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Abstract Recently, environmental temperature has been shown to regulate bone homeostasis. However, the mechanisms by which cold exposure affects bone mass remain unclear. In our present study, we observed that exposure to cold temperature (CT) decreased bone mass and quality in mice. Furthermore, a transplant of exosomes derived from the plasma of mice exposed to cold temperature (CT-EXO) can also impair the osteogenic differentiation of BMSCs and decrease bone mass by inhibiting autophagic activity. Rapamycin, a potent inducer of autophagy, can reverse cold exposure or CT-EXO-induced bone loss. Microarray sequencing revealed that cold exposure increases the miR-25-3p level in CT-EXO. Mechanistic studies showed that miR-25-3p can inhibit the osteogenic differentiation and autophagic activity of BMSCs. It is shown that inhibition of exosomes release or downregulation of miR-25-3p level can suppress CT-induced bone loss. This study identifies that CT-EXO mediates CT-induced osteoporotic effects through miR-25-3p by inhibiting autophagy via targeting SATB2, presenting a novel mechanism underlying the effect of cold temperature on bone mass.

Abstract Objectives Castanopsis is the third largest genus in the Fagaceae family and is essentially tropical or subtropical in origin. The species in this genus are mainly canopy-dominant trees, and the key components of evergreen broadleaved forests play a crucial role in the maintenance of local biodiversity. Castanopsis chinensis, distributed from South China to Vietnam, is a representative species. It currently suffers from a high disturbance of human activity and climate change. Here, we present its assembled genome to facilitate its preliminary conservation and breeding on the genome level. Data description The C. chinensis genome was assembled and annotated by Nanopore and MGI whole-genome sequencing and RNA-seq reads using leaf tissues. The assembly was 888,699,661 bp in length, consisting of 133 contigs and a contig N50 of 23,395,510 bp. A completeness assessment of the assembly with Benchmarking Universal Single-Copy Orthologs (BUSCO) indicated a score of 98.3%. Repetitive elements comprised 471,006,885 bp, accounting for 55.9% of the assembled sequences. A total of 51,406 genes that coded for 54,310 proteins were predicted. Multiple databases were used to functionally annotate the protein sequences.

The spotted wing drosophila, Drosophila suzukii (Matsumura), is currently distributed in the main soft-skinned fruits production areas in China and 59 other countries, presenting a significant threat to importing nations. Optimal phytosanitary treatments, including fumigation, irradiation, and cold treatment, have been developed to prevent the international movement of this invasive fly. To determine the most cold-tolerant stage and facilitate the development of the technical schedules requested by the Technical Panel on Phytosanitary Treatment (TPPT), cold treatments of D. suzukii immature stages in ‘Red Globe’ grapes were conducted. Dose–mortality data at 0 °C and 2 °C from repeated trials were subjected to analysis of covariance, linear regression, and probit analysis. Results identified 3 d old pupae as the most cold-tolerant stage, followed by 1 d old pupae, 4 d old larvae, and 6 h old eggs with similar tolerance. The 2 d old larvae were the most sensitive stage. In subsequent confirmatory tests, 3 d old pupae were subjected to cold treatment at 0 °C for 9 and 10 days, and at 2 °C for 10 and 12 days, based on the probit estimation of the probit-9 value. No adult emergence occurred in the confirmatory tests except for one deformed adult from a 2 °C 10 d treatment. Therefore, the recommended treatment schedule requires fruit temperatures below 0.00 °C (or 1.62 °C) for no less than 10 (or 12) continuous days, with treatment efficacy not less than 99.9960% (or 99.9955%) at a 95% confidence level, respectively. These schedules are intended for submission to TPPT for the development of phytosanitary treatment standards.

Endothelial hyperpermeability is pivotal in sepsis-associated multi-organ dysfunction. Increased von Willebrand factor (vWF) plasma levels, stemming from activated platelets and endothelium injury during sepsis, can bind to integrin αvβ3, exacerbating endothelial permeability. Hence, targeting this pathway presents a potential therapeutic avenue for sepsis. Recently, we identified isaridin E (ISE), a marine-derived fungal cyclohexadepsipeptide, as a promising antiplatelet and antithrombotic agent with a low bleeding risk. ISE’s influence on septic mortality and sepsis-induced lung injury in a mouse model of sepsis, induced by caecal ligation and puncture, is investigated in this study. ISE dose-dependently improved survival rates, mitigating lung injury, thrombocytopenia, pulmonary endothelial permeability, and vascular inflammation in the mouse model. ISE markedly curtailed vWF release from activated platelets in septic mice by suppressing vesicle-associated membrane protein 8 and soluble N-ethylmaleide-sensitive factor attachment protein 23 overexpression. Moreover, ISE inhibited healthy human platelet adhesion to cultured lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs), thereby significantly decreasing vWF secretion and endothelial hyperpermeability. Using cilengitide, a selective integrin αvβ3 inhibitor, it was found that ISE can improve endothelial hyperpermeability by inhibiting vWF binding to αvβ3. Activation of the integrin αvβ3-FAK/Src pathway likely underlies vWF-induced endothelial dysfunction in sepsis. In conclusion, ISE protects against sepsis by inhibiting endothelial hyperpermeability and platelet-endothelium interactions.

Aging treatment is an effective way of strengthening high-Mn strip steels based on automotive industry. However, the role of this method in enhancing yield strength and cryogenic toughness (−196 °C) of high-Mn steels has still unclear so far. Besides, solute segregation has always been a vital factor affecting the mechanical properties of high-Mn steels, whereas it is still lacking in adequate attention. In the present work, the microstructural evolution, including solute macrosegregation, grain boundary segregation and precipitation, and the resultant mechanical properties under different aging treatment were elaborated. It was found that the banded segregation of C, Mn and V elements formed during aging treatment strongly affects the cryogenic toughness. Tridimensional EPMA analyses demonstrate that there exists dense banded segregation of C, V and Mn elements in longitudinal section and cross section for both aged steels (aging at 500 °C and 800 °C). However, more obvious banded segregation of C and V elements developed in the steel aged at 800 °C (800A), and more micron-scale VC carbides tend to precipitate at segregation band, which leads to the easy initiation and propagation of microcracks along the segregation band. Moreover, numerous nano-scale VC precipitates significantly increase the yield strength of 800A steel by 100 MPa, but there exist severer grain boundary segregation and precipitation after aging treatment, which enhances the twining stress by increasing local SFE of grain boundary regions. The twinning formation hence became harder, further deteriorating the cryogenic toughness of the 800A steel.

Abstract Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term ‘epigenetics’ was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term ‘epigenetics’. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.

Emerging evidence has shown the importance of the tumor microenvironment in tumorigenesis and progression. Cancer-associated fibroblasts (CAFs) are one of the most infiltrated stroma cells of the tumor microenvironment in gastrointestinal tumors. CAFs play crucial roles in tumor development and therapeutic response by biologically secreting soluble factors or structurally remodeling the extracellular matrix. Conceivably, CAFs may become excellent targets for tumor prevention and treatment. However, the limited knowledge of the heterogeneity of CAFs represents a huge challenge for clinically targeting CAFs. In this review, we summarize the newest understanding of gastrointestinal CAFs, with a special focus on their origin, differentiation, and function. We also discuss the current understanding of CAF subpopulations as shown by single-cell technologies.

As a new technology,blockchain has attracted the attention of all walks of life since its birth.Consensus algorithm is one of the core technologies of blockchain technology,and the research of consensus algorithms is also the top priority of blockchain development.Aiming at the problems of PBFT,which is widely used in consortium blockchain,such as the random selection of primary node and the inability of nodes to join and exit dynamically,an dynamic PBFT algorithm(DPBFT) is proposed.Firstly,the selection method of primary node of PBFT is improved,and the trust score is set for every node.The trust score is dynamically updated according to the behavior of the nodes in every round of consensus,and the primary node is selected according to the integral value,which improves the probability that an honest node is elected as the primary node.Secondly,four sub-protocols(JOIN,EXIT,PCLEAR,RCLEAR) are set for PBFT algorithm to solve the problem of joining and exiting nodes respectively and punish the offending nodes,so that the system has a dynamic network structure.It can be proved that the newly added four sub-protocols have good safety and liveness without affecting the safety and liveness of the original PBFT algorithm.At last,experimental results show that DPBFT algorithm has better consensus efficiency than traditional PBFT algorithm.

There exist urgent demands to develop structural materials with superior mechanical properties at 4.2 K. Some high-entropy steels (HESs) show potentials as cryogenic materials, but their deformation behaviors and mechanical properties at 4.2 K have been rarely investigated. Moreover, the aging-induced embrittlement of HESs also severely restricts their applications. In this work, the Fe-Mn-Al-C HESs with different Al contents (0, 4, 10 or 15 at.%) and grain sizes were fabricated, and their deformation behaviors and mechanical properties at 4.2 K were systematically studied. With increasing the Al content, (Fe,Mn)23C6 carbides are effectively inhibited in 10%Al HES after aging at 923 K for 10 days. Therefore, the premature fracture of 10%Al HES is avoided, leading to the excellent combination of high strength (∼1.5 GPa) and high fracture toughness (255 MPa·m1/2) at 4.2 K. The deformation mechanisms shift from the extensive twinning and deformation bands in 0Al HES to the lesser twinning, Taylor lattices and deformation bands in 10%Al HES, which contribute to the high strength and ductility of the 10%Al HES. Furthermore, the 10%Al HES with larger grains displays a much higher fracture toughness at 4.2 K, and this inverse size effect on the cryogenic toughness was elaborately revealed.

Background: Soft-tissue sarcoma (STS) is a massive threat to human health due to its high morbidity and malignancy. STS also represents more than 100 histologic and molecular subtypes, with different prognosis. There is growing evidence that anoikis play a key role in the proliferation and invasion of tumors. However, the effects of anoikis in the immune landscape and the prognosis of STS remain unclear.Methods: We analyzed the genomic and transcriptomic profiling of 34 anoikis-related genes (ARGs) in patient cohort of pan-cancer and STS from The Cancer Genome Atlas (TCGA) database. Single-cell transcriptome was used to disclose the expression patterns of ARGs in specific cell types. Gene expression was further validated by real-time PCR and our own sequencing data. We established the Anoikis cluster and Anoikis subtypes by using unsupervised consensus clustering analysis. An anoikis scoring system was further built based on the differentially expressed genes (DEGs) between Anoikis clusters. The clinical and biological characteristics of different groups were evaluated.Results: The expressions of most ARGs were significantly different between STS and normal tissues. We found some common ARGs profiles across the pan-cancers. Network of 34 ARGs demonstrated the regulatory pattern and the association with immune cell infiltration. Patients from different Anoikis clusters or Anoikis subtypes displayed distinct clinical and biological characteristics. The scoring system was efficient in prediction of prognosis and immune cell infiltration. In addition, the scoring system could be used to predict immunotherapy response.Conclusion: Overall, our study thoroughly depicted the anoikis-related molecular and biological profiling and interactions of ARGs in STS. The Anoikis score model could guide the individualized management.

Abstract Gauge invariance plays an important role in forming topological defects. In this work, from the AdS/CFT correspondence, we realize the clusters of equal-sign vortices during the course of critical dynamics of a strongly coupled superconductor. This is the first time to achieve the equal-sign vortex clusters in strongly coupled systems. The appearance of clusters of equal-sign vortices is a typical character of flux trapping mechanism, distinct from Kibble-Zurek mechanism which merely presents vortex-antivortex pair distributions resulting from global symmetry breaking. Numerical results of spatial correlations and net fluxes of the equal-sign vortex clusters quantitatively support the positive correlations between vortices. The linear dependence between the vortex number and the amplitude of magnetic field at the ‘trapping’ time demonstrates the flux trapping mechanism very well.

ObjectivesTraumatic intracerebellar hematoma (TICH) is a very rare entity with a high morbidity and mortality rate, and there is no consensus on its optimal surgical management. In particular, whether and when to place external ventricle drainage in TICH patients without acute hydrocephalus pre-operation is still controversial.MethodsA single-institutional, retrospective analysis of total of 47 TICH patients with craniectomy hematoma evacuation in a tertiary medical center from January 2009 to October 2020 was performed. Primary outcomes were mortality in hospital and neurological function evaluated by GOS at discharge and 6 months after the ictus. Special attention was paid to the significance of external ventricular drainage (EVD) in TICH patients without acute hydrocephalus on admission.ResultsAnalysis of the clinical characteristics of the TICH patients revealed that the odds of use of EVD were seen in patients with IVH, fourth ventricle compression, and acute hydrocephalus. Placement of EVD at the bedside can significantly improve the GCS score before craniotomy, as well as the neurological score at discharge and 6 months. Compared with the only hematoma evacuation (HE) group, there is a trend that EVD can reduce hospital mortality and decrease the occurrence of delayed hydrocephalus, although the difference is not statistically significant. In addition, EVD can reduce the average NICU stay time, but has no effect on the total length of stay. Moreover, our data showed that EVD did not increase the risk of associated bleeding and intracranial infection. Interestingly, in terms of neurological function at discharge and 6 month after the ictus, even though without acute hydrocephalus on admission, the TICH patients can still benefit from EVD insertion.ConclusionFor TICH patients, perioperative EVD is safe and can significantly improve neurological prognosis. Especially for patients whose GCS dropped by more than 2 points before the operation, EVD can significantly improve the patient's GCS score, reduce the risk of herniation, and gain more time for surgical preparation. Even for TICH patients without acute hydrocephalus on admission CT scan, EVD placement still has positive clinical significance.

Paracoccus marginatus is a highly polyphagous invasive pest that poses a significant quarantine threat to tropical and subtropical countries. Infested commodities in international trade should undergo phytosanitary treatment, and irradiation is recommended as a viable alternative to replace methyl bromide fumigation. Dose-response tests were conducted on the 2-, 4-, and 6-day-old eggs and gravid females of P. marginatus using the X-ray radiation doses of 15–105 Gy with an interval of 15 Gy. Radiotolerance was compared using ANOVA, fiducial overlapping and lethal dose ratio (LDR) test, resulting in no significant difference among treatments, except for the overall mortality and LDR at LD90 (a dose causing 90% mortality at 95% confidence level). The estimated dose for LD99.9968 was 176.5–185.2 Gy, which was validated in the confirmatory tests. No nymphs emerged from a total of 60,386 gravid females exposed to a gamma radiation dose range of 146.8–185.0 Gy in the confirmatory tests. The largest dose in confirmatory tests should be the minimum threshold for phytosanitary treatment, consequently, a minimum dose of 185 Gy is recommended for the phytosanitary irradiation treatment of papaya mealybug-infested commodities, ensuring a treatment efficacy of ≥99.9950% at 95% confidence level.

Abstract Traversing a continuous phase transition at a finite rate leads to the breakdown of adiabatic dynamics and the formation of topological defects, as predicted by the celebrated Kibble-Zurek mechanism (KZM). We investigate universal signatures beyond the KZM, by characterizing the distribution of vortices generated in a thermal quench leading to the formation of a holographic superconductor. The full counting statistics of vortices is described by a binomial distribution, in which the mean value is dictated by the KZM and higher-order cumulants share the universal power-law scaling with the quench time. Extreme events associated with large fluctuations no longer exhibit a power-law behavior with the quench time and are characterized by a universal form of the Weibull distribution for different quench rates.

Abstract We employ holographic techniques to explore the effects of momentum dissipation on the formation of topological defects during the critical dynamics of a strongly coupled superconductor after a linear quench of temperature. The gravity dual is the dRGT massive gravity in which the conservation of momentum in the boundary field theory is broken by the presence of a bulk graviton mass. From the scaling relations of defects number and “freeze-out” time to the quench rate for various graviton masses, we demonstrate that the momentum dissipation induced by graviton mass has little effect on the scaling laws compared to the Kibble-Zurek mechanism. Inspired from Pippard’s formula in condensed matter, we propose an analytic relation between the coherence length and the graviton mass, which agrees well with the numerical results from the quasi-normal modes analysis. As a result, the coherence length decreases with respect to the graviton mass, which indicates that the momentum dissipation will augment the number of topological defects.

The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith, 1797), known as an important agricultural pest around the world, is indigenous to the tropical–subtropical regions in the Western Hemisphere, although its distribution has expanded over large parts of America, Africa, Asia and Oceania in the last few years. The pest causes considerable costs annually coupled with its strong invasion propensity. Temperature is identified as the dominant abiotic factor affecting herbivorous insects. Several efforts have reported that temperature directly or indirectly influences the geographic distribution, phenology and natural enemies of the poikilothermal FAW, and thus may affect the damage to crops, e.g., the increased developmental rate accelerates the intake of crops at higher temperatures. Under some extreme temperatures, the FAW is likely to regulate various genes expression in response to environmental changes, which causes a wider viability and possibility of invasion threat. Therefore, this paper seeks to review and critically consider the variations of developmental indicators, the relationships between the FAW and its natural enemies and the temperature tolerance throughout its developmental stage at varying levels of heat/cold stress. Based on this, we discuss more environmentally friendly and economical control measures, we put forward future challenges facing climate change, we further offer statistical basics and instrumental guidance significance for informing FAW pest forecasting, risk analyses and a comprehensive management program for effective control globally.

Exploring the lowest energy configurations of a quantum system is consistent with the counting statistics of the frequently appearing states from quenching dynamics. By studying the Little-Parks periodicities in a multiply connected ring-shaped geometry from the holographic technique, it is found that the frequently appearing states from dynamics are inclined to have lower free energies. In particular, the resulting winding numbers from quenched dynamics are constrained in a normal distribution for a fixed magnetic flux threading the ring. Varying the magnetic fluxes, Little-Parks periodicities will take place with periods identical to the flux quantum Φ_{0}. Favorable solutions with lowest free energies perform first-order phase transitions which transform between distinct winding numbers as the magnetic flux equals half-integers multiplying Φ_{0}.

Online Social networks exhibit heterogeneous nature with nodes playing far different roles in structure and function. To identify influencers is thus very significant, allowing us to control the outbreak of public negative opinion, to conduct advertisements for e-commercial products, to predict popular scientific publications, and so on. The identification of influencers attracts increasing attentions from both computer science and communication science, with multiple dimensional metrics ranging from structure-based to information-based and action-based. However, most work simply rely on one dimensional metrics. Therefore, in this paper, we analyze three dimensional characteristics (structure-based, information-based, and action-based factors) to develop the multidimensional social influence (MSI) measurement approach. With topic distillation and conditional expectation, the MSI approach can not only measure users topic-level influence, but also measure users global-level influence. Based on data collected from SinaWeibo.com, the experimental results show that the proposed framework outperforms two traditional methods (LeaderRank and FBI) both on the topic-level and the global-level. The proposed framework can be effectively applied to promote word-of-mouth marketing, and to steer public opinion in certain directions, even to support decisions during a negotiation process.

ABSTRACT: The precise correlation of the Ordovician successions in different facies is difficult due to the complex changes of the tecto-paleogeography in South China. Based on previous studies, the authors recognized 10 3rd grade sequences, i. e., Osq1 to Osq10 in ascending order, by the integrated study of chronostratigraphy, biostratigraphy as well as the analysis on the sedimentary facies. The authors are confident to correlate the Ordovician successions precisely in different facies in an isochronous stratigraphic framework with the application of the method of sequence stratigraphy and correlation.

The khapra beetle, Trogoderma granarium Everts, is defined as one of the most important quarantine pests globally, and fumigation with methyl bromide, an ozone-depleting substance, is a common phytosanitary measure currently used. The modified atmosphere (MA), irradiation, and their combination treatments of T. granarium larvae and adults were performed at room temperature (24–26 ℃) to develop an ecofriendly phytosanitary disinfestation measure and to shorten the exposure time and overcome treatment disadvantages of irradiation. Late-stage larvae are determined as the most tolerant stage resulted in large LT99.9968 values of 32.6 (29.2–37.5) and 38.0 (35.1–41.7) days treated under 1% and 2% O2 (with N2 balance) atmosphere, respectively. Ionizing radiation was used to enhance the effect of MA and the mortality was highly significantly affected by all the interaction effects, indicating that the synergistic effects present in all the combined treatments. The synergistic ratios, which is defined as the estimated lethal time for MA treatment (LD90, LD99, and LD99.9968), divided by that of combined treatment, were between 1.47 and 2.47. In the confirmatory tests, no individuals recovered from a sum of 111,366 late-stage larvae treated under 1% O2 atmosphere for 14- or 15-d after 200 Gy irradiation, which resulted in validating the probit estimations and achieving an efficacy of 99.9973% mortality at 95% confidence level. Therefore, these treatment schedules are recommended to disinfest T. granarium infecting commodities for phytosanitary purposes under the warehouse, MA packaging, or in combination with international transportation by train or sea container.

Objective To investigate the relationship between inflammatory factors, oxidative stress and type 1 deiodinase (DIO-1) concentration in patients with chronic renal failure (CRF) with or without euthyroid sick syndrome (ESS). Methods This study recruited patients with CRF and divided them into two groups: group 1 had low free triiodothyronine (FT3) levels; and group 2 had normal FT3 levels. Group 3 consisted of healthy volunteers. Serum levels of interleukin (IL)-6, IL-1β, tumour necrosis factor (TNF)-α, 8-isoprostane and DIO-1 were measured using enzyme-linked immunosorbent assays. Multiple regression analysis was used to analyse correlations between parameters. Results Sixty patients were enrolled into each group and the groups were comparable in terms of vital signs, white blood cell count, free thyroxine and thyroid stimulating hormone concentrations. The serum DIO-1 concentration was significantly higher in group 2 than in groups 1 and 3. Multivariate regression analysis revealed that the DIO-1 concentration was inversely correlated with the TNF-α concentration. Conclusions Patients with CRF without ESS showed higher concentrations of DIO-1 than patients with ESS. The DIO-1 concentration was inversely correlated with the TNF-α concentration, which might indicate that the inflammatory response was milder in the patients with CRF without ESS than in those with ESS.