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Abstract The stratosphere-troposphere and the tropics-Arctic couplings were intermittently enhanced in the 2023/24 winter. Here we used ERA5 reanalysis data and found that due to the amplification of planetary wavenumber 1 and 2 pulses, three displacement-type sudden stratospheric warming events occurred in one winter under the background conditions of warming equatorial middle and east Pacific, active equatorial convections, and easterly stratospheric equatorial winds. During the sudden stratospheric warming events, the stratospheric disturbances propagated downward to the surface, followed by continental cold surges. The residual meridional circulation was strengthened across the tropics and Arctic, anomalously more water vapor was transported into the stratosphere in tropics, while ozone content diminished in the lower stratosphere and grew in the upper stratosphere over the tropics. Meanwhile, water vapor and ozone over the Arctic exhibited a dipping pattern from the upper to the lower stratosphere.

Abstract Background Obesity is well-established as a significant contributor to the development of insulin resistance (IR) and diabetes, partially due to elevated plasma saturated free fatty acids like palmitic acid (PA). Grb10-interacting GYF Protein 2 (GIGYF2), an RNA-binding protein, is widely expressed in various tissues including the liver, and has been implicated in diabetes-induced cognitive impairment. Whereas, its role in obesity-related IR remains uninvestigated. Methods In this study, we employed palmitic acid (PA) exposure to establish an in vitro IR model in the human liver cancer cell line HepG2 with high-dose chronic PA treatment. The cells were stained with fluorescent dye 2-NBDG to evaluate cell glucose uptake. The mRNA expression levels of genes were determined by real-time qRT-PCR (RT-qPCR). Western blotting was employed to examine the protein expression levels. The RNA immunoprecipitation (RIP) was used to investigate the binding between protein and mRNA. Lentivirus-mediated gene knockdown and overexpression were employed for gene manipulation. In mice, an IR model induced by a high-fat diet (HFD) was established to validate the role and action mechanisms of GIGYF2 in the modulation of HFD-induced IR in vivo. Results In hepatocytes, high levels of PA exposure strongly trigger the occurrence of hepatic IR evidenced by reduced glucose uptake and elevated extracellular glucose content, which is remarkably accompanied by up-regulation of GIGYF2. Silencing GIGYF2 ameliorated PA-induced IR and enhanced glucose uptake. Conversely, GIGYF2 overexpression promoted IR, PTEN upregulation, and AKT inactivation. Additionally, PA-induced hepatic IR caused a notable increase in STAU1, which was prevented by depleting GIGYF2. Notably, silencing STAU1 prevented GIGYF2-induced PTEN upregulation, PI3K/AKT pathway inactivation, and IR. STAU1 was found to stabilize PTEN mRNA by binding to its 3’UTR. In liver cells, tocopherol treatment inhibits GIGYF2 expression and mitigates PA-induced IR. In the in vivo mice model, GIGYF2 knockdown and tocopherol administration alleviate high-fat diet (HFD)-induced glucose intolerance and IR, along with the suppression of STAU1/PTEN and restoration of PI3K/AKT signaling. Conclusions Our study discloses that GIGYF2 mediates obesity-related IR by disrupting the PI3K/AKT signaling axis through the up-regulation of STAU1/PTEN. Targeting GIGYF2 may offer a potential strategy for treating obesity-related metabolic diseases, including type 2 diabetes. Graphical Abstract

Background: Diabetes Mellitus (DM), a chronic metabolic disease characterized by elevated blood glucose, is caused by various degrees of insulin resistance and dysfunctional insulin secretion, resulting in hyperglycemia. The loss and failure of functional β-cells are key mechanisms resulting in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Aim of review: Elucidating the underlying mechanisms of β-cell failure, and exploring approaches for β-cell neogenesis to reverse β-cell dysfunction may provide novel strategies for DM therapy. Key scientific concepts of review: Emerging studies reveal that genetic susceptibility, endoplasmic reticulum (ER) stress, oxidative stress, islet inflammation, and protein modification linked to multiple signaling pathways contribute to DM pathogenesis. Over the past few years, replenishing functional β-cell by β-cell neogenesis to restore the number and function of pancreatic β-cells has remarkably exhibited a promising therapeutic approach for DM therapy. In this review, we provide a comprehensive overview of the underlying mechanisms of β-cell failure in DM, highlight the effective approaches for β-cell neogenesis, as well as discuss the current clinical and preclinical agents research advances of β-cell neogenesis. Insights into the challenges of translating β-cell neogenesis into clinical application for DM treatment are also offered.

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators of many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, and inflammation. Accumulating evidence has shown that PGC-1s are implicated in many diseases, such as cancers, cardiac diseases and cardiovascular diseases, neurological disorders, kidney diseases, motor system diseases, and metabolic disorders. Examining the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of PGC-1s. Furthermore, discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention methods. In this review, we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network, discuss the physio-pathological roles of PGC-1s in human diseases, review the application of PGC-1s, including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies, and suggest several directions for future investigations. This review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

In this paper, the design methodology and implementation of single-band and multiple-band elliptic function bandpass filters (BPFs) are presented, based on the concept of bandstop resonator (BSR) sections. One or more single-mode and multiple-mode BSRs can be dangled from a non-resonant node. Each BSR can generate one reflection zeroes (RZ) and one transmission zeroes (TZ). Multiple BSR sections are used to flexibly and independently control the location and bandwidth of the stop bands and therefore the same of the passbands. The method to design single- and multiple-band elliptic function BPFs has been detailed using a number of examples based on waveguide technology. For proof of concept, a 6th-order single-band BPF with six BSR = 2 sections and a 3rd-order dual-band BPF using three BSR = 3 sections are designed and fabricated monolithically using a selective-laser-melting (SLM) 3-D printing technique. Excellent agreement between simulated and measured results verifies the proposed design methodology and its versatility as well as the additive-manufacture approach.

Human–robot (HR) collaboration (HRC) is an emerging research field because of the complementary advantages of humans and robots. An HRC framework for robotic assembly based on impedance control is proposed in this paper. In the HRC framework, the human is the decision maker, the robot acts as the executor, while the assembly environment provides constraints. The robot is the main executor to perform the assembly action, which has the position control, drag and drop, positive impedance control, and negative impedance control modes. To reveal the characteristics of the HRC framework, the switch condition map of different control modes and the stability analysis of the HR coupled system are discussed. In the end, HRC assembly experiments are conducted, where the HRC assembly task can be accomplished when the assembling tolerance is 0.08 mm or with the interference fit. Experiments show that the HRC assembly has the complementary advantages of humans and robots and is efficient in finishing complex assembly tasks.

Abstract Mangrove reforestation with introduced species has been an important strategy to restore mangrove ecosystem functioning. However, how such activities affect microbially driven methane (CH4), nitrogen (N), and sulfur (S) cycling of rhizosphere microbiomes remains unclear. To understand the effect of environmental selection and the evolutionary process on microbially driven biogeochemical cycles in native and introduced mangrove rhizospheres, we analyzed key genomic and functional profiles of rhizosphere microbiomes from native and introduced mangrove species by metagenome sequencing technologies. Compared with the native mangrove (Kandelia obovata, KO), the introduced mangrove (Sonneratia apetala, SA) rhizosphere microbiome had significantly (p

Abstract Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.

Conclusions: Chitosan-based HP treatment could reduce the incidence of vascular complications in patients with uncontrolled hypertension. Nonetheless, applying chitosan-based HP treatment after CAG or PCI procedures is not recommendable for controlled hypertensive patients.

Circular RNAs (circRNAs), a novel type of single-stranded noncoding RNAs with a covalently closed loop structure, are generated in a circular conformation via non-canonical splicing or back-splicing events. Functionally, circRNAs have been elucidated to soak up microRNAs (miRNAs) and RNA binding proteins (RBPs), serve as protein scaffolds, maintain mRNA stability, and regulate gene transcription and translation. Notably, circRNAs are strongly implicated in the regulation of β-cell functions, insulin resistance, adipocyte functions, inflammation as well as oxidative stress via acting as miRNA sponges and RBP sponges. Basic and clinical studies have demonstrated that aberrant alterations of circRNAs expressions are strongly associated with the initiation and progression of diabetes mellitus (DM) and its complications. Here in this review, we present a summary of the biogenesis, transportation, degradation and functions of circRNAs, and highlight the recent findings on circRNAs and their action mechanisms in DM and its complications. Overall, this review should contribute greatly to our understanding of circRNAs in DM pathogenesis, offering insights into the further perspectives of circRNAs for DM diagnosis and therapy.

Abstract Background Mangrove ecosystems are considered as hot spots of biogeochemical cycling, yet the diversity, function and coupling mechanism of microbially driven biogeochemical cycling along the sediment depth of mangrove wetlands remain elusive. Here we investigated the vertical profile of methane (CH4), nitrogen (N) and sulphur (S) cycling genes/pathways and their potential coupling mechanisms using metagenome sequencing approaches. Results Our results showed that the metabolic pathways involved in CH4, N and S cycling were mainly shaped by pH and acid volatile sulphide (AVS) along a sediment depth, and AVS was a critical electron donor impacting mangrove sediment S oxidation and denitrification. Gene families involved in S oxidation and denitrification significantly (P < 0.05) decreased along the sediment depth and could be coupled by S-driven denitrifiers, such as Burkholderiaceae and Sulfurifustis in the surface sediment (0–15 cm). Interestingly, all S-driven denitrifier metagenome-assembled genomes (MAGs) appeared to be incomplete denitrifiers with nitrate/nitrite/nitric oxide reductases (Nar/Nir/Nor) but without nitrous oxide reductase (Nos), suggesting such sulphide-utilizing groups might be an important contributor to N2O production in the surface mangrove sediment. Gene families involved in methanogenesis and S reduction significantly (P < 0.05) increased along the sediment depth. Based on both network and MAG analyses, sulphate-reducing bacteria (SRB) might develop syntrophic relationships with anaerobic CH4 oxidizers (ANMEs) by direct electron transfer or zero-valent sulphur, which would pull forward the co-existence of methanogens and SRB in the middle and deep layer sediments. Conclusions In addition to offering a perspective on the vertical distribution of microbially driven CH4, N and S cycling genes/pathways, this study emphasizes the important role of S-driven denitrifiers on N2O emissions and various possible coupling mechanisms of ANMEs and SRB along the mangrove sediment depth. The exploration of potential coupling mechanisms provides novel insights into future synthetic microbial community construction and analysis. This study also has important implications for predicting ecosystem functions within the context of environmental and global change. Video Abstract

Vascular endothelial cells (ECs) senescence plays a crucial role in vascular aging that promotes the initiation and progression of cardiovascular disease. The mutation of Grb10-interacting GYF protein 2 (GIGYF2) is strongly associated with the pathogenesis of aging-related diseases, whereas its role in regulating ECs senescence and dysfunction still remains elusive. In this study, we found aberrant hyperexpression of GIGYF2 in senescent human ECs and aortas of old mice. Silencing GIGYF2 in senescent ECs suppressed eNOS-uncoupling, senescence, and endothelial dysfunction. Conversely, in nonsenescent cells, overexpressing GIGYF2 promoted eNOS-uncoupling, cellular senescence, endothelial dysfunction, and activation of the mTORC1-SK61 pathway, which were ablated by rapamycin or antioxidant N-Acetyl-l-cysteine (NAC). Transcriptome analysis revealed that staufen double-stranded RNA binding protein 1 (STAU1) is remarkably downregulated in the GIGYF2-depleted ECs. STAU1 depletion significantly attenuated GIGYF2-induced cellular senescence, dysfunction, and inflammation in young ECs. Furthermore, we disclosed that GIGYF2 acting as an RNA binding protein (RBP) enhances STAU1 mRNA stability, and that the intron region of the late endosomal/lysosomal adaptor MAPK and mTOR activator 4 (LAMTOR4) could bind to STAU1 protein to upregulate LAMTOR4 expression. Immunofluorescence staining showed that GIGYF2 overexpression promoted the translocation of mTORC1 to lysosome. In the mice model, GIGYF2flox/flox Cdh-Cre+ mice protected aged mice from aging-associated vascular endothelium-dependent relaxation and arterial stiffness. Our work discloses that GIGYF2 serving as an RBP enhances the mRNA stability of STAU1 that upregulates LAMTOR4 expression through binding with its intron region, which activates the mTORC1-S6K1 signaling via recruitment of mTORC1 to the lysosomal membrane, ultimately leading to ECs senescence, dysfunction, and vascular aging. Disrupting the GIGYF2-STAU1-mTORC1 signaling cascade may represent a promising therapeutic approach against vascular aging and aging-related cardiovascular diseases.

Abstract This study aims to investigate the association between maternal blood parameters and the risk of neonatal pathological jaundice. A retrospective case–control study of 1309 newborns and their mothers from 2019 to 2020 in a single-center tertiary hospital. All mothers received a complete routine blood test prior to delivery, and outcome was neonatal pathological jaundice. We performed stepwise logistic regression modeling to identify maternal blood factors associated with neonatal pathological jaundice. 258 neonates (19.71%) were diagnosed with pathological jaundice. Logistic regression results showed that the odds ratio for pathological jaundice in neonates of mothers with high white blood cell (WBC) count was 1.512 (95% CI 1.145–1.998; P = 0.004). Besides, neonates whose mothers had a high mean corpuscular volume (MCV) during pregnancy doubled the odds of developing pathological jaundice (OR = 1.967; 95% CI 1.043–3.711; P = 0.037). Among neonates, those whose mothers had high levels of WBC count and MCV were at increased risk of pathological jaundice. Regular obstetric examinations and routine blood tests are essential to initiate adapted care.

This article for the first time presents a high-Q cavity resonator manufactured using carbon-fiber reinforced silicon carbide (SiC) ceramic composite material HB-Cesic. This composite has attractive properties of low coefficient of thermal expansion comparable to Invar, low density similar to aluminum, and high thermal conductivity. Its manufacturing process enabled by machining and joining renders useful design flexibility. A high-Q spherical resonator has been used as an example in this investigation. Two resonators, one monolithic version and the other one based on split-block structure have been experimented. The end-to-end processes from machining, assembly or joining, to high-conductivity coating for both structures, have been demonstrated. The RF performance of the resonators and their variation with temperature have been measured. A quality factor of over 10000 has been achieved for both resonators at 11.483 GHz. The measured high thermal stability of the resonator correlates very well with the prediction. This work establishes the feasibility of using HB-Cesic in microwave resonators and paves the way for further development and verification programme for more complex passive microwave devices such as filters and multiplexers for space applications.

The design concept of a pole-generating resonant iris is demonstrated in rectangular waveguide filters in this paper. Different from conventional reactive iris, the resonant iris can generate an extra transmission pole without increasing the number of resonant cavities. As a result, several design advantages can be gained: (i) a more compact filter structure; (ii) an ability to realize strong coupling and therefore wide bandwidth; and (iii) a new polarization rotation capability. Two third-order Chebyshev filters are designed and implemented, demonstrating the miniaturization and polarization rotation feature. A fifth-order Chebyshev filter with 20% fractional bandwidth is presented to show the capability of realizing wideband. This also demonstrates the realization of asymmetric coupling between the resonant iris and the cavity resonator on either side. An approach to control and extract the coupling between the iris and the cavity resonator has also been presented. To manufacture the intricate asymmetric iris structure, all the presented filters are printed monolithically using selective laser melting technique. Excellent agreement between the measurements and simulations has been achieved, verifying the design concept as well as the additive manufacturing capability in microwave waveguide devices.

The aviation assembly domain, which is a complex system, involves the multi-dimensional information of parts, processes, tools, plants and operation projects. In order to assist the knowledge management from natural language text in the aircraft manufacturing process, this paper proposes the corresponding ontology scheme and the joint knowledge extraction model, which is necessary for construct the knowledge graph in the aviation assembly domain. The model is able to automated end-to-end construct knowledge graph. The proposed model, which is based on reinforcement learning approach and a novel labeling scheme, takes the constraint relationships between entities and relations as an important identification basis. The model does not rely on manual feature setting, while it greatly reduces the training cost. The proposed joint knowledge extraction model was testified from the practical scenarios of the general assembly and component assembly. The experimental results showed that the proposed model showed an excellent performance in the aviation assembly domain, with the F1-score of 89.71% for entities, the F1-score of 91.27% for relations, and the overall average F1-score of 82.41%. Based on the superior performance of the model, the knowledge graph of the general assembly and component assembly, which included 1, 308 pairs of triples composed of five kinds of entities and three kinds of relations, was further constructed in the aviation assembly domain.

Purpose The charring tissue formation in the ablated lesion during the microwave ablation (MWA) of tumors would induce various unwanted inflammatory responses. This paper aimed to deliver appropriate thermal dose for effective ablations while preventing tissue carbonization by optimizing the treatment protocol during MWA with the set combinations of temperature control and pulsed microwave energy delivery.Material and methods The thermal phase transition of ex vivo porcine liver tissues were recorded by differential scanning calorimetry (DSC) to determine the temperature threshold during microwave output control. MWA was performed by an in-house built system with the ease of microwave output parameter adjustment and real-time temperature monitoring. The effects of continuous and pulsed microwave deliveries as well as various intermittent time-set of MWA were evaluated by measuring the dimensions of the coagulation zone and the carbonization zone.Results The DSC scans demonstrated that the ex vivo porcine liver tissues have been in a state of endothermic heat during the heating process, where the maximum absorbed heat occurred at the temperature of 105 °C ± 5 °C. The temperature control during MWA resulted in effective coagulative necrosis while preventing tissue carbonization, after setting 100 °C as the upper threshold temperature and 60 °C as the lower threshold. Both the numerical simulation and ex vivo experiments have shown that, upon the optimization of the time-set parameters in the periodic intermittent pulsed microwave output, the tissue carbonization was significantly diminished.Conclusion This study developed a straight-forward anti-carbonization strategy in MWA by modulating the pulsing mode and intermittent time. The programmed protocols of intermittent pulsing MWA have demonstrated its potentials toward future expansion of MWA technology in clinical application.

Abstract Arginase, a binuclear manganese metalloenzyme in the urea, catalyzes the hydrolysis of L-arginine to urea and L-ornithine. Both isoforms, arginase 1 and arginase 2 perform significant roles in the regulation of cellular functions in cardiovascular system, such as senescence, apoptosis, proliferation, inflammation, and autophagy, via a variety of mechanisms, including regulating L-arginine metabolism and activating multiple signal pathways. Furthermore, abnormal arginase activity contributes to the initiation and progression of a variety of CVDs. Therefore, targeting arginase may be a novel and promising approach for CVDs treatment. In this review, we give a comprehensive overview of the physiological and biological roles of arginase in a variety of CVDs, revealing the underlying mechanisms of arginase mediating vascular and cardiac function, as well as shedding light on the novel and promising therapeutic approaches for CVDs therapy in individuals.

The classroom teaching and quality evaluation of college English teachers is an effective way to evaluate the teaching quality and improve the teaching level of teachers. But there is uncertainty and fuzziness in the process of teaching and quality evaluation. Therefore, based on the data mining technology, the analytic hierarchy process is used to construct the evaluation index body. Then the indexes which have important influence on the evaluation result are selected as BP neural network input. Finally, the neural network teaching and quality evaluation model is established, and the improved algorithm is simulated. The validity of this method is verified by experiments, which can improve the accuracy of college English teaching and quality evaluation. With the help of SPSS and Weka data mining tools, this paper uses a variety of data mining means to conduct in-depth mining analysis of various teaching operation status data, explore the complex relationship behind the data and its value significance, then further propose how to effectively use data mining to implement teaching quality monitoring methods and measures, and discuss how to combine the analysis results for optimizing the use of student assessment data, innovating the way of college students The study also discusses how to combine the analysis results to optimize the use of student evaluation data and to innovate the way of guiding the quality assessment of English courses for college students, to provide meaningful references for the implementation of English teaching quality assessment.

The collaborative robot can complete various drilling tasks in complex processing environments thanks to the high flexibility, small size and high load ratio. However, the inherent weaknesses of low rigidity and variable rigidity in robots bring detrimental effects to surface quality and drilling efficiency. Effective online monitoring of the drilling quality is critical to achieve high performance robotic drilling. To this end, an end-to-end drilling-state monitoring framework is developed in this paper, where the drilling quality can be monitored through online-measured vibration signals. To evaluate the drilling effect, a Canny operator-based edge detection method is used to quantify the inclination state of robotic drilling, which provides the data labeling information. Then, a robotic drilling inclination state monitoring model is constructed based on the Resnet network to classify the drilling inclination states. With the aid of the training dataset labeled by different inclination states and the end-to-end training process, the relationship between the inclination states and vibration signals can be established. Finally, the proposed method is verified by collaborative robotic drilling experiments with different workpiece materials. The results show that the proposed method can effectively recognize the drilling inclination state with high accuracy for different workpiece materials, which demonstrates the effectiveness and applicability of this method.

Abstract Background Phosphorus (P) is one of the most essential macronutrients on the planet, and microorganisms (including bacteria and archaea) play a key role in P cycling in all living things and ecosystems. However, our comprehensive understanding of key P cycling genes (PCGs) and microorganisms (PCMs) as well as their ecological functions remains elusive even with the rapid advancement of metagenome sequencing technologies. One of major challenges is a lack of a comprehensive and accurately annotated P cycling functional gene database. Results In this study, we constructed a well-curated P cycling database (PCycDB) covering 139 gene families and 10 P metabolic processes, including several previously ignored PCGs such as pafA encoding phosphate-insensitive phosphatase, ptxABCD (phosphite-related genes), and novel aepXVWPS genes for 2-aminoethylphosphonate transporters. We achieved an annotation accuracy, positive predictive value (PPV), sensitivity, specificity, and negative predictive value (NPV) of 99.8%, 96.1%, 99.9%, 99.8%, and 99.9%, respectively, for simulated gene datasets. Compared to other orthology databases, PCycDB is more accurate, more comprehensive, and faster to profile the PCGs. We used PCycDB to analyze P cycling microbial communities from representative natural and engineered environments and showed that PCycDB could apply to different environments. Conclusions We demonstrate that PCycDB is a powerful tool for advancing our understanding of microbially driven P cycling in the environment with high coverage, high accuracy, and rapid analysis of metagenome sequencing data. The PCycDB is available at https://github.com/ZengJiaxiong/Phosphorus-cycling-database . Video Abstract

Abstract Heart failure (HF), as the leading cause of death, is continuing to increase along with the aging of the general population all over the world. Identification of diagnostic biomarkers for early detection of HF is considered as the most effective way to reduce the risk and mortality. Herein, we collected plasma samples from HF patients (n = 40) before and after medical therapy to determine the change of circulating miRNAs through a quantitative real-time PCR (QRT-PCR)-based miRNA screening analysis. miR-30a-5p and miR-654-5p were identified as the most significantly changed miRNAs in the plasma of patients upon treatment. In consistence, miR-30a-5p showed upregulation and miR-654-5p showed downregulation in the circulation of 30 HF patients, compared to 15 normal controls in the training phase, from which a two-circulating miRNA model was developed for HF diagnosis. Next, we performed the model validation using an independent cohort including 50 HF patients and 30 controls. As high as 98.75% of sensitivity and 95.00% of specificity were achieved. A comparison between the miRNA model and NT-pro BNP in diagnostic accuracy of HF indicated an upward trend of the miRNA model. Moreover, change of the two miRNAs was further verified in association with the therapeutic effect of HF patients, in which miR-30a-5p showed decrease while miR-654-5p showed increase in the plasma of patients after LVAD implantation. In conclusion, the current study not only identified circulating miR-654-5p for the first time as a novel biomarker of HF, but also developed a novel 2-circulating miRNA model with promising potentials for diagnosis and prognosis of HF patients, and in association with therapeutic effects as well.

Abstract Most sepsis deaths are due to the development of multiple organ failure, in which heart failure is a recognized manifestation of sepsis. To date, the role of liver X receptors α (NR1H3) in sepsis is still uncertain. Here, we hypothesized that NR1H3 mediates multiple essential sepsis‐related signalings to attenuate septic heart failure. Adult male C57BL/6 or Balbc mice and HL‐1 myocardial cell line were performed for in vivo and in vitro experiments, respectively. NR1H3 knockout mice or NR1H3 agonist T0901317 was applied to evaluate the impact of NR1H3 on septic heart failure. We found decreased myocardial expression levels of NR1H3‐related molecules while increased NLRP3 level in septic mice. NR1H3 knockout worsensed cardiac dysfunction and injury in mice subjected to cecal ligation and puncture (CLP), in association with exacerbated NLRP3‐mediated inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and apoptosis‐related markers. The administration of T0901317 reduced systemic infection and improve cardiac dysfunction in septic mice. Moreover, Co‐IP assays, luciferase reporter assays, and chromatin immunoprecipitation analysis, confirmed that NR1H3 directly repressed NLRP3 activity. Finally, RNA‐seq detection further clarified an overview of the roles of NR1H3 in sepsis. In general, our findings indicate that NR1H3 had a significant protective effect against sepsis and sepsis‐induced heart failure.

Abstract During the lifetime of females, mammary epithelial cells undergo cyclical expansion and proliferation depending on the cyclical activation of mammary gland stem/progenitor cells (MaSCs) in response to the change of hormone level. The structural shrink of mammary duct tree and the functional loss of mammary gland occur along with inactivation of MaSCs in old females, even leading to breast cancer occasionally. However, the gene expression signature in MaSCs across the lifespan remains unclear. Herein, we tested the tissue regeneration ability of CD24+CD49fhigh MaSCs over six time points from neonatal (4-day-old) to aged mice (360-day-old). Further RNA-seq analyses identified four clusters of gene signatures based on the gene expression patterns. A subset of stemness-related genes was identified, showing the highest level at day 4 of the neonatal age, and the lowest level at the old age. We also identified an aging-related gene signature showing significant change in the old mice, in which an association between aging process and stemness loss was indicated. The aging-related gene signature showed regulation of cancer signaling pathways, as well as aging-related diseases including Huntington disease, Parkinson disease, and Alzheimer disease. Moreover, 425, 1056, 418, and 1107 gene variants were identified at D20, D40, D90, and D180, respectively, which were mostly reported to associated with tumorigenesis and metastasis in cancer. In summary, the current study is the first to demonstrate the gene expression shift in MaSCs from neonatal to aging, which leads to stemness loss, aging, aging-related diseases, and even breast cancer in old mice.

Chitin is one of the most common polysaccharides and is abundant in the cell walls of fungi and the shells of insects and aquatic organisms as a skeleton. The mechanism of how chitin responds to pH is essential to the precise control of brewing and the design of smart chitin materials. However, this molecular mechanism remains a mystery. Results from single-molecule studies, including single-molecule force spectroscopy (SMFS), AFM imaging, and molecular dynamic (MD) simulations, have shown that the mechanical and conformational behaviors of chitin molecules show surprising pH responsiveness. This can be compared with how, in natural aqueous solutions, chitin tends to form a more relaxed spreading conformation and show considerable elasticity under low stretching forces in acidic conditions. However, its molecular chain collapses into a rigid globule in alkaline solutions. The results show that the chain state of chitin can be regulated by the proportions of inter- and intramolecular H-bonds, which are determined via the number of water bridges on the chain under different pH values. This basic study may be helpful for understanding the cellular activities of fungi under pH stress and the design of chitin-based drug carriers.

Sulfur (S) is an essential biological element, and S cycling is mainly driven by metabolically versatile microorganisms. The river–wetland–ocean (RWO) continuum here is defined as the dynamically connected region with estuary, wetland, and near-marine ecosystems, and it is considered a hotspot of biogeochemical cycling, especially a major biotope for S cycling. Various forms and oxidation states of S compounds are considered ideal electron donors or acceptors and are widely utilized by microorganisms via inorganic or organic S-cycling processes. The S-cycling pathways are intimately linked to the carbon (C), nitrogen, phosphorus, and metal cycles, playing crucial roles in biogeochemical cycling, C sequestration, and greenhouse gas emissions through various mechanisms in the RWO continuum. This review provides a comprehensive understanding of microbially driven S cycling in the RWO continuum. We first illustrate the importance of S cycling in this continuum, including key microorganisms and functional processes (e.g., dissimilatory sulfate reduction, S oxidation, dimethylsulfoniopropionate production, and catabolism) as well as their corresponding S flux characteristics. In particular, we emphasize recent advances in the coupling mechanisms of the S cycle with other major element cycles. We further propose important perspectives for developing microbiome engineering of S-cycling microbial communities via integration of current knowledge about the multidimensional diversity, cultivation, evolution, and interaction of S-cycling microorganisms and their coupling mechanisms in the RWO continuum, providing a new window on applying microbiome-based biotechnologies to overcome global climate challenges.

Abstract Background Agricultural food production and distribution industries may play a vital role in determining the current conditions of any country’s food security and sustainable development goals. This paper examined the determinants of food security within three distinct aspects (effective utilization of food, food availability, and food access) within the COVID-19 epidemic situation. Methods The qualitative set-up of the study comprised with the identification of drivers by critical analysis of published papers and discussion held with some practitioners. The quantitative data used in this research were collected from a survey covering the agricultural food supply industry in China (Shaanxi Province). The survey was conducted from November to December 2020 and we mainly focus on three aspects of food security (effective utilization of food, food availability, and food access). The core analytical assumptions were made by employing exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and structural equation modeling (SEM). Results After analyzing the data collected from 257 agricultural food productions and distribution personnel along with the hypothesis testing, it found that the determinants of the effective utilization of food were positively related to the determinants of food access (β = 0.291, p = 0.029) and food availability (β = 0.298, p = 0.011), and the determinants of food availability were positively related to the food access determinants (β = 0.128, p = 0.002). The association and variance values between food availability and food access were 0.659 and 0.407; the association and variance values between for effective utilization of food and food availability aspects were 0.465 and 0.298, and between effective utilization of food and economy were 0.508 and 0.475. Conclusion The study critically evaluated the interconnection among the crucial determinants within the banner of three dimensions, which will act as a major contribution to existing literature. This research will help the government and industry to develop policies and strategies for the successful implementation of all the associated determinants of food security in terms of the epidemic situation.

Arbuscular mycorrhizal fungi (AMF) derived refractory organic matter, mainly in glomalin-related soil protein (GRSP), stores globally significant amounts of carbon, attracting wide attention in response to climatic change. However, there is no synthesis review has been done so far to reveal global research progresses on GRSP, especially its ecological role for climate mitigation. Here,we conducted a bibliometric analysis of the papers on GRSP research from 1998 to 2021, based on the Web of Science (WOS) Core Collection.We collected a total of 634 papers and analyzed the characteristics of publication outputs in various countries and institutions. In addition, keywords analysis was conducted to reveal the main research directions and hot trends in the field of GRSP. We confirmed that 1) the number of papers published per year has gradually increased since 2010, and increased sharply in 2019; 2) the United States was the earliest country to conduct GRSP research, while China currently has the largest number of publications; 3) relevant studies focus on the role from AMF and GRSP in soil health and plant health; 4) the contribution of GRSP to soil carbon and its ecological function in mitigating climate change are the hotspot of research. The benefits of GRSP have become a consensus, however, the nature of glomalin and the mechanisms of GRSP-associated benefits still need to explore. As an important soil recalcitrant organic carbon, further studies are need to elucidate the land-ocean biogeochemical processes of GRSP and its contribution to global blue carbon.

Abstract Excess mental stress may harm health, and even accelerate cancer initiation and progression. One fourth of breast cancer patients suffer mental stress including anxiety, sadness, or depression, which negatively affect prognosis and survival. However, the regulatory mechanism is yet to be determined. Herein, we applied unpredictable stress stimuli to the breast tumor-bearing mice to establish a xenograft model of breast cancer suffering mental stress, followed by behavioral tests, tumor growth tracking, immune analysis, miRNA screening, and tumor cell proliferation analysis as well. As a result, increased stress hormone levels in serum, decreased percentage of T and NK cells in both blood and tumor samples and accelerated tumor growth in vivo were observed in the mice exposed to mental stress. Promoted cell proliferation was observed in both primary tumor cells derived from the stressed mice and 4T1 breast cancer cells treated with stress hormone corticosterone. In addition, a subset of miRNAs including miR-326, 346, 493, 595, 615, and 665 were identified through a miRNA screening with downregulation in tumors of the stressed mice. CCND1 was identified as a common target gene of miR-346 and miR-493, the top two most significantly downregulated miRNAs by stress exposure. The stress-miRNA-CCND1 signaling regulation of the tumor cell proliferation was further validated in 4T1 cells treated with corticosterone in vitro. GO terms and KEGG pathways analyses on the target genes of miR-346 and miR-493 revealed their involvement in the regulation of human cancer and neuron system, indicating the importance of non-coding genome in mediating the mental stress-induced cancer regulation. In conclusion, this study not only explored immune and nonimmune mechanisms through which mental stress exposure contributes to tumor growth in breast cancer, but also suggested a new therapeutic strategy for cancer patients suffering mental stress.

Abstract Ferroptosis, a recently identified and iron-dependent cell death, differs from other cell death such as apoptosis, necroptosis, pyroptosis, and autophagy-dependent cell death. This form of cell death does not exhibit typical morphological and biochemical characteristics, including cell shrinkage, mitochondrial fragmentation, nuclear condensation. The dysfunction of lipid peroxide clearance, the presence of redox-active iron as well as oxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids are three essential features of ferroptosis. Iron metabolism and lipid peroxidation signaling are increasingly recognized as central mediators of ferroptosis. Ferroptosis plays an important role in the regulation of oxidative stress and inflammatory responses. Accumulating evidence suggests that ferroptosis is implicated in a variety of cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure, indicating that targeting ferroptosis will present a novel therapeutic approach against cardiovascular diseases. Here, we provide an overview of the features, process, function, and mechanisms of ferroptosis, and its increasingly connected relevance to oxidative stress, inflammation, and cardiovascular diseases.

Abstract Background miR-1250 is localised to the second intron of AATK at chromosome 17q25. As a CpG island is present at the putative promoter region of its host gene, AATK, we postulated that the intronic miR-1250-5p is a tumor suppressor miRNA co-regulated with its host gene, AATK, by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). Methods AATK/miR-1250 methylation was studied in healthy controls, including ten normal peripheral blood buffy coats and eleven normal tonsils, ten lymphoma cell lines, and 120 primary lymphoma samples by methylation-specific PCR (MSP). The expression of miR-1250-5p and AATK was investigated by quantitative real-time PCR. Tumor suppressor properties of miR-1250-5p were demonstrated by over-expression of precursor miR-1250-5p in lymphoma cells. The target of miR-1250-5p was verified by luciferase reporter assay. Results AATK/miR-1250 methylation was absent in healthy peripheral blood and tonsils, but detected in five (50%) NHL cell lines. AATK/miR-1250 methylation correlated with repression of miR-1250-5p and AATK in NHL cell lines. In completely methylated SU-DHL-6 and SUP-T1 cells, treatment with 5-AzadC led to promoter demethylation and re-expression of both miR-1250-5p and AATK. In primary lymphoma samples, AATK/miR-1250 was frequently methylated in B-cell lymphoma (n = 41, 44.09%) and T-cell lymphoma (n = 9, 33.33%) with a comparable frequency (P = 0.318). In SU-DHL-6 and SU-DHL-1 cells, restoration of miR-1250-5p resulted in decreased cellular proliferation by MTS assay, increased cell death by trypan blue staining and enhanced apoptosis by annexin V-PI assay. Moreover, MAPK1 and WDR1 were verified as direct targets of miR-1250-5p by luciferase assay. In 39 primary NHLs, miR-1250-5p expression was shown to be inversely correlated with each of MAPK1 (P = 0.05) and WDR1 (P = 0.031) by qRT-PCR. Finally, in SU-DHL-1 cells, overexpression of miR-1250-5p led to repression of MAPK1 and WDR1 at both transcript and protein levels, with downregulation of phospho-ERK2 by Western-blotting and inhibition of SDF-1-dependent cell migration by transwell assay. Conclusions miR-1250-5p is a novel tumor suppressive intronic miRNA co-regulated and silenced by promoter DNA methylation of its host gene AATK in NHL. MAPK1 and WDR1 are novel miR-1250-5p direct targets rendering inhibition of MAPK/ERK signaling and SDF-1-dependent cell migration, hence implicated in survival and dissemination of lymphoma. Video Abstract

Abstract Background Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. Methods Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. Results A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. Conclusions Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

Blaps rynchopetera Fairmaire has a long history of use as a folk medicine in China for treating fever, cough, gastritis, boils, and tumors. In the present study, the content analyses, monosaccharide composition analyses, and the macrophage phagocytic activity of rynchopetera polysaccharides (RPS) were reported. B. rhynchoptera is rich in polysaccharides (content value 3.97%). Through PMP (1-phenyl-3-methyl-5-pyrazolone) pre-column derivatization and high performance liquid chromatography (HPLC) testing, the results showed that RPS consist of 8 known monosaccharides, including D-mannose (Man), Rhamnose (Rha), D-glucuronic acid (GlcUA), D-galacturonic acid (GalUA), D-glucose (Glc), D-galactose (Gal), Arabinose (Ara), and Fucose (Fuc), with the total content of 171.70 mg g−1 and Glc has the highest content of 45.40 mg g−1. The phagocytic ability of mouse peritoneal macrophages was investigated after RPS stimulating alone and combined with lipopolysaccharide (LPS). RPS played an important role in the engulfment of mouse peritoneal macrophages and can significantly enhance the phagocytic ability of macrophages. However, no synergistic effects were observed when RPS combined with LPS.

Farmers’ adoption of water-saving irrigation technology (WSIT) is essential for achieving high-quality agricultural development. An in-depth analysis of the impact of risk aversion, technical training and their interaction on farmers’ adoption of WSIT will help the government to promote WSIT to facilitate agricultural resource conservation and sustainable development. The study takes 707 farmers who grow watermelons and muskmelon in Yuncheng and Xian City of Shanxi and Shaanxi provinces as the research object to analyse the influence of risk aversion and technical training and their interaction terms on farmers’ WSIT adoption behaviour. The study uses the Probit and moderating effect models to outline the findings. The empirical analysis reveals the following outcomes: (i) 27.44% of the sample farmers adopt water-saving irrigation technology, indicating that the current adoption rate and the enthusiasm for adoption are relatively low; (ii) risk aversion has a significant negative impact on farmers’ adoption of WSIT; (iii) both online and offline technical training have a significant positive impact on farmers’ adoption of WSIT; (iv) significant group differences exist in the effects of risk aversion, online technical training, offline technical training and interaction items on farmers’ WSIT adoption behaviour. Therefore, the study proposes to strengthen the role of technical training in the diffusion of WSIT and implement differentiated technical training for different types of farmers to reduce the degree of risk aversion of farmers.

Abstract The objective of this study was to investigate the expression and clinical role of ATP-binding cassette transporter 13 (ABCA13) gene previously shown to be associated with schizophrenia (SZ) through Genome-wide association studies studies. Thirty-two first-episode drug-naive SZ patients and forty-eight age and gender-matched healthy controls were enrolled in this study. We measured ABCA13 mRNA expression levels using quantitative real-time PCR at baseline and 12 weeks after antipsychotic therapy. Moreover, clinical symptoms were measured by the Positive and Negative Syndrome Scale (PANSS) at baseline and 12-week follow-up. We found that ABCA13 mRNA levels were significantly lower in SZ patients compared with healthy controls at baseline. SZ patients’ symptoms were decreased, but ABCA13 mRNA levels were increased after 12 weeks antipsychotic therapy. In addition, there was a significant difference in ABCA13 mRNA levels among SZ patients at baseline and 12-week follow-up. The ABCA13 mRNA levels were not associated with age, BMI, years of education. Of the clinical symptoms measured, the ABCA13 mRNA levels were negatively associated with the PANSS scores at baseline and 12-week follow-up. The results indicated that the ABCA13 mRNA expression level is of interest, and upon further studies, it could be used as a biomarker for SZ treatment outcome.

Arginase is a key hydrolase in the urea cycle that hydrolyses L-arginine to urea and L-ornithine. Increasing number of studies in recent years demonstrate that two mammalian arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), were aberrantly upregulated in various types of cancers, and played crucial roles in the regulation of tumor growth and metastasis through various mechanisms such as regulating L-arginine metabolism, influencing tumor immune microenvironment, etc. Thus, arginase receives increasing focus as an attractive target for cancer therapy. In this review, we provide a comprehensive overview of the physiological and biological roles of arginase in a variety of cancers, and shed light on the underlying mechanisms of arginase mediating cancer cells growth and development, as well as summarize the recent clinical research advances of targeting arginase for cancer therapy.

ObjectiveThe management of cardiogenic shock (CS) in the elderly remains a major clinical challenge. Existing clinical prediction models have not performed well in assessing the prognosis of elderly patients with CS. This study aims to build a predictive model, which could better predict the 30-day mortality of elderly patients with CS.MethodsWe extracted data from the Medical Information Mart for Intensive Care III version 1.4 (MIMIC-III) as the training set and the data of validation sets were collected from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University. Three models, including the cox regression model, the Least Absolute Shrinkage and Selection Operator (LASSO) regression model, and the CoxBoost model, were established using the training set. Through the comparison of area under the receiver operating characteristic (ROC) curve (AUC), C index, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and median improvement in risk score, the best model was selected. Then for external validation, compared the best model with the simplified acute physiology score II (SAPSII) and the CardShock risk score.ResultsA total of 919 patients were included in the study, of which 804 patients were in the training set and 115 patients were in the verification set. Using the training set, we built three models: the cox regression model including 6 predictors, the LASSO regression model including 4 predictors, and the CoxBoost model including 16 predictors. Among them, the CoxBoost model had good discrimination [AUC: 0.730; C index: 0.6958 (0.6657, 0.7259)]. Compared with the CoxBoost model, the NRI, IDI, and median improvement in risk score of other models were all

In metaphase I, autosomal bivalents align on the metaphase plate, while naturally-occurring univalent sex chromosomes can display a number of different behaviours depending on cellular conditions. Here we describe the behaviour of the univalent X chromosome in the wide-footed treehopper Enchenopa latipes (Say 1824). We confirm the chromosome number and sex determination method for this species, and that males possess a univalent X chromosome. We show that the univalent X chromosome forms a bipolar attachment to the spindle in metaphase I, and then segregates intact toward one spindle pole in late anaphase I (long after autosomes have initiated poleward movement). Movement of the univalent toward one pole is associated with loss of microtubule connections toward the opposite spindle pole.

Human papillomavirus (HPV) is the most common sexually transmitted infection on U.S. college campuses. Although HPV vaccination is recommended through age 26, current efforts to improve vaccination rates have predominantly focused on adolescents. Consequently, vaccine uptake remains suboptimal among young adults. This represents a significant missed opportunity, as young adults face the highest risk for new HPV infections. To contextualize the factors impacting decision-making process for this vulnerable population, this study reports key themes that emerged from in-depth interviews with participants (N = 30) who had completed an online intervention study for HPV vaccination among college students. Twelve (40%) of the interviewees vaccinated after exposure to the intervention. Findings centered around empowerment among young adults as the facilitator to get the HPV vaccine: key themes emerged were (1) convenience is critical and empowering; (2) adulthood identity, marked by a heightened sense of autonomy, accountability, and responsibility for self/future self and others, is empowering; (3) equal access to health care and preventive resources is empowering, especially for participants with low socioeconomic status; and (4) accurate knowledge provided in the intervention destigmatized HPV vaccination to empower young adults to make informed decisions. Digital interventions with messages highlighting a newly gained autonomy, future-oriented self and social responsibility, inclusive and accurate knowledge, and providing navigation to improve access may enhance HPV vaccination among young adults.

Purpose – The purpose of this paper is to measure Farmer’s adoption tendency towards drought shock, risk-taking networks and modern irrigation technology. Design/methodology/approach – Based on this assumption, this paper evaluated the data gathered from 498 household surveys of Zhangye, Gansu province, PRC, by using the binary probit model. First, the empirical data was analyzed for evaluating the impact of drought shock and risk-taking tendencies on the adoption of modern irrigation technology by farmers. Second, the authors introduced informal risk-bearing networks with formal risks. Final, based on the empirical results, the sustainability test, along with the marginal effect analysis and the degree of impact was carried out. Findings – The results show that the drought shock has a significantly deferent effect on the modern irrigation technology of the farmers. The probability of using technology for each level of drought loss is reduced by 15.02%. The risk-taking network has a significant role in promoting the modern irrigation technology of farmers. The probability of adoption for each additional unit of rural household labor security supply, the likelihood of adoption by farmers increased 23.11%, the probability of approval for each level of relative support, and neighborhood assistance by farmers increased by 13.11% and 17.88% respectively. This study further revealed that insurance purchases enabled farmers to adopt new irrigation technology with the probability increased by 24.99%; easily available bank loans increased the probability of farmers using irrigation technology by 31.89%. From the perspective of interactions between farmers, the risk-taking network can alleviate the inhibitory effect of drought impact towards the adoption of irrigation technology. Among the control variables, the number of years of education, the age of farming, the degree of arable land, the distance from home to the market, and the price of water all has significant effects on the adoption of modern irrigation technology by farmers. Originality/value – The novelty of the study is that it illustrated the interactive influence of drought shock and risk-taking networks on the farmer’s adoption tendencies of modern irrigation technologies, the inner relationship among drought impact, the risk-taking network and the farmer’s adoption behavior and provide an interactive relationship between the formal risk-taking network and the non-risk-taking network in farmer’s technology adoption.

Background: The sodium-glucose co-transporter-2 (SGLT-2) inhibitor dapagliflozin improves cardiovascular outcomes in patients with type 2 diabetes in a manner that is partially independent of its hypoglycemic effect. These observations suggest that it may exert a cardioprotective effect by another mechanism. This study explored the effects of dapagliflozin on myocardial ischemia/reperfusion injury in a mouse model.Materials and Methods: For the in vivo I/R studies, mice received 40 mg/kg/d dapagliflozin, starting 7 days before I/R. Evans Blue/TTC double-staining was used to determine the infarct size. Serum levels of cTnI, CK-MB, and LDH were measured. Inflammation, autophagy protein expression, and caspase-1 activity changes were measured at the protein level. Primary cardiomyocytes were used to investigate the direct effect of dapagliflozin on cardiomyocytes and to verify whether they have the same effect as observed in in vivo experiments.Result: A high dose of dapagliflozin significantly reduced infarct size and decreased the serum levels of cTnI, CK-MB, and LDH. Dapagliflozin also reduced serum levels of IL-1β, reduced expression of myocardial inflammation-related proteins, and inhibited cardiac caspase-1 activity. The treatment restored autophagy flux and promoted the degradation of autophagosomes. Relief of inflammation relied on autophagosome phagocytosis of NLRP3 and autophagosome clearance after lysosome improvement. 10 μM dapagliflozin reduced intracellular Ca2+ and Na+ in primary cardiomyocytes, and increasing NHE1 and NCX expression mitigated dapagliflozin effects on autophagy.Conclusion: Dapagliflozin protects against myocardial ischemia/reperfusion injury independently of its hypoglycemic effect. High-dose dapagliflozin pretreatment might limit NLRP3 inflammasome activation and mediate its selective autophagy. Dapagliflozin directly acts on cardiomyocytes through NHE1/NCX.

The Party in the 1990s merger boom into China, the real estate industry in the “merger and acquisition of the road” can be said to be in full swing With the change of social policies, “business transformation”, that is, seeking diversified development, has become one of the important motivations for M&A in the context of increasingly difficult and expensive “land acquisition” And Sunac China by virtue of the amazing speed and scale of mergers and acquisitions, in the real estate industry of mergers and acquisitions boom to stand out, people’s attention. Therefore, this paper classifies the series of M&A cases of Sunac China according to the M&A motivation, mainly discusses the two M&A cases based on the “business transformation” M&A motivation, analyzes the M&A performance respectively, summarizes the problems that enterprises tend to ignore when making cross-industry investment, and puts forward the corresponding investment countermeasures, which has certain reference significance for enterprises’ cross-industry investment.

China has a rich and colorful culture, and the cultural appreciation value and research value are very high. It should be our important responsibility and obligation to help and guide more tourists to learn, understand, appreciate and appreciate China’s profound cultural accumulation. At present, the rapid development of “Internet” information technology and the gradual popularization of intelligent terminals have provided important opportunities and built an effective platform for the external dissemination of cultural tourist attractions and culture, as well as the development of foreign language identification, interpretation and other services. Shandong is not only our country economic province, and the red tourist attractions, red sites, red resources is very rich, Shandong cultural tourism got rapid development in recent years, under the new situation, how to strengthen the red culture in Shandong province give full play to the advantage, strengthen the effective implementation of cultural drive strategy should be an important research topic. 1This study in the Shandong red culture foreign communication significance and value, on the basis of the red culture resources in Shandong province, analyzes the current Shandong red culture tourism attractions bilingual service present situation and the existing problems, provide improvement and optimization of countermeasures and path, to strengthen the development of Shandong red culture, red culture and promote the direction towards the cultural industry resources and development, really make the red culture effectively into real productivity, into economic benefits, better boost the high quality of economic and social development in Shandong province.

Abstract Background Individuals with autism spectrum disorder (ASD) have social interaction deficits and difficulties in emotional regulation. The neural substrates for these socio-affective deficits are not yet clear, but one potential candidate is maldevelopment of the uncinate fasciculus (UF), a white matter tract thought to be involved in socio-affective processing. However, the developmental trajectory of the UF in young children with social interaction deficits has not been examined. The present study was designed to describe the developmental growth trajectory of the UF and the relationships between UF development and social deficits in ASD. Methods Eigenvalues of the UF were measured by diffusion tensor imaging (DTI)-based tractography in 37 children with ASD and 27 matched 2–3-year-old subjects with developmental delay (DD) at baseline (time 1) and at 2-year follow-up (time 2). Growth rates of the UF were compared between groups and associations with social deficit scores according to the Autism Diagnostic Interview-Revised (ADI-R) analyzed by Pearson’s correlations. Results At time 1, axial diffusivity (AD) of the left UF was significantly larger in the ASD group than the DD group. At time 2, left UF fractional anisotropy (FA) was significantly higher and radial diffusivity (RD) significantly lower in the ASD group than the DD group. The rate of UF growth during this 2-year interval was faster in children with ASD than DD. Significant negative correlations were found between the rise in ADI-R social deficit measures and both right UF RD and left UF mean diffusivity (MD). Conclusions Young children with ASD demonstrate UF overgrowth during the 2-year development period between 2 and 3 and 4–5 years of age, and this white matter abnormality is directly associated with the progression of social deficits. Trial registration World Health Organization class I registered international clinical trial platform, ChiCTR-ROC-17012877.

Maintenance decision-making is essential to achieve safe and reliable operation with high performance for equipment. To avoid unexpected shutdown and increase machine life as well as system efficiency, it is fundamental to design an effective maintenance decision-making scheme for equipment. In this paper, we propose a novel maintenance decision-making method for equipment based on Long Short-Term Memory (LSTM) and Markov decision process, which can provide specific maintenance strategies in different degradation stages of the system. Specifically, the LSTM model is firstly applied to predict the remaining service life of equipment to distinguish its health state quantitatively. Then, based on the bearing residual life prediction curve, the degradation process model is constructed, and the corresponding parameters of the model are identified. Finally, the bearing degradation curve is obtained by the degradation process model, based on which the Markov decision process model is constructed to provide accurate maintenance strategies for different health conditions of system. To demonstrate the effectiveness of the proposed method, an experimental study with the full life cycle data set of rolling bearings is carried out. The experimental results show that the proposed method can achieve efficient maintenance decisions for bearings under different health states, which provides a feasible solution for the maintenance of bearing systems.

The impacts of widespread carbon emission trends possessed tremendous pressure for global food security, sustainable development, and ecosystems. Several temporal and spatial patterns of green technology have been adopted to reduce carbon emissions in different regions of China. In China, agriculture industries may have colossal importance for reducing carbon emissions. On the basis of the data from 1998 to 2018, the study uses the heterogeneous stochastic frontier model to quantify the carbon emission reduction potential of agricultural green technology progress in eastern, central, and western regions of China by using the heterogeneous stochastic frontier model. We also analyze the coefficient of variation and its spatial and temporal evolution pattern of carbon intensity decline potential index and explore the potential factors related to the agriculture green technology progress of China. The finding of the study revealed that the carbon emission rate in the agriculture industry of China is very high, whereas adopting green technology is slower because of economic and policy-related factors—the carbon emission of green technological progress. In terms of spatial variations, the changes in various regions were consistent with the overall fluctuating rate compared with the state of another country, but an increasing trend has been traced within the “east-central-west” regions. The overall regional differences are gradually trending, but differences between regions mainly cause them. The increase in the structure of the agricultural agriculture industry, the level of labor, and the increase in administrative environmental regulations will weaken the obstacles to the carbon emission reduction potential of green technological progress. The increase in urbanization, the level of the agricultural economy, and economic and environmental regulations will increase the carbon emission reduction potential of green technological progress. It is necessary to actively promote exchanges and cooperation in green agricultural technology and advanced management concepts, accelerate the optimization and upgrading of the industrial structure, and achieve the goal of peaking carbon emissions through regional coordinated development. Regionally, the overall external environment and the level of green technology progress in the western region need to be improved in all respects. The central and eastern regions need to focus on combining different policy tools to transform them from hindrance to promotion.

P-element-induced wimpy testis (Piwi)-interacting RNAs (piRNAs) are a class of germline-enriched small non-coding RNA that associate with Piwi family proteins and mostly induce transposon silencing and epigenetic regulation. Emerging evidence indicated the aberrant expression of Piwil proteins and associated piRNAs in multiple types of human cancer including breast cancer. Although the majority of piRNAs in breast cancer remains unclear of the function mainly due to the variety of regulatory mechanisms, the potential of piRNAs serving as biomarkers for cancer diagnosis and prognosis or therapeutic targets for cancer treatment has been demonstrated by in vitro and in vivo studies. Herein we summarized the research progress of oncogenic or tumor suppressing piRNAs and their regulatory mechanisms in regulating human breast cancer, including piR-021285, piR-823, piR-932, piR-36712, piR-016658, piR-016975 and piR-4987. The challenges and perspectives of piRNAs in the field of human cancer were discussed.

BackgroundPrevious neuroimaging studies have described shared and distinct neurobiological mechanisms between autism spectrum disorders (ASDs) and attention-deficit/hyperactivity disorder (ADHD). However, little is known about the similarities and differences in topologically structural connectivity patterns between the two disorders.MethodsDiffusion tensor imaging (DTI) and deterministic tractography were used to construct the brain white matter (WM) structural networks of children and adolescents (age range, 6–16 years); 31 had ASD, 34 had ADHD, and 30 were age- and sex-matched typically developing (TD) individuals. Then, graph theoretical analysis was performed to investigate the alterations in the global and node-based properties of the WM structural networks in these groups. Next, measures of ASD traits [Social Responsiveness Scale (SRS)] and ADHD traits (Swanson, Nolan, and Pelham, version IV scale, SNAP-IV) were correlated with the alterations to determine the functional significance of such changes.ResultsFirst, there were no significant differences in the global network properties among the three groups; moreover, compared with that of the TD group, nodal degree (Ki) of the right amygdala (AMYG.R) and right parahippocampal gyrus (PHG.R) were found in both the ASD and ADHD groups. Also, the ASD and ADHD groups shared four additional hubs, including the left middle temporal gyrus (MTG.L), left superior temporal gyrus (STG.L), left postcentral gyrus (PoCG.L), and right middle frontal gyrus (MFG.R) compared with the TD group. Moreover, the ASD and ADHD groups exhibited no significant differences regarding regional connectivity characteristics. Second, the ADHD group showed significantly increased nodal betweenness centrality (Bi) of the left hippocampus (HIP.L) compared with the ASD group; also, compared with the ADHD group, the ASD group lacked the left anterior cingulate gyrus (ACG.L) as a hub. Last, decreased nodal efficiency (Enodal) of the AMYG.R, Ki of the AMYG.R, and Ki of the PHG.R were associated with higher SRS scores in the ASD group. Decreased Ki of the PHG.R was associated with higher SRS scores in the full sample, whereas decreased Bi of the PHG.R was associated with lower oppositional defiance subscale scores of the SNAP-IV in the ADHD group, and decreased Bi of the HIP.L was associated with lower inattention subscale scores of the SNAP-IV in the full sample.ConclusionFrom the perspective of the topological properties of brain WM structural networks, ADHD and ASD have both shared and distinct features. More interestingly, some shared and distinct topological properties of WM structures are related to the core symptoms of these disorders.

Purpose. The purpose of this study is to trace the theoretical developments of the gravity model of trade. The key question is: what are the dominant features of the development of the gravity trade model? Methodology. This research is conducted by employing a number of methods that include the historical, descriptive and analytical methods. The main contribution of this paper is to trace the historical and theoretical development phases of the gravity model. Findings. This study is a novel attempt in terms of the identification of the four distinctive phases of the development of the gravity model. This work would, therefore, expand the existing literature on the gravity model. We argue that the development of the gravity model is the outcome of many research efforts. A large body of literature has given the model a solid theoretical foundation. But there is no consensus about the proper econometric estimation methods of the model. The gravity model is significant both historically and analytically. It is a useful tool for the analysis of international trade. It has become a popular research device used by the researchers and policy makers around the world. The gravity is regarded as one of the most successful models in the literature of international economics. Originality. The original contributions of this paper lie in streamlining the consistent historical development of the gravity model over a longer period of time-frame, ranging from 1885 to 2018. Limitations and Implications. This work is theoretical aspects of the trade gravity model. Future researchers could overcome the limitations by combining the theoretical and empirical studies in a paper. This paper can help the future researchers in dealing with the broad body of literature of gravity model. Acknowledement. This study was supported by the National Natural Science Foundation of China (grants No.71673223 & 71473197), and a PhD scholarship from the China Scholarship Council (CSC). The first author would like to thank the CSC for the financial support. He also acknowledges the invaluable research advice and guidance received from Dr. Yoto V. Yotov, professor at the School of Economics of the Lebow College of Business at Drexel University, Philadelphia, USA. The authors are highly grateful to the anonymous reviewers, managing editor, and the editor-in chief for their kind help and critical comments on the earlier drafts of the paper. However, the authors are responsible for the contents and limitations of the study. They declared no conflict of interests.