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This study focuses on the development of more cropping systems in response to global warming and food security concerns. A two-year field experiment (2017–2018) was conducted to investigate the effects of greenhouse gases (GHGs), soil environmental factors and yield on traditional double-cropping rice (DR), maize rice (MR) and ratooning rice (Rr). The results showed a significant annual effect of temperature and rainfall on GHG emissions under different cropping systems. Annual CH4 emissions under MR and Rr were significantly lower than under DR. Compared to DR, the highest cumulative N2O emissions were observed in MR (14.9 kg·ha−1) with a reduction of 23.7% in Rr. In addition, the upland crops significantly reduced CH4 emissions for late rice, while N2O emissions increased by 20.6%. Compared with DR and Rr, global warming potential (GWP) and greenhouse gas intensity (GHGI) were significantly lower for MR (p < 0.05). Meanwhile, the annual yield of MR (16.40 t·ha−1) was 8.1% and 2.4% higher than that of DR and Rr, respectively. This study further found that soil temperature and NH4+-N content were positively correlated with CH4 and N2O emissions, and soil moisture was positively correlated with N2O emission. Thus, we concluded that MR has the greatest potential to improve crop yield and mitigate GHG emissions in central China.

Traditional thermal sterilization technology is easy to implement and safe, but it will destroy food nutrition and change food taste. Therefore, people began to turn their attention to non-thermal sterilization. High-voltage pulsed electric field sterilization technology is one of them; it has attracted much attention because of its high efficiency and little damage to food. Different types of loads will cause serious trailing of the pulse falling edge. In view of this situation, this paper proposes a new topology circuit that combines a solid-state switch with a half-bridge Marx generator. It can be used for high-voltage pulsed electric field sterilization. By improving the structure of the classical Marx circuit, the high-voltage pulse power supply of the new topology circuit has the characteristics of steep rising edge and short falling edge delay; does not require isolation inductance or isolation resistance, which solves the isolation problem between the DC charging power supply and the high-voltage terminal; and has a good voltage-clamping function and load adaptability. The working process of the topology circuit under resistive, capacitive and inductive loads and the voltage clamping effect when the solid-state switch does not work properly in the discharge process are analyzed in detail. The power supply is composed of an adjustable DC power supply, five-stage half-bridge Marx generator and control protection circuit. A field programmable gate array (FPGA) is used as the controller to generate control signals, and optical fiber isolation is used to provide control signals for the main loop. The power supply can output a high-voltage square wave pulse with a voltage amplitude of 10 kV, maximum pulse number of 1000 per second, maximum pulse width of 20 μs, pulse rise time of smaller than 300 ns and short pulse drop time, and the repeated voltage amplitude, frequency and pulse width are adjustable, which can meet the requirements of a high-voltage pulse sterilization experiment.

The enzymatic degradation of seaweed polysaccharides is gaining interest for its potential in the production of functional oligosaccharides and fermentable sugars. Herein, a novel alginate lyase, AlyRm3, was cloned from a marine strain, Rhodothermus marinus DSM 4252. The AlyRm3 showed optimal activity (37,315.08 U/mg) at 70 °C and pH 8.0, with the sodium alginate used as a substrate. Noticeably, AlyRm3 was stable at 65 °C and also exhibited 30% of maximal activity at 90 °C. These results indicated that AlyRm3 is a thermophilic alginate lyase that efficiently degrades alginate at high industrial temperatures (>60 °C). The FPLC and ESI−MS analyses suggested that AlyRm3 primarily released disaccharides and trisaccharides from the alginate, polyM, and polyG in an endolytic manner. In the saccharification process of sodium alginate (0.5%, w/v), the AlyRm3 yielded numerous reducing sugars (1.73 g/L) after 2 h of reaction. These results indicated that AlyRm3 has a high enzymatic capacity for saccharifying the alginate, and could be used to saccharify the alginate biomass before the main fermentation process for biofuels. These properties make AlyRm3 a valuable candidate for both fundamental research and industrial applications.

Abstract Background Real-time ultrasound imaging (RUSI) has been increasingly used as a form of biofeedback when instructing and re-training muscle contraction. However, the effectiveness of the RUSI on a single sustained contraction of the lumbar multifidus (LM) and transversus abdominis (TrA) has rarely been reported. This preliminary study aimed to determine if the use of RUSI, as visual biofeedback, could enhance the ability of activation and continuous contraction of the trunk muscles including LM and TrA. Methods Forty healthy individuals were included and randomly assigned into the experimental group and control group. All subjects performed a preferential activation of the LM and/or TrA (maintained the constraction of LM and/or TrA for 30 s and then relaxed for 2 min), while those in the experimental group also received visual feedback provided by RUSI. The thickness of LM and/or TrA at rest and during contraction (Tc-max, T15s, and T30s) were extracted and recorded. The experiment was repeated three times. Results No significant differences were found in the thickness of LM at rest (P > 0.999), Tc-max (P > 0.999), and T15s (P = 0.414) between the two groups. However, the ability to recruit LM muscle contraction differed between groups at T30s (P = 0.006), with subjects in the experimental group that received visual ultrasound biofeedback maintaining a relative maximum contraction. Besides, no significant differences were found in the TrA muscle thickness at rest (P > 0.999) and Tc-max (P > 0.999) between the two groups. However, significant differences of contraction thickness were found at T15s (P = 0.031) and T30s (P = 0.010) between the two groups during the Abdominal Drawing-in Maneuver (ADIM), with greater TrA muscle contraction thickness in the experimental group. Conclusions RUSI can be used to provide visual biofeedback, which can promote continuous contraction, and improve the ability to activate the LM and TrA muscles in healthy subjects.

Here, the authors use whole exome sequencing to determine the effect of tumor mutational burden (TMB) and chromosomal aneuploidy (ANE) on survival outcomes of non-small cell lung cancer patients undergoing radiotherapy. The authors find that a higher TMB and lower ANE were correlated with better survival outcomes and that these factors interact synergistically.

Abstract Soil gross nitrogen (N) transformations could be influenced by land use change, however, the differences in inherent N transformations between different land use soils are still not well understood under subtropical conditions. In this study, an 15N tracing experiment was applied to determine the influence of land uses on gross N transformations in Regosols, widely distributed soils in Southwest China. Soil samples were taken from the dominant land use types of forestland and cropland. In the cropland soils, the gross autotrophic nitrification rates (mean 14.54 ± 1.66 mg N kg−1 day−1) were significantly higher, while the gross NH4 + immobilization rates (mean 0.34 ± 0.10 mg N kg−1 day−1) were significantly lower than those in the forestland soils (mean 1.99 ± 0.56 and 6.67 ± 0.74 mg N kg−1 day−1, respectively). The gross NO3 − immobilization and dissimilatory NO3 − reduction to NH4 + (DNRA) rates were not significantly different between the forestland and cropland soils. In comparison to the forestland soils (mean 0.51 ± 0.24), the cropland soils had significantly lower NO3 − retention capacities (mean 0.01 ± 0.01), indicating that the potential N losses in the cropland soils were higher. The correlation analysis demonstrated that soil gross autotrophic nitrification rate was negatively and gross NH4 + immobilization rate was positively related to the SOC content and C/N ratio. Therefore, effective measures should be taken to increase soil SOC content and C/N ratio to enhance soil N immobilization ability and NO3 − retention capacity and thus reduce NO3 − losses from the Regosols.

Clostridioides difficile sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for C. difficile ST37 isolates. The 325 ST37 genomes from six continents, including North America (n = 66), South America (n = 4), Oceania (n = 7), Africa (n = 9), Europe (n = 138) and Asia (n = 101), were clustered into six major lineages, with region-dependent distributions, harbouring an array of antibiotic-resistance genes. The ST37 strains from China were divided into four distinct sublineages, showing five importation times and international sources. Isolates associated with severe infections exhibited significantly higher toxin productions, tcdB mRNA levels, and sporulation capacities (P

Intensive cereal production has brought about increasingly serious environmental threats, including global warming, environmental acidification, and water shortage. As an important grain producer in the world, the rice cultivation system in central China has undergone excessive changes in the past few decades. However, few articles focused on the environmental impacts of these shifts from the perspective of ecological footprints. In this study, a 2-year field trial was carried out in Hubei province, China, to gain insight into carbon footprint (CF), nitrogen footprint (NF), and water footprint (WF) performance. The three treatments were, namely, double-rice system (DR), ratoon rice system (RR), and rice-wheat system (RW). Results demonstrated that RR significantly increased the grain yield by 10.22–15.09% compared with DR, while there was no significant difference in the grain yield between RW and DR in 2018–2019. All of the calculation results by three footprint approaches followed the order: RR < RW < DR; meanwhile, RR was always significantly lower than DR. Methane and NH3 field emissions were the hotspots of CF and NF, respectively. Blue WF accounts for 40.90–42.71% of DR, which was significantly higher than that of RR and RW, primarily because DR needs a lot of irrigation water in both seasons. The gray WF of RW was higher than those of DR and RR, mainly due to the higher application rate of N fertilizer. In conclusion, RR possesses the characteristics of low agricultural inputs and high grain yield and can reduce CF, NF, and WF, considering the future conditions of rural societal developments and rapid demographic changes; we highlighted that the RR could be a cleaner and sustainable approach to grain production.

Rumen development is a crucial physiological challenge for ruminants. However, the molecular mechanism regulating rumen development has not been clearly elucidated. In this study, we investigated genes involved in rumen development in 13 rumen tissues from three developmental stages (birth, youth, and adult) using RNA sequencing. We identified that 6,048 genes were differentially expressed among three developmental stages. Using weighted correlation network analysis, we found that 12 modules were significantly associated with developmental stages. Functional annotation and protein–protein interaction (PPI) network analysis revealed that CCNB1, CCNB2, IGF1, IGF2, HMGCL, BDH1, ACAT1, HMGCS2, and CREBBP involved in rumen development. Integrated transcriptome with GWAS information of carcass weight (CW), stomach weight (SW), marbling score (MS), backfat thickness (BFT), ribeye area (REA), and lean meat weight (LMW), we found that upregulated DEGs (fold change 0∼1) in birth–youth comparison were significantly enriched with GWAS signals of MS, downregulated DEGs (fold change >3) were significantly enriched with GWAS signals of SW, and fold change 0∼1 up/downregulated DEGs in birth–adult comparison were significantly enriched with GWAS signals of CW, LMW, REA, and BFT. Furthermore, we found that GWAS signals for CW, LMW, and REA were enriched in turquoise module, and GWAS signals for CW was enriched in lightgreen module. Our study provides novel insights into the molecular mechanism underlying rumen development in cattle and highlights an integrative analysis for illustrating the genetic architecture of beef complex traits.

BackgroundSynovial fluid biomarkers have been found to improve the diagnosis of chronic periprosthetic joint infection (PJI); however, no “gold standard” exists yet. Interleukin-4 (IL-4) and polymorphonuclear cell (neutrophil) count in the synovial fluid are crucial in mediating local inflammation during bacterial infections and could be valuable biomarkers for PJI.MethodsThis prospective study was conducted to investigate the diagnostic potential of synovial fluid IL-4 (SF-IL4) and polymorphonuclear cell percentage (SF-PMN%) for chronic PJI. A total of 110 patients who underwent revision arthroplasty between January 2019 and October 2020 were enrolled, and 11 patients were excluded. Of 99 patients, 43 were classified as having PJI and 56 as having aseptic failures according to the 2013 Musculoskeletal Infections Society criteria. In all patients, SF-IL4, SF-PMN%, serum C-reactive protein (CRP), and serum erythrocyte sedimentation rate (ESR) were quantified preoperatively. The diagnostic value for each biomarker was analyzed, and optimal cutoff values were calculated.ResultsThe patient demographics did not significantly vary. The area under the curve of SF-IL4 and SF-PMN% was 0.97 and 0.89, respectively, higher than that for serum ESR (0.72) and serum CRP (0.83). The combination of SF-IL4 and SF-PMN% provided higher specificity (97.0%) and accuracy (96.0%) when the cut-off values were 1.7 pg/mL and 75%, respectively.ConclusionSF-IL4 is a valuable biomarker for chronic PJI detection, and the combination of SF-IL4 and SF-PMN% improved the diagnostic value of chronic PJI, and further studies are needed until its clinical application.

Abstract Exhausted CD8+ T (Tex) cells are caused by persistent antigenic stimulation during chronic viral infection or tumorigenesis. Tex cells upregulate and sustain the expressions of multiple immune inhibitory receptors (IRs). Blocking IRs of Tex cells, exemplified by PD‐1, can partially restore their effector functions and thus lead to viral suppression or tumor remission. Tex cells derived from chronic viral infections share the expression spectrum of IRs with Tex cells derived from tumors; however, whether any IRs are selectively expressed by tumor‐derived Tex cells or virus‐derived Tex cells remains to be learnt. In the study, we found that Tex cells upregulate IR natural killer cell lectin‐like receptor isoform A (NKG2A) specifically in the context of tumor but not chronic viral infection. Moreover, the NKG2A expression is attributed to tumor antigen recognition and thus bias expressed by tumor‐specific Tex cells in the tumor microenvironment instead of their counterparts in the periphery. Such dichotomous NKG2A expression further dictates the differential responsiveness of Tex cells to NKG2A immune checkpoint blockade. Therefore, our study highlighted NKG2A as a disease‐dependent IR and provided novel insights into the distinct regulatory mechanisms underlying T cell exhaustion between tumor and chronic viral infection.

Based on the analysis of the heat generation and heat transfer process of the internal components of an electric vehicle reducer， a thermal network simulation model of an electric vehicle reducer based on AMEsim software is established. It is assumed that under high lubricating conditions， the simulation of heat balance of the reducer under different condition of high-temperature and high-load different vehicle speed is completed. Then the moving particle semi-implicit method （MPS） is used to analyze the agitation flow field of the reduction gearbox at different lubricating oil quantity. Based on this， the convective heat transfer thermal resistance module of the thermal network model of the reducer is modified to obtain optimum oil quantity for reducer. The modified results indicate that under high-temperature and high-load conditions of electric vehicle reducers，a smaller amount of lubricating oil will cause the gears of reducer to be under-lubricated， resulting in higher tooth surface temperatures. Combining the thermal network model with the moving particle semi-implicit method （MPS） provides a new method for the lubrication effect analysis of electric vehicle reducers.

Abstract Background Umbilical cord mesenchymal stem cell (HUCMSC)-based therapies were previously utilised for cartilage regeneration because of the chondrogenic potential of MSCs. However, chondrogenic differentiation of HUCMSCs is limited by the administration of growth factors like TGF-β that may cause cartilage hypertrophy. It has been reported that extracellular vesicles (EVs) could modulate the phenotypic expression of stem cells. However, the role of human chondrogenic-derived EVs (C-EVs) in chondrogenic differentiation of HUCMSCs has not been reported. Results We successfully isolated C-EVs from human multi-finger cartilage and found that C-EVs efficiently promoted the proliferation and chondrogenic differentiation of HUCMSCs, evidenced by highly expressed aggrecan (ACAN), COL2A, and SOX-9. Moreover, the expression of the fibrotic marker COL1A and hypertrophic marker COL10 was significantly lower than that induced by TGF-β. In vivo, C-EVs induced HUCMSCs accelerated the repair of the rabbit model of knee cartilage defect. Furthermore, C-EVs led to an increase in autophagosomes during the process of chondrogenic differentiation, indicating that C-EVs promote cartilage regeneration through the activation of autophagy. Conclusions C-EVs play an essential role in fostering chondrogenic differentiation and proliferation of HUCMSCs, which may be beneficial for articular cartilage repair.

The Natural Resources Conservation Service runoff curve number (NRCS-CN) method is widely used to simulate direct runoff, but the impact of rainfall intensity has not been considered. In this study, a rainfall intensity modification factor (γ) was incorporated into the Ia-S relationship of the NRCS-CN method, and the modified method (NRCS–CN–γ) was compared with the NRCS-CN method with λ = 0.2 and λ = 0.05 in three watersheds of the Walnut Gulch Experimental Watershed (WGEW). The results showed that for 2016–2018 period, the simulation performance of the NRCS–CN–γ method was close to the NRCS-CN (λ = 0.05) method and better than the NRCS-CN (λ = 0.2) method. When the new data (2009 data with high variance) was added, the significant improvement was observed by NRCS–CN–γ method with all the evaluation parameters being the best in the three watersheds, indicating a more adapted capability of the modified method with highly uneven rainfall intensities. The covariance between rainfall intensity and the simulated runoff were 19.01, 15.14, and 16.35 for the three methods, respectively. When the optimal CN changed, the relative errors representing CN sensitivity were 6.25, 6.49 and 17.39 for the methods, respectively. It is suggested that the NRCS–CN–γ method outperformed the other two methods and could contribute to a more accurate estimation of direct runoff where rainfall intensity greatly varied, especially in monsoon region or under the context of climate change.

Abstract In this paper, we consider the initial boundary value problem for a class of nonlinear fractional partial integro-differential equations of mixed type with non-instantaneous impulses in Banach spaces. Sufficient conditions of existence and uniqueness of PC-mild solutions for the equations are obtained via general Banach contraction mapping principle, Krasnoselskii’s fixed point theorem, and α-order solution operator.

Endothelial cell (EC) dysfunction and inflammation contribute to plaque destabilization in atherosclerosis, increasing the risk of thrombotic events. Here, the authors show that epsin promotes EC inflammation via a mechanism involving IP3R1 degradation, and that deletion of epsin in the endothelium prevents EC dysfunctoin and atherosclerosis in mice.

Abstract Background Sleep problems are widespread among college students around the globe, especially in China. This study was designed to investigate the prevalence of poor sleep quality and identify associated factors among college students in Jilin Province, China. Methods A total of 6284 participants were completely collected by stratified cluster sampling in 2016. Information on basic demographics, lifestyles, social and family support, and subjective sleep quality was collected by questionnaire. The Pittsburgh Sleep Quality Index (PSQI) is a self-administered questionnaire used to assess sleep for one month. Results 1951 (31.0%) participants were classified into poor sleep quality group, as defined by a PSQI score > 5. Males scored significantly higher than females on sleep duration and use of sleep medication, while females scored significantly higher than males on PSQI total and sleep disturbances. The results of the multivariate logistic regression show the following factors to be significant predictors of poor sleep quality: freshman (OR = 1.523, 95% CI: 1.168–1.987), alcohol use (OR = 1.634, 1.425–1.874), gambling behaviors (OR = 1.167, 95% CI: 1.005–1.356), exercised for more than 30 min a week on less than one day (OR = 1.234, 95% CI: 1.016–1.498), the feelings of satisfied with parental love (OR = 1.849, 95% CI: 1.244–2.749), and harmonious/neutral relationship with classmates (OR = 2.206, 95% CI: 1.312–3.708; OR = 1.700, 95% CI: 1.414–2.045),. No study pressure of this academic year (OR = 0.210, 95% CI: 0.159–0.276), no truancy in the past month (OR = 0.510, 95% CI: 0.354–0.735), never had self-injurious behaviors (OR = 0.413, 95% CI: 0.245–0.698), very harmonious family relationship (OR = 0.377, 95% CI: 0.219–0.650), frequent communication with parents (OR = 0.524, 95% CI: 0.312–0.880), the feelings of satisfied with maternal love (OR = 0.432, 95% CI: 0.257–0.725), and frequent excursions to gymnasium (OR = 0.770, 95% CI: 0.659–0.899) were the protective factors. Conclusions The implication of the present study may be that college students must be made aware of the consequences of inadequate sleep quality and risk factors could be improved if students tried to change their behavior and subjective consciousness.

Abstract Background The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages. Methods MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund’s Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1β, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis. Results MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1β, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages. Conclusion MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Abstract Background The aim of this study was to describe the clinical features and outcome of infective endocarditis at a general hospital in China and to identify the risk factors associated with in-hospital mortality. Methods A retrospective study was conducted and all patients diagnosed with definite or possible infective endocarditis between January 2013 and June 2018 according to the modified Duke criteria were included. Results A total of 381 patients were included. The mean age was 46 years old and 66.9% patients were male patients. Community acquired IE was the most common type of infective endocarditis and Viridans Group Streptococci (37.5%) was still the most common causative pathogen. The microbial etiology of infective endocarditis varied with location of acquisition. 97 (25.5%) patients had culture-negative infective endocarditis. Vegetations were detected in 85% patients and mitral valve was the most common involved valve. Operations were performed in 72.7% patients and in-hospital mortality rate was 8.4%. The risk factors of in-hospital mortality were age old than 70 years old, heart failure, stroke and medical therapy. Conclusions Older age, heart failure, stroke and medical therapy were risk factors of in-hospital mortality. Infective endocarditis, were mainly caused by Viridans Group Streptococci, characterized by younger patients and lower mortality rate in China.

Abstract Plant pathogenic bacteria engage in an ongoing struggle for survival. Gram negative phytopathogenic prokaryotes deploy type III secretion system to deliver effector proteins into plant cells to manipulate the host cellular environment. In many cases, the targets of these effector proteins are unknown. The bacterial blight pathogen, Xanthomonas oryzae pv. oryzae (Xoo), causes a devastating disease in rice and the Xoo-rice interaction is an example of the ongoing evolutionary battle between plants and pathogens. In this study, we show that an effector XopL from Xoo exhibits E3 ubiquitin ligase activity and induces cell death in the nonhost Nicotiana benthamiana (Nb). Through yeast two-hybrid, co-immunoprecipitation, and biomolecular fluorescence complementation assays, it was shown that XopL interacts with ferredoxin (NbFd), an electron transport molecule in plant chloroplasts. XopL induced defense-related response in Nb and specifically targeted NbFd for ubiquitination and ubiquitin-mediated degradation, a process that increased the production of reactive oxygen species (ROS). This study demonstrates the ubiquitination and degradation of NbFd as a result of XopL activity, which further illustrates the tremendous functional diversity in Xanthomonas effector proteins.

Abstract Background Tobacco exposure (TE) is the major contributor for CVD mortality, but few published studies on CVD mortality attributable to TE have analyzed the potential reasons underlying long-term trends in China. Our studysought to find the potential reasons and compared CVD mortality attributable to TE in China, Japan, the United States of America (USA), and the world between 1990 and 2017. Methods The mortality data in China, Japan, the USA, and the world were obtained from Global Burden of Disease Study 2017(GBD 2017). Joinpoint regression was used to assess the trend magnitude and directions over time for CVD mortality, while the age-period-cohort method was used to analyzethe temporal trends of CVD mortality according to age, period, and cohort. Results A significant downward trend was found in the age-standardised mortality rate (ASMR) of CVD attributable to smoking in four regions. China had the smallest decline and the Chinese ASMR became the highest in 2017. All the annual net drifts in the four regions were negative and the local drifts were below zero. The longitudinal age curves of CVD mortality attributable to smoking increased in four regions,with China having the largest increase. The period or cohort RRs indicated a decline, and China had the smallest decline. The researchers further analyzed the IHD and stroke trends, finding that the morality and period or cohort RR of IHD in China was always at a high level. Conclusions CVD mortality attributable to TE declined in four regions, and was highest in China. The proportion of IHD mortality attributable to TE was similar to stroke, which significantly changed the traditional cognition of CVD composition, but the control measure was not sufficient for IHD in China.

Ammonia (NH3) volatilized from agricultural production and its secondary aerosols contribute greatly to air pollution. Different long-term crop straw management practices may significantly affect the soil fertility and soil nitrogen cycle, however, the effect on NH3 volatilization has not been well studied. Therefore, a one-year field experiment was conducted to evaluate the effect of straw incorporation on NH3 volatilization from subtropical calcareous agricultural soil from a longterm perspective, including four treatments: synthetic fertilizer (CK); synthetic fertilizer incorporation with 100% or 50% of the previous season’s crop straw (SI1 and SI2, respectively); and synthetic fertilizer incorporation with 50% burned crop straw (SI2B). Soil NH3 volatilizations were monitored through a wheat–maize rotation year by using a dynamic chamber method. The results demonstrated that NH3 volatilization primarily occurred within 38 days and 7–10 days following nitrogen fertilization events for the wheat and maize seasons, respectively. Different crop straw management practices mainly impacted the NH3 flux of the basal fertilization rather than the topdressing fertilization; long-term crop straw incorporation effectively lowered NH3 loss (35.1% for SI1 and 16.1% for SI2 compared to CK; and the inhibiting effect increased with increasing straw amount, possibly contributed by the high straw carbon/nitrogen ratio, and enhanced microbial activity, which contributed to inorganic nitrogen immobilization and lower ammonium content in the topsoil. However, SI2B significantly increased (29.9%) the annual NH3 flux compared with SI2, indicating that long-term 100% straw incorporation could be a promising straw management practice for mitigating NH3 loss and increasing soil fertility.

Abstract Background Bacterial blight of cotton (BBC), which is caused by the bacterium Xanthomonas citri pv. malvacearum (Xcm), is a destructive disease in cotton. Transcription activator-like effectors (TALEs), encoded by tal-genes, play critical roles in the pathogenesis of xanthomonads. Characterized strains of cotton pathogenic Xcm harbor 8–12 different tal genes and only one of them is functionally decoded. Further identification of novel tal genes in Xcm strains with virulence contributions are prerequisite to decipher the Xcm-cotton interactions. Results In this study, we identified six tal genes in Xss-V2–18, a highly-virulent strain of Xcm from China, and assessed their role in BBC. RFLP-based Southern hybridization assays indicated that Xss-V2–18 harbors the six tal genes on a plasmid. The plasmid-encoded tal genes were isolated by cloning BamHI fragments and screening clones by colony hybridization. The tal genes were sequenced by inserting a Tn5 transposon in the DNA encoding the central repeat region (CRR) of each tal gene. Xcm TALome evolutionary relationship based on TALEs CRR revealed relatedness of Xss-V2–18 to MSCT1 and MS14003 from the United States. However, Tal2 of Xss-V2–18 differs at two repeat variable diresidues (RVDs) from Tal6 and Tal26 in MSCT1 and MS14003, respectively, inferred functional dissimilarity. The suicide vector pKMS1 was then used to construct tal deletion mutants in Xcm Xss-V2–18. The mutants were evaluated for pathogenicity in cotton based on symptomology and growth in planta. Four mutants showed attenuated virulence and all contained mutations in tal2. One tal2 mutant designated M2 was further investigated in complementation assays. When tal2 was introduced into Xcm M2 and expressed in trans, the mutant was complemented for both symptoms and growth in planta, thus indicating that tal2 functions as a virulence factor in Xcm Xss-V2–18. Conclusions Overall, the results demonstrated that Tal2 is a major pathogenicity factor in Xcm strain Xss-V2–18 that contributes significantly in BBC. This study provides a foundation for future efforts aimed at identifying susceptibility genes in cotton that are targeted by Tal2.

Abstract Background Rearranged during transfection (RET) has been proven to be a tumorigenic target in non-small cell lung cancers (NSCLCs). In RET-rearranged NSCLCs, molecular features and their impact on prognosis were not well illustrated, and the activity of mainstay therapeutics has not currently been well compared. Methods Patients diagnosed with NSCLCs with RET rearrangements were analyzed for concomitant mutations, tumor mutation burden (TMB), PD-L1 expression, T cell receptor repertoire and clinical outcomes with chemotherapy, immune checkpoint inhibitors (ICIs), and multikinase inhibitors (MKIs). Results Among 129 patients with RET-rearranged NSCLC who were analyzed, 41.1% (53/129) had co-occurring genetic alterations by next-generation sequencing, and concomitant TP53 mutation appeared most frequently (20/53, 37.7%). Patients with concurrent TP53 mutation (n = 15) had shorter overall survival than those without (n = 30; median, 18.4 months [95% CI, 8.6–39.1] vs 24.8 months [95% CI, 11.7–52.8]; P < 0.05). Patients with lower peripheral blood TCR diversity (n = 5) had superior overall survival compared with those with higher diversity (n = 6; median, 18.4 months [95% CI, 16.9–19.9] vs 4.8 months [95% CI, 4.5–5.3]; P = 0.035). An association with overall survival was not observed for PD-L1 expression nor for tumor mutation burden level. Median progression-free survival was not significantly different across chemotherapy, ICIs, and MKIs (median, 3.5 vs 2.5 vs 3.8 months). For patients treated with ICIs, the disease control rate was 60% (6/10) and the objective response rate was 20% (2/10). Conclusions RET-rearranged lung cancers can be heterogeneous in terms of concomitant genetic alterations. Patients with concurrent TP53 mutation or high peripheral blood TCR repertoire diversity have relatively inferior overall survival in this series. Outcomes with traditional systemic therapies in general are suboptimal.

Abstract Background Reports of anaesthetic management of paraganglioma resection in patients with isolated L-transposition of the great arteries (L-TGA) are rare. We focus on the preoperative evaluation, intraoperative management, and postoperative care of a frail patient with “physiologically corrected” L-TGA for paraganglioma resection. Case presentation We performed general anaesthesia for a 46-year-old patient with “physiologically corrected” L-TGA undergoing open large retroperitoneal paraganglioma resection. Although the preoperative medical therapy had attained its goals, the patient went through three periods of severe episodic hypertension and tachycardia as tumour manipulation released catecholamines. Goal-directed fluid therapy based on pulse pressure variation (PPV) and point-of-care transesophageal echocardiography (TEE) imaging enabled anaesthesiologists to make rapid judgments and to regulate blood pressure in a timely manner, thereby reducing the risk of heart failure caused by massive rapid fluid bolus therapy. The patient was transferred to the intensive care unit because of intraoperative hemodynamic changes and significant blood loss. Despite transient myocardial injury (elevated troponin I), no lethal arrhythmia or complications occurred perioperatively, and the patient recovered well and was discharged 1 week later. Conclusions Goal-directed fluid therapy combined with the adoption of TEE could effectively guide fluid administration, which is helpful for anaesthesia management during operation. We recommend the routine use of TEE in such cases.

Background:Myocardial impairment is a major complication and an important prognostic predictor of sepsis. Therefore, early and accurate diagnosis as well as timely management of septic cardiomyopathy is critical to achieve favorable outcomes.Aims:To investigate the risk factors of septic cardiomyopathy.Study Design:Cross-sectional study.Methods:This study performed between May 2016 and June 2018 recruited 93 septic patients from the intensive care unit. All patients received standardized treatments. Septic patients were divided into two groups: non cardiomyopathy (n=45) and septic cardiomyopathy group (n=48). Blood samples were collected and transthoracic echocardiography was performed within 24 hours of intensive care unit admission. Septic patients with one ultrasound abnormality but no history of heart disease were diagnosed as having septic cardiomyopathy. Plasma histones, cardiac troponin I, and N-terminal pro-brain natriuretic peptide were measured using ELISA. Sequential Organ Failure Assessment scores, vasopressor use, and the outcomes of intensive care unit stay were analyzed. Spearman rank analysis was used to determine the correlation between plasma histone H4 and other parameters. Binary logistic regression and receiver operating characteristic curve analysis were used to determine the risk factors for septic cardiomyopathy.Results:Compared with the non-cardiomyopathy group, the septic cardiomyopathy group had significantly higher plasma H4 and cardiac troponin I levels, a higher Sequential Organ Failure Assessment score, more frequent vasopressor use, and a higher mortality rate (p

Abstract Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.

Abstract Background Previous studies indicated that type 2 diabetes mellitus (T2DM) is related to an increased lung cancer risk, but its role in the prognosis of NSCLC remains conflicting. This study investigated the impact of blood glucose control on the outcomes in NSCLC patients with T2DM treated with platinum‐based doublets. Methods Clinicopathological and survival data from 191 T2DM patients with advanced NSCLC, who received platinum‐based chemotherapy, were retrospectively analyzed. Based on the blood glucose conditions during chemotherapy, patients were classified into poor (n = 84) and good control (n = 107) groups. Progression‐free survival (PFS) was assessed using the Kaplan‐Meier method. Results The median PFS among patients with good glycemic control [197.0 (95% CI: 136.3‐257.7) days] was longer than that among those with poor control [132.0 (95% CI: 112.5‐151.5) days] (P = .0003). Further subgroup analysis of lung squamous carcinoma and adenocarcinoma patients showed that the median PFS of the good control group was also significantly longer than that of the poor control group [179.0 (95% CI: 78.4‐279.6) days vs 125.0 (95% CI: 110.9‐139.1) days, P = .0014; 197.0 (95% CI: 124.3‐269.7) days vs 154.0 (95% CI: 129.9‐178.1) days, P = .0359; respectively]. The incidence rates of side effects were similar among patients with good glycemic control and those with poor glycemic control (all P > .05). Conclusions Satisfactory glycemic control during platinum‐based chemotherapy might provide a survival benefit to T2DM patients with NSCLC. Further studies are warranted to confirm our findings.

Abstract Background Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China. Methods Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted. Results Among mCRC patients (3878/8136, 48%), the fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first- and second- lines to 34% for the third-line (p

Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer, most NSCLC patients are at advanced stage at the time of diagnosis. For patients without sensitive driven-oncogene mutations, chemotherapy is still the main treatment at present, the overall prognosis is poor. Improving outcomes and obtaining long-term survival are the most urgent needs of patients with advanced NSCLC. In recent years, immunotherapy has developed rapidly. Immune checkpoint inhibitors (ICIs), especially targeting programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1), have made a breakthrough in the treatment of NSCLC, beneficial to patients’ survival and changed the treatment pattern for NSCLC. It shows more and more important role in the treatment of NSCLC. Led by NSCLC expert committee of Chinese society of clinical oncology (CSCO), relevant experts in this field were organized. On the basis of referring to domestic and foreign literature, systematically evaluating the results of Chinese and foreign clinical trials, and combining the experiences of the experts, the experts group reached an agreement to develop this consensus. It will guide domestic counterparts for better application of ICIs to treat NSCLC.

Abstract Background Mounting evidence suggests that complement components promote tumor progression via modulating immune suppression, angiogenesis, or tumor cell proliferation. However, the role of C3a-C3aR signaling in regulating lung metastasis of breast cancer remains unknown. Methods We performed various ex-vivo and in-vivo assays. Genetic and pharmacological C3aR blockade models were applied to investigate the role of C3a-C3aR in metastasis of breast cancer. Results C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Mechanically, C3a-C3aR signaling augments pro-metastatic cytokine secretion and extracellular matrix components expression of CAFs via the activation of PI3K-AKT signaling. Genetic or pharmacological blockade of C3aR signaling effectively inhibited lung metastasis of breast cancer in mouse models. Conclusions C3a-C3aR signaling in CAFs facilitates the metastasis of breast cancer. Targeting C3aR signaling is a potential anti-metastasis strategy for breast cancer therapy.

Abstract Background The purpose of the present study was to obtain information on the use of PD-1/PD-L1 inhibitors by oncologists in China through a national questionnaire survey. Methods Between the 7th and 25th of July in 2019, a questionnaire designed by the Chinese Society of Clinical Oncology Immuno-Oncology (CSCO IO) Committee on the current status of the use of PD-1/PD-L1 inhibitors was distributed online and offline to cancer-related medical departments in thirty different provinces and autonomous regions of China. The national questionnaire consisted of three sections as follows: general information, current status of the application of PD-1/PD-L1 inhibitors in the clinic, and oncologists’ concerns regarding utilization. Results The valid response rate of the current status survey was 76.3%. The proportion of senior doctors (physician-in-charge or a more superior position for more than 3 years) among the respondents was relatively high (67.0% in 588). Of the respondents, 59.2% had prescribed PD-1/PD-L1 inhibitors during clinical treatment, and the most frequent reason for not prescribing these inhibitors was the choice “do not understand the mechanism and the efficacy of PD-1/PD-L1 inhibitors”. In addition, 77.9% of the prescribers used the medications in an off-label situation, and the most important motivation for this use was the fact that “there were indications abroad but not domestically”. In addition, 77.9% of the prescribers believed that “immunotherapy-related adverse effects could be controlled or intervened through follow-up management”. The prescribers were mostly concerned about “how to identify pseudoprogression and hyperprogression” and “immunity-related adverse effects management”. Conclusion The present study highlights the current status of PD-1/PD-L1 inhibitors in China. Increasing numbers of medical oncologists are interested in PD-1/PD-L1 inhibitors, and they are in need of immunotherapy education.

Abstract Background Several reports were published on the relationship between the vascular endothelial growth factor (VEGF) -2578C > A gene polymorphism and lung cancer risk; however, the results are debatable. This meta-analysis was conducted to assess the relationship between VEGF -2578C > A gene polymorphism and lung cancer risk. Methods The associated literatures were identified on the 1st of September 2018 from CBM-disc (China Biological Medicine Database) and PubMed. Result A total of 14 reports were recruited into our meta-analysis to assess the association between VEGF -2578C > A gene polymorphism and lung cancer susceptibility. There was a marked association between VEGF -2578C > A A allele / CC genotype and lung cancer risk in overall and Asian populations (overall populations: A allele: OR = 1.26, 95% CI: 1.08–1.46, P = 0.003; CC genotype: OR = 0.72, 95% CI: 0.54–0.95, P = 0.02; Asians: A allele: OR = 1.33, 95% CI: 1.15–1.55, P = 0.0002; CC genotype: OR = 0.68, 95% CI: 0.50–0.93, P = 0.01). However, VEGF -2578C > A gene polymorphism was not associated with the risk of lung cancer in Caucasians. Conclusion VEGF -2578C > A A allele / CC genotype is associated with the lung cancer susceptibility in Asians and in overall populations.

Diabetes mellitus is a worldwide health problem that usually comes with severe complications. There is no cure for diabetes yet and the threat of these complications is what keeps researchers investigating mechanisms and treatments for diabetes mellitus. Due to advancements in genomics, epigenomics, proteomics, and single-cell multiomics research, considerable progress has been made toward understanding the mechanisms of diabetes mellitus. In addition, investigation of the association between diabetes and other physiological systems revealed potentially novel pathways and targets involved in the initiation and progress of diabetes. This review focuses on current advancements in studying the mechanisms of diabetes by using genomic, epigenomic, proteomic, and single-cell multiomic analysis methods. It will also focus on recent findings pertaining to the relationship between diabetes and other biological processes, and new findings on the contribution of diabetes to several pathological conditions.

The test bench was designed to solve the problem of measuring the oil film thickness of the liquid hydrostatic guideway of machine tools. And based on the fast overshoot of the classical PID control, introducing the self-antidisturbance control algorithm, this study established a mathematical model of the test bench electro-hydraulic servo control system. At the same time, this paper also designed a specific structure of the self-turbulence controller, which adopts optimal quadratic control, pole configuration, PID control, and self-turbulence control to study the control methods of the test bench electro-hydraulic servo system, respectively, and uses the SIMULINK module to establish the system simulation model of the above-mentioned four control methods of the test bench. Simulation results of the test bench control system show that the response speed of the self-turbulence control is 0.4 seconds, 0.2 seconds, and 4.4 seconds faster than PID control, pole configuration, and optimal quadratic control, respectively, and the overshoot is significantly reduced. Finally, the test bench was built to complete the experiments, and the experimental results showed that the followability of the loading force and thickness detection accuracy of the test bench were better after adding the self-turbulence control algorithm and the stability of the oil film thickness was significantly improved by the test bench electro-hydraulic servo control system.

Calreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulatory effects as well as immunoregulation effects on immune cells. Here, we constructed stable B16 melanoma cell lines expressing recombinant CRT/39-272 on the membrane (B16-tmCRT/39-272) to investigate the roles of cell surface CRT on tumor progression. We found that B16-tmCRT/39-272 cells subcutaneously inoculated into C57BL/6 mice exhibited stronger tumorigenicity than the B16-EGFP control cells. The tumor associated macrophages infiltrated in tumors were mainly M2 phenotype. Regulatory T cells (Tregs) were also expanded more in bearing mice. Consistent with the in vivo results, B16-tmCRT/39-272 promoted macrophage polarization toward F4/80+CD206+ M2 macrophages and promoted transforming growth factor beta (TGF-β) secretion in vitro, which could promote naïve CD4+T cell differentiation into Tregs. These results imply that the tmCRT/39-272 could accelerate tumor development by enhancing M2 macrophage polarization to induce TGF-β secretion, and then promoted Treg differentiation in the tumor microenvironment. Our data may provide useful clues for better understanding of the potentiating roles of CRT in tumorigenesis.

Non-small cell lung cancer remains the leading cause of cancer-related deaths worldwide with high morbidity and mortality. There is an urgent need to reveal new molecular mechanisms that contribute to NSCLC progression to facilitate drug development and to improve overall survival. Much attention has been paid to the role of circRNAs in NSCLC development. However, the knowledge of circRNAs in NSCLC is still limited, and need to be further explored. The dysregulation of circACC1 was evaluated by qRT-PCR in NSCLC samples and cell lines. The oncogenic role of circACC1 in NSCLC progression was analyzed by CCK8 and colony formation assays. The interaction between the circACC1 and miR-29c-3p, as well as MCL-1, was verified by qRT-PCR, Western blot, luciferase reporter assay, and RIP experiment. Elevated levels of circACC1 were found in NSCLC patients and were negatively correlated with OS. Ectopic expression of circACC1 promoted the capacity of cell growth and clonogenicity, while the inhibition of circACC1 decreased the proliferation and clonogenicity potential. Mechanism studies elucidated that circACC1 contributes to cell growth via directly binding to miR-29c-3p. Transfection of miR-29c-3p mimic blocked circACC1 mediated NSCLC cell proliferation. MCL-1 is a downstream target of miR-29c-3p in NSCLC cells. The circACC1/miR-29c-3p/MCL-1 axis is important in NSCLS proliferation.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection is the deadliest infectious disease and a global health problem. Macrophages (Mφs) and neutrophils that can phagocytose Mtb represent the first line of immune response to infection. Glycogen synthase kinase-3α/β (GSK-3α/β) represents a regulatory switch in host immune responses. However, the efficacy and molecular mechanisms of how GSK-3α/β interacts with Mtb infection in Mφs remain undefined. Here, we demonstrated that Mtb infection downregulated GSK-3α/β activity and promoted matrix metalloproteinase-1 (MMP-1) and MMP-9 expressions in Mφs derived from acute monocytic human leukemia THP-1 cells (THP-1-Mφs). We confirmed the upregulation of MMP-9 expression in tissues of TB patients compared with patients of chronic inflammation (CI). In THP-1-Mφs and C57BL/6 mice, GSK-3α/β inhibitor SB216763 significantly increased MMP-1/9 production and facilitated Mtb load, while MMP inhibitors blocked MMP-1/9 expression and Mtb infection. Consistently, GSK-3α/β silencing significantly increased MMP-1/9 expression and Mtb infection, while overexpression of GSK-3α/β and constitutive activated GSK-3α/β mutants significantly reduced MMP-1/9 expression and Mtb infection in THP-1-Mφs. MMP-1/9 silencing reduced Mtb infection, while overexpression of MMP-1/9 promoted Mtb infection in THP-1-Mφs. We further found that GSK-3α/β inhibition increased Mtb infection and MMP-1/9 expression was blocked by ERK1/2 inhibitor. Additionally, we showed that protein kinase C-δ (PKC-δ) and mammalian target of rapamycin (mTOR) reduced GSK-3α/β activity and promoted MMP-1/9 production in Mtb-infected THP-1-Mφs. In conclusion, this study suggests that PKC-δ-mTOR axis suppresses GSK-3α/β activation with acceleration of MMP-1/9 expression through phospho-ERK1/2. These results reveal a novel immune escape mechanism of Mtb and a novel crosstalk between these critical signaling pathways in anti-TB immunity.

Folliculogenesis is controlled by intimate communications between oocytes and surrounding follicle cells. Epidermal growth factor (EGF/Egf) is an important paracrine/autocrine factor in vertebrate ovary, and it is well known for its stimulation of oocyte maturation. However, the role of EGF signaling through its receptor (EGFR/Egfr) in ovarian folliculogenesis is poorly understood, especially at early stages of follicle development. In this study, we created zebrafish mutants for Egf (egf−/−) and Egfr (egfra−/− and egfrb−/−) by CRISPR/Cas9 technique. Surprisingly, these mutants all survived well with little abnormality in growth and development. Spermatogenesis and folliculogenesis were both normal in egf−/− males and females. Their fecundity was comparable to that of the wildtype fish at 4 months post-fertilization (mpf); however, the fertilization rate of mutant eggs (egf−/−) decreased significantly at 7 mpf. Interestingly, disruption of egfra (egfra−/−) led to failed follicle activation with folliculogenesis being blocked at primary–secondary growth transition (PG-SG transition), leading to female infertility, whereas the mutant males remained fertile. The mutant ovary (egfra−/−) showed abnormal expression of a substantial number of genes involved in oxidative metabolism, gene transcription, cytomembrane transport, steroid hormone biosynthesis, and immune response. The stunted PG oocytes in egfra−/− ovary eventually underwent degeneration after 6 months followed by sex reversal to males with functional testes. No abnormal phenotypes were found in the mutant of truncated form of EGFR (egfrb). In summary, our data revealed critical roles for EGFR signaling in early folliculogenesis, especially at the PG-SG transition or follicle activation.

Gayal and yak are well adapted to their local high-altitude environments, yet the transcriptional regulation difference of the plateau environment among them remains obscure. Herein, cross-tissue and cross-species comparative transcriptome analyses were performed for the six hypoxia-sensitive tissues from gayal, yak, and cattle. Gene expression profiles for all single-copy orthologous genes showed tissue-specific expression patterns. By differential expression analysis, we identified 3,020 and 1,995 differentially expressed genes (DEGs) in at least one tissue of gayal vs. cattle and yak vs. cattle, respectively. Notably, we found that the adaptability of the gayal to the alpine canyon environment is highly similar to the yak living in the Qinghai-Tibet Plateau, such as promoting red blood cell development, angiogenesis, reducing blood coagulation, immune system activation, and energy metabolism shifts from fatty acid β-oxidation to glycolysis. By further analyzing the common and unique DEGs in the six tissues, we also found that numerous expressed regulatory genes related to these functions are unique in the gayal and yak, which may play important roles in adapting to the corresponding high-altitude environment. Combined with WGCNA analysis, we found that UQCRC1 and COX5A are the shared differentially expressed hub genes related to the energy supply of myocardial contraction in the heart-related modules of gayal and yak, and CAPS is a shared differential hub gene among the hub genes of the lung-related module, which is related to pulmonary artery smooth muscle contraction. Additionally, EDN3 is the unique differentially expressed hub gene related to the tracheal epithelium and pulmonary vasoconstriction in the lung of gayal. CHRM2 is a unique differentially expressed hub gene that was identified in the heart of yak, which has an important role in the autonomous regulation of the heart. These results provide a basis for further understanding the complex transcriptome expression pattern and the regulatory mechanism of high-altitude domestication of gayal and yak.

Signal-to-Noise Ratio (SNR) is the benchmark to evaluate the quality of optical remote sensors. For SNR estimation, most of the traditional methods have complicated processes, low efficiency, and general accuracy. In particular, they are not suitable for the distributed computation on intelligent satellites. Therefore, an intelligent SNR estimation algorithm with strong computing power and more accuracy is urgently needed. Considering the simplicity of distributed deployment and the lightweight goal, our first proposition is to design a convolutional neural network (CNN) similar to VGG (proposed by Visual Geometry Group) to estimate SNR for optical remote sensors. In addition, considering the advantages of multi-branch structures, the second proposition is to train the CNN in a novel method of multi-branch training and parameter-reconstructed inference. In this study, simulated and real remote sensing images with different ground features are utilized to validate the effectiveness of our model and the novel training method. The experimental results show that the novel training method enhances the fitting ability of the network, and the proposed CNN trained in this method has high accuracy and reliable SNR estimation, which achieves a 3.9% RMSE for noise-level-known simulated images. When compared to the accuracy of the reference methods, such as the traditional and typical SNR methods and the denoising convolutional neural network (DnCNN), the performance of the proposed CNN trained in a novel method is the best, which achieves a relative error of 5.5% for hyperspectral images. The study is fit for optical remote sensing images with complicated ground surfaces and different noise levels captured by different optical remote sensors.

Stock (Matthiola incana (L.) R. Br.) is a famous annual ornamental plant with important ornamental and economic value. The lack of DNA molecular markers has limited genetic analysis, genome evolution, and marker-assisted selective breeding studies of M. incana. Therefore, more DNA markers are needed to support the further elucidation of the biology and genetics of M. incana. In this study, a high-quality genome of M. incana was initially assembled and a set of effective SSR primers was developed at the whole-genome level using genome data. A total of 45,612 loci of SSRs were identified; the di-nucleotide motifs were the most abundant (77.35%). In total, 43,540 primer pairs were designed, of which 300 were randomly selected for PCR validation, and as the success rate for amplification. In addition, 22 polymorphic SSR markers were used to analyze the genetic diversity of 40 stock varieties. Clustering analysis showed that all varieties could be divided into two clusters with a genetic distance of 0.68, which were highly consistent with their flower shape (potted or cut type). Moreover, we have verified that these SSR markers are effective and transferable within the Brassicaceae family. In this study, potential SSR molecular markers were successfully developed for 40 M. incana varieties using whole genome analysis, providing an important genetic tool for theoretical and applied research on M. incana.

Abstract Background Acute kidney injury (AKI) commonly occurs in intensive care units (ICUs), leading to adverse clinical outcomes and increasing costs. However, there are limited epidemiological data of AKI in the critically ill in Beijing, China. Methods In this prospective cohort study in 30 ICUs, we screened the patients up to 10 days after ICU admission. Characteristics and outcomes were compared between AKI and non-AKI, renal replacement therapy (RRT) and non-RRT patients. Nomograms of logistic regression and Cox regression were performed to examine potential risk factors for AKI and mortality. Results A total of 3107 patients were included in the final analysis. The incidence of AKI was 51.0%; stages 1 to 3 accounted for 23.1, 11.8, and 15.7%, respectively. The majority (87.6%) of patients with AKI developed AKI on the first 4 days after admission to the ICU. A total of 281 patients were treated with RRT. Continuous RRT with predilution, citrate for anticoagulation and femoral vein for vascular access was the most common RRT pattern (29.9%, 84 of 281). Patients with AKI were associated with longer ICU-LOS and higher mortality and costs (P

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized with heterotopic ossification of the axis joints ligaments, resulting in joint disability. MicroRNAs (miRNAs) are regulators of mRNAs that play a crucial role in the AS pathological process. Here, we showed that the level of miR-17-5p was significantly higher in fibroblasts and ligament tissues from AS patients as compared to the non-AS individuals. Knockdown of the miR-17-5p from the fibroblasts derived from AS patients exhibited decreased osteogenic differentiation and ossification. On the other hand, AS patient-derived fibroblasts overexpressing miR-17-5p displayed the increased osteogenesis. Furthermore, inhibition of miR-17-5p ameliorated osteophyte formation, and the sacroiliitis phenotype in AS rats received emulsified collagen. Mechanistically, miR-17-5p regulated osteogenic differentiation by targeting the 3ʹ UTR of ankylosis protein homolog (ANKH). Also, downregulation of miR-17-5p slowed AS progression through regulation of cytokines, such as dickkopf-1 (DKK1) and vascular endothelial growth factor (VEGF). In conclusion, our findings reveal a role of the miR-17-5p-ANKH axis in the regulation of heterotopic ossification, which is essential for therapeutic intervention in heterotopic ossification in AS.

Applying organic coating is an important and effective approach for the protection of metal from corrosion. Weathering degradation and under-film corrosion are the two major important factors that cause the failure of organic coatings. In this work, the degradation investigation of two epoxy coatings (clear and pigmented coatings) was carried out under the dry–wet circulation of three different water fog solutions (deionized water, 0.5 wt% NaCl, 0.05 wt% NaCl + 0.35 wt% (NH4)2SO4) in 35 days. The apparent performance (pull-off adhesion and surface potentials) and electrochemical features [electrochemical noise and electrochemical impedance spectroscopy (EIS)] of the coating samples were monitored after dry–wet fog exposure. In our three accelerating systems of the fog atmosphere, the time that the detectable defects appeared on the surface of coating samples was far ahead in the mixed salt solution than that in the deionized water or 0.5 wt% NaCl solution. For a defective or damaged coating surface, the derived results by using the standard deviation method (SDM) or Fourier power spectrum (FPS) were rather higher than those obtained from EIS as a whole, while for the same coating, the degradation trend with time derived from EIS, SDM, FPS, and scanning Kelvin probe was consistent with each other.

Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature myeloid cells, has a pivotal role in negatively regulating immune response, promoting tumor progression, creating pre-metastases niche, and weakening immunotherapy efficacy. The underlying mechanisms are complex and diverse, including immunosuppressive functions (such as inhibition of cytotoxic T cells and recruitment of regulatory T cells) and non-immunological functions (mediating stemness and promoting angiogenesis). Moreover, MDSC may predict therapeutic response as a poor prognosis biomarker among multiple tumors. Accumulating evidence indicates targeting MDSC can reverse immunosuppressive tumor microenvironment, and improve therapeutic response either single or combination with immunotherapy. This review summarizes the phenotype and definite mechanisms of MDSCs in tumor progression, and provide new insights of targeting strategies regarding to their clinical applications.

Aboveground biomass (AGB) is an important basis for wheat yield formation. It is useful to timely collect the AGB data to monitor wheat growth and to build high-yielding wheat groups. However, as traditional AGB data acquisition relies on destructive sampling, it is difficult to adapt to the modernization of agriculture, and the estimation accuracy of spectral data alone is low and cannot solve the problem of index saturation at later stages. In this study, an unmanned aerial vehicle (UAV) with an RGB camera and the real-time kinematic (RTK) was used to obtain imagery data and elevation data at the same time during the critical fertility period of wheat. The cumulative percentile and the mean value methods were then used to extract the wheat plant height (PH), and the color indices (CIS) and PH were combined to invert the AGB of wheat using parametric and non-parametric models. The results showed that the accuracy of the model improved with the addition of elevation data, and the model with the highest accuracy of multi-fertility period estimation was PLSR (PH + CIS), with R2, RMSE and NRMSE of 0.81, 1248.48 kg/ha and 21.77%, respectively. Compared to the parametric models, the non-parametric models incorporating PH and CIS greatly improved the prediction of AGB during critical fertility periods in wheat. The inclusion of elevation data therefore greatly improves the accuracy of AGB prediction in wheat compared to traditional spectral prediction models. The fusion of UAV-based elevation data and image information provides a new technical tool for multi-season wheat AGB monitoring.

The variations in the boiler operation conditions have a great effect on the combustion characteristics and the pollutant formation in furnaces. This work aims to investigate the effects of operational parameters on NOx formation and its distribution in furnaces using the numerical simulation method to obtain the optimum control strategy for reducing NOx emissions. The numerical simulation models of pulverized coal combustion in furnaces involving flow, heat transfer, combustion and NOx formation are established. Taking a 600 MW supercritical opposed firing pulverized coal boiler as the study object, a full-scale three-dimensional physical model of the boiler is constructed with Gambit software. On this basis, the pulverized coal combustion and the NOx formation under various boiler loads are numerically simulated using the software of Ansys Fluent 2021R1, and the accuracy and the reliability of the models established are verified by comparing the simulation data with the field test data. According to the combustion numerical simulation of 128 groups of operating conditions, the effects of boiler load, the air rate and the air temperature on combustion and NOx formation have been emphatically investigated. The simulation results indicate that the formation of NOx and the NOx concentration distribution are mainly affected by the oxygen concentration and the temperature in the furnace. Especially, the effects of the variation in the excess air coefficient, the over-fire air (OFA) ratio, the primary air ratio and the internal secondary air ratio on NOx concentration distribution vary greatly. When the air temperature increases the overall NOx concentration in the furnace increases, and the influence of the secondary air temperature and the OFA temperature is greater than that of the primary air temperature. Large amounts of simulation data are a necessary data source for further study on the NOx prediction model at the economizer outlet, which can improve the prediction ability and the generalization ability of the NOx prediction model.

Background: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function. Methods: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer’s disease, Parkinson’s syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models. Results: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19–1.93) or NNO (OR: 1.50, 95%CI: 1.16–1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13–1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment. Conclusions: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.

This study presents the first detailed estimate of Rwanda’s nitrogen (N) flows and N footprint for food (NFfood) from 1961 to 2018. Low N fertilizer inputs, substandard production techniques, and inefficient agricultural management practices are focal causes of low crop yields, environmental pollution, and food insecurity. We therefore assessed the N budget, N use efficiency (NUE), virtual N factors (VNFs), soil N mining factors (SNMFs), and N footprint for the agro-food systems of Rwanda with consideration of scenarios of fertilized and unfertilized farms. The total N input to croplands increased from 14.6 kg N ha−1 yr−1 (1960s) to 34.1 kg N ha−1 yr−1 (2010–2018), while the total crop N uptake increased from 18 kg N ha−1yr−1 (1960s) to 28.2 kg N ha−1yr−1 (2010–2018), reflecting a decline of NUE from 124% (1960s) to 85% (2010–2018). Gaseous N losses of NH3, N2O, and NO increased from 0.45 (NH3), 0.03 (N2O), and 0.00 (NO) Gg N yr−1 (1960s) to 6.98 (NH3), 0.58 (N2O), and 0.10 (NO) Gg N yr−1 (2010–2018). Due to the low N inputs, SNMFs were in the range of 0.00 and 2.99 and the rice production, cash-crop production, and livestock production systems have greater SNMFs in Rwanda. The weighted NFfood per capita that presents the actual situation of fertilized and unfertilized croplands increased from 4.0 kg N cap−1 yr−1 (1960s) to 6.3 kg N cap−1 yr−1 (2010–2018). The NFfood per capita would increase from 3.5 kg N cap−1 yr−1 to 4.8 kg N cap−1 yr−1 under a scenario of all croplands without N fertilizer application and increase from 6.0 to 8.7 kg N cap−1 yr−1 under the situation of all croplands receiving N fertilizer. The per capita agro-food production accounted for approximately 58% of the national NFfood. The present study indicates that Rwanda is currently suffering from low N inputs, high soil N depletion, food insecurity, and environmental N losses. Therefore, suggesting that the implementation of N management policies of increasing agricultural N inputs and rehabilitating the degraded soils with organic amendments of human and animal waste needs to be carefully considered in Rwanda.