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The nonselective calcium‐permeable Transient Receptor Potential Cation Channel Subfamily V Member4 (TRPV4) channel regulates various physiological activities. Dysfunction of TRPV4 is linked to many severe diseases, including edema, pain, gastrointestinal disorders, lung diseases, and inherited neurodegeneration. Emerging TRPV4 antagonists show potential clinical benefits. However, the molecular mechanisms of TRPV4 antagonism remain poorly understood. Here, cryo‐electron microscopy (cryo‐EM) structures of human TRPV4 are presented in‐complex with two potent antagonists, revealing the detailed binding pockets and regulatory mechanisms of TRPV4 gating. Both antagonists bind to the voltage‐sensing‐like domain (VSLD) and stabilize the channel in closed states. These two antagonists induce TRPV4 to undergo an apparent fourfold to twofold symmetry transition. Moreover, it is demonstrated that one of the antagonists binds to the VSLD extended pocket, which differs from the canonical VSLD pocket. Complemented with functional and molecular dynamics simulation results, this study provides crucial mechanistic insights into TRPV4 regulation by small‐molecule antagonists, which may facilitate future drug discovery targeting TRPV4. [ABSTRACT FROM AUTHOR]

Background: Chemotherapeutic agents are used to control tumor proliferation. However, their influence in the pre-metastatic niche of target organs has not been well studied. Oxaliplatin (OXA) is a drug applied in standard treatments of colorectal cancer (CRC), while the direct effect of which on the pre-metastatic microenvironment of the liver remains unclear. Methods: Models of liver metastases were established with luciferase expressing CT26 cells in BALB/c and BALB/c-nude mice. Single-cell RNA Sequencing was performed to examine the immune microenvironment in the liver elicited by OXA. Immunofluorescence and flowcytometry were utilized to confirm the changes in the number of immune cells. LDH, CellTrace CFSE Cell Proliferation and apoptosis assays were conducted to explore the impact of OXA on T cells ex vivo. The correlation between chemotherapy-related lymphopenia and metastases was assessed by meta-analysis. Results: Herein we discovered that administration of OXA prior to the occurrence of liver metastasis actually accelerated tumor development and colonization in the liver. Single-cell RNA sequencing revealed that the landscape of the liver immune microenvironment had been changed to immunosuppressive phenotype. Macrophages after the treatment of OXA exhibited a high ability to inhibit the activation of T cells. Further investigation revealed a significant decrease in the number of T cells in the liver, particularly CD8+ T cells with reduced capacity of proliferation, activation, and killing. When mice were treated with T cell supplementation, the OXA-induced metastasis was notably abolished, indicating that the OXA-primed liver microenvironment could be reversed by the infusion of T cells. Consistent with our findings in mice, a meta-analysis was performed to verify that chemotherapy-related lymphopenia was associated with an inferior prognosis related with high incidence of metastasis, suggesting the pivotal role of chemotherapy in pre-metastatic niche formation. Furthermore, a notable reduction in the count of both macrophages and T cells was observed in the liver of colorectal cancer (CRC) patient undergoing OXA-based chemotherapy. Conclusions: Our findings proposed that immunosuppressive microenvironment in liver induced by OXA enhanced liver metastasis of colorectal cancer, which highlighted a new consideration to balance the pro metastases and anti-cancer possibility of OXA treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] Aqueous Zn-ion battery is expected to become a substitute for Li-ion battery due to its inherent safety, low cost, and environmental friendliness. Dendrite growth and side reaction problems during electroplating lead to its low Coulombic efficiency and unsatisfactory life, which greatly limits its practical application. Here, we propose a dual-salts hybrid electrolyte, which alleviates the above issues by mixing Zn(OTf) 2 to ZnSO 4 solution. Extensive tests and MD simulations have shown that the dual-salts hybrid electrolyte can regulate the solvation structure of Zn2+, facilitating uniform Zn deposition, and inhibiting side reactions and dendrite growth. Hence, the dual-salts hybrid electrolyte exhibits good reversibility in Zn//Zn batteries, which can provide a lifetime of more than 880 h at 1 mA cm−2 and 1 mAh cm−2. Moreover, the average Coulombic efficiency of Zn//Cu cells in hybrid system can reach 98.2% after 520 h, much better than that of 90.7% in pure ZnSO 4 electrolyte and 92.0% in pure Zn(OTf) 2 electrolyte. Benefiting from the fast ion exchange rate and high ion conductivity, Zn-ion hybrid capacitor in hybrid electrolyte also displays excellent stability and capacitive performance. This effective strategy for dual-salts hybrid electrolytes provides a promising direction for designing aqueous electrolytes for Zn-ion batteries. [ABSTRACT FROM AUTHOR]

Background: Chemotherapeutic agents are used to control tumor proliferation. However, their influence in the pre-metastatic niche of target organs has not been well studied. Oxaliplatin (OXA) is a drug applied in standard treatments of colorectal cancer (CRC), while the direct effect of which on the pre-metastatic microenvironment of the liver remains unclear. Methods: Models of liver metastases were established with luciferase expressing CT26 cells in BALB/c and BALB/c-nude mice. Single-cell RNA Sequencing was performed to examine the immune microenvironment in the liver elicited by OXA. Immunofluorescence and flowcytometry were utilized to confirm the changes in the number of immune cells. LDH, CellTrace CFSE Cell Proliferation and apoptosis assays were conducted to explore the impact of OXA on T cells ex vivo. The correlation between chemotherapy-related lymphopenia and metastases was assessed by meta-analysis. Results: Herein we discovered that administration of OXA prior to the occurrence of liver metastasis actually accelerated tumor development and colonization in the liver. Single-cell RNA sequencing revealed that the landscape of the liver immune microenvironment had been changed to immunosuppressive phenotype. Macrophages after the treatment of OXA exhibited a high ability to inhibit the activation of T cells. Further investigation revealed a significant decrease in the number of T cells in the liver, particularly CD8+ T cells with reduced capacity of proliferation, activation, and killing. When mice were treated with T cell supplementation, the OXA-induced metastasis was notably abolished, indicating that the OXA-primed liver microenvironment could be reversed by the infusion of T cells. Consistent with our findings in mice, a meta-analysis was performed to verify that chemotherapy-related lymphopenia was associated with an inferior prognosis related with high incidence of metastasis, suggesting the pivotal role of chemotherapy in pre-metastatic niche formation. Furthermore, a notable reduction in the count of both macrophages and T cells was observed in the liver of colorectal cancer (CRC) patient undergoing OXA-based chemotherapy. Conclusions: Our findings proposed that immunosuppressive microenvironment in liver induced by OXA enhanced liver metastasis of colorectal cancer, which highlighted a new consideration to balance the pro metastases and anti-cancer possibility of OXA treatment. [ABSTRACT FROM AUTHOR]

Background: By comparing the differences in plant use between various cultures or regions, we can gain a better understanding of traditional knowledge of plant use among different groups, which may lead to a more objective understanding. Even though the Tibetan and Daman people live in the same ecosystem in Gyirong town, China, their cultural backgrounds and livelihoods differ. Therefore, the objective of this study is to document the traditional knowledge of plant use among the Daman people and compare it with the local Tibetan knowledge of plant use. By doing so, we aim to explore the relationship between plant selection and use and the cultural backgrounds of different groups. Methods: During fieldwork, ethnobotanical data were collected using various methods including free listings, key informant interviews, and semi-structured interviews. To quantify the importance of plant species in the Daman people's culture, the culture importance index, informant consensus factor index, and The Index of Agreement on Species consensus (IASc) were used. In addition, we cited previous ethnobotanical survey data from the Tibetan in Gyirong. To more comprehensively compare the differences in plant use between the Daman and Tibetan, this study constructed a knowledge network to compare the knowledge differences between the two groups. Results: In this study, traditional knowledge was collected from 32 Daman informants, resulting in a total of 68 species belonging to 39 families mentioned by Daman people and 111 species mentioned by Tibetans. Of these, 58 plants were used by both populations. The plants were classified into 3 categories and 28 subcategories, with 22 identical classes in both groups. The majority of use categories showed a high degree of sharing in both groups, and the Tibetan people had more plant use categories than the Daman people. Five plants with IASc value > 0.5 were identified in both groups: Rhododendron anthopogon D. Don, Artemisia japonica Thunb., Juniperus indica Bertol., Gastrodia elata Blume, and Rheum australe D. Don. The analysis of the knowledge network revealed a 66% overlap between the knowledge of the Daman and the knowledge of the Tibetans. Additionally, the plant knowledge of Tibetan people was found to be richer and more complex than that of the Daman people. However, the Daman people possess 30 unique knowledge items. Conclusions: From the perspective of plant use, the history of the Daman people's discrete migration on the border between China and Nepal allows them to retain their own knowledge of plant use. The status quo of joining Chinese nationality and settling in Gyirong town allows them to gradually integrate into the local Tibetan society. In summary, despite living in the same ecosystem and biodiversity background, the plant utilization of the Daman people and Tibetans still shows significant differences, which are due to their different cultural backgrounds and social status. [ABSTRACT FROM AUTHOR]

It was proposed recently that the fine-grained entropy of the Hawking radiation can be expressed by the semiclassical island formula, which reproduces the unitary Page curve. In this paper, we choose the "in" vacuum state and apply the quantum extremal surface construction to study the Page curve for the step-function Vaidya model of evaporating black holes in four dimensions, which is produced by the spherical null shells. Metrics of the three regions of this spacetimes are obtained. In addition, the entanglement islands for the step-function Vaidya model of evaporating black holes at very late times are studied. When cutoff surface A is located in Minkowski region III with uA< uH at very late times, we find that the location of the boundary of island ∂I depends on the value of 8M − vA + vI. Specifically, ∂I is inside, at or outside the horizon when 8M − vA + vI is less than, equal to or larger than zero respectively. Moreover, when cutoff surface A is located in Minkowski region III with uA> uH after the black hole evaporates completely, we find that entanglement island still exists and ∂I is located on an equal-time Cauchy surface of the observer A when r A 2 ≥ 64GNκc. [ABSTRACT FROM AUTHOR]

Background. Ectodysplasin A (EDA), a member of the TNF family, plays important roles in ectodermal development, while recent studies expanded its regulatory effects on insulin resistance and lipid metabolism. This study was the first time to investigate the correlation between circulating EDA and albuminuria in patients with T2DM. Methods. A total of 189 T2DM and 59 healthy subjects were enrolled in the study. We analyzed the concentrations of EDA by ELISA. Plasma glucose, insulin, HbA1c, lipids, creatinine, BUN, and UACR were also measured. Insulin resistance and pancreatic cell function were assessed by HOMA. Results. Circulating EDA concentration was significantly increased in T2DM patients and increased with the degree of albuminuria. EDA was positively correlated with age, FIns, HOMA-IR, HOMA-β, Scr, and UACR, and negatively correlated with eGFR. Linear stepwise regression showed that FIns, HOMA-β, and UACR were independent influencing factors of EDA. Logistic regression analysis showed that EDA was independently associated with the occurrence of albuminuria in T2DM. ROC curve showed that EDA had an area under the receiver operating curve of 0.701 [ 95 % CI = 0.625 − 0.777 , P < 0.001 ]. Conclusion. EDA is positively correlated with the degree of albuminuria in patients with T2DM and may be involved in the occurrence and progression of diabetic kidney disease (DKD). [ABSTRACT FROM AUTHOR]

Despite the fact that engineered surface enabling remarkable phase change heat transfer have elicited increasing attention due to their ubiquitous applications in thermal management, the underlying mechanisms of intrinsic rough structures as well as the surface wettability on bubble dynamics remain to be explored. Therefore, a modified molecular dynamics simulation of nanoscale boiling was conducted in the present work to investigate bubble nucleation on rough nanostructured substrates with different liquid–solid interactions. Specifically, the initial stage of nucleate boiling was mainly investigated and the bubble dynamic behaviors were quantitively studied under different energy coefficients. Results shows that as the contact angle decreases, the nucleation rate increases, because liquid obtains more thermal energy there compared with that on less wetting surfaces. The rough profiles of the substrate can provide nanogrooves, which can enhance initial nucleate embryos, thereby improving thermal energy transfer efficiency. Moreover, atomic energies are calculated and adopted to explain how bubble nuclei are formed on various wetting substrates. The simulation results are expected to provide guidance towards surface design in state–of–the art thermal management systems, such as the surface wettability and the nanoscale surface patterns. [ABSTRACT FROM AUTHOR]

Lagerstroemia indica L. is a well-known ornamental plant with large pyramidal racemes, long flower duration, and diverse colors and cultivars. It has been cultivated for nearly 1600 years and is essential for investigating the germplasm and assessing genetic variation to support international cultivar identification and breeding programs. In this study, 20 common Lagerstroemia indica cultivars from different varietal groups and flower morphologies, as well as multiple wild relative species, were analyzed to investigate the maternal donor of Lagerstroemia indica cultivars and to discover the genetic variation and relationships among cultivars based on plastome and nuclear ribosomal DNA (nrDNA) sequences. A total of 47 single nucleotide polymorphisms (SNPs) and 24 insertion/deletions (indels) were identified in the 20 L. indica cultivars' plastome and 25 SNPs were identified in the nrDNA. Phylogenetic analysis based on the plastome sequences showed that all the cultivars formed a clade with the species of L. indica, indicating that L. indica was the maternal donor of the cultivars. Population structure and PCA analyses supported two clades of cultivars, which exhibited significant genetic differences according to the plastome dataset. The results of the nrDNA supported that all 20 cultivars were divided into three clades and most of the cultivars had at least two genetic backgrounds and higher gene flow. Our results suggest that the plastome and nrDNA sequences can be used as molecular markers for assessing the genetic variation and relationships of L. indica cultivars. [ABSTRACT FROM AUTHOR]

Background: Gyirong Valley known as the "Back Garden of the Himalayas" is located in the core area of the Everest National Nature Reserve. It is also one of the important ports from ancient Tibet to Kathmandu, Nepal, since ancient times. Over the years, the Tibetans of Gyirong had accumulated sufficient traditional knowledge about local plant resources. However, there is almost no comprehensive report available on ethnobotanical knowledge about the local people. The purposes of this study were to (1) conduct a comprehensive study of wild plants used by Tibetan people in Gyirong Valley and record the traditional knowledge associated with wild useful plants, (2) explore the influence of Tibetan traditional culture and economic development on the use of wild plants by local people, and (3) explore the characteristics of traditional knowledge about wild plants of Tibetans in Gyirong. Methods: Ethnobotanical data were documented through free listings, key informant interviews and semi-structured interviews during fieldwork. The culture importance index and the informant consensus factor index were used as quantitative indices. Results: In total, 120 informants (61 women and 59 men) and 3333 use reports and 111 wild plant species belonging to 39 families and 81 genera were included. These use reports were then classified into 27 categories belonging to three major categories. The use category that contained the most plant species was edible plants (62), followed by medicinal plants (32) and economic plants (22), and other uses (71). Plants with high CI included Allium prattii, Neopicrorhiza scrophulariiflora, Gymnadenia orchidis, Rhododendron anthopogon and Fritillaria cirrhosa. Thirty-six species of plants in the catalog of Gyirong and Yadong were the same, but only 17 species were the same in Gyirong and Burang. There were only 11 overlapping species between all the three regions. Conclusion: Tibetans of Gyirong have rich and unique knowledge about plant use, and wild edible and medicinal plants play an important role in the nutrition and health protection of local people. However, traditional knowledge is slowly being lost and is being hit by modern tourism. In the future, more attention needs to be paid to the important role of traditional knowledge in biodiversity conservation. [ABSTRACT FROM AUTHOR]

Starting from December 2019, the global pandemic of coronavirus disease 2019 (COVID-19) is continuously expanding and has caused several millions of deaths worldwide. Fast and accurate diagnostic methods for COVID-19 detection play a vital role in containing the plague. Chest computed tomography (CT) is one of the most commonly used diagnosis methods. However, a complete CT-scan has hundreds of slices, and it is time-consuming for radiologists to check each slice to diagnose COVID-19. This study introduces a novel method for fast and automated COVID-19 diagnosis using the chest CT scans. The proposed models are based on the state-of-the-art deep convolutional neural network (CNN) architecture, and a 2D global max pooling (globalMaxPool2D) layer is used to improve the performance. We compare the proposed models to the existing state-of-the-art deep learning models such as CNN based models and vision transformer (ViT) models. Based off of metric such as area under curve (AUC), sensitivity, specificity, accuracy, and false discovery rate (FDR), experimental results show that the proposed models outperform the previous methods, and the best model achieves an area under curve of 0.9744 and accuracy 94.12% on our test datasets. It is also shown that the accuracy is improved by around 1% by using the 2D global max pooling layer. Moreover, a heatmap method to highlight the lesion area on COVID-19 chest CT images is introduced in the paper. This heatmap method is helpful for a radiologist to identify the abnormal pattern of COVID-19 on chest CT images. In addition, we also developed a freely accessible online simulation software for automated COVID-19 detection using CT images. The proposed deep learning models and software tool can be used by radiologist to diagnose COVID-19 more accurately and efficiently. [ABSTRACT FROM AUTHOR]

[Display omitted] • Studying coupled effects of hydrogen, temperature, and surface on GS80A mechanics. • Analyzing microstructures in fractures of GS80A at diverse environmental conditions. • Proposing heuristic micro-mechanisms governing temperature and hydrogen effects. In a hydrogen (H) rich environment, metal materials are susceptible to hydrogen embrittlement (HE), resulting in a reduction in mechanical properties and raising safety concerns. Moreover, the mechanical behavior of metals can be markedly influenced by temperature and surface roughness. In the context of ensuring the safety of high-strength GS80A steel bolts submerged in underwater seawater conditions, this study systematically conducts mechanical tests with and without H pre-charging at varying temperatures, using specimens with different surface roughness. It is found that the combined effect of H and temperature on mechanical property losses surpasses the individual effects of H or temperature alone. Notably, observations of fracture surfaces in the broken specimens reveal a significant impact on the area fraction of cleavage steps, strongly associated with material ductility, by both H and temperature. Furthermore, the influence of surface roughness on the H-affected mechanical behavior is minimal compared to the temperature effect, based on our experiments. Finally, the micro-mechanics of the coupled environmental effects are thoroughly discussed. [ABSTRACT FROM AUTHOR]

Post-hoc explaining approaches for deep learning (DL) models has attracted much attention in safety–critical applications such as rotating machinery intelligent fault diagnosis (IFD). However, with the help of the explanation techniques, the models are still fragile to domain shifts caused by varying speeds and loads without help for improving their cross-domain performance. Since humans in the decision-making loop are essential for a reliable diagnostic system to determine the reliability of diagnosis, this paper proposes a causal explaining guided domain generalization (CXDG) method to realize trust worthy IFD with human in the decision loop. Specifically, an explaining model is trained with the conditional mutual information, which is a causal strength metric, and utilized to tell the causal features in the input data as the attributions of the diagnostic model. A translation process of the attributions is proposed to make the explaining process understandable. Furthermore, the aim of this paper is not only explaining but also beyond that the diagnostic model is guided to focus on the causal features to improve its generalization ability in unseen domains. The effectiveness of the method is validated on two experiment datasets. The results show that the proposed method can both explain the attributions of the diagnosis model and be beneficial to the generalization ability. [ABSTRACT FROM AUTHOR]

Introduction: Plant resources gathered from the wild are important sources of livelihood needs, especially for low-income populations living in remote areas, who rely on these plants for food, fuelwood, medicine and building materials. Yadong County is a valley at the border between the China, India and Bhutan in southern Tibet. Yadong is rich in biodiversity and culture, but ethnobotanical knowledge has not been systematically studied. This study aimed to document the ethnobotanical knowledge of Tibetans in Yadong County. Methods: Ethnobotanical data were documented through free listings, key informant interviews, and semi-structured interviews during fieldwork. The culture importance index (CI) and informant consensus factor index (FIC) were used as the quantitative indices. Results: In total, 163 informants (46 women and 117 men). A total of 3,031 use reports and 121 plant species belonging to 52 families and 91 genera were included. These use reports were then classified into 20 categories belonging to 9 major categories. The utilisation category that containing the most plant species was food, followed by economic, medicine, animal feed, social uses, other uses, environmental uses, materials and fuels. Among the economic plants, 32 medicinal plants are traditionally used in the local region. Plants with high CI included Fritillaria cirrhosa, Neopicrorhiza scrophulariiflora, Betula utilis, Rheum nobile, and Urtica hyperborean. Conclusion: This research demonstrates the diversity of the types and functions of Yadong Tibetan traditional plant knowledge. Knowledge of edible and medicinal plants in this area is prominent, reflecting the ability to cope with the lack of fruits and vegetables and basic family medical care. There were exchanges between the traditional plant culture in the study area and its surroundings. With socioeconomic development, the commercial value of medicinal plants has increased, and locals are also seeking ways to adoptsustainable development to cope with the excessive consumption of plant resources. [ABSTRACT FROM AUTHOR]

Background: The wooden bowl is an important symbol of the Tibetan cultures, yet, in China, little has been documented regarding the raw materials used to make these items as well as their cultural significance in Tibet. This study explores the ethnobotanical uses of plants used to make wooden bowls to understand their sustainability, cultural significance, and current status of related traditional knowledge in Gyirong Town, which is one of the most famous places for wooden bowl making. Materials and methods: Between 2019 and 2021, key informant interviews, semi-structured interviews, and participatory observations were used to conduct ethnobotanical field surveys in Gyirong Valley. The field work was performed with the assistance of local guides. In this study, we utilized a use-report (UR) to reflect the number of mentions of a species by locals. Results: Our results show that 16 different plants are used during the wooden bowl making process, of which nine are used as raw materials, three for dyeing, and four for varnishing. Although communities rely heavily on these plants, good management and collection methods were observed. We also documented the use of Fallopia denticulata as a red dye and four species of Impatiens as wood varnishes for the first time. Conclusion: The wooden bowl craftsmen and their housewives have a wealth of traditional knowledge of using plants to make wooden bowls in Gyirong Town. And the wooden bowls are now also offering benefits to the locals as well. The government and local people are committed to the protection and development of traditional knowledge related to wooden bowls, and this knowledge maintains a healthy degree of vitality. This research can provide insights into the vitality of traditional handicrafts that are facing challenges and promote their protection. [ABSTRACT FROM AUTHOR]

A steady flow with a high flow rate, oscillating flow, and audible sound waves can enhance the heat transfer performance in air-to-air heat exchangers, while the comparison of influence mechanisms and degrees of different methods is ignored. This study investigates flow instability and heat transfer characteristics in an air-to-air heat exchanger under steady flow, oscillating flow and sound waves. The results show that steady flow and oscillating flow with different amplitudes have little effect on the distribution characteristics of velocity and vortices. However, the vortices disappear and generate periodically under 140 dB. Moreover, oscillating flow and sound waves exert distinct influences on flow instability. The cold side experiences the highest increase in turbulence kinetic energy when subjected to high-amplitude oscillating flow, while the greatest increase on the hot side occurs under high-amplitude sound waves, and the influence of steady flow on turbulence kinetic energy is relatively low. Additionally, the steady flow enhances the heat transfer performance by increasing flow rate, while the oscillating flow and sound waves promote the heat transfer between the fluid and surface. Under the effect of steady flow, oscillating flow, and sound waves, the values of heat flux are 1.22, 1.24, and 1.31 times that of the initial condition with the amplitude increasing to 0.683 m/s (140 dB). The results demonstrate that with the increase in amplitude acting on the inlet, the sound waves have the greatest impact on heat transfer performance, followed by oscillating flow, and the effect of steady flow is relatively slight. The research can provide guidelines for the development of heat transfer enhancement in air-to-air heat exchangers. • Effects of steady, oscillating flow, and sound waves on heat transfer are compared. • Oscillating flow and sound waves exert the distinct effects on flow instability. • Sound waves with high amplitude alter the evolution of vortex structure. • Increase in flow instability contributes more to heat transfer than that in velocity. • Sound waves with high amplitude enhance the air heat transfer significantly. [ABSTRACT FROM AUTHOR]

Huanglongbing (HLB) is a destructive disease of citrus primarily transmitted by the Asian citrus psyllid (ACP). Biocontrol of ACP is an environmentally sustainable alternative to chemicals. However, the risk of parasitoid rational application in ACP biocontrol has never been evaluated. Here we show, the dominant parasitoid of ACP, Tamarixia radiata, can acquire the HLB pathogen Candidatus Liberibacter asiaticus (CLas) and transmit it horizontally when probing ACP nymphs. If these ACP nymphs survive the probing, develop to adults and move to healthy plants, CLas can be transmitted to citrus leaves during feeding. We illustrate the formerly unrecognized risk that a parasitoid can potentially serve as a phoretic vector of the pathogen transmitted by its host, thus potentially diminishing some of the benefits it confers via biocontrol. Our findings present a significant caution to the strategy of using parasitoids in orchards with different infection status of insect-vectored pathogens. Guo et al. demonstrate the possibility of a parasitoid to contract and transmit a bacterial pathogen via its insect host to the citrus plant it is used to protect. This reduces the efficacy of the biological control agent to protect the plant from ill effects. [ABSTRACT FROM AUTHOR]

• Chlamydomonas reinhardtii serves as a model organism for photosynthesis research. • C. reinhardtii cia5 mutant lacks a functional carbon-concentrating mechanism. • Metabolic profiles of cia5 mutant were changed as compared to a wild type strain. • The cia5 mutant produced substantial amounts of glycolate at the autotrophic phase. • This metabolomic approach is a tool for understanding the photosynthetic mechanisms. The green alga Chlamydomonas reinhardtii serves as a model organism for plant and photosynthesis research due to many commonalities in metabolism and to the fast growth rate of C. reinhardtii which accelerates experimental turnaround time. In addition, C. reinhardtii is a focus of research efforts in metabolic engineering and synthetic biology for the potential production of biofuels and value-added chemicals. Here, we report that the C. reinhardtii cia5 mutant, which lacks a functional carbon-concentrating mechanism (CCM), can produce substantial amounts of glycolate, a high-value cosmetic ingredient, when the mutant is cultured under ambient air conditions. In order to reveal the metabolic basis of glycolate accumulation by the cia5 mutant, we investigated the metabolomes of the cia5 mutant and a wild type strain CC-125 (WT) through the global metabolic profiling of intracellular and extracellular fractions using gas chromatography and mass spectrometry. We observed the intracellular and extracellular metabolic profiles of the WT and the cia5 mutant were similar during the mixotrophic phase at 30 h. However, when the cells entered the photoautotrophic phase (i.e., 96 h and 120 h), both the intracellular and extracellular metabolic profiles of cia5 mutant differed significantly when compared to WT. In the cia5 mutant strain, a group of photorespiration pathway intermediates including glycolate, glyoxylate, glycine, and serine accumulated to significantly higher levels compared to WT. In the photorespiration pathway, glycolate is metabolized to glyoxylate and glycine leading to NH 3 and CO 2 generation during the mitochondrial conversion of glycine to serine. This result provides further evidence that the CIA5 mutation increased the photorespiration rate. Because the cia5 mutant lacks a CCM, and C. reinhardtii might harbor an inefficient or incomplete photorespiration pathway, glycolate may accumulate when the CCM is not functional. We envision that investigating photorespiration controls in C. reinhardtii provides tools for producers to use the cia5 mutant to produce glycolate as well as platform to engineer alternative pathways for glycolate metabolism. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to compare the percutaneous oblique osteotomy (POO) and the open chevron osteotomy technique for correction of hallux valgus deformity at a 2‐year follow‐up. Methods: This is a retrospective study of consecutive patients undergoing operative correction of hallux valgus using one of two techniques (POO vs open chevron osteotomy) from 2014 to 2018. Forty eight feet (41 patients) that underwent the POO was compared with 64 feet (58 patients) that underwent open chevron osteotomy. The hallux valgus angle (HVA), intermetatarsal angle (IMA) and American Orthopedic Foot & Ankle Society Hallux Metatarsophalangeal‐Interphalangeal scores (AOFAS‐HMI) were assessed preoperatively and postoperatively at the 1, 2‐year follow‐up. The Manchester–Oxford Foot Questionnaire (MOXFQ) were assessed preoperatively and postoperatively at the 2‐year follow‐up. The VAS score was collected preoperatively and on 2 weeks,1 year and 2‐year follow‐up. Results: Both groups achieved significant correction of the hallux deformity. The HVA in the POO group during the follow‐up period were 12.5 ± 2.22 and 17.9 ± 9.31, respectively, and in the open chevron group were 14.1 ± 6.78 and 14.8 ± 7.83, respectively. The IMA in the POO group during the follow‐up period were 7.61 ± 1.63 and 6.94 ± 1.53, respectively, and in the open chevron group were 6.89 ± 3.06 and 6.97 ± 2.95, respectively. Postoperative MOXFQ scores in all domains were significantly improved in both groups, however there was no significant difference in the improvement of any domain between POO and open groups at a 2‐year follow‐up. The AOFAS HMI scores in the POO group during the follow‐up period were 86.5 ± 10.7 and 85.2 ± 13.8, respectively, and in the open chevron group were 88.2 ± 10.8 and 79.5 ± 23.7, respectively. The VAS scores in the POO group during the follow‐up period were 2.00 ± 0.98, 2.00 ± 0.99 and 1.55 ± 1.11, respectively, and in the open chevron group were 5.51 ± 1.45, 2.56 ± 2.88 and 2.56 ± 2.88 respectively. The 1‐year and 2‐year follow‐up outcomes between POO and open groups showed no significant difference regarding AOFAS HMI scores and VAS scores, however the POO group showed statistically significant improvement of VAS scores in the postoperative 2 weeks (P < 0.001). There was no statistical significance between the POO and open group in terms of complications rates (8.3% vs 12.5%, P = 0.480). Conclusion: The POO technique is reliable and shows a comparable outcome to the open chevron osteotomy. However, the POO technique shows significantly less pain in the first 2 weeks after surgery. [ABSTRACT FROM AUTHOR]

Emergency communication network (ECN) is the important infrastructure to acquire the real-time information after disaster, which is essential for rescue task. However, the existed routing protocols seldom consider the uneven distribution of rescue area so that cannot satisfy the ECN's requirement and the quality of rescue needs improvement. In this paper, we avoided the traditional linear propulsion from rim to core and proposed a novel four-quadrant mobility model (FQMM), which makes rescuers arrive the most intensity core area first, which can improve the rescue quality. Then, a FQMM-based protocol (FQMMBP) for ECN is designed, which aims to improve the performance of ECN in terms of package delivery rate (PDR) and end-to-end delay. Finally, we set up a virtual earthquake scenario to simulate our proposed protocol in NS2. Results show that the proposed protocol outperforms to the three compared routing protocols, i.e., AODV, DSDV and DSR. The average FDR is improved by 16.31%, and the average reduction of delay is 64.45%, which shows our proposed scheme's advantages in quality of rescue. [ABSTRACT FROM AUTHOR]

Purpose: High‐resolution magnetic resonance imaging (HR‐MRI) has high spatial resolution and can simultaneously perform wall and lumen imaging. Dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) can evaluate the integrity of the blood–brain barrier. In this paper, the result of 3.0T HR‐MRI and 3.0T DCE‐MRI has been evaluated to explore the application value of unilateral middle cerebral artery inflammatory stenosis and changes in vascular permeability parameters of stroke events. Methods: Thirty‐six cases of neurological suspicion of central nervous system vasculitis of our hospital were selected from 20 January 2018 to 1 January 2019, who were diagnosed as unilateral middle cerebral artery M1 stenosis/occlusion by 3D TOF MRA. 3.0T HR‐MRI and 3.0T DCE‐MRI has been applied. Results: Among the 36 patients who met the inclusion criteria, 23 patients with central nervous system vasculitis were diagnosed. The 23 patients with HR‐MRI showed diffuse thickening and enhanced stenosis. The Ktrans value of 10/23 patients with acute–subacute cerebral infarction and 3/23 patients in chronic phase were significantly higher than that of the mirror side, and the Ktrans value of these patients remeasured in the same region of interest is lower than before after 6 months treatment. The Ktrans value in the target area of 10 patients without cerebrovascular events was not statistically significant compared with the mirror side. The Ktrans value of patients with acute–subacute cerebral infarction was significantly higher than that without cerebrovascular events (0.098 ± 0.038 vs. 0.007 ± 0.001, p =.000), and there was no significant difference between Ktrans in the chronic infarction group and the other two groups (0.098 ± 0.038 vs. 0.044 ± 0.012, p =.058; 0.044 ± 0.012 vs. 0.007 ± 0.001, p =.057). Conclusion: HR‐MRI is an accurate direct imaging method and has a high value for the etiological diagnosis of central nervous system vasculitis. DCE‐MRI could be an effective way to evaluate and monitor blood–brain barrier to prevent clinical ischemic stroke. [ABSTRACT FROM AUTHOR]

Hereditary hearing loss is characterized by remarkable phenotypic heterogeneity. Patients with the same pathogenic mutations may exhibit various hearing loss phenotypes. In the Chinese population, the c.235delC mutation is the most common pathogenic mutation of GJB2 and is closely related to hereditary recessive hearing loss. Here, we investigated the hearing phenotypes of patients with hearing loss associated with the homozygous c.235delC mutation, paying special attention to asymmetric interaural hearing loss. A total of 244 patients with the GJB2 c.235delC homozygous mutation encountered from 2007 to 2015 were enrolled. The severity of hearing loss was scaled with the American Speech-Language-Hearing Association (ASHA). Auditory phenotypes were analyzed, and three types of interaural asymmetry were defined based on audiograms: Type A (asymmetry of hearing loss severity), Type B (asymmetry of audiogram shape), and Type C (Type A plus Type B). Of the 488 ears (244 cases) examined, 71.93% (351) presented with profound hearing loss, 14.34% (70) with severe hearing loss, and 9.43% (46) with moderate to severe hearing loss. The most common audiogram shapes were descending (31.15%) and flat (24.18%). A total of 156 (63.93%) of the 244 patients exhibited asymmetric interaural hearing loss in terms of severity and/or audiogram shape. Type A was evident in 14 of these cases, Type B in 106, and Type C in 36. In addition, 211 of 312 ears (67.63%) in the interaural hearing asymmetry group showed profound hearing loss, and 59 (18.91%) exhibited severe hearing loss, with the most common audiogram shapes being flat (27.88%) and descending (22.12%). By contrast, in the interaural hearing symmetry group, profound hearing loss was observed in 140 ears (79.55%), and the most common audiograms were descending (46.59%) and residual (21.59%). Hearing loss associated with the GJB2 c.235delC homozygous mutation shows diverse phenotypes, and a considerable proportion of patients show bilateral hearing loss asymmetry. [ABSTRACT FROM AUTHOR]

The aim of this article is to improve vehicular traffic in terms of both travel time and load balance. To achieve this goal, we propose an optimization model that minimizes the sum of the total travel time in the road network and a time representation of the traffic imbalance effects in the network. This paper presents an analytic formulation of the optimization problem, and an algorithm, Dynamic Interior Point Method (DIPM), that solves this optimization through driver rerouting. Unlike user-optimum traffic optimizations, DIPM leads to better fairness for drivers and works well in case of congestion. Unlike other system-wide traffic optimizations, DIPM considers the effects of the driver behavior on traffic load. Together, these features allow our system to work well in a potential real-world deployment. DIPM benefits from a central server that computes driver routes, which is reachable via cellular networks or vehicular ad hoc networks. Theoretical analysis and simulation results demonstrate that DIPM is fast and can work in real-time. The results of extensive simulations with realistic urban maps and traffic scenarios show that DIPM outperforms other dynamic rerouting algorithms in terms of travel time. DIPM also improves fairness when compared with a user-optimum approach. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is caused by heavy alcohol consumption over a long period. Acetaldehyde-mediated toxicity, oxidative stress, and imbalance of lipid metabolism are generally considered involved in the initiation of ALD. There is an increasing requirement for alternative and natural medicine to treat ALD. Recently, aldose reductase (AR) has been reported to be involved in the development of ALD by affecting inflammatory cytokines, oxidative stress, and lipid metabolism. Here, we review the effect of plant-derived AR inhibitors on ALD in rodents. And we conclude that AR inhibitors of plant origin may enhance antioxidant capacity, inhibit lipid peroxidation and inflammatory cytokines expression, and activate AMP-activated protein kinase thereby subsequently suppressing alcohol-induced lipid synthesis in liver to achieve ALD protection. This review reveals that natural AR inhibitor may be potential therapeutic agent for ALD. [ABSTRACT FROM AUTHOR]

Abstract The unique properties of nanopores depend largely on the functionalization of the pore surface, which has always been a great challenge. In this study, a facile method for functionalizing the surface of a glass nanopipette to establish thiol-based linkage without involving Au film coating was successfully developed by utilizing the thiol–maleimide click reaction which works rapidly and with high specificity. Cysteine was employed as a model molecule to functionalize the nanopipette, resulting in pH-modulated ion-current rectification behavior which showed a good reproducible response to pH. Due to the widespread existence of thiol groups in nature, this nanopipette functionalization method has the potential and versatility to be used in a wide range of applications, including mimicking biological ion channels and fabricating sensing devices. Graphical abstract Unlabelled Image Highlights • A glass nanopipette was functionalised via a thiol–maleimide click reaction without Au film coating. • pH-modulated ion-current-rectification behavior of a cysteine-functionalized glass nanopipette was achieved. • The nanopipette ion-current rectification direction was modulated by pH. [ABSTRACT FROM AUTHOR]

In this work, Qiqunahu (QQH) coal, cotton stalk, cellulose and lignin extracted from cotton stalk were selected as raw materials to study the effects of the co-pyrolysis of coal and cotton stalk. Online thermogravimetric mass spectrometry (TG-MS) was used to analyse mass loss and gas release characteristics during co-pyrolysis. The results reveal that the mixture of cotton stalk and coal can significantly enhance the reactivity of the blends and promote the formation of effective gas. The cellulose in the cotton stalk promotes the generation of H2 and CO2 during the co-pyrolysis of coal and cotton stalks. Lignin promotes the production of CH4 and CO2. Cellulose and lignin show an inhibitory effect on the precipitation of small molecular weight hydrocarbon gases during co-pyrolysis. This study provides a better understanding for the co-pyrolysis of biomass and coal. [ABSTRACT FROM AUTHOR]

Real-time traffic information can efficiently reflect the traffic condition in urban scenarios. However, how to design an efficient real-time information sharing mechanism to achieve the real-time traveling time estimation (TTE) and dynamic path planning still remains a challenging problem. In this paper, we first propose an effective real-time traffic information sharing mechanism based on a distributed transportation system with road-side units, which has lower computing complexity and less redundancy. Then, considering current traffic information, we present a method to estimate the traveling time from a source to a destination in the road network, called TTE, which acts as a metric for path planning. Furthermore, we propose a real-time path planning algorithm based on TTE comparison via information collection to avoid traffic congestion. We verify the complexity and redundancy of our proposed real-time information sharing mechanism via C $^{\#}$. Moreover, we perform extensive simulations in VanetMobiSim to evaluate the proposed real-time path planning algorithm, which uses the real-world traffic scenario and urban map of Songjiang district in Shanghai. The results show that our proposed algorithm outperforms the static path planning algorithm. [ABSTRACT FROM AUTHOR]

ABSTRACT The probiotic yeast Saccharomyces boulardii has been extensively studied for the prevention and treatment of diarrheal diseases, and it is now commercially available in some countries. S. boulardii displays notable phenotypic characteristics, such as a high optimal growth temperature, high tolerance against acidic conditions, and the inability to form ascospores, which differentiate S. boulardii from Saccharomyces cerevisiae. The majority of prior studies stated that S. boulardii exhibits sluggish or halted galactose utilization. Nonetheless, the molecular mechanisms underlying inefficient galactose uptake have yet to be elucidated. When the galactose utilization of a widely used S. boulardii strain, ATCC MYA-796, was examined under various culture conditions, the S. boulardii strain could consume galactose, but at a much lower rate than that of S. cerevisiae. While all GAL genes were present in the S. boulardii genome, according to analysis of genomic sequencing data in a previous study, a point mutation (G1278A) in PGM2, which codes for phosphoglucomutase, was identified in the genome of the S. boulardii strain. As the point mutation resulted in the truncation of the Pgm2 protein, which is known to play a pivotal role in galactose utilization, we hypothesized that the truncated Pgm2 might be associated with inefficient galactose metabolism. Indeed, complementation of S. cerevisiae PGM2 in S. boulardii restored galactose utilization. After reverting the point mutation to a full-length PGM2 in S. boulardii by Cas9-based genome editing, the growth rates of wild-type (with a truncated PGM2 gene) and mutant (with a full-length PGM2) strains with glucose or galactose as the carbon source were examined. As expected, the mutant (with a full-length PGM2) was able to ferment galactose faster than the wild-type strain. Interestingly, the mutant showed a lower growth rate than that of the wild-type strain on glucose at 37°C. Also, the wild-type strain was enriched in the mixed culture of wild-type and mutant strains on glucose at 37°C, suggesting that the truncated PGM2 might offer better growth on glucose at a higher temperature in return for inefficient galactose utilization. Our results suggest that the point mutation in PGM2 might be involved in multiple phenotypes with different effects. IMPORTANCE Saccharomyces boulardii is a probiotic yeast strain capable of preventing and treating diarrheal diseases. However, the genetics and metabolism of this yeast are largely unexplored. In particular, molecular mechanisms underlying the inefficient galactose metabolism of S. boulardii remain unknown. Our study reports that a point mutation in PGM2, which codes for phosphoglucomutase, is responsible for inferior galactose utilization by S. boulardii. After correction of the mutated PGM2 via genome editing, the resulting strain was able to use galactose faster than a parental strain. While the PGM2 mutation made the yeast use galactose slowly, investigation of the genomic sequencing data of other S. boulardii strains revealed that the PGM2 mutation is evolutionarily conserved. Interestingly, the PGM2 mutation was beneficial for growth at a higher temperature on glucose. We speculate that the PGM2 mutation was enriched due to selection of S. boulardii in the natural habitat (sugar-rich fruits in tropical areas). [ABSTRACT FROM AUTHOR]

Alcoholic liver injury results in morbidity and mortality worldwide, but there are currently no effective and safe therapeutics. Previously we demonstrated that aldose reductase (AR) inhibitor ameliorated alcoholic hepatic steatosis. To clarify the mechanism whereby AR inhibitor improves alcoholic hepatic steatosis, herein we investigated the effect of AR inhibitor on hepatic metabolism in mice fed a Lieber-DeCarli liquid diet with 5% ethanol. Nontargeted metabolomics showed carbohydrates and lipids were characteristic categories in ethanol diet-fed mice with or without AR inhibitor treatment, whereas AR inhibitor mainly affected carbohydrates and peptides. Ethanol-induced galactose metabolism and fatty acid biosynthesis are important for the induction of hepatic steatosis, while AR inhibitor impaired galactose metabolism without perturbing fatty acid biosynthesis. In parallel with successful treatment of steatosis, AR inhibitor suppressed ethanol-activated galactose metabolism and saturated fatty acid biosynthesis. Sorbitol in galactose metabolism and stearic acid in saturated fatty acid biosynthesis were potential biomarkers responsible for ethanol or ethanol plus AR inhibitor treatment. In vitro analysis confirmed that exogenous addition of sorbitol augmented ethanol-induced steatosis and stearic acid. These findings not only reveal metabolic patterns associated with disease and treatment, but also shed light on functional biomarkers contribute to AR inhibition therapy. [ABSTRACT FROM AUTHOR]

• Bilateral audible sound waves are incident to enhance the air heat transfer. • Change in SPL and frequency has different effects on the flow instability. • Relationship between local heat flux and flow instability are explored. • Increase in SPL and decrease in frequency can enhance heat transfer. • Sound power efficiency increases with the decrease in sound frequency. To enhance the air heat transfer performance, this study applied the bilateral audible sound waves to an air-to-air heat exchanger. The effect of the frequency and intensity of sound waves on heat transfer performance was investigated from the viewpoint of flow instability and heat flux, and the sound power efficiency was also explored to reveal the efficiency of sound waves on the heat transfer performance. The results showed that the flow instability intensified with the increase in sound pressure level (SPL) and decrease in frequency, which was reflected by the distribution of turbulence kinetic energy. The change in sound waves has different effects on the turbulence kinetic energy at different locations, and the directivity distribution characteristics of the turbulence kinetic energy inside and outside the heat tube caused similar directivity distribution characteristics of the heat flux, in which the maximum value of the heat flux was located perpendicular to the flow direction. Additionally, the heat flux at different locations increased with an increase in SPL and a decrease in frequency. The heat transfer performance was relatively superior when the SPL was higher than 120 dB and the frequency was lower than 100 Hz, and a decrease in frequency could increase the sound power efficiency. This study can guide the application of sound waves in the heat transfer enhancement of air-to-air heat exchange systems. [ABSTRACT FROM AUTHOR]

Accumulation of reduced byproducts such as glycerol and xylitol during xylose fermentation by engineered Saccharomyces cerevisiae hampers the economic production of biofuels and chemicals from cellulosic hydrolysates. In particular, engineered S. cerevisiae expressing NADPH-linked xylose reductase (XR) and NAD-linked xylitol dehydrogenase (XDH) produces substantial amounts of the reduced byproducts under anaerobic conditions due to the cofactor difference of XR and XDH. While the additional expression of a water-forming NADH oxidase (NoxE) from Lactococcus lactis in engineered S. cerevisiae with the XR/XDH pathway led to reduced glycerol and xylitol production and increased ethanol yields from xylose, volumetric ethanol productivities by the engineered yeast decreased because of growth defects from the overexpression of noxE. In this study, we introduced noxE into an engineered yeast strain (SR8) exhibiting near-optimal xylose fermentation capacity. To overcome the growth defect caused by the overexpression of noxE, we used a high cell density inoculum for xylose fermentation by the SR8 expressing noxE. The resulting strain, SR8N, not only showed a higher ethanol yield and lower byproduct yields, but also exhibited a high ethanol productivity during xylose fermentation. As noxE overexpression elicits a negligible growth defect on glucose conditions, the beneficial effects of noxE overexpression were substantial when a mixture of glucose and xylose was used. Consumption of glucose led to rapid cell growth and therefore enhanced the subsequent xylose fermentation. As a result, the SR8N strain produced more ethanol and fewer byproducts from a mixture of glucose and xylose than the parental SR8 strain without noxE overexpression. Our results suggest that the growth defects from noxE overexpression can be overcome in the case of fermenting lignocellulose-derived sugars such as glucose and xylose. [ABSTRACT FROM AUTHOR]

Objective To investigate the characteristics and the results of realignment surgery for the treatment of malunited ankle fracture. Methods Thirty-three patients with malunited fractures of the ankle who underwent reconstructive surgery at our hospital from January 2010 to January 2014 were reviewed. The tibial anterior surface angle ( TAS), the tibiotalar tilt angle ( TTA), the malleolar angle ( MA), and the tibial lateral surface angle ( TLS) were measured. Clinical assessment was performed with use of the American Orthopaedic Foot and Ankle Society ( AOFAS) scale and visual analogue scale ( VAS) scores, and the osteoarthritis stage was determined radiographically with the modified Takakura classification system. The Wilcoxon matched-pairs test was used to analyze the difference between the preoperative and the postoperative data. Results The mean follow-up was 36 months (range, 20-60 months). The mean age at the time of realignment surgery was 37.1 years (range, 18-62 years). Compared with preoperation, the TAS at the last follow-up showed a significant increase (88.50° ± 4.47° vs. 90.80° ± 3.49°, P = 0.0035); similar results were observed in TTA (1.62° ± 1.66° vs. 0.83° ± 0.90°, P < 0.01) and MA (82.30° ± 8.03° vs. 78.70° ± 4.76°, P = 0.005). At the last follow-up, the mean AOFAS score was significantly increased compared with the score at preoperation (44.5 ± 13.7 vs. 78.0 ± 8.9, P < 0.01). Significant differences in VAS scores were found at the last follow-up (6.76 ± 1.03 vs. 2.03 ± 1.21, P < 0.01). There was no significant difference in the Takakura grade between the preoperation and the last follow-up. One patient had increased talar tilt postsurgery; the postoperative talar tilt angle of this patient was 20°. One patient had progressive ankle osteoarthritis, and was treated by ankle joint distraction. Conclusions Realignment surgery for a malunited ankle fracture can reduce pain, improve function, and delay ankle arthrodesis or total ankle replacement. Postoperative large talar tilt and advanced stages of ankle arthritis are the risk factors for the surgery. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease represents a serious threat to human health. In terms of safety and acceptability, thymol is widely used in or on foodstuffs to generate odour and taste. The present study aimed to investigate the therapeutic effect and mechanism of thymol against ethanol-induced injury in liver cells. Here we found that thymol is an effective agent for reducing ethanol-induced reactive oxygen species production in mouse liver cells. Thymol improves ethanol-induced lipid accumulation, and this corresponded to altered DGAT2 mRNA expression levels. Metabolomics data analysis showed that thymol alleviated ethanol-induced changes in the levels of thirty-four metabolites including nicotinic acid and l -arginine. By utilizing pathway enrichment analysis, altered metabolites in cells treated with ethanol and ethanol plus thymol were enriched in fourteen pathways including metabolic pathways and arginine and proline metabolism. We further confirmed the alleviation of overdose nitric oxide production in cells treated with ethanol plus thymol compared with that in ethanol-treated cells. It was interesting that up-regulated LC3-II/LC3-I ratio together with higher SQSTM1 protein abundance in ethanol-treated cells were attenuated by treatment with ethanol plus thymol. Thymol ameliorated ethanol-induced reduction of HSPA8 protein abundance. In addition, chloroquine-treated cells exhibited lower HSPA8 protein abundance compared with cells simulated with ethanol plus thymol. These data reveal that improving effect of thymol on ethanol-induced metabolic alteration is related to autophagic flux restoration. Our findings indicate that thymol is an attractive option for treating ethanol-induced liver damage. • Thymol ameliorates ethanol-induced lipid accumulation and oxidative stress. • Thymol prevents ethanol-induced fluctuation of arginine and proline metabolism. • Thymol suppresses ethanol-induced elevation of nitric oxide production. • Thymol attenuates ethanol-mediated up-regulation of LC3-II/LC3-I ratio and SQSTM1 protein abundance. • Thymol alleviates ethanol-induced reduction of HSPA8 protein abundance. [ABSTRACT FROM AUTHOR]

In this studies, the effect of reaction time, pH, ionic strength and initial U(VI) concentration on the competitive adsorption of U(VI) and Sr(II) onto graphene oxide (GO) was investigated by batch techniques. Adsorption tests showed that the GO presented higher adsorption capacity for U(VI) than Sr(II) in single and binary-solute systems, revealing that electrostatic interaction was the main driving force responsible for the competitive adsorption of U(VI) and Sr(II) on GO. The adsorption kinetics and isotherms of U(VI)/Sr(II) on GO at single- and multi-solute systems can be simulated by pseudo-second-order kinetic model and Langmuir model, respectively. No effect of ionic strength on competitive adsorption of U(VI) and Sr(II) onto GO indicated the inner-sphere surface complexation predominately. The competitive adsorption of U(VI) and Sr(II) on GO can be satisfactorily fitted with two inner-sphere surface complexes using surface complexation modeling by extended triply layer modeling when two surface acidity constants are considered. [ABSTRACT FROM AUTHOR]

The effect of Paecilomyces cateniannulatus ( P. cateniannulatus ) on Th(IV) adsorption by sepiolite were investigated by batch techniques. The batch adsorption showed that the adsorption of Th(IV) on sepiolite and sepiolite + P. catenlannulatus significantly increased with increasing of pH from 3.0 to 6.0, then remained the high-level adsorption. P. cateniannulatus significantly facilitated the adsorption of Th(IV) on sepiolite at pH 2.0–5.0, whereas inhibited adsorption was observed at pH > 6.0. The adsorption of Th(IV) on sepiolite + P. catenlannulatus was independent of ionic strength at pH from 3.0 to 9.0. The adsorption kinetics of Th(IV) on sepiolite and sepiolite + P. catenlannulatus can be satisfactorily simulated by pseudo-second-order kinetic model. The maximum adsorption capacities of sepiolite and sepiolite + P. catenlannulatus for Th(IV) calculated Langmuir model at pH 3.0 and 293 K were 50.76 and 57.80 mg/g, respectively. Based on surface complexation modeling, the adsorption mechanism of Th(IV) on sepiocite + P. catenlannulatus was cation exchange/outer-sphere surface complexation at low pH, whereas inner-sphere surface complexation dominated the Th(IV) adsorption at high pH conditions. The findings presented in this study are of great importance towards understanding of fate and transport of heavy metals under natural aquatic environments. [ABSTRACT FROM AUTHOR]

Lactose is an inevitable byproduct of the dairy industry. In addition to cheese manufacturing, the growing Greek yogurt industry generates excess acid whey, which contains lactose. Therefore, rapid and efficient conversion of lactose to fuels and chemicals would be useful for recycling the otherwise harmful acid whey. Saccharomyces cerevisiae , a popular metabolic engineering host, cannot natively utilize lactose. However, we discovered that an engineered S. cerevisiae strain (EJ2) capable of fermenting cellobiose can also ferment lactose. This finding suggests that a cellobiose transporter (CDT-1) can transport lactose and a β-glucosidase (GH1-1) can hydrolyze lactose by acting as a β-galactosidase. While the lactose fermentation by the EJ2 strain was much slower than the cellobiose fermentation, a faster lactose-fermenting strain (EJ2e8) was obtained through serial subcultures on lactose. The EJ2e8 strain fermented lactose with a consumption rate of 2.16 g/L h. The improved lactose fermentation by the EJ2e8 strain was due to the increased copy number of cdt-1 and gh1-1 genes. Looking ahead, the EJ2e8 strain could be exploited for the production of other non-ethanol fuels and chemicals from lactose through further metabolic engineering. [ABSTRACT FROM AUTHOR]

The aim of this work is to prepare acid-based geopolymer using metakaolin and disused phosphoric acid-based polishing liquid of aluminum alloy, which can be used to substitute pure phosphoric acid activator in the fabrication of acid-based geopolymer. It not only presents a good solidified method of hazardous components in the disused polishing liquid, but also provides an anti-corrosion and heat-resistance geopolymer material. The mechanical performance, phase structure and microstructure of this disused polishing liquid geopolymer are characterized in this study, and the results indicate that the disused polishing liquid had a higher reactive rate to metakaolin than pure phosphoric acid. Through the characterization of the compressive strength, electrical conductance, high temperature resistance and acid or alkali corrosion resistance of the geopolymer, it can be concluded that the disused polishing liquid acid based geopolymer has a higher reactivity than pure phosphoric acid when it developed a reaction with metakaolin. [ABSTRACT FROM AUTHOR]

Layered discretization is an efficient way of realizing thermal cloaks. The aim of this paper is to investigate the effect of nonlinear coordinate transformation on the thermal cloaking performance of multilayered cylindrical thermal cloak. Two indexes are defined to quantify the thermal cloaking performance. Nonlinear coordinate transformations with different forms are established to design the multilayered structures and the thermal cloaking performances are analyzed by full-wave simulations. The results show that the thermal cloaking performances of multilayered structures are directly influenced by the form of coordinate transformation which determines the distributions of heat flows in the cloak region. Through the active changing of the form of coordinate transformation, the thermal cloaking performance of multilayered structure can be controlled and optimized. In addition, a three-piecewise linear coordinate transformation is designed to concentrate the heat flux into the middle region of the cloak and the corresponding multilayered structure is demonstrated to have near-perfect thermal cloaking performance. These results may provide a beneficial guidance to achieve performance improvements for multilayered structures of thermal cloaks. [ABSTRACT FROM AUTHOR]

In this note, we announce some new results on quantitative countable porosity of the branch set of a quasiregular mapping in very general metric spaces. As applications, we solve a recent conjecture of Fässler et al., an open problem of Heinonen–Rickman, and an open question of Heinonen–Semmes. [ABSTRACT FROM AUTHOR]

Industrial polyploid yeast strains harbor numerous beneficial traits but suffer from a lack of available auxotrophic markers for genetic manipulation. Here we demonstrated a quick and efficient strategy to generate auxotrophic markers in industrial polyploid yeast strains with the RNA-guided Cas9 nuclease. We successfully constructed a quadruple auxotrophic mutant of a popular industrial polyploid yeast strain, Saccharomyces cerevisiae ATCC 4124, with ura3, trp1, leu2, and his3 auxotrophies through RNA-guided Cas9 nuclease. Even though multiple alleles of auxotrophic marker genes had to be disrupted simultaneously, we observed knockouts in up to 60% of the positive colonies after targeted gene disruption. In addition, growth-based spotting assays and fermentation experiments showed that the auxotrophic mutants inherited the beneficial traits of the parental strain, such as tolerance of major fermentation inhibitors and high temperature. Moreover, the auxotrophic mutants could be transformed with plasmids containing selection marker genes. These results indicate that precise gene disruptions based on the RNA-guided Cas9 nuclease now enable metabolic engineering of polyploid S. cerevisiae strains that have been widely used in the wine, beer, and fermentation industries. [ABSTRACT FROM AUTHOR]

Sepsis is the major cause of death in the intensive care unit (ICU). Numerous biomarkers have been studied to identify the cause and severity of sepsis but these factors cannot differentiate between infectious and non-infectious inflammatory response. MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate the expression of genes by repressing translation or degrading mRNA. Importantly, miRNAs can be released outside cells and easily detectable in bodily fluids such as blood, sweat, urine and breast milk. Numerous studies have explored the idea of utilizing extracellular miRNAs as biomarkers for sepsis by profiling the dysregulation of miRNAs in blood samples of sepsis patients. So far, miR-223, miR-146a and miR-150 have been identified to have promising prognostic and diagnostic value to sepsis. In addition, various intracellular miRNAs have been implicated to play critical roles in regulating the TLR-NF-κB pathway, which is a well-known inflammatory signaling pathway involved in the process of sepsis. Here, we summarize the recent progress on the role of extracellular and intracellular miRNAs in sepsis. Specifically, we discuss the possible role of circulating miRNA biomarkers for the diagnosis of sepsis and how intracellular miRNAs regulate the inflammatory responses in sepsis. [ABSTRACT FROM AUTHOR]

This paper studies the existence and long time behavior of the solutions to the coupled Burgers-complex Ginzburg-Landau (Burgers-CGL) equations, which are derived from the nonlinear evolution of the coupled long-scale oscillatory and monotonic instabilities of a uniformly propagating combustion wave governed by a sequential chemical reaction, having two flame fronts corresponding to two reaction zones with a finite separation distance between them. This paper firstly shows the existence of the global solutions to these coupled equations via subtle transforms, delicate a priori estimates and a so-called continuity method, then prove the existence of the global attractor and establish the estimates of the upper bounds of Hausdorff and fractal dimensions for the attractor. [ABSTRACT FROM AUTHOR]

A 'two-incision' approach for en bloc resection of periacetabular tumors and prosthesis reconstruction is described. The first incision begins in the middle of the iliac crest, continues over the inguinal ligament, extends to the symphysis pubis and then turns down to ischial tuberosity. The muscles attached to the iliac crest are only separated from its internal side. All the attachments of the abductor muscles to the iliac crest are left intact. The second incision runs from the sacroiliac joint to the greater trochanter and is curved in shape, providing external exposure of the sciatic notch and ischial tuberosity. Communication between the two approaches is possible inside and outside under the abductor muscles or through the sciatic notch. En bloc resection of the tumor is performed by cutting the pubic symphysis and iliac as planned preoperatively. The iliac osteotomy is performed by using a Gigli saw that has been led through the sciatic notch and under the abductor muscles. This 'two-incision' approach not only provides enough exposure to perform en bloc resection of periacetabular tumors, but also protects the continuity of the abductor muscles between the pelvis and greater trochanter, thus preventing prosthesis dislocation. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae, long recognized as a mammalian pathogen, is an emerging concern with regard to fish. In this study, we used a mouse model and in vitro cell infection to evaluate the pathogenetic characteristics of S. agalactiae GD201008-001, isolated from tilapia in China. This bacterium was found to be highly virulent and capable of inducing brain damage by migrating into the brain by crossing the blood–brain barrier (BBB). The phagocytosis assays indicated that this bacterium could be internalized by murine macrophages and survive intracellularly for more than 24 h, inducing injury to macrophages. Further, selective capture of transcribed sequences (SCOTS) was used to investigate microbial gene expression associated with intracellular survival. This positive cDNA selection technique identified 60 distinct genes that could be characterized into 6 functional categories. More than 50% of the differentially expressed genes were involved in metabolic adaptation. Some genes have previously been described as associated with virulence in other bacteria, and four showed no significant similarities to any other previously described genes. This study constitutes the first step in further gene expression analyses that will lead to a better understanding of the molecular mechanisms used by S. agalactiae to survive in macrophages and to cross the BBB. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury‐induced spinal microglial proliferation plays a pivotal role in neuropathic pain. So far, key intracellular druggable molecules involved in this process are not identified. The nuclear factor of activated T‐cells (NFAT1) is a master regulator of immune cell proliferation. Whether and how NFAT1 modulates spinal microglial proliferation during neuropathic pain remain unknown. Here it is reported that NFAT1 is persistently upregulated in microglia after spinal nerve ligation (SNL), which is regulated by TET2‐mediated DNA demethylation. Global or microglia‐specific deletion of Nfat1 attenuates SNL‐induced pain and decreases excitatory synaptic transmission of lamina II neurons. Furthermore, deletion of Nfat1 decreases microglial proliferation and the expression of multiple microglia‐related genes, such as cytokines, transmembrane signaling receptors, and transcription factors. Particularly, SNL increases the binding of NFAT1 with the promoter of Itgam, Tnf, Il‐1b, and c‐Myc in the spinal cord. Microglia‐specific overexpression of c‐MYC induces pain hypersensitivity and microglial proliferation. Finally, inhibiting NFAT1 and c‐MYC by intrathecal injection of inhibitor or siRNA alleviates SNL‐induced neuropathic pain. Collectively, NFAT1 is a hub transcription factor that regulates microglial proliferation via c‐MYC and guides the expression of the activated microglia genome. Thus, NFAT1 may be an effective target for treating neuropathic pain. [ABSTRACT FROM AUTHOR]

Glycerol is a major by-product in bioethanol fermentation by the yeast Saccharomyces cerevisiae, and decreasing glycerol formation for increased ethanol yield has been a major research effort in the bioethanol field. A new strategy has been used in the present study for reduced glycerol formation and improved ethanol fermentation performance by finely modulating the expression of GPD1 in the KAM15 strain (fps1▵ pPGK1-GLT1 gpd2▵ ). The GPD1 promoter was serially truncated from the 3= end by 20 bp to result in a different expression strength of GPD1. The two engineered promoters carrying 60- and 80-bp truncations exhibited reduced promoter strength but unaffected osmostress response. These two promoters were integrated into the KAM15 strain, generating strains LE34U and LE35U, respectively. The transcription levels of LE34U and LE35U were 37.77 to 45.12% and 21.34 to 24.15% of that of KAM15U, respectively, depending on osmotic stress imposed by various glucose concentrations. In very high gravity (VHG) fermentation, the levels of glycerol for LE34U and LE35U were reduced by 15.81% and 30.66%, respectively, compared to KAM15U. The yield and final concentration of ethanol for LE35U were 3.46% and 0.33% higher, respectively, than those of KAM15U. However, fermentation rate and ethanol productivity for LE35U were reduced. On the other hand, the ethanol yield and final concentration for LE34U were enhanced by 2.28% and 2.32%, respectively, compared to those of KAM15U. In addition, a 2.31% increase in ethanol productivity was observed for LE34U compared to KAM15U. These results verified the feasibility of our strategy for yeast strain development. [ABSTRACT FROM AUTHOR]

Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. It is becoming increasingly clear that microRNAs (miRNAs or miRs), a group of highly conserved small (∼18–24 nucleotide) non-coding RNAs, fulfil specific functions in the reperfused myocardium towards post-infarct remodelling. While miR-21, -133, -150, -195, and -214 regulate cardiomyocyte hypertrophy, miR-1/-133 and miR-208 have been elucidated to influence myocardial contractile function. In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis. Myocardial fibrosis can be regulated by the miR-29 family and miR-21. Moreover, miR-126 and miR-210 augment I/R-induced angiogenesis, but miR-24, -92a, and -320 suppress post-infarct neoangiogenesis. In this review, we summarize the latest advances in the identification of myocardial ischaemia-associated miRNAs and their functional significance in the modulation of I/R-triggered remodelling. Controversial effects of some miRNAs in post-infarct remodelling will be also discussed. [ABSTRACT FROM PUBLISHER]

The recombinant xylose-fermenting Saccharomyces cerevisiae strain harboring xylose reductase (XR) and xylitol dehydrogenase (XDH) from Scheffersomyces stipitis requires NADPH and NAD+, creates cofactor imbalance, and causes xylitol accumulation during growth on D-xylose. To solve this problem, noxE, encoding a water-forming NADH oxidase from Lactococcus lactis driven by the PGKI promoter, was introduced into the xylose-utilizing yeast strain KAM-3X. A cofactor microcycle was set up between the utilization of NAD+ by XDH and the formation of NAD+ by water-forming NADH oxidase. Overexpression of noxE significantly decreased xylitol formation and increased final ethanol production during xylose fermentation. Under xylose fermentation conditions with an initial D-xylose concentration of 50 glliter, the xylitol yields for of KAM-3X(pPGK1-noxE) and control strain KAM-3X were 0.058 g/g xylose and 0.191 g/g, respectively, which showed a 69.63% decrease owing to noxE overexpression; the ethanol yields were 0.294 g/g for KAM-3X(pPGK1-noxE) and 0.211 g/g for the control strain KAM-3X, which indicated a 39.33% increase due to noxE overexpression. At the same time, the glycerol yield also was reduced by 53.85% on account of the decrease in the NADH pool caused by overexpression of noxE. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The histidine-rich Ca-binding protein (HRC) is a Ca-storage protein in cardiac sarcoplasmic reticulum. Recent transgenic studies revealed that this protein inhibits the maximal rates of sarcoplasmic reticulum Ca-transport, leading to cardiac dysfunction. In view of the role of sarcoplasmic reticulum Ca-cycling in myocardial ischemia/reperfusion injury, we designed this study to gain further insight into the role of HRC during ischemia/reperfusion. Methods and results: The transgenic mouse model with cardiac-specific overexpression of HRC was utilized and cardiac contractile parameters were assessed before and after ischemia/reperfusion injury by Langendorff perfusion. After a 20-min stabilization period, the hearts were subjected to 40 min of global ischemia, followed by 60 min of reperfusion. We found that although transgenic (TG) hearts showed depressed cardiac function (25%) compared to wild types (WTs) at baseline, they exhibited better recovery of left ventricular developed pressure (86.6±2.6% in TGs vs. 58.3±4.0% in WTs of pre-ischemic values, P <0.05) and higher rates of contraction and relaxation after ischemia/reperfusion than WTs. This improvement was accompanied by smaller infarcts (23.1±1.7% in TGs vs. 41.1±2.5% in WTs of infarct region-to-risk region ratio, P <0.05) and lower creatine kinase release. Notably, the extent of apoptotic cell death was significantly attenuated, as evidenced by decreased DNA fragmentation, upregulation of the antiapoptotic protein Bcl-2, and downregulation of the active caspases (3, 9 and 12) following ischemia/reperfusion in TG hearts, compared with WTs. Extension of these studies to an in vivo model of 30-min myocardial ischemia, via coronary artery occlusion, followed by 24-h reperfusion, showed that the infarct region-to-risk region ratio was 9±0.9% in TGs, compared with 20.4±2.9% in WTs (P <0.05). Conclusions: Our findings suggest that increased cardiac HRC expression protects against ischemia/reperfusion injury in the heart, resulting in improved recovery of function and reduced infarction. [Copyright &y& Elsevier]