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Abstract Sol–gel processed zinc oxide (ZnO) is one of the most widely used electron transport layers (ETLs) in inverted organic solar cells (OSCs). The high annealing temperature (≈200 °C) required for sintering to ensure a high electron mobility however results in severe damage to flexible substrates. Thus, flexible organic solar cells based on sol–gel processed ZnO exhibit significantly lower efficiency than rigid devices. In this paper, an indium‐doping approach is developed to improve the optoelectronic properties of ZnO layers and reduce the required annealing temperature. Inverted OSCs based on In‐doped ZnO (IZO) exhibit a higher efficiency than those based on ZnO for a range of different active layer systems. For the PM6:L8‐BO system, the efficiency increases from 17.0% for the pristine ZnO‐based device to 17.8% for the IZO‐based device. The IZO‐based device with an active layer of PM6:L8‐BO:BTP‐eC9 exhibits an even higher efficiency of up to 18.1%. In addition, a 1.2‐micrometer‐thick inverted ultrathin flexible organic solar cell is fabricated based on the IZO ETL that achieves an efficiency of 17.0% with a power‐per‐weight ratio of 40.4 W g−1, which is one of the highest efficiency for ultrathin (less than 10 micrometers) flexible organic solar cells.

The Kadsura coccinea fruit is a wild fruit that may be eaten and used medicinally. Its seeds are rich in nutrients but are typically thrown away without processing.The physicochemical characterization, volatiles, fatty acids, lipids and concomitants of cold-processed seed oils from four kinds of K. coccinea were evaluated. The average kernel yield and oil yield of K. coccinea seeds were 68.21 % and 30.44 %, respectively. The seed oil contains a moderate level of total phenolics (368.99–503.99 mgGAE/100 g), total flavonoids (95.01–126.18 mg RE/100 g), and β-sitosterol (1498.8–1712.7 mg/kg) with higher iodine value, lower acid value, saponification value and shorter induction time. GC analysis reveals appreciable amounts of linoleic acid (64.91–68.05 %) and squalene in seed oil. GC–MS analysis showed that the major volatile compounds were γ-muurolene (27.25–31.7 %), β-himachalene (19.51–20.37 %) and β-curcumene (15.78–16.78 %). Moreover, 16 terpenoids, 14 phenolics were identified by UPLC-QTOF-MS/MS. These results suggest that K. coccinea seed seems an promising alternative oilseed with biological ingredients for food, cosmetics and pharmaceutical industries.

Abstract Objective Glioma, a malignant primary brain tumor, is notorious for its high incidence rate. However, the clinical application of temozolomide (TMZ) as a treatment option for glioma is often limited due to resistance, which has been linked to hypoxic glioma cell-released exosomes. In light of this, the present study aimed to investigate the role of exosomal pyruvate kinase M2 (PKM2) in glioma cells that exhibit resistance to TMZ. Methods Sensitive and TMZ-resistant glioma cells were subjected to either a normoxic or hypoxic environment, and the growth patterns and enzymatic activity of glycolysis enzymes were subsequently measured. From these cells, exosomal PKM2 was isolated and the subsequent effect on TMZ resistance was examined and characterized, with a particular focus on understanding the relevant mechanisms. Furthermore, the intercellular communication between hypoxic resistant cells and tumor-associated macrophages (TAMs) via exosomal PKM2 was also assessed. Results The adverse impact of hypoxic microenvironments on TMZ resistance in glioma cells was identified and characterized. Among the three glycolysis enzymes that were examined, PKM2 was found to be a critical mediator in hypoxia-triggered TMZ resistance. Upregulation of PKM2 was found to exacerbate the hypoxia-mediated TMZ resistance. Exosomal PKM2 were identified and isolated from hypoxic TMZ-resistant glioma cells, and were found to be responsible for transmitting TMZ resistance to sensitive glioma cells. The exosomal PKM2 also contributed towards mitigating TMZ-induced apoptosis in sensitive glioma cells, while also causing intracellular ROS accumulation. Additionally, hypoxic resistant cells also released exosomal PKM2, which facilitated TMZ resistance in tumor-associated macrophages. Conclusion In the hypoxic microenvironment, glioma cells become resistant to TMZ due to the delivery of PKM2 by exosomes. Targeted modulation of exosomal PKM2 may be a promising strategy for overcoming TMZ resistance in glioma.

Brain glioma, which is highly invasive and has a poor prognosis, is the most common primary intracranial tumor. Several studies have verified that the extent of resection is a considerable prognostic factor for achieving the best results in neurosurgical oncology. To obtain gross total resection (GTR), neurosurgery relies heavily on generating continuous, real-time, intraoperative glioma descriptions based on image guidance. Given the limitations of existing devices, it is imperative to develop a real-time image-guided resection technique to offer reliable functional and anatomical information during surgery. At present, the application of intraoperative ultrasound (IOUS) has been indicated to enhance resection rates and maximize brain function preservation. IOUS, which is promising due to its lower cost, minimal operational flow interruptions, and lack of radiation exposure, can enable real-time localization and precise tumor size and form descriptions while assisting in discriminating residual tumors and solving brain tissue shifts. Moreover, the application of new advancements in ultrasound technology, such as contrast-enhanced ultrasound (CEUS), three-dimensional ultrasound (3DUS), noninvasive ultrasound (NUS), and ultrasound elastography (UE), could assist in achieving GTR in glioma surgery. This article reviews the advantages and disadvantages of IOUS in glioma surgery.

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects. Common mechanisms in treating IBD and colon cancer mainly include regulating inflammation-related signaling pathways such as nuclear factor-kappa B, mitogen-activated protein kinase, phosphatidylinositol 3-kinase, NOD-like receptor heat protein domain-related protein 3, and wingless-type MMTV integration site family; NF-E2-related factor 2 and hypoxia-inducible factor 1α to inhibit oxidative stress; mitochondrial autophagy and endoplasmic reticulum stress; intestinal immune cell differentiation and function through the Janus kinase/signal transducer and activator of transcription pathway; and improving the gut microbiota and intestinal barrier. Overall, existing evidence suggests the potential of the Sishen pill to improve IBD and suppress inflammation-to-cancer transformation. However, large-scale randomized controlled clinical studies and research on the safety of these clinical applications are urgently required.

Abstract Background Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. Methods In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. Results The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of “Nervous headache” was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. Conclusions While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

The online detection of fertilizer information is pivotal for precise and intelligent variable-rate fertilizer application. However, traditional methods face challenges such as the complex quantification of multiple components and sensor-induced cross-contamination. This study investigates integrating near-infrared principles with machine learning algorithms to identify fertilizer types and concentrations. We utilized near-infrared transmission spectroscopy and applied Partial Least Squares Discriminant Analysis (PLS-DA), Support Vector Machine (SVM), and Back-Propagation Neural Network (BPNN) algorithms to analyze full spectrum data. The BPNN model, using S-G smoothing, demonstrated a superior classification performance for the nutrient ions of four fertilizer solutions: HPO42−, NH4+, H2PO4− and K+. Optimization using the competitive adaptive reweighted sampling (CARS) method yielded BPNN model RMSE values of 0.3201, 0.7160, 0.2036, and 0.0177 for HPO42−, NH4+, H2PO4−, and K+, respectively. Building on this foundation, we designed a four-channel fertilizer detection device based on the Lambert–Beer law, enabling the real-time detection of fertilizer types and concentrations. The test results confirmed the device’s robust stability, achieving 93% accuracy in identifying fertilizer types and concentrations, with RMSE values ranging from 1.0034 to 2.4947, all within ±8.0% error margin. This study addresses the practical requirements for online fertilizer detection in agricultural engineering, laying the groundwork for efficient water–fertilizer integration technology aligned with sustainable development goals.

Organic solar cells (OSCs) are one of the most promising photovoltaic technologies due to their affordability and adaptability. However, upscaling is a critical issue that hinders the commercialization of OSCs. A significant challenge is the lack of cost-effective and facile techniques to modulate the morphology of the active layers. The slow solvent evaporation leads to an unfavorable phase separation, thus resulting in a low power conversion efficiency (PCE) of organic solar modules. Here, a nitrogen-blowing assisted method is developed to fabricate a large-area organic solar module (active area = 12 cm2) utilizing high-boiling-point solvents, achieving a PCE of 15.6%. The device fabricated with a high-boiling-point solvent produces a more uniform and smoother large-area film, and the assistance of nitrogen-blowing accelerates solvent evaporation, resulting in an optimized morphology with proper phase separation and finer aggregates. Moreover, the device fabricated by the nitrogen-blowing assisted method exhibits improved exciton dissociation, balanced carrier mobility, and reduced charge recombination. This work proposes a universal and cost-effective technique for the fabrication of high-efficiency organic solar modules.

The health benefits of anthocyanins have attracted extensive research interest. However, anthocyanins are sensitive to certain environmental and gastrointestinal conditions and have low oral bioavailability. It has been reported that delivery systems made in different ways could improve the stability, bioavailability and bioactivity of anthocyanins. This present review summarizes the factors affecting the stability of anthocyanins and the reasons for poor bioavailability, and various technologies for encapsulation of anthocyanins including microcapsules, nanoemulsions, microemulsions, Pickering emulsions, nanoliposomes, nanoparticles, hydrogels and co–assembly with amphiphilic peptides were discussed. In particular, the effects of these encapsulation technologies on the stability, bioavailability and bioactivities of anthocyanins in vitro and in vivo experiments are reviewed in detail, which provided scientific insights for anthocyanins encapsulation methods. However, the application of anthocyanins in food industry as well as the biological fate and functional pathways in vivo still need to be further explored.

Introduction: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. Methods: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. Results: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01–1.11; P = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤ 23.9 kg/m2), those with Q4 (BMI ≥ 28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; P = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. Conclusion: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

The coronavirus disease 2019 (COVID-19) has been associated with various psychological symptoms. We report a case of a female patient who was diagnosed with persistent insomnia and anxiety associated with COVID-19, which was successfully treated with nine treatment sessions of auricular acupuncture. This case report provides preliminary evidence to support further research into auricular acupuncture as a potential therapy for persistent insomnia and anxiety associated with COVID-19.

IntroductionCognitive dysfunction has frequently been found in patients with migraine. The so-called contingent negative variation (CNV) and EEG power spectral densities may be the best choices to explore the underlining pathophysiology, such as cortical inhibition and habituation.MethodsThirty migraine patients without aura and healthy controls matched for sex, age, and education were recruited separately for CNV recording. The amplitudes, latencies, and squares of different CNV components, such as oCNV, iCNV, tCNV, and PINV, were selected and analyzed. Behavioral data, such as manual reaction time (RT), were analyzed. We used the Person correlation coefficient R to analyze different ERP components in relation to clinical characteristics. A multiple regression analysis was conducted for the migraine group. Spectral analysis of EEG data from all channels using the fast Fourier transform (FFT).ResultsThe migraine group had longer A-latency, C-latency, and iCNV-latency than the control group. The migraine group had higher iCNV-amplitude, oCNV-amplitude, and tCNV-amplitude than the control group, especially those located in the occipital area. The iCNV-square, oCNV-square, tCNV-square, or PINV-square in the migraine group was significantly larger than the control group. Different correlations were found between clinical characteristics and ERP components. The delta or theta activity in the migraine group was statistically lower than in the control group.DiscussionOur study has revealed that migraine attacks may influence responsivity, pre-activation, habituation, and cortical inhibition not only on the behavioral level but also on the electrophysiological level. Abnormal changes in cortical habituation and inhibition can be interpreted as CNV components. Additionally, analyses have revealed correlations between CNV components and various factors, including age, the clinical course of the condition, attack frequency, pain intensity, and duration. Thus, repetitive migraine attacks can lead to a reduction in cortical inhibition and subsequent impairment in executive function.

Abstract Background To our knowledge, carbon loaded with nano-ZnO (NZnOC) represents a new nutritional additive for the animal husbandry industry. However, the mechanism by which NZnOC mediates beef cattle growth and intestinal health is not fully understood. This study aimed to investigate the effects of carbon loaded with nano-ZnO (NZnOC) supplementation on growth performance, gut microbiota, bile acid (BAs) metabolism and intestinal immunity in fattening cattle. Twenty cattle (16 ± 0.95 months) were randomly assigned to two dietary groups: CON (control, without feed additive) and NZnOC (diet supplemented with 80 mg NZnOC/kg diet dry matter basic) for 60 d. The colon digesta microbiota composition and BAs concentration were determined by microbiota metagenomics and gas chromatography methods, respectively. Results The results showed that the NZnOC-supplemented cattle had greater final weight, average daily gain and gain-to-feed ratio than those in the CON group. Cattle fed the NZnOC diet had a higher relative abundance of the secondary BAs synthesizing phyla Firmicutes, Tenericutes and Actinobacteria than those fed the CON diet. Dietary supplementation with NZnOC increased the relative abundance of the secondary BAs synthesis microbiota genera Clostridium, Ruminococcus, Eubacterium, and Brevibacillus in colon digesta. Cattle fed the NZnOC diet had increased activities of 3α-hydroxysteroid dehydrogenase (EC: 1.1.1.52) and bile acid-CoA ligase BaiB (EC: 6.2.1.7) in the colon digesta compared with those fed the CON diet. The primary BAs taurocholic acid, taurochenodeoxycholic acid and taurodeoxycholate acid were significantly decreased by dietary NZnOC supplementation, while the secondary BAs deoxycholic acid, taurolithocholic acid, beta-muricholic acid, 12-ketolithocholic acid and ursodeoxycholic acid were significantly increased. Dietary supplementation with NZnOC increased the mRNA abundance of G protein-coupled bile acid receptor 1, protein kinase cAMP-activated catalytic subunit alpha, cyclic-AMP response element binding protein 1 and interleukin (IL)-10 in the colon mucosa of cattle, while the mRNA abundance of tumor necrosis factor and IL-1β were significantly decreased. Conclusions In summary, dietary supplementation with NZnOC can facilitate the growth performance and intestinal immune function of cattle by improving BAs metabolism. NZnOC can be supplemented in the diet as a safe regulator of gut microbiota and as a feed additive in the ruminants industry.

High-crystallinity poly(ethylene terephthalate) is a major recycling challenge. Here, the authors show an engineered whole-cell biocatalyst showing adhesive hydrophobin and PETase on the surface of cells, for biodegradation of PET.

BackgroundGastric cancer with synchronous distant metastases indicates a dismal prognosis. The success in survival improvement mainly relies on our ability to predict the potential benefit of a therapy. Our objective is to develop an artificial intelligence annotated clinical-pathologic risk model to predict its outcomes.MethodsIn participants (n=47553) with gastric cancer of the surveillance, epidemiology, and end results program, we selected patients with distant metastases at first diagnosis, complete clinical-pathologic data and follow-up information. Patients were randomly divided into the training and test cohort at 7:3 ratio. 93 patients with advanced gastric cancer from six other cancer centers were collected as the external validation cohort. Multivariable analysis was used to identify the prognosis-related clinical-pathologic features. Then a survival prediction model was established and validated. Importantly, we provided explanations to the prediction with artificial intelligence SHAP (Shapley additive explanations) method. We also provide novel insights into treatment options.ResultsData from a total 2549 patients were included in model development and internal test (median age, 61 years [range, 53-69 years]; 1725 [67.7%] male). Data from an additional 93 patients were collected as the external validation cohort (median age, 59 years [range, 48-66 years]; 51 [54.8%] male). The clinical-pathologic model achieved a consistently high accuracy for predicting prognosis in the training (C-index: 0.705 [range, 0.690-0.720]), test (C-index: 0.737 [range, 0.717-0.757]), and external validation (C-index: 0.694 [range, 0.562-0.826]) cohorts. Shapley values indicated that undergoing surgery, chemotherapy, young, absence of lung metastases and well differentiated were the top 5 contributors to the high likelihood of survival. A combination of surgery and chemotherapy had the greatest benefit. However, aggressive treatment did not equate to a survival benefit. SHAP dependence plots demonstrated insightful nonlinear interactive associations among predictors in survival benefit prediction. For example, patients who were elderly, or poor differentiated, or presence of lung or bone metastases had a worse prognosis if they undergo surgery or chemotherapy, while patients with metastases to liver alone seemed to gain benefit from surgery and chemotherapy.ConclusionIn this large multicenter cohort study, we developed an artificial intelligence annotated clinical-pathologic risk model to predict outcomes of advanced gastric cancer. It could be used to discuss treatment options.

Photothermal interfacial evaporation with low cost and environmental friendliness has attracted much attention. However, there are still many problems with this technology, such as heat loss and salt accumulation. Due to their different structures and adjustable chemical composition, electrospun nanofiber materials generally exhibit some unique properties that provide new approaches to address the aforementioned issues. In this review, the rational design principles for improving the total efficiency of solar evaporation are described for thermal/water management systems and salt-resistance strategies. And we review the state-of-the-art advancements in photothermal evaporation based on nanofiber materials and discuss their derivative applications in desalination, water purification, and power generation. Finally, we highlight key challenges and opportunities in both fundamental research and practical applications to inform further developments in the field of interfacial evaporation.

The changes of bioactive substances in peels and sarcocarps of three different varieties of Kadsura coccinea (Dahong, Fenhong, and Zihei) were evaluated by an in vitro simulation model. In this study, three varieties of K. coccinea fruits were digested in vitro to compare the changes and differences in antioxidant activity (DPPH, ABTS, FRAP) and bioaccessibility. The results showed that before digestion the highest content of total phenolics (TPC) (2.265 ± 0.127 mg GAE/g DW) and the highest content of flavonoids contents (TFC) (10.379 ± 0.093 mg GAE/g DW) were found in Fenhong fruit. The highest release of TPC and TFC after simulated gastric digestion was observed in the Dahong and Zihei sarcocarp, which increased by 98.7 and 20%, respectively. During oral and intestinal digestion, the content of bioactive compounds showed a decreasing trend. The radical scavenging ability of 1, 1-diphenyl-2-picrylhydrazyl (DPPH), [2,2-azino-bis(3-ethylbenzothiazoline) (ABTS)] sulfonic acid free radical scavenging ability, and ferric ion reducing antioxidant power (FRAP) results showed that the antioxidant capacity of K. coccinea fruits increased most significantly (26.9∼181%) in gastric digestion stage and then decreased after intestinal digestion stage. The recoveries of TPC and TFC were all increased after whole simulated digestion, as well as their bioaccessibility in sarcocarps was higher than those in peels, especially for the bioaccessibility of TPC and TFC in Dahong reached 50.53 and 48.19%, respectively. These results indicated that the peel and sarcocarp of K. coccinea had good antioxidant activity, with high bioaccessibility of phenolics could be a promising antioxidant source for the food industry.

With the upgrading of people’s consumption patterns, the omni-channel supply chain becomes the mainstream form of e-commerce platform enterprise development. Aiming at two different e-commerce enterprises, we construct an evolutionary game model for enterprises’ “online+offline” omni-channel construction strategy by self-build or cooperating with brick-and-mortar stores. It is based on the Stackelberg and Cournot competition model, combined with the omni-channel pricing strategy, using the theory of perfect rationality and bounded rationality, and combing the non-cooperative game and evolutionary game to realize. Moreover, the evolutionary game process is simulated. Through the dynamic changes of the system, the strategy selection behavior mechanism of the retail channel subjects is deeply analyzed. It is found that enterprises’ strategy choices are influenced by both competitors and profits, and evolutionary stabilization strategies are not unique. In addition, changes in consumer loyalty, physical feelings, and sharing ratio during the evolutionary process will affect the stability rate of enterprises’ behavioral choices.

ABSTRACT: Objectives: The aim of this study was to characterise a novel tet(X6)-carrying plasmid detected in a livestock-associated Acinetobacter towneri isolate. Methods: PCR screening was performed to detect tet(X) variants in livestock-associated Acinetobacter spp. isolates. The tet(X6)-positive isolate was analysed by whole-genome sequencing. Functional cloning was performed to detect the activity of Tet(X6). Antibiotic susceptibility was determined by broth dilution and microbiological degradation assays. Site-directed mutagenesis was performed to identify the role of 23-Ala residue of Tet(X6) in tigecycline resistance. Results: The tet(X6) gene was detected on a 159-kb plasmid (pAT205) carried by a tigecycline-susceptible A. towneri isolate recovered from a swine faecal sample. The genetic context of tet(X6) [ΔISVsa3–tet(X6)–abh–guaA–ISVsa3] is highly similar to that of the reported plasmid-borne tet(X) variants, suggesting that it may represent a common structure mediating the dissemination of plasmid-borne tet(X) genes. Additional resistance genes detected on pAT205 were carried by a Tn6205-like region and a disrupted class 2 integron. Gene expression and microbiological degradation assays consistently suggested that the activity of tet(X6) is weaker than that of tet(X3) and tet(X4). The 23-Ala residue of the first FAD-binding site conferred higher activity to Tet(X6) than the Gly reside conserved in the other plasmid-borne tet(X) variants, indicating that the site might be under selection. Conclusion: This study alerts to the silent dissemination possibility of tigecycline resistance mediated by a novel plasmid. Continuous monitoring of plasmid-borne tet(X) is imperative for tackling its dissemination.

Abstract Calcium dysregulation is a key pathological event in Alzheimer’s disease (AD). In studying approaches to mitigate this calcium overload, we identified the collapsin response mediator protein 2 (CRMP2), an axonal guidance protein that participates in synapse dynamics by interacting with and regulating activity of N-methyl-D-aspartate receptors (NMDARs). We further identified a 15 amino acid peptide from CRMP2 (designated CBD3, for calcium-binding domain 3), that reduced NMDAR-mediated Ca2+ influx in cultured neurons and post-synaptic NMDAR-mediated currents in cortical slices. Whether targeting CRMP2 could be therapeutically beneficial in AD is unknown. Here, using CBD3, we tested the utility of this approach. Employing the APP/PS1 mouse model of AD which demonstrates robust pathophysiology including Aβ1–42 deposition, altered tau levels, and diminished cognitive functions, we asked if overexpression of CBD3 could rescue these events. CBD3 was engineered into an adeno-associated vector and nasally delivered into APP/PS1 mice and then biochemical (immunohistochemistry, immunoblotting), cellular (TUNEL apoptosis assays), and behavioral (Morris water maze test) assessments were performed. APP/PS1 mice administered adeno-associated virus (AAV, serotype 2) harboring CBD3 demonstrated: (i) reduced levels of Aβ1–42 and phosphorylated-tau (a marker of AD progression), (ii) reduced apoptosis in the hippocampus, and (iii) reduced cognitive decline compared with APP/PS1 mice or APP/PS1 administered a control virus. These results provide an instructive example of utilizing a peptide-based approach to unravel protein-protein interactions that are necessary for AD pathology and demonstrate the therapeutic potential of CRMP2 as a novel protein player in AD.

Abstract Background The SH3RF2 gene is a protein-coding gene located in a quantitative trait locus associated with body weight, and its deletion has been shown to be positively associated with body weight in chickens. Results In the present study, CNV in the SH3RF2 gene was detected in 4079 individuals from 17 populations, including the “Gushi ×Anka” F2 resource population and populations of Chinese native chickens, commercial layers, and commercial broilers. The F2 resource population was then used to investigate the genetic effects of the chicken SH3RF2 gene. The results showed that the local chickens and commercial layers were all homozygous for the wild-type allele. Deletion mutation individuals were detected in all of the commercial broiler breeds except Hubbard broiler. A total of, 798 individuals in the F2 resource group were used to analyze the effects of genotype (DD/ID/II) on chicken production traits. The results showed that CNV was associated with 2-, 6-, 10-, and 12-week body weight (P = 0.026, 0.042, 0.021 and 0.039 respectively) and significantly associated with 8-week breast bone length (P = 0.045). The mutation was significantly associated with 8-week body weight (P = 0.007) and 4-week breast bone length (P = 0.010). CNV was significantly associated with evisceration weight, leg muscle weight, carcass weight, breast muscle weight and gizzard weight (P = 0.032, 0.033, 0.045, 0.004 and 0.000, respectively). Conclusions CNV of the SH3RF2 gene contributed to variation in the growth and weight gain of chickens.

ABSTRACTTigecycline is one of the last-resort antibiotics to treat severe infections. Recently, tigecycline resistance has sporadically emerged with an increasing trend, and Tet(X) family represents a new resistance mechanism of tigecycline. In this study, a novel chromosome-encoded tigecycline resistance gene, tet(X14), was identified in a tigecycline-resistant and colistin-resistant Empedobacter stercoris strain ES183 recovered from a pig fecal sample in China. Tet(X14) shows 67.14-96.39% sequence identity to the other variants [Tet(X) to Tet(X13)]. Overexpression of Tet(X14) in Escherichia coli confers 16-fold increase in tigecycline MIC (from 0.125 to 2 mg/L), which is lower than that of Tet(X3), Tet(X4) and Tet(X6). Structural modelling predicted that Tet(X14) shared a high homology with the other 12 variants with RMSD value from 0.003 to 0.055, and Tet(X14) can interact with tetracyclines by a similar pattern as the other Tet(X)s. tet(X14) and two copies of tet(X2) were identified on a genome island with abnormal GC content carried by the chromosome of ES183, and no mobile genetic elements were found surrounding, suggesting that tet(X14) might be heterologously obtained by ES183 via recombination. Blasting in Genbank revealed that Tet(X14) was exclusively detected on the chromosome of Riemerella anatipestifer, mainly encoded on antimicrobial resistance islands. E. stercoris and R. anatipestifer belong to the family Flavobacteriaceae, suggesting that the members of Flavobacteriaceae maybe the major reservoir of tet(X14). Our study reports a novel chromosome-encoded tigecycline resistance gene tet(X14). The expanded members of Tet(X) family warrants the potential large-scale dissemination and the necessity of continuous surveillance for tet(X)-mediated tigecycline resistance.

Abstract Background Plant NADPH oxidase (NOX), also known as respiratory burst oxidase homolog (rboh), encoded by the rboh gene, is a key enzyme in the reactive oxygen species (ROS) metabolic network. It catalyzes the formation of the superoxide anion (O2 •−), a type of ROS. In recent years, various studies had shown that members of the plant rboh gene family were involved in plant growth and developmental processes as well as in biotic and abiotic stress responses, but little is known about its functional role in upland cotton. Results In the present study, 26 putative Ghrboh genes were identified and characterized. They were phylogenetically classified into six subfamilies and distributed at different densities across 18 of the 26 chromosomes or scaffolds. Their exon-intron structures, conserved domains, synteny and collinearity, gene family evolution, regulation mediated by cis-acting elements and microRNAs (miRNAs) were predicted and analyzed. Additionally, expression profiles of Ghrboh gene family were analyzed in different tissues/organs and at different developmental stages and under different abiotic stresses, using RNA-Seq data and real-time PCR. These profiling studies indicated that the Ghrboh genes exhibited temporal and spatial specificity with respect to expression, and might play important roles in cotton development and in stress tolerance through modulating NOX-dependent ROS induction and other signaling pathways. Conclusions This comprehensive analysis of the characteristics of the Ghrboh gene family determined features such as sequence, synteny and collinearity, phylogenetic and evolutionary relationship, expression patterns, and cis-element- and miRNA-mediated regulation of gene expression. Our results will provide valuable information to help with further gene cloning, evolutionary analysis, and biological function analysis of cotton rbohs.

Silica aerogels are one of the most widely used aerogels, exhibiting excellent thermal insulation performance and ultralow density. However, owing to their plenitude of Si-O-Si bonds, they possess high infrared emissivity in the range of 8–13 µm and are potentially robust passive radiative cooling (PRC) materials. In this study, the PRC behavior of traditional silica aerogels prepared from methyltrimethoxysilane (MTMS) and dimethyldimethoxysilane (DMDMS) in outdoor environments was investigated. The silica aerogels possessed low thermal conductivity of 0.035 W/m·K and showed excellent thermal insulation performance in room environments. However, sub-ambient cooling of 12 °C was observed on a clear night and sub-ambient cooling of up to 7.5 °C was achieved in the daytime, which indicated that in these cases the silica aerogel became a robust cooling material rather than a thermal insulator owing to its high IR emissivity of 0.932 and high solar reflectance of 0.924. In summary, this study shows the PRC performance of silica aerogels, and the findings guide the utilization of silica aerogels by considering their application environments for achieving optimal thermal management behavior.

BackgroundThe study of the immune microenvironment in prostate cancer (PRAD) has brought new opportunities for the current traditional treatment regimens. Therefore, our goal is to develop a universal immunodiagnostic marker to improve patient survival.MethodsBioinformatics analysis: We collected 591 samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts and evaluated the abundance and distribution of immune cell members in the PRAD expression profile matrix in the mixed cell population by CIBERSORT, ESTIMATE, single-sample gene set enrichment analysis (ssGSEA), and other methods. The target genes related to PRAD immune microenvironment and tumor mutation load were obtained by overlap analysis and verified by pan-cancer analysis. Cell experiment: The cell transfection scheme was designed, and the experiment was divided into three groups: overexpressing lactoferrin (LTF) group, empty plasmid group, and control group. After obtaining cells in each group, the gene and protein expression levels of LTF and signal transduction of signal transducer and activator of transcription 3 (STAT3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the above three groups were detected by real-time PCR and Western blot, respectively. Finally, the level of GM-CSF secretion in the three groups was detected by ELISA.ResultsMacrophages, resting mast cells, and plasma cells play an important role in PRAD immune microenvironment. In addition, high tumor mutation load [tumor mutational burden (TMB)] was positively correlated with lymph node metastasis in patients with PRAD. As the core gene of the PRAD immune microenvironment, the low expression of LTF in PRAD promotes the occurrence of immunodeficiency, PRAD, and the enrichment of the Janus kinase (JAK)/STAT3 signal pathway. Through cell experiments, it was found that the content of LTF mRNA and protein increased significantly, while the content of STAT3 and GM-CSF mRNA and protein decreased significantly in the overexpressed LTF group. The level of GM-CSF in the supernatant of cell culture was significantly decreased in the overexpression group of LTF.ConclusionThe core gene we proposed is one of the most promising biomarkers to improve the overall survival rate of PRAD and provides an important theoretical basis for the study of the mechanism of the LTF-mediated JAK/STAT3 pathway in PRAD.

Cerebrovascular remodeling is the most common cause of hypertension and stroke. Ubiquitin E3 ligase RING finger protein 34 (RNF34) is suggested to be associated with the development of multiple neurological diseases. However, the importance of RNF34 in cerebrovascular remodeling and hypertension is poorly understood. Herein, we used mice with a global RNF34 knockout as well as RNF34 floxed mice to delete RNF34 in endothelial cells and smooth muscle cells (SMCs). Our results showed that global RNF34 knockout mice substantially promoted angiotensin II (AngII)-induced middle cerebral artery (MCA) remodeling, hypertension, and neurological dysfunction. Endothelial cell RNF34 did not regulate the development of hypertension. Rather, SMC RNF34 expression is a critical regulator of hypertension and MCA remodeling. Loss of RNF34 enhanced AngII-induced mouse brain vascular SMCs (MBVSMCs) proliferation, migration and invasion. Furthermore, MCA and MBVSMCs from SMC RNF34-deficient mice showed increased superoxide anion and reactive oxygen species (ROS) generation as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, but exhibited no marked effect on mitochondria-derived ROS. Knockout of RNF34 promoted p22phox expression, leading to increased binding of p22phox/p47phox and p22phox/NOX2, and eventually NADPH oxidase complex formation. Immunoprecipitation assay identified that RNF34 interacted with p22phox. RNF34 deletion increased p22phox protein stability by inhibiting ubiquitin-mediated degradation. Blockade of NADPH oxidase activity or knockdown of p22phox significantly abolished the effects of RNF34 deletion on cerebrovascular remodeling and hypertension. Collectively, our study demonstrates that SMC RNF34 deficiency promotes cerebrovascular SMC hyperplasia and remodeling by increased NADPH-derived ROS generation via reducing p22phox ubiquitin-dependent degradation.

Recycling channel construction plays an important role in the development of closed-loop supply chains. In particular, the emergence of online recycling channels has made up for the shortcomings of traditional recycling channels with poor information and limited markets. This paper constructs an evolutionary game model to investigate the cooperation between manufacturers and e-commerce platforms with government intervention or not. The result shows that whether an enterprise actively participates in the cooperative recycling depends on the actual cost of establishing the cooperative recycling system. Additionally, the government support and supervision will affect the actual cost of cooperation. When the actual cost of establishing a collaborative recovery system is very large, under the influence of government interventions, there will be two kinds of evolutionary results for enterprises, either with cooperation or not at the same time. On the contrary, when the actual cost is small or medium, both manufacturers and the platforms will choose to cooperate. Thus, government participation in a cooperative recovery system is the best strategic option.

Introduction: The efficacy of conventional treatments for treating postherpetic neuralgia (PHN) remains unsatisfactory. Thus, this multicentre, randomized controlled, assessor-blinded trial aims to investigate the efficacy and safety of electroacupuncture (EA) therapy in patients with PHN.Methods and Analysis: This multicentre randomized controlled trial will enroll 132 patients with PHN from 3 hospitals. All patients will be randomly assigned to either the EA combined with medication group or medication group through a computerized central randomization system in a 1:1 ratio. Outcome measures will be assessed before intervention, at 2, 4, 6 weeks after intervention and at the end of 8-week follow-up. Primary outcomes will be sensory thresholds and pain intensity. Secondary outcomes will include dosage of analgetic, quality of life, anxiety, and depression severity and sleep quality. All adverse effects will be assessed during the trial.Conclusions: This study will provide evidence to ascertain whether EA is effective and safe for treating PHN.Ethics and Dissemination: Ethics approval (No.ZSLL-KY-2017-025) has been obtained from the Ethics Committee of The Third Affiliated Hospital of Zhejiang Chinese Medical University. Informed consent will be signed prior to subject enrolment. The results will be submitted to international peer-reviewed journals and presented at international conferences.Trial Registration Number: The study protocol has been registered in the clinicaltrials registry with the identification code NCT04594226.

Abstract Background Long non-coding (lnc) RNAs are a class of functional RNA molecules greater than 200 nucleotides in length, and lncRNAs play important roles in various biological regulatory processes and response to the biotic and abiotic stresses. LncRNAs associated with salt stress in cotton have been identified through RNA sequencing, but the function of lncRNAs has not been reported. We previously identified salt stress-related lncRNAs in cotton (Gossypium spp.), and discovered the salt-related lncRNA-lncRNA973. Results In this study, we identified the expression level, localization, function, and preliminary mechanism of action of lncRNA973. LncRNA973, which was localized in the nucleus, was expressed at a low level under nonstress conditions but can be significantly increased by salt treatments. Here lncRNA973 was transformed into Arabidopsis and overexpressed. Along with the increased expression compared with wild type under salt stress conditions in transgenic plants, the seed germination rate, fresh weights and root lengths of the transgenic plants increased. We also knocked down the expression of lncRNA973 using virus-induced gene silencing technology. The lncRNA973 knockdown plants wilted, and the leaves became yellowed and dropped under salt-stress conditions, indicating that the tolerance to salt stress had decreased compared with wild type. LncRNA973 may be involved in the regulation of reactive oxygen species-scavenging genes, transcription factors and genes involved in salt stress-related processes in response to cotton salt stress. Conclusions LncRNA973 was localized in the nucleus and its expression was increased by salt treatment. The lncRNA973-overexpression lines had increased salt tolerance compared with the wild type, while the lncRNA973 knockdown plants had reduced salt tolerance. LncRNA973 regulated cotton responses to salt stress by modulating the expression of a series of salt stress-related genes. The data provides a basis for further studies on the mechanisms of lncRNA973-associated responses to salt stress in cotton.

Software defined networking (SDN) has re-defined the way data center networks are deployed and functioned. The ability to separate the control plane and data plane have led to the simpler design and easier management. In SDN, the data plane and control plane are separately managed, so building an additional wired network to connect the control plane and the data plane can lead to a high cabling complexity. This paper proposes an end-to-end end wireless control plane architecture for SDN-enabled data center networks. In the proposed architecture, the switches form clusters that are wirelessly connected to the controller via access points (APs) and relay nodes (RNs). The switches use the 2.4/5-GHz band to connect with the APs, whereas the APs and the RNs are connected to the controller using the 60-GHz band. We have presented an analytical model to derive achievable data rates in our wireless control plane. We have also proposed two algorithms that allow an optimal number of a cluster size of the switches to be connected with the Controller via minimum number to APs/RNs such that the control traffic demands of the switches is guaranteed in interference constrained environment. Through extensive simulations, the results of our proposed architecture show that the cabling complexity in the control plane is reduced to zero and additional switches may be easily added in SDN data center. Thus, a pure wireless solution for building a control plane in a data center network is feasible.

A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a Ki of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC50 values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of lymphoma, whose treatment still has a major challenge of achieving a satisfactory curative effect. The underlying mechanisms also have not been fully illustrated. N6-Methyladenosine (m6A) has been identified as the most prevalent internal modification of mRNAs present in eukaryotes, which is involved in the pathogenesis of cancers. It remains unclear how m6A mRNA methylation is functionally linked to the pathogenesis of DLBCL. In this study, we sought to explore the roles of METTL3 on DLBCL development. The results showed that m6A level for RNA methylation and the expression level of METTL3 were upregulated in DLBCL tissues and cell lines. Functionally, downregulated METTL3 expression in DLBCL cells inhibited the cell proliferation ability. Further mechanism analysis indicated that METTL3 knockdown abates the m6A methylation and total mRNA level of pigment epithelium-derived factor (PEDF). However, Wnt/β-catenin signaling was not thus activated. Overexpressed PEDF abrogates the inhibition of cell proliferation in DLBCL cells that is caused by METTL3 silence. In summary, the above-mentioned results demonstrated that the METTL3 promotes DLBCL progression by regulating the m6A level of PEDF.

Abstract Background Stroke is the second leading cause of death worldwide and the most common cause of adult-acquired disability in many nations. Thus, attenuating the damage after ischemic injury and improving patient prognosis are of great importance. We have indicated that ischemic preconditioning (IP) can effectively reduce the damage of ischemia reperfusion and that inhibition of gap junctions may further reduce this damage. Although we confirmed that the function of gap junctions is closely associated with glutamate, we did not investigate the mechanism. In the present study, we aimed to clarify whether the blockade of cellular communication at gap junctions leads to significant reductions in the levels of glutamate released by astrocytes following cerebral ischemia. Methods To explore this hypothesis, we utilized the specific blocking agent carbenoxolone (CBX) to inhibit the opening and internalization of connexin 43 channels in an in vitro model of oxygen-glucose deprivation/re-oxygenation (OGD/R), following IP. Results OGD/R resulted in extensive astrocytic glutamate release following upregulation of hemichannel activity, thus increasing reactive oxygen species (ROS) generation and subsequent cell death. However, we observed significant increases in neuronal survival in neuron-astrocyte co-cultures that were subjected to IP prior to OGD/R. Moreover, the addition of CBX enhanced the protective effects of IP during the re-oxygenation period following OGD, by means of blocking the release of glutamate, increasing the level of the excitatory amino acid transporter 1, and downregulating glutamine expression. Conclusions Our results suggest that combined use of IP and CBX represents a novel therapeutic strategy to attenuate damage from cerebral ischemia with minimal adverse side effects.

CYTL1 is a novel cytokine that was first identified in CD34+ hematopoietic cells. We previously prepared recombinant CYTL1 and verified that it chemoattracted human monocytes via the CCR2/ERK pathway. It has been reported that CYTL1 plays contradictory roles in neuroblastoma and lung cancer. We found that the expression level of CYTL1 was notably decreased and it was hypermethylated in various tumors, including breast and lung cancer, by bioinformatics analyses. After validating the expression of CYTL1 in lung cancer, we identified that CYTL1 exerted no obvious effect on tumor cell proliferation but inhibited their migration and invasion, and these effects were accompanied by decreasing STAT3 phosphorylation, using recombinant CYTL1 and CYTL1-overexpressing tumor cell lines. Furthermore, we constructed experimental and spontaneous metastasis models of breast cancer in BALB/c mice and found that CYTL1 significantly inhibited tumor metastasis in vivo. In summary, CYTL1 is a cytokine with tumor-suppressing characteristics that inhibits tumor metastasis and STAT3 phosphorylation in multiple types of tumors.

Long non-coding (lnc) RNAs are non-coding RNAs longer than 200 nt. lncRNAs primarily interact with mRNA, DNA, protein, and miRNA and consequently regulate gene expression at the epigenetic, transcriptional, post-transcriptional, translational, and post-translational levels in a variety of ways. They play important roles in biological processes such as chromatin remodeling, transcriptional activation, transcriptional interference, RNA processing, and mRNA translation. lncRNAs have important functions in plant growth and development; biotic and abiotic stress responses; and in regulation of cell differentiation, the cell cycle, and the occurrence of many diseases in humans and animals. In this review, we summarize the functions and mechanisms of lncRNAs in plants, humans, and animals at different regulatory levels.

The dynamic models are proposed to investigate the influence node activity has on rumor spreading process in both homogeneous and heterogeneous networks. Different from previous studies, we believe that the activity of nodes in complex networks affects the process of rumor spreading. An active node can have contact with all the nodes it directly links to, while an inactive node could only interact with its active neighbors. We explore the joint effort of activity rate, spreading rate and network topology on rumor spreading process by mean-field equations and numerical simulations, which reveals that there exists a critical curve consisting of critical activity rate and spreading rate; meanwhile, activity rate and spreading rate both have influence on the final rumor spreading scale.

On the basis of nonlinear dynamic model, we research the propagation of rumors after emergencies, describe the impact of media coverage and emergency strategies by government on the transmission dynamics of information, and then obtain the basic reproduction number of rumor spreading. In order to overcome the limit of traditional methods of the static decision problem, the dynamic optimal control model for the rumor spreading is proposed based on the theorem of the optimal control. An optimal objective based on the maximum social utility is established and the optimal solution is acquired by using the Pontryagin Maximum Principle. Finally, numerical simulations show that the dynamic optimal control method has obvious superiority in modeling compared with the method without control. By means of the dynamic optimal control of media coverage and emergency strategies for government, the final rumor scale and the peak of spreaders can be effectively reduced.

Identification of novel stimulatory cytokines with antitumor function would have great value in tumor immunotherapy investigations. Here, we report LYG1 (Lysozyme G-like 1) identified through the strategy of Immunogenomics as a novel classical secretory protein with tumor-inhibiting function. LYG1 recombinant protein (rhLYG1) could significantly suppress the growth of B16 tumors in WT B6 mice, but not in SCID-beige mice, Rag1−/− mice, CD4+- or CD8+ T cell-deleted mice. It could increase the number of CD4+ and CD8+ T cells in tumor-infiltrating lymphocytes, tumor-draining lymph nodes, and spleens, and promote IFNγ production by T cells in tumor-bearing mice. In vitro experiments demonstrated that rhLYG1 could directly enhance IFNγ secretion by CD4+ T cells, but not CD8+ T cells. Moreover, it could promote the activation, proliferation, and IFNγ production of tumor antigen-specific CD4+ T cells. The tumor-inhibiting effect of LYG1 was eliminated in Ifng−/− mice. Furthermore, LYG1 deficiency accelerated B16 and LLC1 tumor growth and inhibited the function of T cells. In summary, our findings reveal a tumor-inhibiting role for LYG1 through promoting the activation, proliferation, and function of CD4+ T cells in antitumor immune responses, offering implications for novel tumor immunotherapy.

Nanochitin whisker (NC) with a cationic nature could enhance plant photosynthesis, grain yield, and quality of wheat, but have not been systematically studied. This study was designed to investigate the stimulatory effects of NC on dry matter (DM) and nitrogen (N) accumulation and translocation, and on the metabolism of carbon (C) and N in later growth stages of winter wheat to reveal the enhancement mechanism of grain yield and crude protein concentration. Different parts of NC-treated plants from pot grown experiments were collected at the pre- and post-anthesis stages. The accumulation, translocation, and contributions of DM and N from pre-anthesis vegetation organs to grains, as well as key metabolic enzyme activities, including sucrose phosphate synthase (SPS) and phosphoenolpyruvate carboxylase (PEPC), were examined. The results showed that, at an application rate of 6 mg·kg−1 of NC in the soil, the accumulation of DM and N were significantly enhanced by 16.2% and 38.8% in pre-anthesis, and by 15.4% and 30.0% in post-anthesis, respectively. Translocation of N and DM in the post-anthesis periods were enhanced by 38.4% and 50.9%, respectively. NC could also stimulate enzyme activities, and increased 39.8% and 57.1% in flag leaves, and by 36.0% and 58.8% in spikes, respectively, at anthesis. SPS and PEPC increased by 28.2% and 45.1% in flag leaves, and by 42.2% and 56.5% in spikes, respectively, at 15 days after anthesis. The results indicated that the NC promoted N metabolism more than C metabolism, and resulted in the enhancement of grain yield by 27.56% and of crude protein concentration in grain by 13.26%, respectively.

Catalases (CATs), which were coded by the catalase gene family, were a type notably distinguished ROS-metabolizing proteins implicated to perform various physiological functions in plant growth, development and stress responses. However, no systematical study has been performed in cotton. In the present study, we identified 7 and 7 CAT genes in the genome of Gossypium hirsutum L. Additionally, G. barbadense L., respectively. The results of the phylogenetic and synteny analysis showed that the CAT genes were divided into two groups, and whole-genome duplication (WGD) or polyploidy events contributed to the expansion of the Gossypium CAT gene family. Expression patterns analysis showed that the CAT gene family possessed temporal and spatial specificity and was induced by the Verticillium dahliae infection. In addition, we predicted the putative molecular regulatory mechanisms of the CAT gene family. Based on the analysis and preliminary verification results, we hypothesized that the CAT gene family, which might be regulated by transcription factors (TFs), alternative splicing (AS) events and miRNAs at different levels, played roles in cotton development and stress tolerance through modulating the reactive oxygen species (ROS) metabolism. This is the first report on the genome-scale analysis of the cotton CAT gene family, and these data will help further study the roles of CAT genes during stress responses, leading to crop improvement.

Dickeya zeae is the causal agent of rice foot rot and maize stalk rot diseases, which could cause severe economic losses. The pathogen is known to produce two phytotoxins known as zeamine and zeamine II which are also potent antibiotics against both gram-positive and gram-negative bacteria pathogens. Zeamine II is a long-chain aminated polyketide and zeamine shares the same polyketide structure as zeamine II, with an extra valine derivative moiety conjugated to the primary amino group of zeamine II. In this study, we have identified a gene designated as zmsK encoding a putative nonribosomal peptide synthase (NRPS) by screening of the transposon mutants defective in zeamine production. Different from most known NRPS enzymes, which are commonly multidomain proteins, ZmsK contains only a condensation domain. High-performance liquid chromatography and mass spectrometry analyses showed that the ZmsK deletion mutant produced only zeamine II but not zeamine, suggesting that ZmsK catalyzes the amide bond formation by using zeamine II as a substrate to generate zeamine. We also present evidence that a partially conserved catalytic motif within the condensation domain is critical for zeamine production. Furthermore, we show that deletion of zmsK substantially decreased the total antimicrobial activity and virulence of D. zeae. Our findings provide a new insight into the biosynthesis pathway of zeamines and the virulence mechanisms of the bacterial pathogen D. zeae.

MicroRNAs (miRNAs) are a class of noncoding small RNAs, which play a crucial role in post-transcriptional gene regulation. Recently, various reports revealed that miRNAs could be transmitted between species to mediate cross-kingdom regulation by integrating into a specific target gene-mediated regulatory pathway to exert relevant biological functions. Some scholars and researchers have observed this as an attractive hypothesis that may provide a foundation for novel approaches in the diagnosis, prognosis, and treatment of disease. Meanwhile, others deem the mentioned results were obtained from a “false positive effect” of performed experiments. Here, we focus on several current studies concerning plant miRNA-mediated cross-kingdom regulation (from both fronts) and discuss the existing issues that need further consideration. We also discuss possible miRNA horizontal transfer mechanisms from one species to another and analyze the relationship between miRNA-mediated cross-kingdom regulation and coevolution during a long-term specific host–pathogen interaction.

Dickeya zeae strain EC1 was recently shown to produce a new type of phytotoxins designated as zeamine and zeamine II, which are potent wide-spectrum antibiotics against Gram-positive and Gram-negative bacterial pathogens, suggesting their promising potential as clinical medicines. In this study, the optimized medium composition and culture conditions for biosynthesis of novel antibiotics zeamines have been established by using response surface methodology, largely increasing the yield of zeamines from original about 7.35 µg · mL(-1) in minimal medium to about 150 µg · mL(-1) in LS5 medium. The study identified the major factors contributing to zeamines production, which include nitrate, sucrose, asparaginate, mineral elements Mg2+ and K+, and optimized amount of phosphate. In addition, the results showed that overexpression of zmsK in D. zeae strain EC1 could further increase zeamines yield to about 180 µg · mL(-1) in LS5 medium. The findings from this study could facilitate further characterization and utilization of these two novel antibiotics, and also provide useful clues for understanding the regulatory mechanisms that govern D. zeae virulence.