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ABSTRACT Bacterial motility has great medical and ecological significance because of its essential role in bacterial survival and pathogenesis. Cyclic dimeric GMP (c-di-GMP), a second messenger in bacteria, is the predominant regulator of flagellar synthesis and motility and possesses turnover mechanisms that have been thoroughly investigated. Therefore, much attention has been focused on identifying the upstream stimulatory signals and downstream modules that respond to altered c-di-GMP levels. Here, we systematically analyzed c-di-GMP cyclases and phosphodiesterases in Stenotrophomonas maltophilia to screen for motility regulators. Of these enzymes, we identified and characterized a new phosphodiesterase named SisP, which was found to facilitate bacterial swimming upon stimulation with ferrous iron. SisP-mediated degradation of c-di-GMP leads to FsnR-dependent transcription of flagellar genes. Remarkably, c-di-GMP controls FsnR via two independent mechanisms: by direct binding and indirectly by modulating its phosphorylation state. In this study, we deciphered a novel “one stone, two birds” regulatory strategy of c-di-GMP and uncovered the signal that stimulates c-di-GMP hydrolysis. Facilitation of bacterial swimming motility by ferrous iron might contribute to the higher risk of bacterial infection in acutely ill patients. IMPORTANCE Stenotrophomonas maltophilia has become a great threat to human health because of the high mortality of infected patients. Swimming motility plays a crucial role in regulating bacterial virulence and adaptation. However, limited progress has been made in cyclic dimeric GMP (c-di-GMP) controlling swimming motility of S. maltophilia. Here, we characterized c-di-GMP turnover enzymes encoded by S. maltophilia and dissected the regulatory details of a phosphodiesterase named SisP. We demonstrated that SisP degrades c-di-GMP to fully activate FsnR through directly releasing FsnR from the FsnR-c-di-GMP complex and indirectly increasing its phosphorylation level. This finding uncovered a quantitative, rather than an on-off, regulatory manner employed by c-di-GMP to regulate activities of its effectors. Identification of the specific activation of SisP by ferrous iron proposes SisP as a putative drug-target for controlling bacterial infection and ferrous iron at the wounds or cuts as a putative factor contributing to the higher risk of bacterial infection.

Weld shape and track precise identification is one of the key problems for automatic welding technology. In this paper, a weld track identification method based on illumination correction and center point extraction is proposed to extract welds with different shapes and non-uniform illumination. Firstly, an image pre-processing algorithm based on illumination correction is designed to eliminate the lighting influence. Secondly, an image extraction algorithm based on iterative threshold segmentation and morphological processing is proposed to obtain a continuous weld binary image. Thirdly, sub-pixel center point extraction algorithm and least-square based polynomial fitting is used to obtain the center fitting curve of welding seam. Experimental results show that the proposed method can realize accurate recognition of welding seam track under different illumination conditions effectively. The recognition error for welding seams with different typical shapes is within 4 pixels, and the average fitting error is less than 1.8 pixels. The welding seam identification and fitting method shows great application potential in the field of automatic assembling and robotic welding.

To improve understanding of the characteristics of extreme summer rainfall and its water vapor transport in the eastern part of southwestern China (ESWC), this study analyzed data on daily precipitation from 118 meteorological stations in the ESWC from 1979 to 2020, as well as daily reanalysis data from ERA5 and daily reanalysis data from NCEP/NCAR. The study employed polynomial fitting, correlation, regression, clustering, and mixed single-particle Lagrangian trajectory (HYSPLITv5.0) modeling methods to simulate extreme summer precipitation and its water vapor transport characteristics in the ESWC and its possible formation mechanism. The results show that: (1) The contribution rate of extreme precipitation in the ESWC from 1979 to 2020 varied significantly on the interannual time scale. When the number of extreme precipitation days is high (low), the contribution rate of extreme precipitation is also high (low), while the contribution rate of general precipitation (the percentage of the sum of general precipitation to the total summer precipitation of that year) is often low (high). (2) When extreme precipitation occurs in the ESWC, compared with general precipitation, the high-level potential vortices are stronger, and the cold air from higher latitude is more likely to move southward. Meanwhile, the amount of water vapor input to the region is significantly larger than that of general precipitation. (3) There are four channels of water vapor sources in the ESWC during the period of extreme precipitation: the Bay of Bengal, the Arabian Sea, the western Pacific, and the northwest. The contribution of water vapor from the Bay of Bengal is the highest. The number of extreme summer precipitation days in the ESWC is significantly negatively correlated with the water vapor budget of the eastern boundary and positively correlated with Indian Ocean Basin-Wide (IOBW) index in the previous winter. (4) When the winter SST is high in the IOBW mode, it can cause the western Pacific subtropical high and the South Asian high to be stronger and shifted southward in summer, resulting in an increase in the number of extreme precipitation days in the ESWC.

This paper studies how autonomous vehicles (AVs) influence future traffic and energy consumption when adopting various route guidance strategies, which can be divided into global information strategies and local information strategies according to the scope of information collection. A mixed traffic flow model is established. Then, an autonomous vehicle model is improved to investigate the impact of six route guidance strategies. The selected strategies are specifically evaluated in a double-route scenario, considering both single-exit and dual-exit configurations. Three indicators are chosen to evaluate traffic efficiency, including traffic flow, average speed and quantity of vehicles. Consumption per unit flux is the indicator of energy consumption level. Simulation results show that autonomous vehicles can improve traffic efficiency and reduce energy consumption.

This research proposes a virtual restoration system and method for 3D digital cultural relics based on a fuzzy logic algorithm, aiming to solve the problems of the low classification accuracy and poor splicing effect of Terra Cotta Warrior fragments. This method adopts a series of steps to improve the efficiency and accuracy of fragment splicing. Firstly, features such as curvature, torsion, and left and right chord lengths were extracted from the fracture surface contour lines of the cultural relic fragments to form feature vectors. Then, the feature vector was fused and compressed by using the multilayer perceptron. The multilayer perceptron is a neural network model that can process and learn input data via multiple levels of computation, resulting in more expressive feature representations. Next, we used the calculation results of the multilayer perceptron to perform the splicing operation on the fragments. This means that, based on the calculation results of the feature vectors, the system can automatically select appropriate splicing methods to accurately match and splice fragments. Finally, by adjusting the weight of the multilayer perceptron, the error rate of fragment splicing can be reduced, further improving the accuracy of repair. The experimental results show that the method proposed in this article is significantly better than traditional methods in terms of time consumption and can effectively improve the efficiency of fragment matching and stitching. Conclusion: The fragment-stitching algorithm based on multi-feature adaptive fusion improved the speed and effectiveness of stitching in fragment-stitching tasks. In summary, the fragment-stitching algorithm based on multi-feature adaptive fusion can improve the speed and effectiveness of stitching in fragment-stitching tasks. The application of this method is expected to play an important role in the field of cultural relic protection, such as the restoration of Terra Cotta Warrior fragments.

Abstract Objective To study the relationship between DNA double-strand break (DSB) repair gene mutations and the risk of papillary thyroid microcarcinoma (PTMC). Methods One hundred patients with PTMC or benign thyroid nodules (BTNs) at Henan Cancer Hospital were retrospectively analyzed. The DSB repair capacity of peripheral blood T lymphocytes in the two groups was assessed by flow cytometry. Data were compared using Student’s t-test to evaluate the relationship between DSB repair capacity and the risk of PTMC. Factors influencing DSB repair capacity were analyzed by multivariate logistic regression analysis. The relationship between PTMC and DSB repair capacity was analyzed by univariate analysis. Targeted next-generation DNA sequencing was applied to screen and analyze DSB repair genes related to PTMC. Results The DSB repair capacity was 31.30% in the PTMC group and 44.40% in the BTN group, with that of the former being significantly lower (P

Abstract Background A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia. Methods Six pigs were randomly divided into two groups of three pigs each, namely, the high-fat diet and the balanced diet groups, which were fed a high-fat diet and balanced diet separately for six months. HDL was separated from plasma, which was followed by dissociation of the miRNA bound to HDL. miRNA sequencing of the isolated miRNA was performed to identify the differential expression profiles between the two groups, which was validated by real-time PCR. TargetScan, miRDB, and miRWalk were used for the prediction of genes targeted by the differential miRNAs. Results Compared with the balanced diet group, the high-fat diet group had significantly higher levels of TG, TC, LDL-C and HDL-C at six months. miRNA sequencing revealed 6 upregulated and 14 downregulated HDL-bound miRNAs in the high-fat diet group compared to the balanced diet group, which was validated by real-time PCR. GO enrichment analysis showed that dysregulated miRNAs in the high-fat diet group were associated with the positive regulation of lipid metabolic processes, positive regulation of lipid biosynthetic processes, and positive regulation of Ras protein signal transduction. Insulin resistance and the Ras signalling pathway were enriched in the KEGG pathway enrichment analysis. Conclusions Twenty HDL-bound miRNAs are significantly dysregulated in high-fat diet-induced dyslipidaemia. This study presents an analysis of a new set of HDL-bound miRNAs that are altered by a high-fat diet and offers some valuable clues for novel mechanistic insights into high-fat diet-induced dyslipidaemia. Further functional verification study using a larger sample size will be required.

Italy is among the countries with the highest ozone concentration in Europe. However, the mortality burden of ozone and related economic loss has not been fully characterized. This study aimed to estimate the ozone-mortality association in Italy and evaluate attributable mortality burden and related economic loss in 2015–2019. We collected daily all-cause mortality data stratified by age and sex from 2015 to 2019 in 107 provinces of Italy. A two-stage time-series framework was applied to estimate the association between daily maximum eight-hour average ozone and mortality as well as economic loss. An overall increase in the risk of mortality (RR=1.0043, 95% CI: 1.0029, 1.0057) was associated with every 10 µg/m3 increase in ozone. Generally, a total of 70,060 deaths and $65 billion economic loss were attributed to ozone exposure, corresponding to 3.11% of mortality and about 0.5% of the national GDP during the study period, respectively. The highest ozone-related mortality burden (30,910 deaths) and economic loss ($29.24 billion) were observed in the hot season. This nationwide study suggested considerable mortality burden and economic loss were associated with exposure to ozone. More actions and policies should be proposed to reduce ozone levels and help the public protect their health.

Endometriosis is a chronic, inflammatory, estrogen-dependent gynecological disease characterized by the growth of endometrial stromal cells and glands outside the uterine cavity in response to hormones, which commonly occurs in reproductive-age women. Zearalenone (ZEA) is a toxic metabolite produced by Fusarium, which acts as estrogen activity because of the similarity of its structure to estrogen. In this study, we used an endometriosis mouse model: 15 days after ovariectomy, endometrial fragments were sutured on the pelvic wall, and exogenous estrogen was supplied using an estrogen-releasing silicone tube embedded subcutaneously. Mice were treated with different doses of ZEA by gavage for 21 days. The results show that ZEA significantly inhibited the growth of ectopic endometrium in a dose-dependent manner. The proliferation of cells decreased while apoptosis increased in the ectopic tissues of ZEA-treated mice compared to the vehicle group. The expression of estrogen receptor-α and its downstream targets MUC1 and p-AKT decreased, indicating an impaired estrogen signaling activity by ZEA treatment. In addition, the decreased expression of pro-inflammatory cytokine Tnf-α, Il-1β, and Il-6, the lower number of macrophages and neutrophils cells, and the inhibited NF-κB signaling pathway suggest the inflammatory response in the ectopic endometrium was also suppressed by ZEA treatment. However, when the exogenous estrogen supply is removed, ZEA, in turn, plays an estrogen-like role that promotes cell proliferation in the ectopic endometrium. In summary, our data suggest ZEA acts as an antagonist in endometriotic tissue when estrogen is sufficient but turns to estrogenic activity in the absence of estrogen in the development of endometriosis. ZEA also inhibits ectopic tissue growth by inhibiting inflammatory response in the endometriosis model.

The role of GABAergic cell transplantation in improving neuropathic pain is controversial. We comprehensively searched the relevant literature to identify animal studies of GABAergic cell transplantation that recorded pain behaviors as an outcome according to the Cochrane Handbook 5.0.2. Controlled studies assessing the administration of GABAergic neurons or GABAergic neuronal progenitor cells to rat or mouse neuropathic pain animal models were included. Basic design information and mechanical allodynia thresholds and heat hyperalgesia thresholds data were collected. The risk of bias for the animal experiments was assessed according to the SYRCLE's tool. This study included 10 full-text articles. GABAergic cells transplantation leads to a statistically significant improvement of allodynia (SMD = 5.26; 95% confidence interval: 3.02–7.51; P < 0.001) and hyperalgesia (SMD: 4.10; 95% confidence interval: 1.84–6.35; P < 0.001). Differentiated GABAergic cells and without antibiotics using may have a better effect for improving neuropathic pain. GABAergic cell transplantation is a promising treatment for improving neuropathic pain. This systematic review and meta-analysis evaluated the effects of GABAergic cell transplantation on neuropathic pain, which can guide future clinical trials and possible clinical treatments, and better attenuate neuropathic pain caused by abnormal circuit hyperexcitability.

Background: Evidence have shown that gut microbiota plays an important role in the development of severe acute pancreatitis (SAP). In addition, matrix metalloproteinase-9 (MMP9) plays an important role in intestinal injury in SAP. Thus, we aimed to determine whether gut microbiota could regulate the intestinal injury during SAP via modulating MMP9.Methods: In this study, the fecal samples of patients with SAP (n = 72) and healthy controls (n = 32) were analyzed by 16S rRNA gene sequencing. In addition, to investigate the association between gut microbiota and MMP9 in intestinal injury during SAP, we established MMP9 stable knockdown Caco2 and HT29 cells in vitro and generated a MMP9 knockout (MMP9−/−) mouse model of SAP in vivo.Results: We found that the abundance of Clostridium butyricum (C. butyricum) was significantly decreased in the SAP group. In addition, overexpression of MMP9 notably downregulated the expressions of tight junction proteins and upregulated the expressions of p-p38 and p-ERK in Caco2 and HT29 cells (p < 0.05). However, C. butyricum or butyrate treatment remarkably upregulated the expressions of tight junction proteins and downregulated the expressions of MMP9, p-p38 and p-ERK in MMP9-overexpressed Caco2 and HT29 cells (p < 0.05). Importantly, C. butyricum or butyrate could not affect the expressions of tight junction proteins, and MMP9, p-p38 and p-ERK proteins in MMP9-knockdown cells compared with MMP9-knockdown group. Consistently, C. butyricum or butyrate could not attenuate pancreatic and intestinal injury during SAP in MMP9−/− mice compared with the SAP group.Conclusion: Collectively, C. butyricum could protect against pancreatic and intestinal injury after SAP via downregulation of MMP9 in vitro and in vivo.

Xuefu Zhuyu decoction (XFZYD) is used to treat traumatic brain injury (TBI). XFZYD-based therapies have achieved good clinical outcomes in TBI. However, the underlying mechanisms of XFZYD in TBI remedy remains unclear. The study aimed to identify critical miRNAs and putative mechanisms associated with XFYZD through comprehensive bioinformatics analysis. We established a controlled cortical impact (CCI) mice model and treated the mice with XFZYD. The high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) confirmed the quality of XFZYD. The modified neurological severity score (mNSS) and Morris water maze (MWM) tests indicated that XFZYD improved the neurological deficit (p < 0.05) and cognitive function (p < 0.01). Histological analysis validated the establishment of the CCI model and the treatment effect of XFZYD. HE staining displayed that the pathological degree in the XFZYD-treated group was prominently reduced. The transcriptomic data was generated using microRNA sequencing (miRNA-seq) of the hippocampus. According to cluster analysis, the TBI group clustered together was distinct from the XFZYD group. Sixteen differentially expressed (5 upregulated; 11 downregulated) miRNAs were detected between TBI and XFZYD. The reliability of the sequencing data was confirmed by qRT-PCR. Three miRNAs (mmu-miR-142a-5p, mmu-miR-183-5p, mmu-miR-96-5p) were distinctively expressed in the XFZYD compared with the TBI and consisted of the sequencing results. Bioinformatics analysis suggested that the MAPK signaling pathway contributes to TBI pathophysiology and XFZYD treatment. Subsequently, the functions of miR-96-5p, miR-183-5p, and miR-142a-5p were validated in vitro. TBI significantly induces the down-expression of miR-96-5p, and up-expression of inflammatory cytokines, which were all inhibited by miR-96-5p mimics. The present research provides an adequate fundament for further knowing the pathologic and prognostic process of TBI and supplies deep insights into the therapeutic effects of XFZYD.

Abstract Comprehensive comparison of paleoclimate change based on records constrained by precise chronology and high-resolution is essential to explore the correlation and interaction within earth climate systems. Here, we propose a new stalagmite-based multidecadal resolved Asian summer monsoon (ASM) record spanning the past thirty-seven thousand years (ka BP, before ad 1950) from Furong Cave, southwestern China. This record is consistent with the published Chinese stalagmite sequences and shows that the dominant controls of the ASM dynamics include not only insolation and solar activity but also suborbital-scale hydroclimate events in the high latitudes of the northern hemisphere, such as the Heinrich events, Bølling-Allerød (BA), and Younger Dryas (YD). Benefit from the unprecedented accurate chronology, the timings of these events are precisely dated, with uncertainties of, at most, 40 years (2σ). The onset of the weak ASM during the YD began at 12.92 ka BP and lasted for 430 years. The occurrence of the 200-yr Older Dryas during the BA period was dated from 13.87 to 14.06 ka BP. The durations of the three Heinrich (H) events, H1, H2, and H3, are 14.33–18.29, 23.77–24.48, and 28.98–30.46 ka BP, respectively. Furong record shows surprisingly variable onset transitions of 980, 210, and 40 years for the corresponding weak ASM events. These discrepancies suggest different influences of the H events on ASM dynamics. During the periods of H 1–3, the obvious difference between our Furong record and NGRIP δ18O record indicated the decoupling correlation between the mid-low latitudes and high latitudes. On the other hand, synchronous climate change in high and low latitudes suggests another possibility which different to the dominant role of Northern high latitudes in triggering global climate change. Our high quality records also indicate a plausible different correlation between the high and mid-low latitudes under glacial and inter-glacial background, especially for the ASM regimes.

Abstract Background Quite a few traumatic spinal cord injuries (TSCI) were caused by falls. However, the comparison of different causes of TSCI or the epidemiological characteristics of TSCI caused by falls of different heights are rare. This study investigated the epidemiological characteristics of TSCI caused by falls and conducted a comparison between low falls and high falls. Method Data from cases with TSCI admitted to China Rehabilitation Research Center from 2010 to 2019 were collected, including age, gender, occupation, cause, neurological level, and severity of the injury in admission, combined injuries, complications, and rehabilitation length of stay. Mann-Whitney U and chi-square (χ 2) tests were used to assess the differences between two groups at a statistical significance level of 0.05. Result A total of 1858 TSCI cases were included and 41.7% were caused by falls, 11.4% by low falls and 30.3% by high falls, respectively. Patients with fall-induced TSCI were older and had a shorter rehabilitation length of stay than those with non-fall-induced TSCI. Patients with high fall-induced TSCI were younger and more likely to suffer from paraplegia, severer injuries, and combined injuries, and had longer time from injury to rehabilitation and rehabilitation length of stay, compared with patients with low fall-induced TSCI. Conclusion Falls is the leading causes of TSCI and high fall is becoming more common. Attention not only should be paid to high falls for the severe injury and longer hospitalization, but also low falls due to the higher neurological level of the injury and the aging of population in China.

In conventional photo-thermal-electric conversion systems, the photo-thermal conversion module is coupled to a thermoelectric conversion module. However, the physical contact interface between the modules causes serious energy loss. In order to solve this problem, a novel photo-thermal-electric conversion system with an integrated support material has been developed, with a photo-thermal conversion component at the top, an inside thermoelectric conversion component, and a cooling component at the bottom, surrounded by a water conduction component. The supporting materials of each part are polydimethylsiloxane (PDMS), and there is no apparent physical interface between each part. This integrated support material reduces the heat loss caused by the mechanically coupled interfaces in traditional components. In addition, the confined edge 2D water transport path effectively reduces the heat loss due to water convection. Under 1 sun irradiation, the water evaporation rate and open-circuit voltage of the integrated system reach 2.46 kg m−2 h−1 and 30 mV, respectively, and are nearly 1.4 times and 5.8 times higher than those of non-integrated systems.

Abstract Although the significant progress in the power conversion efficiencies (PCEs) of non‐fullerene polymer solar cells (PSCs) has proved their commercial potential, the development of efficient photovoltaic materials from easily available raw materials and simple chemical synthesis is still lagging. In this work, three copolymers donors (PTEI‐H, PTEI‐F, and PTEI‐Cl) based on easily synthesized (Z)‐3‐(thiophen‐2‐yl‐methylene)‐indolin‐2‐one (TEI) as electron‐deficient unit were synthesized and characterized. As compared to the polymer PTEI‐H, the fluorinated and chlorinated polymers (PTEI‐F and PTEI‐Cl) show broader band gaps and deeper HOMO energy levels. However, after blending with small molecule acceptor Y6, the as‐cast PTEI‐H devices exhibit a PCE of 8.27%, outperforming those of the PTEI‐F devices (7.22%) and PTEI‐Cl devices (6.50%). The relatively high photovoltaic performance of the PTEI‐H devices are associated with their increased short‐circuit current density and fill factor values, resulting from the efficient exciton dissociation and charge generation, balanced charge transport properties, and reduced recombination loss. In consideration of the merits of the structural simplicity and synthetic accessibility of TEI unit, we believe it is a potential electron‐deficient moiety in developing high‐performance polymer donors for possible mass‐production of non‐fullerene PSCs.

Amygdalin is widely distributed in the plant kingdom. Oral delivery of amygdalin releases hydrogen cyanide upon endogenous enzymes causing potential toxic effects to humans. Here, we fabricate Fmoc-Tyr–OH–amygdalin hydrogel (FTOA) which represents L-tyrosine derived low molecular weight hydrogelator entrapping amygdalin. Fourier Transform Infrared Spectroscopy and the Fluorescent Emission Spectrum elucidated the complexation process between the amygdalin and Fmoc-Tyr-OH (FTO). Amygdalin was sustainably released from FTOA at different pH buffer. The rheological behavior similar to the brain supported that the hydrogel tended to be a preferable neural scaffold. Moreover, animal studies showed FTOA significantly promoted neural-functional recovery. This hydrogel achieved a great decrease in damage volume according to H&E staining. Additionally, we found that FTOA enhanced tissue recovery. Simultaneously, the released amygdalin gave a markedly neural inflammatory suppression. Taken together, this study highlights that Fmoc-based gelator encapsulate amygdalin forming a stable hydrogel to perform sustained-release and improve efficacy with minimal side effects.

As more and more unconventional energy sources are being applied in the field of power generation, the frequency fluctuation of power system becomes more and more serious. The frequency modulation of thermal power unit has disadvantages such as long response time and slow climbing speed. Battery energy storage has gradually become a research hotspot in power system frequency modulation due to its quick response and flexible regulation. This article first introduced the control method based on the signal of ACE (Area Control Error), which is the basic way of secondary frequency modulation and analyzed the features of the basic control mode. Then it zoned the signal of ACE and SOC of the battery energy storage system. On this basis, different frequency modulation methods were proposed according to the requirements of frequency modulation and the characteristics of the output of different regions. In addition, the fuzzy controller is used to smooth the output of the energy storage system under the normal adjustment of the regional control deviation and the normal charging and discharging state of SOC. Finally, a two-region interconnection simulation system was established based on the MATLAB simulation platform, and the simulation results verified the effectiveness of the proposed control strategy.

Context Rosmarinic acid (RA) dose-dependently ameliorates acetaminophen (APAP) induced hepatotoxicity in rats. However, whether RA hepatoprotective effect is by regulating RACK1 and its downstream signals is still unclear. Objective This study explores the RA protective effect on APAP-induced ALI and its mechanism. Materials and methods Sixty Kunming mice 6–8 weeks old were randomly separated into six groups (n = 10) and pre-treated with normal saline, ammonium glycyrrhetate (AG) or RA (10, 20 or 40 mg/kg i.p./day) for two consecutive weeks. Then, APAP (300 mg/kg, i.g.) was administrated to induce ALI, except for the control. Serum alanine/aspartate aminotransferases (ALT and AST), malondialdehyde (MDA), superoxide dismutase (SOD) and histopathology were used to authenticate RA effect. The liver RACK1 and TNF-α were measured by western blot. Results Compared with the APAP group, different dosages RA significantly decreased ALT (52.09 ± 7.98, 55.13 ± 10.19, 65.08 ± 27.61 U/L, p

Both the magnetic field treatment and the microwave treatment can affect the concentration of aroma compounds in liquor, but there are few researches on the composite treatment that combining the two. In this study, the effects of separate pulsed magnetic field (PMF), microwave field, and PMF-microwave composite treatment on Chinese soy-sauce flavor liquor were investigated. The concentration changes of various aroma compounds in liquor were analyzed by gas chromatograph, and the change of water-ethanol association structure in liquor was analyzed by proton nuclear magnetic resonance spectroscopy. Sensory evaluation of liquor subjected to different processes was carried out. The results showed that the sensory characteristic of liquor after composite treatment was improved, and the change of aroma compounds is close to that in traditional aging. The PMF treatment can significantly improve the taste of liquor. The results prove that the PMF-microwave composite treatment is a potential artificial aging method.

Summary: Background: Increased mortality risk is associated with short-term temperature variability. However, to our knowledge, there has been no comprehensive assessment of the temperature variability-related mortality burden worldwide. In this study, using data from the MCC Collaborative Research Network, we first explored the association between temperature variability and mortality across 43 countries or regions. Then, to provide a more comprehensive picture of the global burden of mortality associated with temperature variability, global gridded temperature data with a resolution of 0·5° × 0·5° were used to assess the temperature variability-related mortality burden at the global, regional, and national levels. Furthermore, temporal trends in temperature variability-related mortality burden were also explored from 2000–19. Methods: In this modelling study, we applied a three-stage meta-analytical approach to assess the global temperature variability-related mortality burden at a spatial resolution of 0·5° × 0·5° from 2000–19. Temperature variability was calculated as the SD of the average of the same and previous days’ minimum and maximum temperatures. We first obtained location-specific temperature variability related-mortality associations based on a daily time series of 750 locations from the Multi-country Multi-city Collaborative Research Network. We subsequently constructed a multivariable meta-regression model with five predictors to estimate grid-specific temperature variability related-mortality associations across the globe. Finally, percentage excess in mortality and excess mortality rate were calculated to quantify the temperature variability-related mortality burden and to further explore its temporal trend over two decades. Findings: An increasing trend in temperature variability was identified at the global level from 2000 to 2019. Globally, 1 753 392 deaths (95% CI 1 159 901–2 357 718) were associated with temperature variability per year, accounting for 3·4% (2·2–4·6) of all deaths. Most of Asia, Australia, and New Zealand were observed to have a higher percentage excess in mortality than the global mean. Globally, the percentage excess in mortality increased by about 4·6% (3·7–5·3) per decade. The largest increase occurred in Australia and New Zealand (7·3%, 95% CI 4·3–10·4), followed by Europe (4·4%, 2·2–5·6) and Africa (3·3, 1·9–4·6). Interpretation: Globally, a substantial mortality burden was associated with temperature variability, showing geographical heterogeneity and a slightly increasing temporal trend. Our findings could assist in raising public awareness and improving the understanding of the health impacts of temperature variability. Funding: Australian Research Council, Australian National Health & Medical Research Council.

MicroRNAs (miRNAs/miRs) have aroused increasing attention in colorectal cancer (CRC) therapy. This study is designed for a detailed analysis of the roles of miR-16-5p and forkhead box K1 (FOXK1) in cell angiogenesis and proliferation during CRC in addition to their underlying mechanisms. CRC tissues and colon cancer cell lines (SW620 and HCT8) were investigated. qRT-PCR and Western blot were utilized to evaluate miR-16-5p and FOXK1 expression. Following gain- and loss-of-function assays on miR-16-5p or FOXK1, the effects of miR-16-5p and FOXK1 were assessed on cell angiogenesis and proliferation in CRC cells. A dual-luciferase reporter assay was employed to evaluate the binding relationship of miR-16-5p and FOXK1. Western blot was used to determine the effects of miR-16-5p and FOXK1 on key molecules of the PI3K/Akt/mTOR pathway. Highly expressed FOXK1 and lowly expressed miR-16-5p were observed in CRC cells and tissues. miR-16-5p overexpression or FOXK1 knockdown reduced CRC cell proliferation and angiogenesis of human umbilical vein endothelial cells co-cultured with the supernatant of CRC cells, whereas miR-16-5p silencing or FOXK1 upregulation caused opposite trends. Additionally, miR-16-5p negatively modulated FOXK1 expression. The blockade of the PI3K/Akt/mTOR pathway was triggered by miR-16-5p overexpression or FOXK1 silencing. In conclusion, miR-16-5p hampers cell angiogenesis and proliferation during CRC by targeting FOXK1 to block the PI3K/Akt/mTOR pathway.

Finding glycoproteins related to both biomarkers and therapeutic targets is essential prerequisite. Unfortunately, the glycoproteins are hard to directly detect by mass spectrometry due to their low abundance and abundant of interferents. Herein, we report a systematic integration of enrichment and comparative analysis strategy using the hydrophilic magnetic covalent organic frameworks (COFs) as the platform to fish the glycopeptides from normal and colorectal cancer (CRC) cell lysates by bottom-up methods. The layer of COF was controlled growth on the surface of Fe3O4 nanoparticles and the hydrophilicity increased with L-cysteine (L-Cys) was modified. The Fe3O4@PVP/PEI@COF-L-Cys nanoparticles have exhibited the excellent selectivity (IgG/BSA, 1:2000) and high sensitivity (0.1 fmol) for glycopeptide enrichment. A total of 214 glycopeptides and 597 glycosites belonged to 289 glycoproteins were enriched in FHC cell lysate by magnetic COFs. And 711 glycopeptides, 824 glycosites belonged to 440 N-glycoproteins were enriched in HT-29 cell lysate. Furthermore, the differential glycoproteins were comparatively analyzed through gene ontology for verifying biomarkers (LGALS3BP, PDIA3, etc.), therapeutic targets (TM9SF3, etc.), CRC pathological process, and differential glycoprotein’s function. This strategy bridges the enrichment technology and clinical requirements, has great potential for helping illuminate the mapping of CRC differential glycoproteomics.

Nitric oxide (NO) is tightly associated with plant response against cadmium (Cd) stress in rice since NO impacts Cd accumulation via modulating cell wall components. In the present study, we investigated that whether and how NO regulates Cd accumulation in root in two rice lines with different Cd accumulation ability. The variation of polysaccharides in root cell wall (RCW) of a high Cd-accumulating rice line Lu527–8 and a normal rice line Lu527–4 in response to Cd stress when exogenous NO supplied by sodium nitroprusside (SNP, a NO donor) was studied. Appreciable amounts of Cd distributed in RCW, in which most Cd ions were bound to pectin for the two rice lines when exposed to Cd. Exogenous NO upregulated the expression of OsPME11 and OsPME12 that were involved in pectin demethylesterification, resulting in more low methyl-esterified pectin and therefore stronger pectin-Cd binding. Exogenous NO also enhanced the concentration of hemicellulose and the amount of Cd ions in it. These results demonstrate that NO-induced more Cd binding in RCW in the two rice lines through promoting pectin demethylesterification and increasing hemicellulose accumulation. Higher OsPMEs expression and more hemicellulose synthesis contributed to more Cd immobilization in RCW of the high Cd-accumulating rice line Lu527–8. The main findings of this study reveal the regulation of NO on cell wall polysaccharides modification under Cd stress and help to elucidate the physiological and molecular mechanism of NO participating in Cd responses of rice.

Traumatic brain injury (TBI) is a complex injury with a multi-faceted recovery process. Long non-coding RNAs (lncRNAs) are demonstrated to be involved in central nervous system (CNS) disorders. However, the roles of lncRNAs in long-term neurological deficits post-TBI are poorly understood. The present study depicted the microarray’s lncRNA and messenger RNA (mRNA) profiles at 14 days in TBI mice hippocampi. LncRNA and mRNA microarray was used to identify differentially expressed genes. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to validate the microarray results. Bioinformatics analysis [including Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, lncRNA-mRNA co-expression network, and lncRNA-miRNA-mRNA network] were applied to explore the underlying mechanism. A total of 264 differentially expressed lncRNAs and 232 expressed mRNAs were identified (fold change > 1.5 and P-value < 0.05). Altered genes were enriched in inflammation, immune response, blood–brain barrier, glutamatergic neurological effects, and neuroactive ligand-receptor, which may be associated with TBI-induced pathophysiologic changes in the long-term neurological deficits. The lncRNAs-mRNAs co-expression network was generated for 74 lncRNA-mRNA pairs, most of which are positive correlations. The lncRNA-miRNA-mRNA interaction network included 12 lncRNAs, 59 miRNAs, and 25 mRNAs. Numerous significantly altered lncRNAs and mRNAs in mice hippocampi were enriched in inflammation and immune response. Furthermore, these dysregulated lncRNAs and mRNAs may be promising therapeutic targets to overcome obstacles in long-term recovery following TBI.

Photovoltaic agriculture is a newly emerging ecological planting pattern. In view of the adverse effect on production, a better understanding of photovoltaic adaptation responses is essential for the development of the innovative agriculture mode in sustainable crop production. Here, we investigated the impact of photovoltaic condition on endogenous hormone composition and transcriptome profile of Tetrastigma hemsleyanum. A total of 16 differentially accumulated phytohormones and 12,615 differentially expressed genes (DEGs) were identified. Photovoltaic adaptation significantly decreased the contents of phytohormones especially salicylic acid (SA) and jasmonic acid (JA). DEGs were the most relevant to photosynthesis and mitogen-activated protein kinase (MAPK) signaling pathway especially the key genes encoding proteins involved in photosystem I (PS I) and photosystem II (PS II) reaction center. Nitric oxide (NO), JA, and SA treatment alone significantly enhanced the photosynthetic efficiency which was decreased by exposure to photovoltaic condition, but the combined treatment of “NO + SA” could weaken the enhancement effect by regulating the expression level of psaL, CHIL, petF1, psbQ, and psaE genes. Exogenous phytohormones and NO treatment mitigated the accumulation of reactive oxygen species (ROS) and potentiated antioxidant capacity, which would be weakened by the combined treatment of “NO + SA.” SA and JA significantly decreased endogenous NO burst triggered by photovoltaic adaptation. SA might be a potent scavenger of NO and counter the restoration effect of NO on growth and photosynthetic potential in T. hemsleyanum. The results could provide reference for the application of phytohormones/other signaling molecules in photovoltaic agriculture.

Objective: Due to the initiation of the priority review program in China, many antitumor drugs have been approved for marketing based on phase II clinical trials and short-term surrogate endpoint indicators. This study used approved targeted drugs for the treatment of non-small-cell lung cancer (NSCLC) in China as an example to evaluate the association between short-term surrogate endpoints [objective response rate (ORR) and disease control rate (DCR)] and median progression-free survival (mPFS) and median overall survival (mOS).Methods: Five databases, i.e., MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Data were searched, for phase II or phase III clinical trials of all molecular targeted drugs that have been marketed in China for the treatment of NSCLC. After screening the literature and extracting information, both univariate and multivariate linear regression were performed on the short-term surrogate indicators and mPFS and mOS to explore the relationship.Results: A total of 63 studies were included (25 studies with only ORR, DCR, and mPFS and 39 studies with ORR, DCR, mPFS, and mOS). In terms of the targeted drugs for the treatment of NSCLC, in addition to the good but not excellent linear relationship between DCR and mOS (0.4 < R2adj = 0.5653 < 0.6), all other short-term surrogate endpoint indicators had excellent linear relationships with mPFS and mOS (R2adj≥0.6), while mPFS and mOS had the most excellent linear relationships (R2adj = 0.8036).Conclusion: For targeted drugs for the treatment of NSCLC, short-term surrogate endpoint indicators such as ORR and DCR may be reliable surrogate indicators for mPFS and mOS. However, whether short-term surrogate endpoint indicators can be used to predict final endpoints remains to be verified.

Protection against harmful chemical compounds is a major social concern, especially chemical warfare agents (CWAs) that are easy to synthesize and can cause mass casualties. The metal oxides with large surface area, porous structures, and a large number of active sites have shown outstanding performance for the adsorption and decontamination of CWAs. However, single-component metal oxides show a lower degradation rate for chemical warfare agents. Here, we demonstrate a convenient homogeneous hydrolysis method for the synthesis of mesoporous manganese-based multi-component metal oxides. Our strategy enables Ce or/and Zr to be doped into the δ-MnO2 structure during the forming process, remarkably enlarging the surface area and providing rich active sites for CWA catalysis. The as-synthesized multi-component metal oxides exhibit excellent performance for the CWA degradation. It is surprising to find that the best degree of removal of mustard gas (HD), soman (GD), and the VX nerve agent (VX) is 90.60%, 87.32%, and 100%, respectively, reaction with multi-component samples in 4 h, 2.92-fold increase to HD, 8.28-fold increase to GD, and 1.67-fold increase to VX contrast with undoped δ-MnO2. This work may provide an avenue for developing new generation chemical warfare agent decontamination materials and other catalysts.

Abstract Background The feasibility of submandibular gland (SMG) preservation in oral squamous cell carcinoma (SCC) has occasionally been analyzed, but the differences in survival associated with the presence or absence of SMG preservation remain unknown. We aimed to prospectively evaluate the oncologic results of SMG preservation in cT1-2 N0 buccal SCC. Methods This was a prospective, non-randomized cohort study. Patients with surgically treated cT1-2 N0 buccal SCC were prospectively enrolled and divided into two groups based on the management of the SMG. Level 1b lymph nodes were categorized into six groups based on the positional relationship between the lymph node and the SMG. The main study endpoints were locoregional control (LRC) and disease-specific survival (DSS). Results A total of 31 of the 137 included patients underwent SMG-sparing neck dissection. Patients with SMG preservation were likely to be young persons. Superior metastasis occurred in 11 patients with a prevalence of 8.0%, followed by an anterior metastasis rate of 5.1%, and no metastases developed deeply or within the SMG. The 5-year LRC rates in the SMG-sparing and SMG-excision groups were 74 and 75%, respectively, and the difference was not significant (p = 0.970). The 5-year DSS rates in the SMG-sparing and SMG-excision groups were 74 and 69%, respectively, and the difference was not significant (p = 0.709). Conclusions SMG involvement was rare, and the superior group carried the highest risk for lymph node metastasis. SMG-sparing neck dissection is selectively suggested in cT1-2 N0 buccal SCC patients, and could avoid postoperative asymmetric appearance and dry mouth.

In this work, we demonstrate that an organometallic perovskite (OP) single crystal for effective photodetection can be grown on a gold (Au)-decorated substrate using liquid phase epitaxy. The covered gold could both control the shape of the epitaxial layer and act as its electrodes. An MAPbCl3 single crystal and an MAPbBr1.5Cl1.5 single crystal were used as the substrate and the epitaxial layer, respectively. The device, with an Au-perovskite-Au structure, can be fully characterized. Due to the high-quality epitaxial layer, the maximum external quantum efficiency (EQE) value is over 60% under the voltage of −20 V. In addition, the response speed can reach 200 and 500 ns (ns) rise and fall, respectively. Our work provides an effective and promising method to fabricate efficient perovskite-based photodetectors.

The leaves of Lindera aggregate (Sims) Kosterm. are traditionally used as healthy tea for the prevention and treatment of hyperlipidemia in Chinese. The aim of this study was to evaluate the antihyperlipidemic effects and potential mechanisms of the aqueous extracts from L. aggregate leaves (AqLA-L) on normal and hypercholesterolemic (HCL) mice. HCL mice were induced by high fat diet (HFD) and orally administrated with or without AqLA-L for ten days. The results showed that AqLA-L (0.3, 0.6, 1.2 g/kg) significantly reduced serum TG, ALT, but elevated fecal TG in normal mice. AqLA-L (0.3, 0.6, 1.2 g/kg) also remarkably lowered serum TC, TG, LDL, N-HDL, ALT, GLU, APOB, hepatic GLU and increased serum HDL, APOA-I, fecal TG levels in HCL mice. These results revealed that AqLA-L treatment regulated the disorders of the serum lipid and liver function, reduced hepatic GLU contents both in normal and HCL mice. The potential mechanisms for cholesterol-lowering effects of AqLA-L might be up-regulation of cholesterol 7-alpha-hydroxylase (CYP7A1) and ATP-binding cassette transporter A1 (ABCA1), as well as down-regulation of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). The data indicated that AqLA-L has potential therapeutic value in treatment of hyperlipidemia with great application security. Keywords: Lindera aggregate leaves, Hypercholesterolemic mice, Lipids, Cholesterol metabolism

Thermal instability is a critical bottleneck for bulk heterojunction organic solar cells. Here Yang et al. use barely 1 wt% of a polymer acceptor as an additive to simultaneously improve the device efficiency and thermal stability of several state-of-the-art organic photovoltaic systems at high temperatures.

Establishing a reliable and stable model to predict a target by using insufficient labeled samples is feasible and effective, particularly, for a sensor-generated data-set. This paper has been inspired with insufficient data-set learning algorithms, such as metric-based, prototype networks and meta-learning, and therefore we propose an insufficient data-set transfer model learning method. Firstly, two basic models for transfer learning are introduced. A classification system and calculation criteria are then subsequently introduced. Secondly, a dataset of plantar pressure for comfort shoe design is acquired and preprocessed through foot scan system; and by using a pre-trained convolution neural network employing AlexNet and convolution neural network (CNN)- based transfer modeling, the classification accuracy of the plantar pressure images is over 93.5%. Finally, the proposed method has been compared to the current classifiers VGG, ResNet, AlexNet and pre-trained CNN. Also, our work is compared with known-scaling and shifting (SS) and unknown-plain slot (PS) partition methods on the public test databases: SUN, CUB, AWA1, AWA2, and aPY with indices of precision (tr, ts, H) and time (training and evaluation). The proposed method for the plantar pressure classification task shows high performance in most indices when comparing with other methods. The transfer learning-based method can be applied to other insufficient data-sets of sensor imaging fields.

With the increasing penetration of renewable distributed generations (DGs), large numbers of “energy prosumers” are emerging rapidly. There will be severe impacts on the utility grid if these renewable DGs are not managed properly. Smart electrical power devices which enable high flexibility in energy management, alleviation in harmonic pollutions and friendly interactions with the utility grid are needed urgently. To meet all these requirements, a novel energy router which enables a unique parallel operation mode to the energy prosumer is presented. Facilitated with a bi-directional DC/AC converter, a switch array module and a fuzzy logic based hierarchical control strategy, the presented energy router enables plug-and-play connections and reliable energy management for the energy prosumer. The switch array and the parallel mode enable the loads to be flexibly scheduled to reduce energy cost and improve system performance. MATLAB/Simulink model of the energy prosumer is set up and a fuzzy logic based hierarchical control strategy is implemented for transient power balance control in various operation modes. Simulation results have demonstrated high flexibility, stability and feasibility of the proposed energy router in energy management of the prosumer, which will contribute to the better utilization of the ever-growing renewable energies.

In delivering perishable goods, certain unexpected disruptive events may cause the initial routing scheme to be infeasible. A new routing scheme must be generated quickly to alleviate delivery disturbances. According to the idea of disruption management, a disruption recovery model with a distinctive type of split delivery is developed for inter-route recourse based on an initial time-dependent vehicle routing model with time windows, which synthesizes the perishable nature of delivered goods and dynamic travel route choice in urban road networks. Then, a tabu search algorithm is proposed to solve the initial routing problem and further extended to generate the disruption recovery plan. Three computational experiments on the instances adapted from Solomon's and Gehring and Homberger's benchmark problems are conducted to illustrate the effectiveness of the proposed model and algorithm. Supplementary data associated with this article can be found at https://www.amazon.com/clouddrive/share/foL0Vfo5C0GUjTrdO2UwljhZ9j6nNnHcD2Q0bKCTXJS.

Summary: Background: Climate change is increasing the risks of injuries, diseases, and deaths globally. However, the association between ambient temperature and renal diseases has not been fully characterized. This study aimed to quantify the risk and attributable burden for hospitalizations of renal diseases related to ambient temperature. Methods: Daily hospital admission data from 1816 cities in Brazil were collected during 2000 and 2015. A time-stratified case-crossover design was applied to evaluate the association between temperature and renal diseases. Relative risks (RRs), attributable fractions (AFs), and their confidence intervals (CIs) were calculated to estimate the associations and attributable burden. Findings: A total of 2,726,886 hospitalizations for renal diseases were recorded during the study period. For every 1°C increase in daily mean temperature, the estimated risk of hospitalization for renal diseases over lag 0–7 days increased by 0·9% (RR = 1·009, 95% CI: 1·008–1·010) at the national level. The associations between temperature and renal diseases were largest at lag 0 days but remained for lag 1–2 days. The risk was more prominent in females, children aged 0–4 years, and the elderly ≥ 80 years. 7·4% (95% CI: 5·2–9·6%) of hospitalizations for renal diseases could be attributable to the increase of temperature, equating to 202,093 (95% CI: 141,554–260,594) cases. Interpretation: This nationwide study provides robust evidence that more policies should be developed to prevent heat-related hospitalizations and mitigate climate change. Funding: China Scholarship Council, and the Australian National Health and Medical Research Council

Background: The health impact of short-term heat exposure is well documented. However, limited studies explored the association between life-time summer heat exposure and lung function. Objective: To examine the association between life-time summer heat exposure and lung function among young adults. Methods: We conducted a retrospective cohort study among 1928 college students in Shandong, China from September 4, 2020 to November 15, 2020. Life-time summer heat exposure for participants were estimated based on the nearest station meteorological data after the participant’s birth date and divided by their learning phases. Lung function indicators included forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). A multiple linear regression model was conducted to examine the associations between summer heat exposure and lung function. Stratification analysis by cooling facilities and respiratory diseases history were also conducted. Results: The study subjects had a slight majority of women (58.8%), age 19.2 ± 0.6 years. Each 1 °C increase in life-time summer mean temperature was associated with 1.07% [95% confidence interval (CI): −1.95–0.18%] decrease in FVC and 0.88% (95 %CI: −1.71, −0.05%) decrease in FEV1. Participants with respiratory diseases and non-cooling facility users were more susceptible to summer heat exposure. The usage of fan and air condition could effectively reduce the deleterious heat effects on lung function. Conclusion: Life-time summer heat exposure is significantly associated with the reduction of lung function in young adults. Cooling facilities are necessary for pre-school children to reduce heat effects. Fan and air-condition are effective cooling facilities, especially for people with respiratory diseases.

The endometrial gland is one of the most important components of the mammalian uterus. However, few studies have been conducted on the regulatory mechanisms of adenogenesis during the development of endometrium. In the present study, we detected the genes expression of 35 different prolactin family members (PRLs) together with the prolactin receptor (PRL-R) in the endometrium of neonatal mice along with the adenogenesis process, to address which prolactin-like genes play a key role during gland development in mice. We found that: (1) The expression of Prl1a1, Prl3d1, Prl5a1, Prl7a1, Prl7a2, Prl7d1, Prl8a6, Prl8a8, and Prl8a9 genes were significantly increased along with the development of uterine glands. Prl7c1 and Prl8a1 were observably up-regulated on Postnatal day 5 (PND5) when the uterine glandular bud invagination begins. Prl3a1, Prl3b1, and Prl7b1 suddenly increased significantly on PND9. But, Prl3c1 and Prl8a2 were markedly down-regulated on PND5 and the expression of Prl6a1 and Prlr were stable extremely. (2) After continuous injection of Progesterone (P4), a well-known method to suppress the endometrial adenogenesis, the expression of Prl1a1, Prl3d1, Prl5a1, Prl7a1, Prl7a2, Prl7d1, Prl8a6, Prl8a8, Prl8a9, and Prlr were suppressed on PND7. And on PND9, Prl1a1, Prl3d1, Prl8a6, Prl8a8, and Prl8a9 were significantly inhibited. (3) Further analysis of the epithelial and stroma showed that these PRLs were mainly expressed in the endometrial stroma of neonatal mice. Our results indicate that multiple PRLs are involved in uterine development and endometrial adenogenesis. Continued progesterone therapy may alter the expression pattern of these PRLs in endometrial stromal cells, thereby altering the interaction and communication between stroma and epithelium, and ultimately leading to complete suppression of endometrial adenogenesis.

Kaposi’s sarcoma-associated herpesvirus (KSHV) has two life cycle modes: the latent and lytic phases. The endoplasmic reticulum (ER) is the site for KSHV production. Furthermore, ER stress can trigger reactivation of KSHV. Little is known about the nature of the ER factors that regulate KSHV replication. Atlastin proteins (ATLs which include ATL1, ATL2, and ATL3) are large dynamin-related GTPases that control the structure and the dynamics of the ER membrane. Here, we show that ATLs can regulate KSHV lytic activation and infection. Overexpression of ATLs enhances KSHV lytic activation, whereas ATLs silence inhibits it. Intriguingly, we find that silencing of ATLs impairs the response of cells to ER stress, and ER stress can promote the lytic activation of KSHV. Our study establishes that ATLs plays a critically regulatory role in KSHV infection, thus expanding the known scope of biological processes controlled by ATLs to include KSHV infection.

Zinc finger-homeodomain (ZF-HD) transcription factors play an important role in the regulation of plant growth and development, as well as the regulation of stress responses. Studies on the ZF-HD family genes have been conducted in many plants, however, the characteristics of this family in apple (Malus domestica) fruit remains to be poorly understood. In this study, we identified nineteen ZF-HD family genes in apple at the whole-genome scale, which were unevenly located on ten chromosomes. These MdZF-HD genes were phylogenetically divided into two subfamilies: zinc finger-homeodomain (ZHD) and MINI ZINC FINGER (MIF), and the ZHD subfamily was further classified into five groups (ZHDI–ZHDV). Analysis of the gene structures showed that most MdZF-HD genes lack introns. Gene expression analysis indicated that nine selected MdZF-HD genes were differentially responsive to 1-MCP (1-methylcyclopropene) treatment during the postharvest storage of “Qinguan” apple fruit. Moreover, the transcripts of six genes were further validated in “Golden Delicious” apple fruit, and five genes (MdZHD1/2/6/10/11) were significantly repressed and one gene (MdZHD7) was slightly induced by ethylene treatment. These results indicated that these six MdZF-HD genes may involve in the regulation of ethylene induced ripening process of postharvest apple fruit. These findings provide new clues for further functional investigation of ZF-HD genes, such as their roles in the regulation of fruit ripening.

Enrichment of exosomes with high structural and functional integrity is a critically important step before downstream applications in biological and clinical domains. In this work, dynamic biological interfaces functionalized fructose-responsive immunomagnetic beads (Fr-IMBs) were fabricated by incorporating the dynamic biological interfaces composed of dopamine and 4-carboxyphenylboronic acid with immunomagnetic beads. These fabricated Fr-IMBs were successfully applied to capture the MCF-7 exosomes with a high capture efficacy of 91.0%. After incubation with fructose, the molecular structure of the dopamine-boronic acid complexation can be rearranged and the antibody (anti-CD63) bound exosomes were released competitively, with a yield greater than 79.8%. Those exosomes that underwent both immunomagnetic separation and fructose triggered release remained their good bioactivity to promote MCF-7 cell migration. Better yet, exosomes enriched by Fr-IMBs possessed higher purity and better preservation of tumor-related molecular information of the exosomal proteins than those obtained through the ultracentrifugation approach, as proved by the comparative proteomics. These proposed sugar-responsive immunomagnetic beads may serve as biofriendly candidates in enriching useful biomarkers (e.g., cells, nucleic acids, proteins, etc.) efficiently from complex biological samples with high purity.

ObjectivesTo compare the oncologic outcomes in patients with cT1N0 tongue squamous cell carcinoma (SCC) who underwent different neck management strategies stratified by sonographic depth of invasion (DOI).MethodsThe included patients were retrospectively enrolled, and divided into two groups: observation (OBS) and elective neck dissection (END). The regional control (RC) and disease-specific survival (DSS) rates were compared and stratified by sonographic DOI.ResultsThe mean sonographic and pathologic DOIs were 3.8 and 3.7 mm, respectively; the two DOIs were significantly correlated (Spearman correlation coefficient 0.974. p

EDI is a hot topic in the research of multimodal transportation informatization, which determines the exchange level of intermodal transportation information. However, its high cost, large system coupling degree and low performance threshold cannot adapt to mass data exchange in high concurrent environment. Therefore, a decentralized, scalable, distributed and efficient data exchange system is formed. It plays a key role in realizing the comprehensive sharing of interdepartmental intermodal information in the cloud environment. In order to solve the problem of mismatching between application load and computing resource capacity and realize on-demand resource allocation and low carbon emission, this paper proposes to build an Extensible EDI system (XEDI) based on MSA and studies the scaling mechanism in container environment. Based on the resource scheduling characteristics of container cloud and considering the distribution and heterogeneity of intermodal cloud computing platform from the perspective of resource allocation, the automatic scaling mechanism of XEDI is established, the scaling model is established, and the automatic scaling algorithm is proposed. For Dominant Resource Fairness for XEDI (XDRF) resource allocation algorithm and Dominant Resource Fairness for XEDI (CXDRF) based on carbon considering energy consumption, the CXDRF algorithm is proved by quantitative experiments to achieve system performance optimization on the basis of ensuring system reliability and effectively reducing energy consumption. XEDI can not only meet the demand of dynamic load and improve service quality, but also reduce resource occupation and save energy by releasing virtual resources when resource utilization rate is low. It has great research significance and practical value for mass data application under low energy consumption conditions.

In recent years, the world has been actively promoting the development of wind power, photovoltaic, and other new energy. The inherent randomness and intermittency of wind power output have led to the reduction of supply-side controllability and stability, and the power system is facing severe challenges. Aiming at the irregular fluctuation of wind power output and the restriction between the charge and discharge depth and service life of hybrid energy storage equipment, a hierarchical control strategy for a hybrid energy storage system based on improved GA-SVR wind power prediction is proposed. First of all, the short-term prediction of wind power output is carried out using Support Vector Regression (SVR), and the improved genetic algorithm is used for optimization. Then, the result obtained from the prediction calculation is used as the wind power output, and the internal initial power of each energy storage element is obtained through the hybrid energy storage capacity configuration method and further controlled through hierarchical control regulation. Finally, a simulation experiment is carried out on the proposed control strategy. The simulation algorithm shows that the proposed method can not only enhance the effective output of new energy but also extend the service life of energy storage and ensure the safe and stable operation of the power system.

As a predominant phenolic compound in apple fruits, chlorogenic acid (CGA) benefits human health due to its various antioxidant properties. However, little has been known regarding the molecular mechanism underlying the CGA accumulation in apple fruits. In this study, we measured the CGA content and relative enzymes’ activities during fruit development in two different flesh-colored cultivars ‘Huashuo’ and ‘Red Love’. The CGA content in both cultivars decreased sharply from 30 days after full bloom (DAFB) to 60 DAFB. Notably, the CGA content in fruit flesh was relatively higher than that in the peel. Further, the activities of C3H and HCT enzymes downstream of the CGA biosynthesis showed the similar changing trend as CGA content. Based on the transcriptome data of ‘Huashuo’ fruit at 30 DAFB and 60 DAFB, 23 differentially expressed CGA synthesis-related genes were screened. Gene expression analyses further showed that MdHCT1/2/4/5/6 and MdC3H1/2/3 were positively correlated to the variation of CGA content in two cultivars. These findings establish a theoretical foundation for further mechanism study on CGA biosynthesis and provide guidance for nutrient improvement in apple breeding programs.

Understanding the role of climate change and catchment characteristics in hydrological activity is important for the efficient use of water resources. In this study, a Budyko framework suitable for non-steady conditions was used to assess the impacts of climate change and catchment characteristics on the long-term changes in annual and seasonal runoff in the Second Songhua River (SSR) basin during the last 30 years. Based on the analysis of the hydro-meteorological series of the SSR, the runoff in the SSR basin showed a non-significant increasing trend. The hydro-meteorological elements changed abruptly in 2009, and the study period was divided into a baseline period (1989–2009) and a disturbed period (2010–2018). Runoff increased during the disturbed period compared to the baseline period, with a significant increase in spring runoff in the upstream area and summer runoff in the downstream area. The attribution analysis results indicated that the annual runoff was mainly affected by climatic factors, and 66.8–99.6% of yearly runoff changes were caused by climate change. Catchment characteristics had little effect on yearly runoff but significantly affected seasonal runoff. The catchment characteristics affecting runoff were mainly increased water withdrawal, changes in snowfall, degradation of permafrost, and changes in reservoir operation. This study provides a basis for further understanding the intra-annual runoff variability for SSR and other similar rivers.

This study aimed to determine the metabolites associated with ventricular septal defect (VSD) and the underlying mechanisms. Blood samples and thymus tissues were collected from VSD patients to perform LC-MS-based metabolomics assay and generate iPS cell-derived cardiomyocytes, respectively. VSD rat model was used in vivo study. RT-PCR, western blotting, immunohistochemistry, luciferase activity assay, GFP-LC3 adenovirus and GFP and RFP tfLC3 assay, and transmission electron microscopy were performed to investigate the underlying mechanisms. The metabolites uric acid (UA) and sphingomyelin (SM) increased in the serum of VSD patients, along with enhanced autophagy. The combination of UA and SM treatment could promote autophagy and inhibit EGFR and AKT3 expressions. Overexpression of EGFR and AKT3 suppressed autophagy in UA and SM-treated cardiomyocytes, respectively. Also, lncRNA MEG3 knockdown and overexpression could enhance and inhibit autophagy in UA and SM-treated cardiomyocytes, respectively, through targeting miR-7-5p. Moreover, miR-7-5p mimics and inhibitors promoted and inhibited autophagy in UA and SM-treated cardiomyocytes, respectively, via target EGFR. In VSD rat model, upregulation of MEG3 could reverse high level of autophagy and decrease serum UA and SM. In conclusion, UA and SM are essential VSD-associated metabolic biomarkers and MEG3/miR-7-5p/EGFR axis is critical to the regulation of autophagy in cardiomyocytes.