particle size on the thermal conductivity and dynamic mechanical property of epoxy resin by the transient planar hot plate method and DMA (Dynamic mechanical analysis). The experimental results show that with the same amount of alumina filling, the thermal conductivity and Tg (glass transition temperature) of epoxy/Al2O3 composite material decrease with the increase of alumina particle size. The maximum thermal conductivity of the composite material is 0.679 (W/mK), while the energy storage modulus of epoxy/Al2O3 composite material increases with the increase of alumina particle size, and the maximum energy storage modulus of the composite material is 160MPa. Compared with pure epoxy resin, the thermal conductivity and energy storage modulus have increased by 2.7 and 3.2 times, respectively. The epoxy/Al2O3 composite was applied to the COB (Chips On Board) type LED package, and the substrate temperature of the LED dropped to the lowest after 1.5 hours of operation using EP-A5 composite, and the temperature was stabilized at 38.2°C, indicating that the addition of 5-micron alumina composite has the best heat dissipation in the COB type LED package. These results are critical for the implementation of particulate-filled polymer composites in practical applications because relaxed material specifications and handling procedures can be incorporated in production environments to improve efficiency.

Aspergillus nidulans has been more extensively characterized than other Aspergillus species considering its morphology, physiology, metabolic pathways, and genetic regulation. As it has a rapid growth rate accompanied by simple nutritional requirements and a high tolerance to extreme cultural conditions, A. nidulans is a promising microbial cell factory to biosynthesize various products in industry. However, it remains unclear for whether it is also a suitable host for synthesizing abundant L-malic acid. In this study, we developed a convenient and efficient double-gene-editing system in A. nidulans strain TN02A7 based on the CRISPR–Cas9 and Cre-loxP systems. Using this gene-editing system, we made a L-malic acid-producing strain, ZQ07, derived from TN02A7, by deleting or overexpressing five genes (encoding Pyc, pyruvate carboxylase; OahA, oxaloacetate acetylhydrolase; MdhC, malate dehydrogenase; DctA, C4-dicarboxylic acid transporter; and CexA, citric acid transporter). The L-malic acid yield in ZQ07 increased to approximately 9.6 times higher (up to 30.7 g/L titer) than that of the original unedited strain TN02A7, in which the production of L-malic acid was originally very low. The findings in this study not only demonstrate that A. nidulans could be used as a potential host for biosynthesizing organic acids, but also provide a highly efficient gene-editing strategy in filamentous fungi.

BackgroundBone age assessment (BAA) is an essential tool utilized in outpatient pediatric clinics. Three major BAA methods, Greulich–Pyle (GP), Tanner–Whitehouse 3 (TW3), and China 05 RUS–CHN (RUS–CHN), were applied to comprehensively compare bone age (BA) and chronological age (CA) in a Chinese sample of preschool children. This study was designed to determine the most reliable method.MethodsThe BAA sample consisted of 207 females and 183 males aged 3–6 years from the Zhejiang Province in China. The radiographs were estimated according to the GP, TW3, and RUS–CHN methods by two pediatric radiologists. The data was analyzed statistically using boxplots, the Wilcoxon rank test, and Student’s t-test to explore the difference (D) between BA and CA.ResultsAccording to the distributions of D, the boxplots showed that the median D of the TW3 method was close to zero for both male and female subjects. The TW3 and RUS–CHN methods overestimated the age of both genders. The TW3 method had the highest correct classification rate for males but a similar rate for females. The GP method did not show any significant difference between the BA and CA when applied to 3-year-old males and 4-year-old females while the TW3 method showed similar results when applied to 6-year-old females. The RUS–CHN method showed the least consistent results among the three methods.ConclusionThe TW3 method was superior to the GP and RUS–CHN methods but not reliable on its own. It should be noted that a precise age diagnosis for preschool children cannot be easily made if only one of the methods is utilized. Therefore, it is advantageous to combine multiple methods when assessing bone age.

Bismuth telluride (Bi2Te3) has attracted much attention in the field of thermoelectrics since it is one kind of commercial room-temperature thermoelectric material. Herein three kinds of Bi2Te3 thermoelectric fibers with internal tensile stress are fabricated utilizing an optical fiber template method. The effects of internal stress on the microstructure and the electrical transportation of Bi2Te3 thermoelectric fibers are investigated. The Bi2Te3 cores in the fibers are highly crystalline and possess a tensile nanosheet structure with preferential orientation as evidenced by X-ray diffraction and Raman studies. Tensile stress can enhance electrical properties of the fibers. And a paper cup generator covered with 20 pieces of optimized fibers provides a μW-level output power. It is inferred that tensile stress tuning can be an effective tool for the material optimization of thermoelectric performance.

Despite their wide presence in hcp metals, incoherent tilt grain boundaries (ITGBs) are rarely studied. In this work, first-principles calculations were combined with atomic-resolution HAADF-STEM analyses to investigate the structure and formation of one special type ITGB in an Mg-Gd alloy featured with a unique Gd-rich cluster segregation pattern. Our results suggested this ITGB as a mirror-glide boundary formed by gliding the atoms along [ $20\bar{2}\bar{1} $] of a { $10\bar{1}4 $}< $20\bar{2}\bar{1} $> coherent twin boundary due to its interaction with stacking faults. The ITGB can be further stabilized by partial-column Gd substitution, leading to the observed unique segregation pattern.

Abstract Thickness‐dependent chemical and physical properties have gained tremendous interest since the emergence of two‐dimensional (2D) materials. Despite attractive prospects, the thickness‐controlled synthesis of ultrathin nanosheets remains an outstanding challenge. Here, a chemical vapor deposition (CVD) route is reported to controllably synthesize high‐quality PtSe2 nanosheets with tunable thickness and explore their thickness‐dependent electronic and magnetotransport properties. Raman spectroscopic studies demonstrate all Eg, A1g, A2u, and Eu modes are red shift in thicker nanosheets. Electrical measurements demonstrate the 1.7 nm thick nanosheet is a semiconductor with room temperature field‐effect mobility of 66 cm2 V−1 s−1 and on/off ratio of 106. The 2.3–3.8 nm thick nanosheets show slightly gated modulation with high field‐effect mobility up to 324 cm2 V−1 s−1 at room‐temperature. When the thickness is over 3.8 nm, the nanosheets show metallic behavior with conductivity and breakdown current density up to 6.8 × 105 S m–1 and 6.9 × 107 A cm−2, respectively. Interestingly, magnetoresistance (MR) studies reveal magnetic orders exist in this intrinsically non‐magnetic material system, as manifested by the thickness‐dependent Kondo effect, where both metal to insulator transition and negative MR appear upon cooling. Together, these studies suggest that PtSe2 is an intriguing system for both developing novel functional electronics and conducting fundamental 2D magnetism study.

Tourism consumption is not only an important means by which to improve residents' sense of happiness but is also the main way to promote national economic development. In a traditional relational society such as China, it remains unclear how social network affects tourism consumption by households. Here, we evaluated the impact of the social network on tourism consumption by Chinese households using the data of 3254 samples from the China Family Panel Studies. The empirical results from the ordinary least square method showed that the social network promotes tourism consumption, which can be projected to increase by about 28% for every 1% increase in social network strength. This was further confirmed using the instrumental variable method to address the issue of endogenous social network formation, as well as other robustness checks. The impact of the social network on tourism consumption was heterogeneous. Compared with other residents, there were higher positive effects for high-income families, households with a head aged 35-44 years, urban families, and households in eastern China. The quantile regression results revealed that the impact of the social network was weakened with increasing tourism consumption by households. These results are crucial for policymakers, in that they could form good habits of tourism consumption and strengthen tourism market management, especially for the management of tourism negative events in the context of new media.

Cu-Se alloy core fibers with glass cladding were fabricated by a thermal drawing method of a reactive molten core. The composition, crystallography, and photoelectric/thermoelectric performance of the fiber cores were investigated. The X-ray diffraction spectra of the Cu-Se alloy core fibers illustrate the fiber cores being polycrystalline with CuSe and Cu3Se2 phases. Interestingly, the fiber cores show a lower electrical conductivity under laser irradiation than under darkness at room temperature. Meanwhile, the fiber cores possess a power factor of ~1.2 mWm−1K−2 at room temperature, which is approaching the value of the high thermoelectric performance bulk of Cu2Se polycrystals. The flexible Cu-Se fibers and their micro–nano tapers have potential multifunctional applications in the field of photoelectric detection and thermoelectric conversion on curved surfaces.

High-performance thermoelectric fibers with n-type bismuth telluride (Bi2Te3) core were prepared by thermal drawing. The nanosheet microstructures of the Bi2Te3 core were tailored by the whole annealing and Bridgman annealing processes, respectively. The influence of the annealing processes on the microstructure and thermoelectric performance was investigated. As a result of the enhanced crystalline orientation of Bi2Te3 core caused by the above two kinds of annealing processes, both the electrical conductivity and thermal conductivity could be improved. Hence, the thermoelectric performance was enhanced, that is, the optimized dimensionless figure of merit (ZT) after the Bridgman annealing processes increased from 0.48 to about 1 at room temperature.

In order to improve the downlink communication performance of the traditional LoRa wide area network (LoRaWAN), a LoRaWAN downlink routing control strategy based on the software defined networks (SDN) framework and the improved auto-regressive integrated moving average (ARIMA) model is proposed. The SDN architecture is used to monitor the network traffic, and the link bandwidth occupancy rate is calculated based on the monitored downlink traffic. Taking into account the impact of data volatility on the accuracy of the prediction results, the Savitzky–Golay (S–G) smoothing filter and the sliding window method are introduced for data pre-processing. Stationarity processing is carried out for the time series data in the window, and the ARIMA model is developed to predict the downlink bandwidth occupancy rate. The triangle module operator is then used to incorporate multiple path parameters to finally calculate the selectivity of different paths, and the optimal path for LoRaWAN downlink communication is then provided. Simulation and experimental results show that the root mean square error of the improved ARIMA prediction model is reduced by 87% compared with the standard ARIMA model. The proposed routing control strategy effectively reduces the service transmission delay and packet loss rate. In the LoRaWAN test environment, as the downlink load rate increases, the average link bandwidth occupancy rate of this solution increases by 12% compared with the traditional method.

The authority of journals is usually a key indicator in guiding people to choose important journals, and the journal ranking is a common way to distinguish the journals' authority. The common ranking methods or models are based on citation data, such as the impact factor (IF), the PageRank algorithm, and the hyperlink-induced topic search algorithm. In this paper, we present a new model, named the reputation analysis of citation behavior (RACB) model, which not only considers the number of citations but also considers the reputation of inter-citation behavior. First, the model fits the function relation of the citation desire index (CDI) based on the citation data of the most reputable journal (named the top journal in the remainder of this paper). Then, the CDI values of the target journals are calculated by using the function relation of the top journal. An improved gray correlation analysis is used to describe the deviation between the CDI and the actual citation rate, named the random citation rate, indicating the inter-citation reputation value of the target journals. Finally, a case study showed that the ranking result of the RACB model has a high similarity with the IF values of 2017, which indicates that the ranking results of the RACB model that considered journal reputation evaluations are more reasonable than those of the traditional PageRank algorithm. This paper proposes a new method of journal ranking from the perspective of reputation evaluation, which can rank the journals more reasonably. It encourages researchers to cite articles more fairly in order to avoid a situation in which the low reputation of the citation behavior affects the quality of the journal that published the article.

N-type bismuth telluride (Bi2Te3) based thermoelectric (TE) fibers were fabricated by thermal drawing and Bridgman annealing, and the influence of Bridgman annealing on the TE properties of n-type Bi2Te3-based TE fibers was studied. The Bridgman annealing enhanced the electrical conductivity and Seebeck coefficient because of increasing crystalline orientation and decreasing detrimental elemental enrichment. The TE performance of n-type Bi2Te3-based TE fibers was improved significantly by enhancing the power factor. Hence the power factor increased from 0.14 to 0.93 mW/mK2, and the figure-of-merit value is from 0.11 to 0.43 at ~300 K, respectively.

Objective: To investigate the clinical features, skeletal muscle imaging, and muscle pathological characteristics of late-onset GSD IIIa caused by mutation of the AGL gene in adults.Methods: The clinical data, skeletal muscle imaging, pathological data, and gene test results of a family with late-onset GSD IIIa in adulthood were collected in detail in November 2019.Results: The proband is a 40-years-old male, who was admitted into our hospital due to a 2-years history of limb weakness. The proband was diagnosed with the following syndrome: he had a 15-years history of elevated muscle enzymes; the cranial nerve examinations showed no abnormal findings; the muscle tension in both upper and lower limbs was low, and tendon reflexes were absent; the proband's muscle strength was 5 in the proximal muscles and 4 in the distal muscles of the upper limbs, with 3 in the proximal muscles and 4 in the distal muscles of the lower limbs; Magnetic Resonance Imaging (MRI) revealed abnormally high signal intensity changes in the posterior thigh muscle group, and the posterior-medial calf muscle group; and vacuoles were evident in some muscle fibers biopsied from the gastrocnemius muscle. Periodic acid-Schiff staining stained the cytoplasm of muscle fibers a dark red color. The proband's older brother exhibited the same clinical features. DNA analysis identified mutations in the AGL gene in the proband, his older brother, and parents. The proband and his older brother both carried two compound heterozygous mutations, c.866G>A and c.2855_2856insT. Pedigree analysis demonstrated that c.866G>A and c.2855_2856insT mutations had been inherited from the mother and father, respectively.Conclusion: Late-onset GSD IIIa in adults is clinically characterized by muscle weakness, muscle atrophy, and mainly occurred in the posterior thigh muscle group. We also identified two novel compound heterozygous mutations (c.866G> A and c.2855_2856insT) in the AGL gene.

Background: Industry funding in continuing medical education has been extensively studied in the USA. Although continuing medical education is also a requirement for Chinese physicians, little is known about Chinese physician perceptions of industry support in continuing medical education. Objective: We aim to determine perceptions regarding industry support for CME among Chinese physicians at a large CME course, examine potential associations between Chinese physicians’ perceptions and their demographic characteristics, and compare Chinese and US physicians’ perceptions of industry support for CME. Design: We performed a cross-sectional survey of physicians at a nephrology continuing medical education conference in China. All participants received a previously published, anonymous survey consisting of 4 items, with questions asked in English and Mandarin Chinese. Responses were compared with those of a previous cohort in the USA. Results: The response rate was 24% (128/541). Most respondents were nephrologists (112/126, 89%), women (91/128, 71%), and aged 20 to 40 years (79/127, 62%). Most respondents preferred industry-supported continuing medical education (84/123, 68%) or had no preference (33/123, 27%). More clinicians than clinical researchers supported industry offsetting costs (76.9% vs 58.3%; P = .03). Almost half of participants (58/125, 46%) stated that industry-supported continuing medical education was biased in support of industry. Compared with US physicians, Chinese physicians were more likely to believe, or had no opinion, that industry-supported courses were biased (67.2% vs 47.0%; P

Accumulation of amyloid β (Aβ) induces neuronal, synaptic, and cognitive deficits in patients and animal models of Alzheimer's disease (AD). The underlying mechanisms, however, remain to be fully elucidated. In the present study, we found that Aβ interacted with ErbB4, a member of the receptor tyrosine kinase family and mainly expressed in GABAergic interneurons. Deleting ErbB4 in parvalbumin-expressing neurons (PV neurons) significantly attenuated oligomeric Aβ-induced suppression of long term potentiation (LTP). Furthermore, specific ablation of ErbB4 in PV neurons via Cre/loxP system greatly improved spatial memory and synaptic plasticity in the hippocampus of hAPP-J20 mice. The deposition of Aβ detected by 3D6 and Thioflavin S staining and the proteolytic processing of hAPP analyzed by western blotting were not affected in the hippocampus of hAPP-J20 mice by deleting ErbB4 in PV neurons. Our data suggested that ErbB4 in PV neurons mediated Aβ-induced synaptic and cognitive dysfunctions without affecting Aβ levels.

Rubella virus (RuV) is the infectious agent of a series of birth defect diseases termed congenital rubella syndrome, which is a major public health concern all around the world. RNA interference (RNAi) is a crucial antiviral defense mechanism in eukaryotes, and numerous viruses have been found to encode viral suppressors of RNAi (VSRs) to evade antiviral RNAi response. However, there is little knowledge about whether and how RuV antagonizes RNAi. In this study, we identified that the RuV capsid protein is a potent VSR that can efficiently suppress shRNA- and siRNA-induced RNAi in mammalian cells. Moreover, the VSR activity of the RuV capsid is dependent on its dimerization and double-stranded RNA (dsRNA)-binding activity. In addition, ectopic expression of the RuV capsid can effectively rescue the replication defect of a VSR-deficient virus or replicon, implying that the RuV capsid can act as a VSR in the context of viral infection. Together, our findings uncover that RuV encodes a VSR to evade antiviral RNAi response, which expands our understanding of RuV–host interaction and sheds light on the potential therapeutic target against RuV.

Adult hippocampal neurogenesis was impaired in several Alzheimer's disease models overexpressing mutant human amyloid precursor protein (hAPP). However, the effects of wild-type hAPP on adult neurogenesis and whether the impaired adult hippocampal neurogenesis was caused by amyloid β (Aβ) or APP remained unclear. Here, we found that neurogenesis was impaired in the dentate gyrus (DG) of adult mice overexpressing wild-type hAPP (hAPP-I5) compared with controls. However, the adult hippocampal neurogenesis was more severely impaired in hAPP-I5 than that in hAPP-J20 mice, which express similar levels of hAPP mRNA but much higher levels of Aβ. Furthermore, reducing Aβ levels did not affect the number of doublecortin-positive cells in the DG of hAPP-J20 mice. Our results suggested that hAPP was more likely an important factor inhibiting adult neurogenesis, and Aβ was not the major factor affecting neurogenesis in the adult hippocampus of hAPP mice.

A dual-porosity medium with micro-fractured spherical matrix blocks was achieved on the basis of the structure characteristics of nano-micro pores and micro-fractures in shale gas reservoirs. The Laplace space solution of the dimensionless bottom hole pressure of fractured well production was obtained in consideration of the seepage,diffusion and desorption mechanism of shale gas and applying the Laplace transform and the Stehfest numerical inversion. Type curves of dimensionless production were plotted and the influencing factors of the type curves were identified. The results show that the matrix surface improves gas transfer from the matrix medium to the fracture network due to matrix micro fractures. Increasing the permeability and length of micro fractures accelerate the productivity significantly.

Bi2Te3-based materials have been reported to be one of the best room-temperature thermoelectric materials, and it is a challenge to substantially improve their thermoelectric properties. Here novel Bi2Te3 core fibers with borosilicate glass cladding were fabricated utilizing a modified molten core drawing method. The Bi2Te3 core of the fiber was found to consist of hexagonal polycrystalline nanosheets, and polycrystalline nanosheets had a preferential orientation; in other words, the hexagonal Bi2Te3 lamellar cleavage more tended to be parallel to the symmetry axis of the fibers. Compared with a homemade 3-mm-diameter Bi2Te3 rod, the polycrystalline nanosheets’ preferential orientation in the 89-μm-diameter Bi2Te3 core increased its electrical conductivity, but deduced its Seebeck coefficient. The Bi2Te3 core exhibits an ultrahigh ZT of 0.73 at 300 K, which is 232% higher than that of the Bi2Te3 rod. The demonstration of fibers with oriented nano-polycrystalline core and the integration with an efficient fabrication technique will pave the way for the fabrication of high-performance thermoelectric fibers.

Serum Cl (sCl) alterations in hospitalized patients have not been comprehensively studied in recent years. The aim of this study is to investigate the prevalence and outcome significance of (1) sCl alterations on hospital admission, and (2) sCl evolution within the first 48 hr of hospital admission. We conducted a retrospective study of all hospital admissions in the years 2011-2013 at Mayo Clinic Rochester, a 2000-bed tertiary medical center. Outcome measures included hospital mortality, length of hospital stay and discharge disposition. 76,719 unique admissions (≥18 years old) were studied. Based on hospital mortality, sCl in the range of 105-108 mmol/L was found to be optimal. sCl 108 (n = 11,395) mmol/L independently predicted a higher risk of hospital mortality, longer hospital stay and being discharged to a care facility. 13,089 patients (17.1%) had serum anion gap >12 mmol/L; their hospital mortality, when compared to 63,630 patients (82.9%) with anion gap ≤12 mmol/L, was worse. Notably, patients with elevated anion gap displayed a progressively worsening mortality with rising sCl. sCl elevation within 48 hr of admission was associated with a higher proportion of 0.9% saline administration and was an independent predictor for hospital mortality. Moreover, the magnitude of sCl rise was inversely correlated to the days of patient survival. In conclusion, serum Cl alterations on admission predict poor clinical outcomes. Post-admission sCl increase, due to Cl-rich fluid infusion, independently predicts hospital mortality. These results raise a critical question of whether iatrogenic cause of hyperchloremia should be avoided, a question to be addressed by future prospective studies.

This article proposes a new model to address the design problem of a sustainable regional logistics network with uncertainty in future logistics demand. In the proposed model, the future logistics demand is assumed to be a random variable with a given probability distribution. A set of chance constraints with regard to logistics service capacity and environmental impacts is incorporated to consider the sustainability of logistics network design. The proposed model is formulated as a two-stage robust optimization problem. The first-stage problem before the realization of future logistics demand aims to minimize a risk-averse objective by determining the optimal location and size of logistics parks with CO 2 emission taxes consideration. The second stage after the uncertain logistics demand has been determined is a scenario-based stochastic logistics service route choices equilibrium problem. A heuristic solution algorithm, which is a combination of penalty function method, genetic algorithm, and Gauss–Seidel decomposition approach, is developed to solve the proposed model. An illustrative example is given to show the application of the proposed model and solution algorithm. The findings show that total social welfare of the logistics system depends very much on the level of uncertainty in future logistics demand, capital budget for logistics parks, and confidence levels of the chance constraints.

Itk is a member of the Tec family of kinases that is expressed predominantly in T cells. Itk regulates the T cell receptor signaling pathway to modulate T cell development and T helper cell differentiation, particularly Th2 differentiation. Itk is also important for the development and function of iNKT cells. In this review we discuss current progress on our understanding of the structure, activation and signaling pathway of Itk, in addition to inhibitors that have been developed, which target this kinase. We also place in context the function of Itk, available inhibitors and potential use in treating disease.

We systematically study, by using first-principles calculations, stabilities, electronic properties, and optical properties of GexSn1-xSe alloy made of SnSe and GeSe monolayers with different Ge concentrations x = 0.0, 0.25, 0.5, 0.75, and 1.0. Our results show that the critical solubility temperature of the alloy is around 580 K. With the increase of Ge concentration, band gap of the alloy increases nonlinearly and ranges from 0.92 to 1.13 eV at the PBE level and 1.39 to 1.59 eV at the HSE06 level. When the Ge concentration x is more than 0.5, the alloy changes into a direct bandgap semiconductor; the band gap ranges from 1.06 to 1.13 eV at the PBE level and 1.50 to 1.59 eV at the HSE06 level, which falls within the range of the optimum band gap for solar cells. Further optical calculations verify that, through alloying, the optical properties can be improved by subtle controlling the compositions. Since GexSn1-xSe alloys with different compositions have been successfully fabricated in experiments, we hope these insights will contribute to the future application in optoelectronics.

We investigated the association between two single nucleotide polymorphisms (SNPs) in the adiponectin gene (rs822395 and rs266729) and coronary artery disease (CAD) in a case-control study of 198 unrelated Chinese CAD patients (with ; 70% coronary stenosis or previous myocardial infarction) and 237 non-CAD controls. The ligase reaction was used to detect SNPs rs822395 and rs266729, and the allelic association of these SNPs with the occurrence and severity of CAD was assessed. There were no significant differences in the genotypic or allelic frequencies of the two SNPs between control and CAD individuals. In addition, there was no association between the two SNPs and the severity of CAD based on the number of diseased vessels. The frequencies of alleles C and G at rs266729 differed significantly between females in the CAD and control groups, but not between males. Female carriers of allele G at rs266729 had a higher risk of CAD compared with allele C carriers (OR = 1.30, 95% CI: 1.09-2.64, p = 0.02). These results indicate a gender-specific effect of the adiponectin gene rs266729 variant in modulating the risk of CAD in women.

Background. The study investigates the occurrence, severity, and outcomes of acute kidney injury (AKI) in octogenarians following heart valve surgery. Methods. All patients, age >80 years, not on dialysis and without kidney transplant, undergoing heart valve replacement at Mayo Clinic, Rochester, in the years 2002-2003 were enrolled. AKI was diagnosed based on AKIN criteria. Results. 209 octogenarians (88.0% aortic valve, 6.2% mitral valve, 1.0% tricuspid valve, and 4.8% multivalve) with (58.4%) and without CABG were studied. 34 (16.3%) had preexisting CKD. After surgery, 98 (46.8%) developed AKI. 76.5% of the AKI were in Stage 1, 9.2% in Stage 2, and 14.3% in Stage 3. 76.5% CKD patients developed AKI. Length of hospital stay was longer for AKI patients. More AKI patients were discharged to care facilities. Patient survival at 30 days and 1 year for AKI versus non-AKI was 88.8 versus 98.7%, p=0.003, and 76.5 versus 88.3%, p=0.025, respectively. With follow-up of 3.94±0.28 years, Kaplan-Meier analysis showed a reduced survival for AKI octogenarians. Preexisting CKD and large volume intraoperative fluid administration were independent AKI predictors. Conclusions. Nearly half of the octogenarians developed AKI after valve replacement surgery. AKI was associated with significant functional impairment and reduced survival.