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Diabetic neuropathy is a debilitating disorder characterized by spontaneous and mechanical allodynia. The role of skin mechanoreceptors in the development of mechanical allodynia is unclear. We discovered that mice with diabetic neuropathy had decreased sirtuin 1 (SIRT1) deacetylase activity in foot skin, leading to reduced expression of brain-derived neurotrophic factor (BDNF) and subsequent loss of innervation in Meissner corpuscles, a mechanoreceptor expressing the BDNF receptor TrkB. When SIRT1 was depleted from skin, the mechanical allodynia worsened in diabetic neuropathy mice, likely due to retrograde degeneration of the Meissner-corpuscle innervating Aβ axons and aberrant formation of Meissner corpuscles which may have increased the mechanosensitivity. The same phenomenon was also noted in skin-keratinocyte specific BDNF knockout mice. Furthermore, overexpression of SIRT1 in skin induced Meissner corpuscle reinnervation and regeneration, resulting in significant improvement of diabetic mechanical allodynia. Overall, the findings suggested that skin-derived SIRT1 and BDNF function in the same pathway in skin sensory apparatus regeneration and highlighted the potential of developing topical SIRT1-activating compounds as a novel treatment for diabetic mechanical allodynia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: A deeper understanding of acute rejection in vascularized composite allotransplantation is paramount for expanding its utility and longevity. There remains a need to develop more precise and accurate tools for diagnosis and prognosis of these allografts, as well as alternatives to traditional immunosuppressive regimens., Methods: Twenty-seven skin biopsies collected from 3 vascularized composite allotransplantation recipients, consisting of face and hand transplants, were evaluated by histology, immunohistochemistry staining, and gene expression profiling., Results: Biopsies with clinical signs and symptoms of rejection, irrespective of histopathological grading, were significantly enriched for genes contributing to the adaptive immune response, innate immune response, and lymphocyte activation. Inflammation episodes exhibited significant fold change correlations between the face and hands, as well as across patients. Immune checkpoint genes were upregulated during periods of inflammation that necessitated treatment. A gene signature consisting of CCL5 , CD8A , KLRK1 , and IFNγ significantly predicted inflammation specific to vascularized composite allografts that required therapeutic intervention., Conclusions: The mechanism of vascularized composite allograft-specific inflammation and rejection appears to be conserved across different patients and skin on different anatomical sites. A concise gene signature can be utilized to ascertain graft status along with a continuous scale, providing valuable diagnostic and prognostic information to supplement current gold standards of graft evaluation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cancer cells largely rely on aerobic glycolysis or the Warburg effect to generate essential biomolecules and energy for their rapid growth. The key modulators in glycolysis including glucose transporters and enzymes, e.g. hexokinase 2, enolase 1, pyruvate kinase M2, lactate dehydrogenase A, play indispensable roles in glucose uptake, glucose consumption, ATP generation, lactate production, etc. Transcriptional regulation and post-translational modifications (PTMs) of these critical modulators are important for signal transduction and metabolic reprogramming in the glycolytic pathway, which can provide energy advantages to cancer cell growth. In this review we recapitulate the recent advances in research on glycolytic modulators of cancer cells and analyze the strategies targeting these vital modulators including small-molecule inhibitors and microRNAs (miRNAs) for targeted cancer therapy. We focus on the regulation of the glycolytic pathway at the transcription level (e.g., hypoxia-inducible factor 1, c-MYC, p53, sine oculis homeobox homolog 1, N 6 -methyladenosine modification) and PTMs (including phosphorylation, methylation, acetylation, ubiquitination, etc.) of the key regulators in these processes. This review will provide a comprehensive understanding of the regulation of the key modulators in the glycolytic pathway and might shed light on the targeted cancer therapy at different molecular levels., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Inflammatory epithelial diseases are spurred by the concomitant dysregulation of immune and epithelial cells. How these two dysregulated cellular compartments simultaneously sustain their heightened metabolic demands is unclear. Single-cell and spatial transcriptomics (ST), along with immunofluorescence, revealed that hypoxia-inducible factor 1α (HIF1α), downstream of IL-17 signaling, drove psoriatic epithelial remodeling. Blocking HIF1α in human psoriatic lesions ex vivo impaired glycolysis and phenocopied anti-IL-17 therapy. In a murine model of skin inflammation, epidermal-specific loss of HIF1α or its target gene, glucose transporter 1, ameliorated epidermal, immune, vascular, and neuronal pathology. Mechanistically, glycolysis autonomously fueled epithelial pathology and enhanced lactate production, which augmented the γδ T17 cell response. RORγt-driven genetic deletion or pharmacological inhibition of either lactate-producing enzymes or lactate transporters attenuated epithelial pathology and IL-17A expression in vivo. Our findings identify a metabolic hierarchy between epithelial and immune compartments and the consequent coordination of metabolic processes that sustain inflammatory disease., Competing Interests: Declaration of interests I. Subudhi, P.K., and S.N. have filed a provisional patent for HIF1α inhibition in inflammatory skin diseases (U.S. serial number 63/540,794, filed September 27, 2023). N.A. is a consultant for Immunitas, 23 and me, Cellino Pharmaceuticals, and Janssen and serves on the SAB of Shennon Bio. S.N. is on the SAB of Seed Inc., is a consultant for BiomX, and receives funding from Takeda Pharmaceuticals. This activity is not relevant to the content of this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The COVID-19 pandemic underscored the criticality and complexity of decision making for novel treatment approval and further research. Our study aims to assess potential decision-making methodologies, an evaluation vital for refining future public health crisis responses., Methods: We compared 4 decision-making approaches to drug approval and research: the Food and Drug Administration's policy decisions, cumulative meta-analysis, a prospective value-of-information (VOI) approach (using information available at the time of decision), and a reference standard (retrospective VOI analysis using information available in hindsight). Possible decisions were to reject, accept, provide emergency use authorization, or allow access to new therapies only in research settings. We used monoclonal antibodies provided to hospitalized COVID-19 patients as a case study, examining the evidence from September 2020 to December 2021 and focusing on each method's capacity to optimize health outcomes and resource allocation., Results: Our findings indicate a notable discrepancy between policy decisions and the reference standard retrospective VOI approach with expected losses up to $269 billion USD, suggesting suboptimal resource use during the wait for emergency use authorization. Relying solely on cumulative meta-analysis for decision making results in the largest expected loss, while the policy approach showed a loss up to $16 billion and the prospective VOI approach presented the least loss (up to $2 billion)., Conclusion: Our research suggests that incorporating VOI analysis may be particularly useful for research prioritization and treatment implementation decisions during pandemics. While the prospective VOI approach was favored in this case study, further studies should validate the ideal decision-making method across various contexts. This study's findings not only enhance our understanding of decision-making strategies during a health crisis but also provide a potential framework for future pandemic responses., Highlights: This study reviews discrepancies between a reference standard (retrospective VOI, using hindsight information) and 3 conceivable real-time approaches to research-treatment decisions during a pandemic, suggesting suboptimal use of resources.Of all prospective decision-making approaches considered, VOI closely mirrored the reference standard, yielding the least expected value loss across our study timeline.This study illustrates the possible benefit of VOI results and the need for evidence accumulation accompanied by modeling in health technology assessment for emerging therapies., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Dijk reports grants from the Gordon and Betty Moore Foundation during the conduct of the study and grants from the German Innovation Fund outside the submitted work. Dr. Krijkamp reports grants and personal fees from the Society for Medical Decision Making fellowship through a grant from the Gordon and Betty Moore Foundation (GBMF7853) outside the submitted work. Dr. Kunst has nothing to disclose. Dr. Gross reports grants from the American Cancer Society, Johnson & Johnson, Pfizer, Flatiron Health, and Genentech outside the submitted work. Dr. Labrecque is supported by an NWO/ZonMW Veni grant (09150162010213). Mrs. Pandit has nothing to disclose. Ms. Lu has nothing to disclose. Dr. Visser has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Hunink reports grants from the Gordon and Betty Moore Foundation during the conduct of the study; other support from the European Society of Radiology, the European Institute for Biomedical Imaging Research, and Cambridge University Press; grants from the American Diabetes Association, the Netherlands Organization for Health Research and Development, the German Innovation Fund, and the Netherlands Educational Grant (“Studie Voorschot Middelen”) outside the submitted work. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by the Gordon and Betty Moore Foundation through grant GBMF9634 to Johns Hopkins University to support the work of the Society for Medical Decision Making COVID-19 Decision Modeling Initiative. The funding sources played no role in the writing or submission of this article. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.

Background: Hidradenitis suppurativa (HS) is a debilitating cutaneous disease characterized by severe painful inflammatory nodules/abscesses. At present, data regarding the epidemiology and pathophysiology of this disease are limited., Objective: To define the prevalence and comorbidity associations of HS., Methods: This was a cross-sectional study of EPIC TM Cosmos © examining over 180 million US patients. Prevalences were calculated by demographic and odds ratios (OR) and identified comorbidity correlations., Results: All examined metabolism-related, psychological, and autoimmune/autoinflammatory (AI) diseases correlated with HS. The strongest associations were with pyoderma gangrenosum [OR 26.56; confidence interval (CI): 24.98-28.23], Down syndrome (OR 11.31; CI 10.93-11.70), and polycystic ovarian syndrome (OR 11.24; CI 11.09-11.38). Novel AI associations were found between HS and lupus (OR 6.60; CI 6.26-6.94) and multiple sclerosis (MS; OR 2.38; CI 2.29-2.48). Cutaneous malignancies were largely not associated in the unsegmented cohort; however, among Black patients, novel associations with melanoma (OR 2.39; CI 1.86-3.08) and basal cell carcinoma (OR 2.69; CI 2.15-3.36) were identified., Limitations: International Classification of Diseases (ICD)-based disease identification relies on coding fidelity and diagnostic accuracy., Conclusion: This is the first study to identify correlations between HS with melanoma and basal cell carcinoma (BCC) among Black patients as well as MS and lupus in all patients with HS., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Students in health professions often face high levels of stress due to demanding academic schedules, heavy workloads, disrupted work-life balance, and sleep deprivation. Addressing stress during their education can prevent negative consequences for their mental health and the well-being of their future patients. Previous reviews on the effectiveness of mindfulness-based interventions (MBIs) focused on working health professionals or included a wide range of intervention types and durations. This study aims to investigate the effect of 6- to 12-week MBIs with 1- to 2-h weekly sessions on stress in future health professionals. We conducted a systematic review and meta-analysis of randomized controlled trials published in English by searching Embase, Medline, Web of Science, Cochrane Central Register of Controlled Trials, and PsycINFO. We used post-intervention stress levels and standard deviations to assess the ability of MBIs to reduce stress, summarized by the standardized mean difference (SMD). This review is reported according to the PRISMA checklist (2020). We identified 2932 studies, of which 11 were included in the systematic review and 10 had sufficient data for inclusion in the meta-analysis. The overall effect of MBIs on reducing stress was a SMD of 0.60 (95% CI [0.27, 0.94]). Our study provides evidence that MBIs have a moderate reducing effect on stress in students in health professions; however, given the high risk of bias, these findings should be interpreted with caution, and further high-quality studies are needed., (© 2023 The Authors. Applied Psychology: Health and Well‐Being published by John Wiley & Sons Ltd on behalf of International Association of Applied Psychology.)

Recently, populations of Chinese spiny frogs (Quasipaa spinosa), an important amphibian species in China, have decreased, mainly due to a disease caused by the gram-negative bacteria Proteus mirabilis. To elucidate the immune response of the frogs, this study aimed to identify novel candidate genes functionally associated with P. mirabilis infection-induced "rotting skin" disease. Chinese spiny frogs were infected with P. mirabilis, and the skin transcriptome was sequenced using the MGISEQ-2000 platform. A total of 233,965 unigenes were obtained by sequencing, of which 27.23 % were known genes. Screening of differentially expressed genes (DEGs) indicated 210 unigenes differentially expressed after P. mirabilis infection, of which 132 unigenes were up-regulated, and 78 unigenes were down-regulated. Using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, DEGs were identified as enriched in signal pathways, such as oxidative phosphorylation, apoptosis, and the Janus kinase-signal transducer and activator of transcription pathway. Of the DEGs, there was a significant upregulation of the colony stimulating factor 2 receptor beta common subunit, interleukin 2 receptor subunit gamma, cathelicidin antimicrobial peptide, interleukin-17 receptor E, receptor-interacting serine/threonine-protein kinase 3, and pulmonary surfactant-associated protein D immune genes following P. mirabilis infection. Conversely, scavenger receptor cysteine-rich domain-containing group B protein, tumor protein p53 inducible nuclear protein 2, suppressor of cytokine signaling 2, and metalloreductase STEAP3 were significantly downregulated. In conclusion, the first skin transcriptome database of Chinese spiny frogs was established, and several immune genes were identified to elucidate the pathogenic mechanism of "skin rot" in Chinese spiny frogs and other cultured frogs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Rejection is common and pernicious following Vascularized Composite Allotransplantation (VCA). Current monitoring and diagnostic modalities include the clinical exam which is subjective and biopsy with dermatohistopathologic Banff grading, which is subjective and invasive. We reviewed literature exploring non- and minimally invasive modalities for diagnosing and monitoring rejection (NIMMs) in VCA., Methods: PubMed, Cochrane, and Embase databases were queried, 3125 unique articles were reviewed, yielding 26 included studies exploring 17 distinct NIMMs. Broadly, NIMMs involved Imaging, Liquid Biomarkers, Epidermal Sampling, Clinical Grading Scales, and Introduction of Additional Donor Tissue., Results: Serum biomarkers including MMP3 and donor-derived microparticles rose with rejection onset. Epidermal sampling non-invasively enabled measurement of cytokine & gene expression profiles implicated in rejection. Both hold promise for monitoring. Clinical grading scales were useful diagnostically as was reflection confocal microscopy. Introducing additional donor tissue showed promise for preemptively identifying rejection but requires additional allograft tissue burden for the recipient., Conclusion: NIMMs have the potential to dramatically improve monitoring and diagnosis in VCA. Many modalities show promise however, additional research is needed and a multimodal algorithmic approach should be explored., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Two organic-inorganic hybrid zinc phosphites incorporating 1,2,4,5-tetrakis(imidazol-1-ylmethyl)benzene (TIMB) molecules were synthesized under hydro(solvo)thermal methods and structurally characterized by single-crystal X-ray diffraction (SCXD). Interestingly, the solvent ratio of water to dimethylformamide induced the formation of a new compound of Zn 2 (TIMB) 0.5 (HPO 3 ) 2 ·3H 2 O ( 1 ) and our previously reported structure of Zn 2 (TIMB) 0.5 (HPO 3 ) 2 ·H 2 O ( 2 ). Additionally, their dehydrated crystals ( 1a and 2a ) were prepared through heat treatment at 150 °C. SCXD and powder X-ray diffraction showed that all four compounds share the same framework formula of Zn 2 (TIMB) 0.5 (HPO 3 ) 2 but exhibit a huge difference in their inorganic components and final structures. In 1 and 1a , the inorganic units formed two-dimensional zincophosphite layers, while in 2 and 2a , they formed one-dimensional chains. The inorganic parts of 1 ( 1a ) and 2 ( 2a ) were bridged with TIMB linkers, resulting in 3D structures with rectangular and tubular windows, respectively. Furthermore, 1 was coated on the screen-printed carbon electron as a hybrid material, displaying excellent performance while having a linear relationship with an R 2 value of 0.99 within the concentration range of 10 -10 to 10 -6 mol/L for detecting tryptamine (Try) molecules. Moreover, the results showed that 1 exhibits an ultralow limit of detection of 5.43 × 10 -11 mol/L and high specificity toward Try over histamine, ascorbic acid, uric acid, and glucose. The synthesis, structural diversity, stability, and sensing ability are also discussed.

Chrysanthemum tea is commonly consumed by Chinese consumers mainly due to the Chrysanthemum flower being a potential source of antioxidants. The current study investigates the effects of extraction time and temperature on Chrysanthemum flower aqueous extract (CFAE) antioxidant capacity, including Trolox equivalent antioxidant capacity (TEAC), ferrous iron-chelating activity, and superoxide radical scavenging capacity (SRSC) using a two-factor, three-level factorial design of the response surface method (RSM). The TEAC and SRSC of CFAE are higher at higher temperatures and longer times up to a certain point, and the highest TEAC and SRSC are achieved at a 100 °C extraction temperature for 45 min. The fructose induced-αA-crystallin (Cry) glycation model system was used to evaluate the effects of the CFAE on anti-glycoxidation activities. The antioxidant ingredients obtained from CFAE significantly impede the production of advanced glycation end products from protein glycoxidation products (dityrosine, kynurenine, and N'-methylkynurenine) in the glycation process of αA-Cry and exhibit strong anti-glycating activity. The glycation inhibitory effects of CFAE are concentration-dependent. C. indicum L. exhibits greater potential for preventing cataracts compared to C. morifolium Ramat CFAE's antioxidant and anti-glycation properties suggest its potential application as a natural ingredient in the development of agents to combat glycation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Surgeons determine the treatment method for patients with epiglottis obstruction based on its severity, often by estimating the obstruction severity (using three obstruction degrees) from the examination of drug-induced sleep endoscopy images. However, the use of obstruction degrees is inadequate and fails to correspond to changes in respiratory airflow. Current artificial intelligence image technologies can effectively address this issue. To enhance the accuracy of epiglottis obstruction assessment and replace obstruction degrees with obstruction ratios, this study developed a computer vision system with a deep learning-based method for calculating epiglottis obstruction ratios. The system employs a convolutional neural network, the YOLOv4 model, for epiglottis cartilage localization, a color quantization method to transform pixels into regions, and a region puzzle algorithm to calculate the range of a patient's epiglottis airway. This information is then utilized to compute the obstruction ratio of the patient's epiglottis site. Additionally, this system integrates web-based and PC-based programming technologies to realize its functionalities. Through experimental validation, this system was found to autonomously calculate obstruction ratios with a precision of 0.1% (ranging from 0% to 100%). It presents epiglottis obstruction levels as continuous data, providing crucial diagnostic insight for surgeons to assess the severity of epiglottis obstruction in patients.

The genus Thunnus (family Scombridae) comprises eight species of tunas of which all but one are targeted by industrialized fisheries. Although intact individuals of these species can be distinguished by morphological characteristics, researchers and managers often rely on dressed, frozen, juvenile or larval fish samples, which often necessitates the identification of molecular species. Here the authors investigate short amplicon (SA) and unlabelled probe high-resolution melting analysis (UP-HRMA) as a low-cost, high-throughput molecular genotyping assay capable of distinguishing between albacore tuna (Thunnus alalunga), blackfin tuna (Thunnus atlanticus), bigeye tuna (Thunnus obesus), Atlantic bluefin tuna (Thunnus thynnus) and yellowfin tuna (Thunnus albacares) in the Gulf of Mexico. Although SA-HRMA of variable regions in the NADH dehydrogenase subunit 4 (ND4) and subunit 5 (ND5), and subunit 6 (ND6) of the mtDNA genome did yield some species-specific diagnostic melting curves (e.g., ND4 assay can reliably distinguish Atlantic bluefin tuna), genotype masking produced excessive variation in melting curves for reliable multi-species identification. To minimize the genotyping masking of SA-HRMA a 26 base pair long UP containing four SNPs was developed within a 133 bp segment of ND4. The UP-HRMA is able to reliably distinguish Gulf of Mexico species T. thynnus, T. obesus, T. albacares and T. atlanticus by UP melting temperature at 67, 62, 59 and 57°C, respectively. The developed UP-HRMA assay is a lower-cost, higher-throughput, alternative to previously published molecular assays for tuna identification that can be easily automated for large data sets, including ichthyological larval surveys, fisheries specimens lacking distinguishing morphological characteristics or detection of fraudulent trading of tuna species., (© 2023 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)

Taking coal under hydro-mechanical coupling as the research object, the discrete element software PFC3D (particle flow code) was used to analyze the relationships among the force, acoustic emission (AE), and energy during coal fracture. Based on the moment tensor (MT) inversion, we revealed the AE event distribution and source type during crack initiation and propagation until the final failure of coal. Meanwhile, we examined the relationships among the stress, number and type of cracks, magnitude, K E , and b value of AE under different water and confining pressures. The results show that the numerical simulation can effectively determine the microscopic damage mechanism of coal under different conditions. Moreover, the rupture type of the numerical simulation is consistent with the field investigations, which verifies the rationality of the simulation. These research results can provide reference for safety production evaluation of water inrush mines.

The slip and instability mechanisms of coal-rock parting-coal structures under uniaxial loading conditions were investigated using experiments and case verification. The slip and the corresponding precursors were described by monitoring the displacement, strain, and acoustic emissions (AEs) of coal and rock parting blocks during testing, and the experimental results were verified by analyzing the microseismic (MS) effects during the working face advancing in a coal seam bifurcation area. The main conclusions were as follows: (1) each slip of the discontinuities sandwiched between coal and rock parting produced shear and tensile cracks, but the shear cracks was dominant; (2) for the instability mode that was characterized by low peak stress, high energy release, and a stable b value of AE, each slip corresponds to a peak frequency of AE, which can reveal the final instability mode; (3) the sudden drop in the fault total area of AE can be regarded as a precursor for the warning fracture or slip instability of a discontinuity; and (4) the MS events in the coal seam bifurcation area were mainly characterized by a wide frequency and high amplitude, especially near the coal bifurcation line, where there were obvious characteristics of low-frequency shear fracture for the MS events. This study is relevant for the early warning of coal-rock dynamic disasters triggered by the slip, fracture, and instability of coal-rock parting compound structures in coal mines., (© 2022. The Author(s).)

National Cheng Kung University (NCKU) promotes university social responsibility and strives to ensure that all of its teaching staff and students engage in academics in a manner that incorporates both social awareness and social practice. The NCKU team has launched a series of social practice and research projects focused on accompanying and caring for older adults who live in the community, looking to establish a social practice model that bridges university teaching and research to practical community needs. The objective of this initiative is to develop an innovative model of social support and a new model for younger generations to work with older adults living in the community. The results of this survey project show better well-being in older adults to be associated with the following sets of traits: exercising regularly and lacking dental problems; engaging in daily laughter and holding positive aging perceptions; and having a higher subjective social status, more family support, and a sense of community attachment. The study results imply that multiple factors affect well-being in the context of caring for community-dwelling older adults and social development, especially during the current COVID-19 pandemic.

Glands in the skin are essential for various physiological functions involving exocrine secretion. Like other tissues and organs, they possess the ability to repair injury and self-renew during homeostasis. Progenitor cells in glands are mostly unipotent but include some multipotent stem cells that function when extensive remodelling or regeneration is required. In this review, using two glandular models in skin, mouse sweat gland and mammary gland, we discuss lineage restriction that develops during glandular morphogenesis, as well as the mechanisms regulating cell fate and plasticity during wound repair and regeneration. Understanding the intrinsic and extrinsic factors that control the behaviours of glandular stem cell and maintain glandular functions will provide insight into future prospects for glandular regeneration., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mono-ubiquitination on H2B (H2Bub1) is an evolutionarily conserved histone post-translational modification implicated in various important physiological processes including DNA replication, transcription activation, and DNA damage repair. The Bre1/Rad6 ubiquitination machinery is currently considered to be the sole writer of H2Bub1, but the mechanistic basis by which it operates is unclear. Recently, the RING-type E3 ligase Bre1 was proposed to associate with the E2 enzyme Rad6 through a novel interaction between Bre1 RBD (Rad6 binding domain) and Rad6; and the RING domain of Bre1 that is responsible for the nucleosomal acidic patch binding also interacts with Rad6 to stimulate its catalytic activity. Recent discoveries have yielded evidence for the phenomenon of liquid-liquid phase separation in the context of H2Bub1, and its regulation by other histone post-translational modifications. This review summarizes current knowledge about Bre1/Rad6-mediated H2B ubiquitination, including the physiological functions and the molecular basis for writing and regulation of this central histone ubiquitin mark. Possible models for the Bre1/Rad6 machinery bound to nucleosomes bearing different modifications in the writing step are also disclosed.

Exploring strategies to treat cancer has always been an aim of medical researchers. One of the available strategies is to use targeted therapy drugs to make the chromosomes in cancer cells unstable such that cell death can be induced, and the elimination of highly proliferative cancer cells can be achieved. Studies have reported that the mitotic defects and micronuclei in cancer cells can be used as biomarkers to evaluate the instability of the chromosomes. Researchers use these two biomarkers to assess the effects of drugs on eliminating cancer cells. However, manual work is required to count the number of cells exhibiting mitotic defects and micronuclei either directly from the viewing window of a microscope or from an image, which is tedious and creates errors. Therefore, this study aims to detect cells with mitotic defects and micronuclei by applying an approach that can automatically count the targets. This approach integrates the application of a convolutional neural network for normal cell identification and the proposed color layer signature analysis (CLSA) to spot cells with mitotic defects and micronuclei. This approach provides a method for researchers to detect colon cancer cells in an accurate and time-efficient manner, thereby decreasing errors and the processing time. The following sections will illustrate the methodology and workflow design of this study, as well as explain the practicality of the experimental comparisons and the results that were used to validate the practicality of this algorithm.

Tissue homeostasis and regeneration rely on resident stem cells (SCs), whose behaviour is regulated through niche-dependent crosstalk. The mechanisms underlying SC identity are still unfolding. Here, using spatiotemporal gene ablation in murine hair follicles, we uncover a critical role for the transcription factors (TFs) nuclear factor IB (NFIB) and IX (NFIX) in maintaining SC identity. Without NFI TFs, SCs lose their hair-regenerating capability, and produce skin bearing striking resemblance to irreversible human alopecia, which also displays reduced NFIs. Through single-cell transcriptomics, ATAC-Seq and ChIP-Seq profiling, we expose a key role for NFIB and NFIX in governing super-enhancer maintenance of the key hair follicle SC-specific TF genes. When NFIB and NFIX are genetically removed, the stemness epigenetic landscape is lost. Super-enhancers driving SC identity are decommissioned, while unwanted lineages are de-repressed ectopically. Together, our findings expose NFIB and NFIX as crucial rheostats of tissue homeostasis, functioning to safeguard the SC epigenome from a breach in lineage confinement that otherwise triggers irreversible tissue degeneration.

One of the common methods for measuring distance is to use a camera and image processing algorithm, such as an eye and brain. Mechanical stereo vision uses two cameras to shoot the same object and analyzes the disparity of the stereo vision. One of the most robust methods to calculate disparity is the well-known census transform, which has the problem of conversion window selection. In this paper, three methods are proposed to improve the performance of the census transform. The first one uses a low-pass band of the wavelet to reduce the computation loading and a high-pass band of the wavelet to modify the disparity. The main idea of the second method is the adaptive size selection of the conversion window by edge information. The third proposed method is to apply the adaptive window size to the previous sparse census transform. In the experiments, two indexes, percentage of bad matching pixels (PoBMP) and root mean squared (RMS), are used to evaluate the performance with the known ground truth data. According to the results, the computation required can be reduced by the multiresolution feature of the wavelet transform. The accuracy is also improved with the modified disparity processing. Compared with previous methods, the number of operation points is reduced by the proposed adaptive window size method.

Based on experimental and in-situ tests, the propagation and attenuation rules of seismic wave in the intact and jointed rocks subjected to conventional triaxial loading condition were investigated, especially the influencing effects of joints and beddings on the attenuation. Meanwhile, the frequency-spectrum evolutions during the process of attenuation were analysed in detail. To verify the outcomes obtained from the laboratory, the attenuation characteristics of seismic wave generated by blasting in underground strata were tested, and the attenuation rules by the joints between strata was summarized. Finally, the seismic response of joints and beddings in rocks was revealed. This work put forward some references for early weakening and controlling coal-rock dynamic disasters triggered by seismic wave in coal mines based on the attenuation effect of artificial discontinuity such as joint and bedding., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Touch sensation is initiated by mechanosensory neurons that innervate distinct skin structures; however, little is known about how these neurons are patterned during mammalian skin development. We explored the cellular basis of touch-receptor patterning in mouse touch domes, which contain mechanosensory Merkel cell-neurite complexes and abut primary hair follicles. At embryonic stage 16.5 (E16.5), touch domes emerge as patches of Merkel cells and keratinocytes clustered with a previously unsuspected population of Bmp4 -expressing dermal cells. Epidermal Noggin overexpression at E14.5 disrupted touch-dome formation but not hair-follicle specification, demonstrating a temporally distinct requirement for BMP signaling in placode-derived structures. Surprisingly, two neuronal populations preferentially targeted touch domes during development but only one persisted in mature touch domes. Finally, Keratin-17-expressing keratinocytes but not Merkel cells were necessary to establish innervation patterns during development. These findings identify key cell types and signaling pathways required for targeting Merkel-cell afferents to discrete mechanosensory compartments., Competing Interests: BJ, NF, CL, EL No competing interests declared, EF Reviewing editor, eLife, (© 2019, Jenkins et al.)

The objective of this study was to evaluate the antioxidant activities of Mesona procumbens ethanolic extracts (MPEEs) which displayed variable antioxidant levels with different ethanolic concentrations. Compared to MPEEs with 20, 40 and 80% ethanol, the 60% MPEE exhibited a higher total phenol content (TPC), total flavonoid content (TFC), 1,1-diphenyl-2-picryl hydrazyl (DPPH)- and 2,2-azino-bis-(3-ethyl benzothiazoline-6-sulphonic acid (ABTS)-scavenging activities, reducing power, protection of Raw 264.7 mouse macrophages against H 2 O 2 -induced damage, and inhibition of reactive oxygen species (ROS) induced by 2,2-azobis(2-amidino propane) dihidrochloride (AAPH). IC 50 values of DPPH and ABTS radicals by MPEEs were highly and significantly associated with TPCs and TFCs. The most significant protective effect against oxidative DNA damage was also found to be the 60% MPEE at a concentration of 3.6 mg/mL. In addition, the cell viability test showed that none of the MPEEs had any cell toxicity up to a concentration of 250 μg/mL. The 60% MPEE exhibited higher in vitro and ex vivo antioxidant activities, possessed a protective capability for the biological membrane system, and can be used as a functional ingredient representing a potential source of natural antioxidants to prevent and treat oxidative stress-related disorders.

Sleep disturbance is a common complaint in cancer patients. However, less is known about the parameters of sleep in patients with nasopharyngeal cancer (NPC) and their family caregivers (FCs) when they are about to begin treatment. We investigated the sleep quality in patients with NPC and their FCs before treatment and determined the related factors that predict sleep disturbance in these patients before therapy. A total of 101 patient-FC dyads were recruited. They completed the Pittsburgh Sleep Quality Index (PSQI) prior to treatment. No differences were found in sleep disturbance between patients (38.6%) and their FCs (31.7%). Patients reported significantly higher rates of short sleep duration than their FCs (P = 0.011). Logistic regression analyses showed that older patients were more prone to suffer from poor sleep quality before treatment (OR = 1.06, 95% CI = 1.01-1.10, P = 0.008), while patients with a higher BMI were less likely to experience sleep disturbance (OR = 0.83, 95% CI = 0.71-0.96, P = 0.012). Sleep disturbance is a significant problem in patients with NPC and their FCs before therapy. Older patients and those with a lower BMI appear to be more inclined to suffer from poor sleep before treatment.

Black soybeans are commonly consumed as health foods and used in traditional Chinese medicine, but they are rarely cultivated as edible sprouts. During germination, the composition of seeds undergoes distinct changes that cause variations in bioactivities. In this study, the water-soluble black soybean polysaccharide (BSPS) was isolated from sprouts harvested at two-day intervals during the first week of seedling growth. The chromatographic profiles of the BSPS in ungerminated seeds showed fraction 1 (F1, about 64kDa) and fraction 2 (F2, <1kDa) that degraded during germination. The polysaccharide in F1 fraction of ungerminated seeds was covalently associated with the protein and mainly contained arabinose, galactose, glucose, and galacturonic acid at various levels during germination. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) scavenging activities and the reducing power of F1 were highest on the seventh day of germination. The phenolic and flavonoid content significantly increased after the fifth day of germination, suggesting that these ingredients also contributed to the antioxidant activities. During long-term germination, the polysaccharide-protein conjugate in the F1 fraction with enhanced antioxidant activities is regarded as a potential natural antioxidant for the development of functional foods., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The genetic basis for phenicol resistance was examined in 38 phenicol-resistant clinical Escherichia coli isolates from poultry. Out of 62 isolates, 38 showed resistance for chloramphenicol and nine for florfenicol, respectively. Each strain also demonstrated resistance to a variety of other antibiotics. Molecular detection revealed that the incidence rates of the cat1, cat2, flo, flo-R, cmlA, and cmlB were 32, 29, 18, 13, 0, and 0%, respectively. Nineteen strains were tolerant to organic solvents. PCR amplification of the complete acrR (regulator/repressor) gene of five isolates revealed the amino acid changes in four isolates. DNA sequencing showed the non-synonymous mutations which change the amino acid, silent mutation, and nucleotide deletion in four isolates. MY09C10 showed neither deletion nor mutation in nucleotide. The AcrA protein of the AcrAB multidrug efflux pump was overexpressed in these strains. Complementation with a plasmid-borne wild-type acrR gene reduced the expression level of AcrA protein in the mutants and partially restored antibiotic susceptibility one- to fourfold. This study shows that mutations in acrR are an additional genetic basis for phenicol resistance.

The impact of global warming on the growth and development of natural vegetation is an important concern worldwide. Based on the data from the vegetation normalization index, daytime temperature (T max ), nighttime temperature (T min ), precipitation, and elevation from 1982 to 2015, we examined the day-night warming response of 42 types of natural vegetation in China. The results showed that both the temperature at day and night was significantly increased in the study area, with obvious asymmetry. The night warming was about 1.6 times as high as that at daytime. The T min was more conducive to vegetation growth than the T max . The proportion of vegetation types with positive relationship with T min was greater than the T max , with significant spatial difference. Subtropical vegetation accounted for 85.7% of vegetation with positive correlation with T max . The temperate alpine, mountainous, and desert vegetation responded more positively to T min . The increase of T min was not conducive to the growth and development of vegetation at high altitudes, while that of T max was the opposite. The correlations of vegetation growth with T max and T min were as follows: steppe > meadow > needleleaf forest > desert vegetation > broadleaf forest; meadow > desert vegetation > broadleaf forest > steppe > needleleaf forest.

Macrophages and inflammasome pathway are involved in high-glucose toxicity and development of insulin resistance. Silymarin (SMR) was known to modulate glucose homeostasis and reduce inflammation. However, it is still unknown whether SMR possess anti-hyperglycemic effects in diabetic-like knockout mice (Hnf-1α kin/- /Ins.cre mice) with insulin resistance and also unclear how SMR regulates LPS induced stress markers and pro-inflammatory cytokines under stresses of high glucose (HG) or NLRP3 inflammasome activation. Current results show that oral administration of SMR (100 mg/kg) reduced hyperglycemia in the mouse model of maturity-onset diabetes of the young type 3-like mice. In cultured macrophages, SMR (5-20 μg/ml) reduces high glucose (HG)-enhanced expressions of inducible nitric oxide synthase, nitric oxide generation stimulated by LPS; however, no effects on COX-2 expressions. The enhanced interleukin-1β (ΙL-1β) secretions in the presence of HG or palmitate were also significantly down regulated by SMR in dose-dependent manner in LPS-treated macrophages. Such observations may result from the decreased extracellular signal-regulated kinase 1/2 phosphorylation, while without affecting protein kinase C-α phosphorylation and nuclear factor-κB activation. These findings together show that SMR acts as a protector against HG-related stresses not only by lowering hyperglycemia but also suppressing HG- and inflammasome-mediated IL-1β expressions to improve insulin resistance., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)-(+)-isochaihulactone (1) exhibited significant inhibition against multiple-drug-resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off-target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β-unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI-oriented activity-based proteome profiling. By MS/MS and computer-guided molecular biology approaches, an affinity-driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the "ON/OFF" switch of apoptosis through non-canonically nuclear GAPDH translocation, which bypasses the common apoptosis-resistant route of MDR cancers., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The sperm of Eriocheir sinensis has a cup-shaped nucleus that contains several mitochondria embedded at the opening of the cup. The acrosome vesicle also contains derivants of mitochondria. The mitochondria distribution pattern involves a decrease in the number and changes in the structure and transportation of these organelles. The decreased number of sperm mitochondria is achieved through autophagy or the ubiquitination pathway. Prohibitin (PHB), the mitochondria inner membrane protein, is an evolutionarily highly conserved protein, is closely associated with spermatogenesis and sperm quality control and is also a potential substrate of ubiquitination. However, whether PHB protein mediates the ubiquitination pathway of sperm mitochondria in crustacean animals remains poorly understood. In the present study, we revealed that PHB, a substrate of ubiquitin, participates in the ubiquitination and degradation of mitochondria during spermiogenesis in E. sinensis . To confirm this finding, we used shRNA interference to reduce PHB expression and an overexpression technique to increase PHB expression in vitro . The interference experiment showed that the reduced PHB expression directly affected the polyubiquitination level and mitochondria status, whereas PHB overexpression markedly increased the polyubiquitination level. In vitro experiments also showed that PHB and its ubiquitination decide the fate of mitochondria., Competing Interests: CONFLICTS OF INTEREST The authors confirm that this article has no conflicts of interest.

Tissue stem cells contribute to tissue regeneration and wound repair through cellular programs that can be hijacked by cancer cells. Here, we investigate such a phenomenon in skin, where during homeostasis, stem cells of the epidermis and hair follicle fuel their respective tissues. We find that breakdown of stem cell lineage confinement-granting privileges associated with both fates-is not only hallmark but also functional in cancer development. We show that lineage plasticity is critical in wound repair, where it operates transiently to redirect fates. Investigating mechanism, we discover that irrespective of cellular origin, lineage infidelity occurs in wounding when stress-responsive enhancers become activated and override homeostatic enhancers that govern lineage specificity. In cancer, stress-responsive transcription factor levels rise, causing lineage commanders to reach excess. When lineage and stress factors collaborate, they activate oncogenic enhancers that distinguish cancers from wounds., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The gain of eccrine sweat glands in hairy body skin has empowered humans to run marathons and tolerate temperature extremes. Epithelial-mesenchymal cross-talk is integral to the diverse patterning of skin appendages, but the molecular events underlying their specification remain largely unknown. Using genome-wide analyses and functional studies, we show that sweat glands are specified by mesenchymal-derived bone morphogenetic proteins (BMPs) and fibroblast growth factors that signal to epithelial buds and suppress epithelial-derived sonic hedgehog (SHH) production. Conversely, hair follicles are specified when mesenchymal BMP signaling is blocked, permitting SHH production. Fate determination is confined to a critical developmental window and is regionally specified in mice. In contrast, a shift from hair to gland fates is achieved in humans when a spike in BMP silences SHH during the final embryonic wave(s) of bud morphogenesis., (Copyright © 2016, American Association for the Advancement of Science.)

Aged skin heals wounds poorly, increasing susceptibility to infections. Restoring homeostasis after wounding requires the coordinated actions of epidermal and immune cells. Here we find that both intrinsic defects and communication with immune cells are impaired in aged keratinocytes, diminishing their efficiency in restoring the skin barrier after wounding. At the wound-edge, aged keratinocytes display reduced proliferation and migration. They also exhibit a dampened ability to transcriptionally activate epithelial-immune crosstalk regulators, including a failure to properly activate/maintain dendritic epithelial T cells (DETCs), which promote re-epithelialization following injury. Probing mechanism, we find that aged keratinocytes near the wound edge don't efficiently upregulate Skints or activate STAT3. Notably, when epidermal Stat3, Skints, or DETCs are silenced in young skin, re-epithelialization following wounding is perturbed. These findings underscore epithelial-immune crosstalk perturbations in general, and Skints in particular, as critical mediators in the age-related decline in wound-repair., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To evaluate the results of the orthognathic surgery with computer aided simulation-three-dimensional(3D) printed surgical guide and dental model surgery in the treatmemt of patients with mandibular excess and facial asymmetries. Methods: The coordinate system was built in ProPlan CMF 2.0 software, and the horizontal plane consisted of PoL, PoR, OrL, middle sagittal plane through nasion point and basion point and the plane perpendicular to the horizontal plane, coronoid plane through nasion point and the plane perpendicular to the horizontal plane and middle sagittal plane. The orientation of maxilla and mandibular distal segment was calculated by each triangle(U1-U6L-U6R, L1-L6L-L6R, Me-M5L-M5R) before and after orthognathic surgery. A total of 60 mandibular excess patients with facial asymmetries were enrolled in this retrospective study. They were divided into two groups, group Ⅰ with computer aided simulation, group Ⅱ with dental model surgery. The difference of maxillary occlusal plane roll and yaw angle, mandibular occlusal plane roll and yaw angle, and mandibular body plane roll and yaw angle were calculated. Statistical analysis was performed with SPSS 17.0 software. Results: The yaw angle of mandibular occlusal plane of the dental model surgery and computer aided simulation was 0.36°± 0.48° and 0.84° ± 0.36° ( P= 0.043), respectively. The roll angle of mandibular occlusal plane of the dental model surgery and computer aided simulation was 0.26°±0.79° and 0.54°±0.40°( P= 0.032), respectively. The yaw angle of mandibular body plane of the dental model surgery and computer aided simulation was 0.60°± 1.04° and 0.23°±0.52°( P= 0.008), respectively. The roll angle of mandibular body plane of the dental model surgery and computer aided simulation was 0.82° ± 0.72° and 0.53° ± 0.37° ( P= 0.028), respectively. The changes in computer aided simulation group were more obvious than that in the dental model surgery group, but the difference was not significant in the yaw angle of maxillary occlusal plane and the roll angle of maxillary occlusal plane between the two groups( P >0.05). Conclusions: It was more effective to correct mandibular asymmetry by computer aided simulation than dental model surgery.

One-atom-thick crystalline layers and their vertical heterostructures carry the promise of designer electronic materials that are unattainable by standard growth techniques. To realize their potential it is necessary to isolate them from environmental disturbances, in particular those introduced by the substrate. However, finding and characterizing suitable substrates, and minimizing the random potential fluctuations they introduce, has been a persistent challenge in this emerging field. Here we show that Landau-level (LL) spectroscopy offers the unique capability to quantify both the reduction of the quasiparticles' lifetime and the long-range inhomogeneity due to random potential fluctuations. Harnessing this technique together with direct scanning tunneling microscopy and numerical simulations we demonstrate that the insertion of a graphene buffer layer with a large twist angle is a very effective method to shield a 2D system from substrate interference that has the additional desirable property of preserving the electronic structure of the system under study. We further show that owing to its remarkable nonlinear screening capability a single graphene buffer layer provides better shielding than either increasing the distance to the substrate or doubling the carrier density and reduces the amplitude of the potential fluctuations in graphene to values even lower than the ones in AB-stacked bilayer graphene.

This study investigated the propylene glycol alginate (PGA)-induced coacervation of β-conglycinin (7S), glycinin (11S) and isoflavones in heated soymilk. The addition of 0.9% PGA caused 7S, 11S, daidzein and genistein to coacervate following a 1h incubation period. SDS-PAGE showed that the protein bands corresponding to the 7S α', 7S α, 7S β, 11S A3, and 11S acidic subunits and the 11S basic proteins in the soymilk supernatant fraction (SSF) decreased to 37.7 ± 12.7%, 24.7 ± 3.9%, 4.9 ± 1.8%, 8.5 ± 2.7%, 18.1 ± 1.8% and 6.0 ± 1.6%, respectively. In addition, isoflavones including daidzein and genistein were also coacervated from the SSF into the soymilk pellet fraction (SPF) following incubation with 0.9% PGA for 1h. The amounts of daidzein and genistein in the SSF decreased to 8.6 ± 1.6% and 2.0 ± 1.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound to the 7S and 11S proteins. These results suggested that daidzein and genistein were co-precipitated with the 7S and 11S proteins into the SPF by 0.9% PGA. Our results demonstrated that PGA is a potent coagulant for the coacervation of 7S, 11S, daidzein and genistein., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Based on the integrated model of emergy-ecological footprint approaches, the ecological security of Liaoning Province, a typical case for the old industrial area, was quantitatively evaluated from 2003 to 2012, followed by a scenario analysis on the development trend of the ecological secu-rity by employing the gray kinetic model. The results showed that, from 2003 to 2012, the value of emergy ecological-capacity per capita in Liaoning Province decreased from 3.13 hm 2 to 3.07 hm 2 , while the emergy-ecological footprint increased from 13.88 hm 2 to 21.96 hm 2 , which indicated that the ecological deficit existed in Liaoning Province and the situation was getting worse. The ecological pressure index increased from 4.43 to 7.16 during the studied period, and the alert level of ecological security changed from light to middle level. According to the development trend, the emergy ecological capacity per capita during 2013-2022 would correspondingly decrease from 3.04 hm 2 to 2.98 hm 2 , while the emergy ecological footprint would increase from 22.72 hm 2 to 35.87 hm 2 , the ecological pressure index would increase from 7.46 to 12.04, and the ecological deficit would keep increasing and the ecological security level would slide into slightly unsafe condition. The alert level of ecological security would turn to be middle or serious, suggesting the problems in ecological safety needed to be solved urgently.

Streptococcus equi ssp. zooepidemicus (S. equi spp. zooepidemicus) is an opportunistic pathogen that causes major economic losses in the swine industry in China and is also a threat for human health. Biofilm formation by this bacterium has been previously reported. In this study, we used an immunoproteomic approach to search for immunogenic proteins expressed by biofilm-grown S. equi spp. zooepidemicus. Seventeen immunoreactive proteins were found, of which nine common immunoreactive proteins were identified in planktonic and biofilm-grown bacteria. The immunogenicity and protective efficacy of the S. equi spp. zooepidemicus immunoreactive GroEL chaperone protein was further investigated in mice. The protein was expressed in vivo and elicited high antibody titers following S. equi spp. zooepidemicus infections of mice. An animal challenge experiment with S. equi spp. zooepidemicus showed that 75% of mice immunized with the GroEL protein were protected. Using in vitro biofilm inhibition assays, evidence was obtained that the chaperonin GroEL may represent a promising target for the prevention and treatment of persistent S. equi spp. zooepidemicus biofilm infections. In summary, our results suggest that the recombinant GroEL protein, which is involved in biofilm formation, may efficiently stimulate an immune response, which protects against S. equi spp. zooepidemicus infections. It may therefore be a candidate of interest to be included in vaccines against S. equi spp. zooepidemicus infections.

Autotransporters (ATs) are associated with pathogenesis of Avian Pathogenic Escherichia coli (APEC). The molecular characterization of APEC ATs can provide insights about their relevance to APEC pathogenesis. Here, we characterized a conventional autotransporter UpaB in APEC DE205B genome. The upaB existed in 41.9 % of 236 APEC isolates and was predominantly associated with ECOR B2 and D. Our studies showed that UpaB mediates the DE205B adhesion in DF-1 cells, and enhances autoaggregation and biofilm formation of fimbria-negative E. coli AAEC189 (MG1655Δfim) in vitro. Deletion of upaB of DE205B attenuates the virulence in duck model and early colonization in the duck lungs during APEC systemic infection. Furthermore, double and triple deletion of upaB, aatA, and aatB genes cumulatively attenuated DE205B adhesion in DF-1 cells, accompanying with decreased 50 % lethal dose (LD50) in duck model and the early colonization in the duck lungs. However, DE205BΔupaB/ΔaatA/ΔaatB might "compensate" the influence of gene deletion by upregulating the expression of fimbrial adhesin genes yqiL, yadN, and vacuolating autotransporter vat during early colonization of APEC. Finally, we demonstrated that vaccination with recombinant UpaB, AatA, and AatB proteins conferred protection against colisepticemia caused by DE205B infection in duck model.

Background: The porcine circovirus-like agent P1 is a newly discovered DNA virus with a single-stranded circular genome that is highly homologous to that of porcine circovirus type 2. P1 infection can cause symptoms resembling postweaning multisystemic wasting syndrome. This study aims to develop a rapid, sensitive and specific method to detect P1., Results: A pair of primers was designed and used to amplify a 119 bp DNA fragment to generate a recombinant plasmid which was served as the standard. A SYBR I qPCR protocol was established using the P1 recombinant plasmid standard and the sensitivity, specificity and stability of this method was analyzed. The results demonstrate a strong correlation with P1 recombinant plasmid titers when virus DNA copy numbers fall in between 10(0) ~ 10(9) copies/μL. This method doesn't detect pseudo rabies, porcine parvovirus or porcine reproductive and respiratory syndrome virus; moreover it can distinguish porcine circovirus type 2 from P1 by melting temperature analysis. Coefficient of variation for each batch of reaction is less than 5%. The serum virus titers of P1 positive in this study were measured by this protocol to be 10(3) to 10(7) copies/mL., Conclusions: The established qPCR is sensitive, specific, and reliable, which could be a useful tool when applied to quantification of P1 in a variety of samples from infected pigs.

Previous genetic studies of Atlantic swordfish (Xiphias gladius L.) revealed significant differentiation among Mediterranean, North Atlantic and South Atlantic populations using both mitochondrial and nuclear DNA data. However, limitations in geographic sampling coverage, and the use of single loci, precluded an accurate placement of boundaries and of estimates of admixture. In this study, we present multilocus analyses of 26 single nucleotide polymorphisms (SNPs) within 10 nuclear genes to estimate population differentiation and admixture based on the characterization of 774 individuals representing North Atlantic, South Atlantic, and Mediterranean swordfish populations. Pairwise FST values, AMOVA, PCoA, and Bayesian individual assignments support the differentiation of swordfish inhabiting these three basins, but not the current placement of the boundaries that separate them. Specifically, the range of the South Atlantic population extends beyond 5°N management boundary to 20°N-25°N from 45°W. Likewise the Mediterranean population extends beyond the current management boundary at the Strait of Gibraltar to approximately 10°W. Further, admixture zones, characterized by asymmetric contributions of adjacent populations within samples, are confined to the Northeast Atlantic. While South Atlantic and Mediterranean migrants were identified within these Northeast Atlantic admixture zones no North Atlantic migrants were identified respectively in these two neighboring basins. Owing to both, the characterization of larger number of loci and a more ample spatial sampling coverage, it was possible to provide a finer resolution of the boundaries separating Atlantic swordfish populations than previous studies. Finally, the patterns of population structure and admixture are discussed in the light of the reproductive biology, the known patterns of dispersal, and oceanographic features that may act as barriers to gene flow to Atlantic swordfish.

One of the enduring challenges in graphene research and applications is the extreme sensitivity of its charge carriers to external perturbations, especially those introduced by the substrate. The best available substrates to date, graphite and hexagonal boron nitride (h-BN), still pose limitations: graphite being metallic does not allow gating, while both h-BN and graphite, having lattice structures closely matched to that of graphene, may cause significant band structure reconstruction. Here we show that the atomically smooth surface of exfoliated MoS(2) provides access to the intrinsic electronic structure of graphene without these drawbacks. Using scanning tunneling microscopy and Landau-level (LL) spectroscopy in a device configuration that allows tuning of the carrier concentration, we find that graphene on MoS(2) is ultraflat, producing long mean free paths, while avoiding band structure reconstruction. Importantly, the screening of the MoS(2) substrate can be tuned by changing the position of the Fermi energy with relatively low gate voltages. We show that shifting the Fermi energy from the gap to the edge of the conduction band gives rise to enhanced screening and to a substantial increase in the mean free path and quasiparticle lifetime. MoS(2) substrates thus provide unique opportunities to access the intrinsic electronic properties of graphene and to study in situ the effects of screening on electron-electron interactions and transport.

Streptococcus equi ssp. zooepidemicus (SEZ) is responsible for a wide variety of infections in many species, including pigs, horses and humans. Biofilm formation is essential for pathogenesis, and the ability to resist antibiotic treatment results in difficult-to-treat and persistent infections. However, the ability of SEZ to form biofilms is unclear. Furthermore, the mechanisms underlying SEZ biofilm formation and their attributes are poorly understood. In this study, scanning electron microscopy (SEM) demonstrated that SEZ strain ATCC35246 formed biofilms comprising a thick, heterogeneous layer with clumps on the coverslips when incubated for 24 h. In addition, we used a two-dimensional gel electrophoresis (2-DE) based approach to characterize differentially expressed protein in SEZ biofilms compared with their planktonic counterparts. The results revealed the existence of 24 protein spots of varying intensities, 13 of which were upregulated and 11 were downregulated in the SEZ biofilm compared with the planktonic controls. Most of proteins expressed during biofilm formation were associated with metabolism, adhesion, and stress conditions. These observations contribute to our understanding of the SEZ biofilm lifestyle, which may lead to more effective measures to control persistent SEZ infections.

Streptococcus suis (SS) is an important zoonotic pathogen causing a variety of life-threatening infections in pigs and humans. Tran, a novel transcriptional regulator which was identified to be an infection-related factor in S. suis serotype 2 using suppression subtractive hybridization (SSH), has been reported by our group. In this study, a tran deletion mutant was constructed to compare with the wild-type ZY05719 in some biological characteristics. It is suggested that longer chains and relatively slower growth could be observed in tran deletion mutants. In order to identify gene transcription profiles, microarray analysis was performed. It indicated that the inactivation of Tran led to 130 differentially expressed genes spread throughout the genome. Among these, 21 genes were upregulated, and 109 genes were downregulated. Most of the differentially expressed genes were involved in bacterial metabolism, such as the phosphotransferase system (PTS), and heat shock proteins. In the case of glucose scarcity, the growth characteristics of tran deletion mutants were impacted significantly, meanwhile Δtran mutant was highly sensitive to environmental stresses. Moreover, cell adherence decreased by 22.2%, and virulence in zebrafish declined to more than five times in Δtran mutants. These data demonstrate the role of Tran in regulation in S. suis serotype 2, that is affect bacterial virulence by influencing bacterial metabolism and stress tolerance of external environment., (Copyright © 2014 Elsevier GmbH. All rights reserved.)