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Esophageal squamous cell carcinoma (ESCC) is a serious malignancy with poor prognosis, necessitating identification of oncogenic mechanisms for novel therapeutic strategies. Recent studies have highlighted the significance of the transcription factor forkhead box K1 (FOXK1) in diverse biological processes and carcinogenesis of multiple malignancies, including ESCC. However, the molecular pathways underlying FOXK1’s role in ESCC progression are not fully understood, and its potential role in radiosensitivity remains unclear. Here, we aimed to elucidate the function of FOXK1 in ESCC and explore the underlying mechanisms. Elevated FOXK1 expression levels were found in ESCC cells and tissues, positively correlated with TNM stage, invasion depth, and lymph node metastasis. FOXK1 markedly enhanced the proliferative, migratory and invasive capacities of ESCC cells. Furthermore, silencing FOXK1 resulted in heightened radiosensitivity by impeding DNA damage repair, inducing G1 arrest, and promoting apoptosis. Subsequent studies demonstrated that FOXK1 directly bound to the promoter regions of CDC25A and CDK4, thereby activating their transcription in ESCC cells. Moreover, the biological effects mediated by FOXK1 overexpression could be reversed by knockdown of either CDC25A or CDK4. Collectively, FOXK1, along with its downstream target genes CDC25A and CDK4, may serve as a promising set of therapeutic and radiosensitizing targets for ESCC.

Asthenozoospermia (AZS) is a severe form of male infertility with no clear pathogenesis, despite numerous research efforts, there is no consensus on this. This study was to investigate the expression of gene-associated with retinoid-interferon-induced mortality 19 (GRIM-19) in the sperm of patients with asthenozoospermia and the regulation of GC-2 spd cell proliferation, apoptosis and migration. We analyzed the sperm samples from 82 asthenozoospermia and normal patients were collected in the First People's Hospital of Shangqiu and the First Affiliated Hospital of Zhengzhou University. Immunofluorescence, western blots and RT-qPCR analyses were used to verify the expressions of GRIM-19. MTT assays were used to assess cell proliferations, flow cytometry was performed to assess cell apoptosis, wound‑healing was performed to measure cell migration. Immunofluorescence showed that GRIM-19 is predominantly expressed in the sperm mid-piece, the mRNA expressions of GRIM-19 in sperms of the asthenozoospermia group were significantly low, relative to the normal group (OR 0.266; 95% CI = 0.081–0.868; P = 0.028). The protein expressions of GRIM-19 in sperms of the asthenozoospermia group were significantly lower than that of the normal group as well (GRIM-19/GAPDH: 0.827 ± 0.063 vs 0.458 ± 0.033; P

Studies on trace element (TE) pollution in abiotic matrices have typically focused on water, sediment, and soil, either separately or in pairs. The importance of multi-media connectivity has been ignored. This study analyzed the concentrations of 6 TEs in three connected environmental compartments of a 28-km section of the lower reach of the Jinsha River. The ecological risk posed by TEs was higher in soil than in sediment. The contribution of exposure pathways to human health risk were ranked as ingestion > dermal contact > inhalation. An improved regional environmental risk index (RERI) method was then developed to evaluate the comprehensive risk on both ecology and human health caused by TEs. The average RERI value was generally higher in the wet season (0.42) than in the dry (0.41) and dry-to-wet transition seasons (0.08) because of the combined effects of the high TE concentrations in riparian soil and the long exposure time. Source apportionment indicated that industrial activities, weathering of parent rock, and agricultural activities were possible sources of TEs in this region. The methods and results of this study could inform local environmental management and provide references for similar cases wherein multiple compartments of river systems should be considered.

Natural gas is increasingly seen as the fossil fuel of choice for China as it transitions to renewable sources. The significant development of China’s LNG vehicle application and fueling stations and the urgency of climate changes make it particularly important to quantify methane emission from LNG stations, where the data are extremely rare. We carried out a pilot study on direct measurement and quantitative analysis of methane emission from five LNG fueling stations located in Shandong, China following the standard stationary EPA OTM 33A method. The measured methane emission of these five stations vary from 0.01 to 8.76 kg/h. The loss rates vary from 0.004 to 0.257%. We demonstrated that the emission from LNG stations consist of continuous and intermittent contents. The intermittent emission shows a strong temporal variation. If a station is only monitored for 20 min, it may either under-estimate or over-estimate the total emission. Both the distribution of emission events and total emission rates among different stations are highly skewed. We found that these LNG fueling station emission can be categorized into 3 grades, as low, medium and high, corresponding to emission rates below 0.1 kg/h; between 0.1 and 1 kg/h and above 1 kg/h, which can be characterized by the measured average methane concentration enhancement.

Functional fabrics with antibacterial performance are more welcome nowadays. However, the fabrication of functional fabrics with durable, steady performance via a cost-effective way remains a challenge. Polypropylene (denoted as PP) nonwoven fabric was modified by polyvinyl alcohol (denoted as PVA), followed by the in-situ deposition of silver nanoparticles (denoted as Ag NPs) to afford PVA-modified and Ag NPs-loaded PP (denoted as Ag/PVA/PP) fabric. The encapsulation of PP fiber by PVA coating contributes to greatly enhancing the adhesion of the loaded Ag NPs to the PP fiber, and the Ag/PVA/PP nonwoven fabrics exhibit significantly improved mechanical properties as well as excellent antibacterial activity against Escherichia coli (coded as E. coli). Typically, the Ag/PVA/PP nonwoven fabric obtained at a silver ammonia concentration of 30 mM has the best mechanical properties and the antibacterial rate reaches 99.99% against E. coli. The fabric retains excellent antibacterial activity even after washing for 40 cycles, showing prospects in reuse. Moreover, the Ag/PVA/PP nonwoven fabric could find promising application in industry, thanks to its desired air-permeability and moisture-permeability. In addition, we developed a roll-to-roll production process and conducted preliminary exploration to verify the feasibility of this method.

As an important embodiment of a country's economic strength and national health, pharmaceutical manufacturing industry has made rapid development in China in recent years. But at the same time, the pharmaceutical manufacturing industry is facing many environmental problems, such as large pollution emissions, complex pollution components, controlling difficulties and so on. This paper measures the total factor productivity of pharmaceutical manufacturing industry (HTFP) by using data envelopment analysis with unexpected output, which is more accurate and effective than the traditional model. It also studies the effect of environmental regulation on the total factor productivity of pharmaceutical manufacturing industry (HTFP) by establishing panel data regression model and spatial econometric model based on 30 provinces in China from 2004 to 2019, which enriches the research results in the field of cleaning in pharmaceutical manufacturing industry. The conclusions are as follows: (1) Environmental regulation and total factor productivity of pharmaceutical manufacturing industry have significant spatial autocorrelation, showing "high-high" or "low-low" spatial aggregation characteristics; (2) Environmental regulation has a significant promoting effect on improving pharmaceutical manufacturing total factor productivity in local and surrounding areas, and there are differences in the impact of eastern, central and western regions; (3) Green technology, production technology and industrial structure play an important role in the impact of environmental regulation on pharmaceutical manufacturing total factor productivity, which provides theoretical guidance and policy recommendations for improving the level of total factor productivity of pharmaceutical manufacturing industry in the environmental aspect.

We explored the independent risk factors associated with cases of spontaneous abortion in infertile patients treated with human-assisted reproductive technology (ART) and established a smooth curve fit and perform a threshold effect analysis can provide guidance and a valuable reference for predicting the probability of spontaneous abortion. This was a retrospective cohort study of 16,097 patients successfully conceived with ART in Shangqiu First People's Hospital from June 2013 to December 2018. Overall, 2,378 (14.77%) had an abortion and 13,719 (85.23%) did not have an abortion. Multivariate logistic regression analysis showed that female age (OR 1.050; 95% CI 1.032–1.069; P P P P 32 years (cut-off point) old, age and the risk of spontaneous abortion were positively correlated. When follicular-stimulating hormone > 6.1 IU/L (cut-off point), follicular-stimulating hormone was positively correlated with the occurrence of spontaneous abortion, When anti-Mullerian hormone ≤ 3.1 ng/mL (cut-off point), anti-Mullerian hormone was negatively correlated with the occurrence of spontaneous abortion and there was a linear positive correlation between antral Follicle Counting and live birth. In addition, the older the male age, the higher the incidence of abortion. The smooth curve fit and threshold effect analyses can provide a more detailed estimate of the probability of spontaneous abortion for pregnant couples.

Diagnosis of pediatric paragonimiasis is difficult because of its non-specific clinical manifestations. We retrospectively reviewed the records of pediatric paragonimiasis in Children’s Hospital of Fudan University from January 2011 to May 2019. The confirmed diagnosis of paragonimiasis was based on positive anti-parasite serological tests from the local Center for Disease Control (CDC). A total of 11 patients (mean age: 7.7 ± 3.1, male–female ratio: 7:4) diagnosed as paragonimiasis were included. 81.8% were from endemic areas such as Sichuan and Yunnan, and 36% had a clear history of raw crab or crayfish consumption. The characteristic clinical features of pediatric paragonimiasis were eosinophilia (100%), pleural effusion (81.8%), hepatomegaly (54.5%), ascites (54.5%), and subcutaneous nodules (45.5%). Misdiagnosed with other diseases including tuberculosis (18.2%), pneumonia (9.1%), intracranial space-occupying lesions (9.1%) and brain abcess (9.1%) led to rehospitalization and prolonged hospitalization. For treatment, a 3-day course of 150 mg/kg praziquantel (PZQ) didn’t show ideal treatment effectivity and 63.6% needed more than one course of PZQ, while triclabendazole in a total dose of 10 mg/kg had a better efficacy to stubborn manifestations. This study indicated that pediatric paragonimiasis was often misdiagnosed, and the treatment with a 3-day course of 150 mg/kg PZQ had a high rate of failure.

Background Accumulated evidences indicate that elevated levels of circulating ErbB2 are closely associated with increased incidence of diabetes. However, the relationship between ErbB2 concentration and glycemic variations (GV) in type 2 diabetic (T2D) patients remains elucidated. The aim of this study was to assess whether there is an association between serum ErbB2 concentration and GV in newly diagnosed T2D patients. Methods This was a three-center, and observational study. Between April 2019 and July 2019, a total of 106 newly diagnosed T2D patients were recruited. All recruited subjects were admitted as inpatients and received anti-diabetes agents free during the study period. At baseline, fasting serum was collected for ErbB2 measurement and all recruited patients were subjected a prospective CGM for at least 3 days. The primary endpoint was the relationships between ErbB2 concentrations and GV in T2D patients. Results Data of a total of 95 subjects who met the inclusion criteria were analyzed at the endpoint. Subjects were divided into quartiles according to their serum ErbB2 concentrations. We observed that subjects with an elevated level of ErbB2 had a higher value of GV in terms of mean amplitude of glucose excursion (MAGE), standard deviation of mean glucose (SDMG), and the coefficient of variation (CV%) than those with lower levels (all P

Salvia miltiorrhiza-Dalbergia odorifera coupled-herbs (SMDOCH) has been used to treat coronary heart disease (CHD) for thousands of years, but its unclear bioactive components and mechanisms greatly limit its clinical application. In this study, for the first time, we used network pharmacology to elucidate the mechanisms of action of SMDOCH on CHD. We collected 270 SMDOCH-related targets from 74 bioactive components and 375 CHD-related targets, with 58 overlapping common targets. Next, we performed enrichment analysis for common-target network and protein-protein interaction (PPI) network. The results showed that SMDOCH affected CHD mainly through 10 significant signaling pathways in three biological processes: ‘vascular endothelial function regulation’, ‘inflammatory response’, and ‘lipid metabolism’. Six pathways belonged to the ‘vascular endothelial function regulation’ model, which primarily regulated hormone (renin, angiotensin, oestrogen) activity, and included three key upstream pathways that influence vascular endothelial function, namely KEGG:04933, KEGG:05418, and KEGG:04066. Three pathways, namely KEGG:04668, KEGG:04064, and KEGG:04620, belonged to the ‘inflammatory response’ model. One pathway (KEGG:04920) belonged to the ‘lipid metabolism’ model. To some extent, this study revealed the potential bioactive components and pharmacological mechanisms of SMDOCH on CHD, and provided a new direction for the development of new drugs for the treatment of CHD.

Chinese cabbage that prefers cold conditions is also affected by low-temperature stress, such as the accumulation of leaf anthocyanins. Research on anthocyanin biosynthesis and regulation mechanisms has made great progress. However, research on anthocyanin accumulation for resistance to biological and non-biological stress is still lacking. To study the relationship between anthocyanin accumulation of Chinese cabbage and resistance under low-temperature conditions, RNA sequencing (RNA-seq) was performed on Chinese cabbage ‘Xiao Baojian’ grown at a low temperature for four time periods and at a control temperature for five time periods. In Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, 7954 differentially expressed genes (DEGs) were enriched, of which 587 DEGs belonged to "biosynthesis of other secondary metabolites." Gene temporal expression patterns were used to discover enriched genes related to phenylpropanoid biosynthesis; flavonoid biosynthesis and anthocyanin biosynthesis pathways were found in cluster 1. The interaction networks were constructed, and hub genes were selected, showing that flavonoid biosynthesis pathway genes (DFR, ANS, F3H, FLS1, CHS1, CHS3, and TT8) and defense mechanisms-related genes (DFR, SNL6, and TKPR1) interact with each other. Anthocyanin biosynthesis DEGs in Chinese cabbage were evaluated under low-temperature conditions to map the relevant pathways, and expression maps of transcription factors in the flavonoid pathway were created at various periods. Low temperature upregulated the expression of genes related to anthocyanin biosynthesis. Taken together, our results provide further analysis of the relationship between plant anthocyanin synthesis and stress resistance and may also provide further insights for the future development of high-quality color and cold-tolerant Chinese cabbage germplasm resources.

There are limited studies investigating the combined effects of biological, environmental, and human factors on the activity of the domestic dog. Sled dogs offer a unique opportunity to examine these factors due to their close relationship with handlers and exposure to the outdoors. Here, we used accelerometers to measure the activity of 52 sled dogs over 30 days from two locations in Canada. The two locations differ in the working demands of dogs, therefore we used linear mixed effects models to assess how different factors impact daytime and nighttime activity of working versus nonworking dogs. During the daytime, we found that males were more active than females among nonworking dogs and younger dogs were more active than older dogs among working dogs. Alaskan huskies had higher activity levels than non-Alaskan husky breeds in working sled dogs during the day. Nonworking dogs were slightly more active during colder weather, but temperature had no effect on working dogs’ activity. The strongest predictor of daytime activity in working dogs was work schedule. These results indicate that the influence of biological factors on activity varied depending on dogs’ physical demands and human activity was the most powerful driver of activity in working dogs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

As we reported in our previous studies, TMTP1, a tumor-homing peptide, selectively targets highly metastatic tumors and their metastatic foci. Aminopeptidase P2 (XPNPEP2) is a receptor for TMTP1 tumor-homing peptide. However, the biological and clinical significance of Aminopeptidase P2 in human cancers remains unknown. In this study, the high-density multiple organ tumor tissue array was employed for the analysis of XPNPEP2 expression profiles in human specimens. The results showed that XPNPEP2 was moderately expressed in the normal prostate tissues, but significantly decreased in the prostate cancer. Hence we used TCGA, IHC, and ELISA to further analyze the expression of XPNPEP2 in tissues and serum of prostate cancer patients. In general, XPNPEP2 expression was lower in prostate cancer tissue than in normal prostate tissue, but was higher in prostate cancer tissues with local invasion and LN metastasis than in tissues with localized Pca. Western blot clarified XPNPEP2 had a secreted form in the serum. Then the serums of 128 Pca patients, 70 healthy males and 40 prostate hyperplasia patients were obtained for detecting serum XPNPEP2 levels.The results indicated that the concentration of XPNPEP2 in serums of Pca patients with LN metastasis (142.7 ± 14.40 ng/mL) were significantly higher than levels in Pca patients without LN metastasis (61.63 ± 5.50 ng/mL) (p

Plant dwarfism is a desirable agronomic trait in non-timber trees, but little is known about the physiological and molecular mechanism underlying dwarfism in woody plants. Castor bean (Ricinus communis) is a typical woody oilseed crop. We performed cytological observations within xylem, phloem and cambia tissues, revealing that divergent cell growth in all tissues might play a role in the dwarf phenotype in cultivated castor bean. Based on bulked segregant analyses for a F2 population generated from the crossing of a tall and a dwarf accession, we identified two QTLs associated with plant height, covering 325 candidate genes. One of these, Rc5NG4-1 encoding a putative IAA transport protein localized in the tonoplast was functionally characterized. A non-synonymous SNP (altering the amino acid sequence from Y to C at position 218) differentiated the tall and dwarf plants and we confirmed, through heterologous yeast transformation, that the IAA uptake capacities of Rc5NG4-1Y and Rc5NG4-1C were significantly different. This study provides insights into the physiological and molecular mechanisms of dwarfing in woody non-timber economically important plants, with potential to aid in the genetic breeding of castor bean and other related crops.

LIM homeobox 4 (LHX4) is expressed in the photoreceptors (PRs) of the outer nuclear layer (ONL) and bipolar cells (BCs) of the inner nuclear layer (INL) in mouse and chicken retina. It regulates the subtype-specific development of rod BCs and cone BCs in the mouse retina. However, no report has been published on its expression and function in the zebrafish retina. In this study, we assessed the expression of Lhx4 using in situ hybridization (ISH) technique and explored its role in zebrafish (Danio rerio) retinal development via morpholino (MO) technology. We found that the expression of lhx4 in the zebrafish retina begins 48 h post-fertilization (hpf) and is continuously expressed in the ONL and INL. A zebrafish model constructed with lhx4 knockdown in the eyes through vivo-MO revealed that: lhx4 knockdown inhibits the differentiation of Parvalbumin+ amacrine cells (ACs) and Rhodopsin+ rod photoreceptors (RPs), enhances the expression of visual system homeobox 2 (vsx2); and damages the responses of zebrafish to light stimulus, without affecting the differentiation of OFF-BCs and rod BCs, and apoptosis in the retina. These findings reveal that lhx4 regulates neural differentiation in the retina and visual function during zebrafish embryonic development.

The study of companion (pet) dogs is an area of great translational potential, as they share a risk for many conditions that afflict humans. Among these are conditions that affect sleep, including chronic pain and cognitive dysfunction. Significant advancements have occurred in the ability to study sleep in dogs, including development of non-invasive polysomnography; however, basic understanding of dog sleep patterns remains poorly characterized. The purpose of this study was to establish baseline sleep–wake cycle and activity patterns using actigraphy and functional linear modeling (FLM), for healthy, adult companion dogs. Forty-two dogs were enrolled and wore activity monitors for 14 days. FLM demonstrated a bimodal pattern of activity with significant effects of sex, body mass, and age; the effect of age was particularly evident during the times of peak activity. This study demonstrated that FLM can be used to describe normal sleep–wake cycles of healthy adult dogs and the effects of physiologic traits on these patterns of activity. This foundation makes it possible to characterize deviations from normal patterns, including those associated with chronic pain and cognitive dysfunction syndrome. This can improve detection of these conditions in dogs, benefitting them and their potential as models for human disease.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Discovering anticancer drugs that do not have adverse side effects has been a developing research field worldwide in recent decades. In this work, four previously undescribed cytotoxic diterpenoids were isolated from the aerial parts of Isodon excisoides. Interestingly, these four diterpenoids were two pairs of tautomers that were first reported in plants. Their structures were further elucidated using various spectroscopic methods. The tautomerization phenomenon and mechanism for these two pairs of tautomers were emphatically described. The theoretical simulation results indicated that the diterpene tautomerization is greatly related to certain factors, including the existence of a transition state, the change of bond length and the level of conversion energy; the tautomerization for the two pairs of tautomers is mainly caused by proton transfer. For bioassays, the cytotoxicities of the tautomers against five human cancer cell lines were also investigated. The results indicated that each of the four diterpenoids showed significant cytotoxicity in at least three cell lines and could serve as potential anticancer agents for further investigation.

Herbivorous attack induces plant defenses. There is evidence that some pests suppress these defenses by interfering with signaling pathways. We here report that infestation by the white-backed planthopper, Sogatella furcifera, induces defense responses in rice and infection of the southern rice black-streaked dwarf virus in the planthoppers partially suppresses the planthopper-induced plant defenses. Salicylic acid (SA) levels generally showed a temporal increase pattern while jasmonic acid (JA) levels generally exhibited a decrease pattern in the planthopper-infested plants, irrespective of virus infection status in the insects. The increase in SA was less while the decrease in JA was more in the viruliferous insect-infested plants than in the nonviruliferous insect-infested plants at both 48 and 72 h post infestation. The phytohormone levels corresponded to the patterns of relative expression levels of SA-marker genes (ICS1 and NPR1) and JA-marker gene (AOS2) in the plant treatments. Planthoppers performed better on the uninfested plants than on the previously infested plants and were of not significant increase in performance on the plants previously attacked by viruliferous planthoppers in comparison with the plants previously attacked by nonviruliferous insects. Our results indicate that the virus plays a role in partially suppressing the plant defenses induced by the planthopper. These findings provide a new perspective on plant–virus-vector interactions.

When comets interacting with solar wind, straight and narrow plasma tails will be often formed. The most remarkable phenomenon of the plasma tails is the disconnection event, in which a plasma tail is uprooted from the comet’s head and moves away from the comet. In this paper, the interaction process between a comet and solar wind is simulated by using a laser-driven plasma cloud to hit a cylinder obstacle. A disconnected plasma tail is observed behind the obstacle by optical shadowgraphy and interferometry. Our particle-in-cell simulations show that the difference in thermal velocity between ions and electrons induces an electrostatic field behind the obstacle. This field can lead to the convergence of ions to the central region, resulting in a disconnected plasma tail. This electrostatic-field-induced model may be a possible explanation for the disconnection events of cometary tails.

It is unknown whether YOD (young onset diabetes) and LOD (late onset diabetes) require similar insulin doses for intensive insulin therapy with a metformin add-on to achieve glycemic control. We analyzed data from our two previously performed randomized, controlled open-label trials. Patients were randomized to receive either continuous subcutaneous insulin infusion (CSII) therapy or CSII combined with metformin therapy for 4 weeks. The studies concentrated on the differences in the insulin doses used for the two groups. We included 36 YOD (age 40 yrs) patients. YOD patients who received metformin combined with CSII therapy required significantly lower insulin doses to maintain euglycemic control compared to patients with LOD. A multivariate analysis, controlled for gender and the fasting blood concentration, was performed to determine the significance of the differences between groups, particularly with respect to the total and basal insulin doses. There was a trend toward improvement in β-cell function and insulin resistance in terms of ΔHOMA-B and ΔHOMA-IR in patients with YOD compared to those with LOD. Newly diagnosed T2D patients with YOD required significantly lower insulin doses, particularly basal insulin doses, to maintain glycemic control compared to the LOD patients.

Intrahepatic cholestasis induced by drug toxicity, bile salt export pump (BSEP) deficiency, or pregnancy frequently causes cholestatic liver damage, which ultimately may lead to liver fibrosis and cirrhosis. Here, the preventive and therapeutic effects of peroxisome proliferator-activated receptor α (PPARα) signaling activated by fenofibrate was evaluated on cholestatic liver damage. Metabolomic analysis revealed that alpha-naphthyl isothiocyanate (ANIT)-induced intrahepatic cholestasis resulted in the accumulation of serum long-chain acylcarnitines and triglyceride, and the reduced expression of four fatty acid β-oxidation (β-FAO) relevant genes (Cpt1b, Cpt2, Mcad and Hadha), indicating the disruption of β-FAO. The increase of acylcarnitines in hepatic cell resulted in the enhanced expression of anti-oxidative genes glutathione S-transferases (Gsta2 and Gstm3) directly. As direct PPARα-regulated genes, Cpt1b, Cpt2, and Mcad were up-regulated after pretreatment with PPARα agonist, fenofibrate, indicating the improvement of β-FAO. In the end, the disrupted bile acid metabolism in the enterohepatic circulation and the enhanced oxidative stress and inflammation cytokines induced by ANIT exposure were significantly recovered with the improvement of β-FAO using fenofibrate treatment. These findings provide the rationale for the use of PPARα agonists as therapeutic alternatives for cholestatic liver damage.

Plant resistance to herbivores is a key component in integrated pest management. In most cases, silicon (Si) amendment to plants enhances resistance to herbivorous insects. The increase of plant physical barrier and altered insect behaviors are proposed as mechanisms for the enhanced resistance in Si-amended plants, but our understanding of the induced mechanisms involved in Si-enhanced plant resistance to phloem-feeding insects remains unclear. Here, we show that Si amendment to rice (Oryza sativa) plants impacts multiple plant defense responses induced by a phloem-feeder, the brown planthopper (Nilaparvata lugens, BPH). Si amendment improved silicification of leaf sheaths that BPH feed on. Si addition suppressed the increase of malondialdehyde concentration while encouraged increase of H2O2 concentration in plants attacked by BPH. Higher activities of catalase and superoxide dismutase were recorded in Si-amended than in non-amended BPH-infested plants. BPH infestation activated synthases for secondary metabolites, polyphenol oxidase and pheny-lalanine ammonia-lyase, and β-1,3-glucanase, but the activation was greater in Si-amended than in non-amended plants. Taken together, our findings demonstrate that Si amendment interacts with BPH infestation in the induction of plant defense responses and consequently, to confer enhanced rice plant resistance.

To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P 1c values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

Venoms secreted by the venom gland (VG) of parasitoid wasp help ensure successful parasitism by host immune suppression and developmental regulation. Cotesia vestalis, a larval endoparasitoid, and Diadromus collaris, a pupal endoparasitoid, parasitize the diamondback moth (DBM), Plutella xylostella. To explore and compare the venom components of two endoparasitoids, we sequenced transcriptomes of the VGs and wasp bodies without VGs (BWVGs) of the two endoparasitoids. Statistically enriched GO terms and KEGG pathways of the two VGs compared to respective whole-body background were similar and reflected active protein biosynthesis activities in the two VGs. 1,595 VG specific genes of the D. collaris VG and 1,461 VG specific genes of the C. vestalis VG were identified by comparative transcript profiling. A total of 444 and 513 genes encoding potential secretory proteins were identified and defined as putative venom genes in D. collaris VG and C. vestalis VG, respectively. The putative venom genes of the two wasps showed no significant similarity or convergence. More venom genes were predicted in D. collaris VG than C. vestalis VG, especially hydrolase-coding genes. Differences in the types and quantities of putative venom genes shed light on different venom functions.

Although the evolutionary changes of viral quasispecies are correlated to the pathological status of a disease, little is known in the coexistence of hepatitis B surface antigen (HBsAg) and antibodies to these antigens (anti-HBs). To examine evolutionary changes in hepatitis B virus (HBV) and their relationship to the coexistence of HBsAg and anti-HBs antibodies, HBV genomes in patients with a coexistence of HBsAg and anti-HBs antibodies (experimental group) and HBsAg positive without anti-HBs (control group) were assessed. Our results showed that quasispecies diversity was significantly higher in the experimental group for large HBsAg (LHBsAg), middle HBsAg (MHBsAg), and HBsAg genes. LHBsAg harbored dN/dS values eight times higher in the experimental group; however, the mean dN/dS ratios in genes HbxAg, Pol and PreC/C of the experimental patients had an opposite trend. Phylogenetic trees in the experimental group were more complex than the control group. More positive selection sites, mutations and deletions were observed in the experimental group in specific regions. Furthermore, several amino acid variants in epitopes were potentially associated with the immune evasion. In conclusion, cumulative evolutionary changes in HBV genome that facilitate immune evasion provide insights into the genetic mechanism of a coexistence of HBsAg and anti-HBs antibodies.

The present study aimed at systematically investigating the endophytic communities of dominant plants in the karst ecosystem. Soil and plant materials were collected and after sequencing of the 16 s RNA, the diversity and abundance of the endophytic community structures in leaves were examined. Our results showed that abundant and diverse endogenous bacteria were associated with the leaves of common dominant plants living in the karst ecological environment. Notably, common traits and significant differences in the endophytic community structures were recorded among different plant species with different leaf grown in soils with different calcium contents. These observations implied that plants may adopt different strategies to adapt to the karst ecological environment. In addition, the endophytic bacteria associated with the leaves may be involved in different physiological strategies used by the plants to adapt to the karst ecological environment. These findings provide new avenues for developing microbial agents that could be suitable for the karst ecological environment and will provide sustainable solutions for improving the ability of plants to adapt to karst special adversities, and thus for karst geomorphological environmental protection and agricultural development.

Castor bean (Ricinus communis L., Euphorbiaceae) is a critical biodiesel crop and its seed derivatives have important industrial applications. Due to lack of a high-density genetic map, the breeding and genetic improvement of castor bean has been largely restricted. In this study, based on a recombinant inbred line (RIL) population consisting of 200 individuals, we generated 8,896 high-quality genomic SNP markers and constructed a high-resolution genetic map with 10 linkage groups (LGs), spanning 1,852.33 centiMorgan (cM). Based on the genetic map, 996 scaffolds from the draft reference genome were anchored onto 10 pseudo-chromosomes, covering 84.43% of the castor bean genome. Furthermore, the quality of the pseudo-chromosome scale assembly genome was confirmed via genome collinearity analysis within the castor bean genome as well as between castor bean and cassava. Our results provide new evidence that the phylogenetic position of castor bean is relatively solitary from other taxa in the Euphorbiaceae family. Based on the genetic map, we identified 16 QTLs that control seed size and weight (covering 851 candidate genes). The findings will be helpful for further research into potential new mechanisms controlling seed size and weight in castor bean. The genetic map and improved pseudo-chromosome scale genome provide crucial foundations for marker-assisted selection (MAS) of QTL governing important agronomic traits, as well as the accelerated molecular breeding of castor bean in a cost-effective pattern.

Research based on quantitative analysis, pharmacokinetics and metabolomics was conducted to explore the effects of salt-processing on Psoraleae Fructus (PF). Quantitative analysis showed that the contents of bioactive components were higher in salt-processed Psoraleae Fructus (SPF) extract than in PF extract. Pharmacokinetics indicated that the overall AUC and tmax levels was higher, while Cmax was lower in the SPF group. In the metabolomics study, the differential influences of PF and SPF on 22 common biomarkers and associated metabolic pathways showed that salt-processing could enhance the effect of PF and reduce toxicity in the cardiovascular and renal systems. The internal correlations among these results, together with the influence of salt-processing, suggested that the effects of heating and newly generated surfactants during the salt-processing procedure were the primary causes of the changes in chemical composition and absorption characteristics, as well as the subsequent enhanced efficacy and minor toxicity.

Soil respiration (Rs) is an important source of atmospheric CO2 flux and is sensitive to changes in soil nutrient and water contents. Despite extensive studies on the effects of enhanced atmospheric nitrogen (N) deposition and changes in precipitation (P) on Rs, few studies have taken into account the effects of interactions between these factors on Rs of alpine grasslands. To address these questions, we investigated the effects of N addition (10 g N m−2 yr−1), changes in precipitation (±50% precipitation), and their interaction on soil respiration and its components, including heterotrophic respiration (Rh) and autotrophic respiration (Ra),in a Tibetan alpine steppe during three consecutive growing seasons. We found that Rs differed in its response to N addition and precipitation regimes. Specifically, decreased precipitation led to a significant reduction in Rs during the last two years, whereas N addition minimally impacted Rs. Another important finding was that soil respiration components differed in their response to N addition and precipitation regimes. Nitrogen addition significantly enhanced Ra, whereas Rh was not altered in response to N addition. By contrast, the precipitation regime led to marked changes in Rh, but exhibited marginally significant effects on Ra. Therefore, our findings highlighted that soil respiration differed in its response to N addition and precipitation regimes mainly due to the different responses of soil respiration components to these factors. Therefore, carbon dynamics should take soil respiration components into account under global change scenarios.

Plant potyviruses require eukaryotic translation initiation factors (eIFs) such as eIF4E and eIF(iso)4E to replicate and spread. When Turnip mosaic virus (TuMV) infects a host plant, its viral protein linked to the genome (VPg) needs to interact with eIF4E or eIF(iso)4E to initiate translation. TuMV utilizes BraA.eIF4E.a, BraA.eIF4E.c, BraA.eIF(iso)4E.a, and BraA.eIF(iso)4E.c of Brassica rapa to initiate translation in Arabidopsis thaliana. In this study, the BraA.eIF4E.a, BraA.eIF4E.c, BraA.eIF(iso)4E.a, and BraA.eIF(iso)4E.c genes were cloned and sequenced from eight B. rapa lines, namely, two BraA.eIF4E.a alleles, four BraA.eIF4E.c alleles, four BraA.eIF(iso)4E.a alleles, and two BraA.eIF(iso)4E.c alleles. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) analyses indicated that TuMV VPg could not interact with eIF4E, but only with eIF(iso)4E of B. rapa. In addition, the VPgs of the different TuMV isolates interacted with various eIF(iso)4E copies in B. rapa. In particular, TuMV-UK1/CDN1 VPg only interacted with BraA.eIF(iso)4E.c, not with BraA.eIF(iso)4E.a. Some single nucleotide polymorphisms (SNPs) were identified that may have affected the interaction between eIF(iso)4E and VPg such as the SNP T106C in BraA.eIF(iso)4E.c and the SNP A154C in VPg. Furthermore, a three-dimensional structural model of the BraA.eIF(iso)4E.c-1 protein was constructed to identify the specific conformation of the variable amino acids from BraA.eIF(iso)4E.c. The 36th amino acid in BraA.eIF(iso)4E.c is highly conserved and may play an important role in establishing protein structural stability. The findings of the present study may lay the foundation for future investigations on the co-evolution of TuMV and eIF(iso)4E.

This study investigated the concentrations of Zn, Cu, Cr, Pb, As and Cd in different tissues of E. crassipes from Honghu Lake. The total concentrations of trace elements in E. crassipes were observed in descending order: Zn (111.6162) > Cu (15.7494) > Cr (7.0466) > Pb (5.6251) > As (3.6831) > Cd (0.1941) mg/kg. The order of the bioconcentration factor (BCF) measured in E. crassipes was Zn > As > Cr > Cu > Pb > Cd > 1, indicating that E. crassipes possessed a strong biological enrichment ability to accumulate a variety of trace elements. The translocation factor (TF) values decreased in the order of Cu > Zn > Cr > As > Pb > Cd, all of which were lower than 1, which showed that the absorption of the trace elements by E. crassipes was mainly accomplished in the roots. Moreover, the health risk assessments showed that the carcinogenic and noncarcinogenic risks of the edible parts of E. crassipes were 26.1 and 4.6 times higher than the maximum acceptable value recommended by the USEPA for adults and children of approximately 39.2- and 6.9-fold, respectively. Children were more sensitive than adults. The main trace elements that led to noncarcinogenic risks were As, Cr and Cu, while Cr and As led to carcinogenic risks. The results of the Pearson correlation showed positive correlations with the concentrations of Zn, Cr and As between E. crassipes and the water as well as negative correlations of the contents of all six trace elements between E. crassipes and the sediment.

To investigate whether metformin add-on to the continuous subcutaneous insulin infusion (Met + CSII) therapy leads to a significant reduction in insulin doses required by type 2 diabetes (T2D) patients to maintain glycemic control, and an improvement in glycemic variation (GV) compared to CSII only therapy. We analyzed data from our two randomized, controlled open-label trials. Newly diagnoses T2D patients were randomized assigned to receive either CSII therapy or Met + CSII therapy for 4 weeks. Subjects were subjected to a 4-day continuous glucose monitoring (CGM) at the endpoint. Insulin doses and GV profiles were analyzed. The primary endpoint was differences in insulin doses and GV between the two groups. A total of 188 subjects were admitted as inpatients. Subjects in metformin add-on therapy required significantly lower total, basal and bolus insulin doses than those of control group. CGM data showed that patients in Met + CSII group exhibited significant reduction in the 24-hr mean amplitude of glycemic excursions (MAGE), the standard deviation, and the coefficient of variation compared to those of control group. Our data suggest that metformin add-on to CSII therapy leads to a significant reduction in insulin doses required by T2D patients to control glycemic variations.

Mangroves are critical in global carbon budget while vulnerable to exotic plant invasion. Spartina alterniflora, one of typical salt marsh plant grows forcefully along the coast of China, has invaded the native mangrove habitats in Zhangjiang Estuary. However, the effects of S. alterniflora invasion on soil carbon gases (CH4 and CO2) emission from mangroves are not fully understood. Accordingly, we conducted a field experiment to investigate the soil CH4 and CO2 emission during growing seasons in 2016 and 2017 at four adjacent wetlands, namely bare mudflat (Mud), Kandelia obovata (KO), Avicennia marina (AM) and S. alterniflora (SA). Potential methane production (PMP), potential methane oxidation (PMO), functional microbial abundance and soil biogeochemical properties were measured simultaneously. Our results indicate that S. alterniflora invasion could dramatically increase soil CH4 emissions mainly due to the enhancement in PMP which facilitated by soil EC, MBC, TOC and mcrA gene abundance. Additionally, S. alterniflora invasion decreases soil CO2 emission. Both heterotrophic microbial respiration (16S rRNA) and methane oxidation (pmoA and ANME-pmoA) are responsible for CO2 emission reduction. Furthermore, S. alterniflora invasion greatly increases GWP by stimulating CH4 emissions. Thus, comparing with mangroves, invasive S. alterniflora significantly (p 4 emission while reduces CO2 emission.

Eosinophil infiltration is considered a hallmark in allergic airway inflammation, and the blockade of eosinophil differentiation may be an effective approach for treating eosinophil-related disorders. Mammalian target of rapamycin (mTOR) is a vital modulator in cell growth control and related diseases, and we have recently demonstrated that rapamycin can suppress eosinophil differentiation in allergic airway inflammation. Considering its critical role in haematopoiesis, we further investigated the role of mTOR in eosinophil differentiation in the context of asthmatic pathogenesis. Intriguingly, the inhibition of mTOR, either by genetic deletion or by another pharmacological inhibitor torin-1, accelerated the eosinophil development in the presence of IL-5. However, this was not observed to have any considerable effect on eosinophil apoptosis. The effect of mTOR in eosinophil differentiation was mediated by Erk signalling. Moreover, myeloid specific knockout of mTOR or Rheb further augmented allergic airway inflammation in mice after allergen exposure. Ablation of mTOR in myeloid cells also resulted in an increased number of eosinophil lineage-committed progenitors (Eops) in allergic mice. Collectively, our data uncovered the differential effects of mTOR in the regulation of eosinophil development, likely due to the distinct functions of mTOR complex 1 or 2, which thus exerts a pivotal implication in eosinophil-associated diseases.