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ObjectiveTo explore the potential strategies and mechanisms for enhancing the bioavailability of Rhodiola rosea.Methods36 Sprague–Dawley rats (8-weeks-old) were randomly assigned to six groups (n = 6 per group). Groups I and II received nano-dose forms of R. rosea, groups III and IV received normal dose form of R. rosea, and groups V and VI served as distilled water control groups. Groups II, IV, and VI were combined with moderate -intensity treadmill exercise. Each group received a daily gavage with 0.5 mL of nano -R. rosea solution (0.01 mg/mL), normal R. rosea solution, and distilled water. All rats were subjected to exhaustive swimming after 4 weeks. Outcome measures include GSH-px activity, T-AOC activity, MDA content, hepatic glycogen content, and T-SOD activity.ResultsFor plasma MDA content, group I was lower than group III (p

Abstract Background The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. Methods The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3–6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. Result A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. Conclusion Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. Trial registration ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Abstract Background Feline calicivirus (FCV) infection causes severe upper respiratory disease in cats, but there are no effective vaccines available for preventing FCV infection. Subunit vaccines have the advantages of safety, low cost and excellent immunogenicity, but no FCV subunit vaccine is currently available. The CDE protein is the dominant neutralizing epitope region of the main antigenic structural protein of FCV, VP1. Therefore, this study evaluated the effectiveness of the CDE region as a truncated FCV VP1 protein in preventing FCV infection to provide a strategy for developing potential FCV subunit vaccines. Results Through the prediction of FCV VP1 epitopes, we found that the E region is the dominant neutralizing epitope region. By analysing the spatial structure of VP1 protein, 13 amino acid sites in the CD and E regions were found to form hydrogen bonding interactions. The results show the presence of these interaction forces supports the E region, helping improve the stability and expression level of the soluble E protein. Therefore, we selected the CDE protein as the immunogen for the immunization of felines. After immunization with the CDE protein, we found significant stimulation of IgG, IgA and neutralizing antibody production in serum and swab samples, and the cytokine TNF-α levels and the numbers of CD4+ T lymphocytes were increased. Moreover, a viral challenge trial indicated that the protection generated by the CDE subunit vaccine significantly reduced the incidence of disease in animals. Conclusions For the first time, we studied the efficacy of the CDE protein, which is the dominant neutralizing epitope region of the FCV VP1 protein, in preventing FCV infection. We revealed that the CDE protein can significantly activate humoral, mucosal and cellular immunity, and the resulting protective effect can significantly reduce the incidence of animal disease. The CDE region of the FCV capsid is easy to produce and has high stability and excellent immunogenicity, which makes it a candidate for low-cost vaccines.

The application of straw-degrading microbes (SDMs) with straw returned to the field is an effective measure to improve soil quality, increase yield, and maintain soil microorganisms. However, the utilization of SDMs in winter in north China is limited by the poor effects at low temperatures. This study investigated the effects of a new compound SDM, including a novel low-temperature fungus Pseudogymnoascus sp. SDF-LT, on winter wheat yield, soil improvement, and soil microbial diversity. A 2-year field experiment was conducted in two different soil textures of wheat–maize rotation fields with full corn straw return and application of SDMs at an amount of 67.5 kg hm−2. After 2 years of continuous application of SDMs, the winter wheat yield increased significantly, reaching 9419.40 kg hm−2 in Ningjin (NJSDM) and 9107.25 kg hm−2 in Mancheng (MCSDM). The soil properties have been significantly improved compared with the single straw return group, especially the sandy loam soil, whose quality is relatively low. The analysis of soil microbial diversity showed that SDMs significantly reduced the Chao1, Shannon, Simpson, and observed species of the sandy loam soil in the MCSDM group. The Simpson and Shannon indexes of fungi diversity in the two experimental sites were significantly increased by SDMs. The negative correlation of fungi increased from 47.1 to 48.85% in the SDM groups. The soil-dominant microbes changed in the SDM groups, in which the interactions between microbes were enhanced. These results suggested that the SDMs changed the the soil microbial community structure and its diversity and complexity, which is beneficial for crop growth. Our study provided sufficient evidence for the utilization of low-temperature SDMs with straw return in cold winter, which plays a role in soil improvement, especially for low-quality soils, to increase crop yield.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease of unknown etiology. Pirfenidone (PFD) and nintedanib (NDN) were both conditionally recommended in the clinical practice guideline published in 2015. Safety and tolerability are related to the risk of treatment discontinuation. Therefore, this study evaluated and compared the adverse events (AEs) of PFD and NDN in a large real-world population by analyzing data from the FDA Adverse Event Reporting System (FAERS) to provide a reference for their rational and safe use.MethodsThe AEs of PFD and NDN were extracted from the FAERS database. The pharmacovigilance online analysis tool OpenVigil 2.1 was used to retrieve data from the FAERS database from the first quarter of 2012 to the second quarter of 2022. The reporting odds ratio (ROR) and proportional reporting ratio were used to detect the risk signals.ResultsThe database included 26,728 and 11,720 reports for PFD and NDN, respectively. The most frequent AEs of PFD and NDN were gastrointestinal disorders. The RORs for these drugs were 5.874 and 5.899, respectively. “Cardiac disorders” was the most statistically significant system order class for NDN with an ROR of 9.382 (95% confidence interval = 8.308–10.594). Furthermore, the numbers of designated medical events of PFD and NDN were 552 and 656, respectively. Notably, liver injury was reported more frequently for NDN (11.096%) than for PFD (6.076%).ConclusionThis study revealed differences in the reporting of AEs between PFD and NDN. The findings provide reference for physicians in clinical practice. Attention should be paid to the risks of cardiac disorders and liver injury associated with NDN.

Abstract Considering the non‐linear characteristics of both the input and output of photovoltaic (PV) modules and quasi‐Z‐source inverters, as well as the unpredictable natural factors such as large disturbances caused by changes in illumination and temperature, an average state model for the PV quasi‐Z‐source inverter is established. This paper uses the output current of photovoltaic module, DC‐link capacitor voltage and its integral as state variables, then an adaptive reaching law with second‐order sliding mode characteristics is designed by combining with power reaching law and variable speed reaching law. By using the sliding mode controller based on the adaptive reaching law to control the stability of the DC‐link voltage of the quasi‐Z‐source inverter and the small capacitor voltage ripple, the photovoltaic system can operate stably at the maximum power point when the temperature and illumination conditions change abruptly, and the grid‐connected effect is improved. Through SIMULINK and RT‐LAB real‐time simulation, the effectiveness of the proposed adaptive sliding mode control strategy is verified when the environment changes, which effectively improves the dynamic response speed and grid‐connected effect of the system, and ensures the global robustness of the grid‐connected system.

Ensuring optimal infant nutrition is crucial for the health and development of children. Many infants aged 0–6 months are fed with infant formula rather than breast milk. Research on cancer cell lines and animal models is limited to examining the nutrition effects of formula and breast milk, as it does not comprehensively consider absorption, metabolism, and the health and social determinants of the infant and its physiology. Our study utilized small intestine organoids induced from human embryo stem cell (ESC) to compare the nutritional effects of breast milk from five donors during their postpartum lactation period of 1–6 months and three types of Stage 1 infant formulae from regular retail stores. Using transcriptomics and untargeted metabolomics approaches, we focused on the differences such as cell growth and development, cell junctions, and extracellular matrix. We also analyzed the roles of pathways including AMPK, Hippo, and Wnt, and identified key genes such as ALPI, SMAD3, TJP1, and WWTR1 for small intestine development. Through observational and in-vitro analysis, our study demonstrates ESC-derived organoids might be a promising model for exploring nutritional effects and underlying mechanisms.

IntroductionMany women experience fear toward pregnancy, which can impact their desire to have children and the national birth rate. Thus, assessing women’s fear of pregnancy is of great importance. However, there is currently no specialized tool for assessing women’s fear of pregnancy in China. The purpose of this study is to translate the Fear of Pregnancy Scale into Chinese and test its reliability and validity among women of childbearing age.MethodsUsing convenience sampling combined with a snowballing method, a cross-sectional survey was conducted on 886 women of childbearing age in two cities in China. The translation was strictly carried out according to the Brislin model. Item analysis, validity analysis, and reliability analysis were employed for psychometric assessment.ResultsThe Chinese version of the Fear of Pregnancy Scale comprises 28 items. Exploratory factor analysis extracted four factors with a cumulative variance contribution rate of 72.578%. Confirmatory factor analysis showed: NFI = 0.956, CFI = 0.986, GFI = 0.927, IFI = 0.986, TLI = 0.985, RMSEA = 0.032, and χ2/df = 1.444. The scale’s Cronbach’s α coefficient is 0.957, split-half reliability is 0.840, and test–retest reliability is 0.932.ConclusionThe Chinese version of the Fear of Pregnancy Scale possesses robust psychometric properties and can assess the degree of pregnancy fear among Chinese women of childbearing age. It provides a reference for formulating relevant policies in the prenatal care service system and implementing targeted intervention measures.

Maize productivity in the central belt plays a significant role in the food security of China. With good adaptability and disease resistance, landrace germplasm is important for maize improvement. A total of 246 landrace accessions were collected from the maize belts in central China and genotyped with the SLAF-seq (Specific-Locus Amplified Fragment Sequencing) method, and 144,650 SNPs were obtained for each accession. The results showed that the landrace accessions could be divided into three major groups. In the cluster results, Group I included 64 accessions, which mainly belonged to the landrace of White horse teeth; Group II had 71 accessions, which mainly belonged to the lantern red landraces; the rest of the 116 accessions were clustered as Group III, including a variety of types landraces and seven indicator inbred lines. In the results of structure and multidimensional scaling, the accessions’ attribution differed with the clusters, the main reason for which is the attribution change in intermediate germplasms. Linkage disequilibrium decay distance was 0.98 kb, which was much lower than that of temperate and tropical maize inbred lines, indicated the much higher genetic diversity of landrace germplasms. The results can help us select suitable landrace germplasms and speed up the process of inbred line development and maize improvement.

Abstract Background Multiparametric magnetic resonance imaging (MP-MRI) has high sensitivity for diagnosing breast cancers but cannot always be used as a routine diagnostic tool. The present study aimed to evaluate whether the diagnostic performance of perfluorobutane (PFB) contrast-enhanced ultrasound (CEUS) is similar to that of MP-MRI in breast cancer and whether combining the two methods would enhance diagnostic efficiency. Patients and methods This was a head-to-head, prospective, multicenter study. Patients with breast lesions diagnosed by US as Breast Imaging Reporting and Data System (BI-RADS) categories 3, 4, and 5 underwent both PFB-CEUS and MP-MRI scans. On-site operators and three reviewers categorized the BI-RADS of all lesions on two images. Logistic-bootstrap 1000-sample analysis and cross-validation were used to construct PFB-CEUS, MP-MRI, and hybrid (PFB-CEUS + MP-MRI) models to distinguish breast lesions. Results In total, 179 women with 186 breast lesions were evaluated from 17 centers in China. The area under the receiver operating characteristic curve (AUC) for the PFB-CEUS model to diagnose breast cancer (0.89; 95% confidence interval [CI] 0.74, 0.97) was similar to that of the MP-MRI model (0.89; 95% CI 0.73, 0.97) (P = 0.85). The AUC of the hybrid model (0.92, 95% CI 0.77, 0.98) did not show a statistical advantage over the PFB-CEUS and MP-MRI models (P = 0.29 and 0.40, respectively). However, 90.3% false-positive and 66.7% false-negative results of PFB-CEUS radiologists and 90.5% false-positive and 42.8% false-negative results of MP-MRI radiologists could be corrected by the hybrid model. Three dynamic nomograms of PFB-CEUS, MP-MRI and hybrid models to diagnose breast cancer are freely available online. Conclusions PFB-CEUS can be used in the differential diagnosis of breast cancer with comparable performance to MP-MRI and with less time consumption. Using PFB-CEUS and MP-MRI as joint diagnostics could further strengthen the diagnostic ability. Trial registration Clinicaltrials.gov; NCT04657328. Registered 26 September 2020. IRB number 2020-300 was approved in Chinese PLA General Hospital. Every patient signed a written informed consent form in each center.

The collection of tree canopy samples in forest ecosystems has been challenging for researchers and managers during the past decades. Various methods, including pole pruner, tree climber, shooter, throw-line launcher, hydraulic lift (e.g., tower crane) and UAV (unmanned aerial vehicle)-based devices, have been used, however, they are limited by sampling height restrictions, safety hazards to a climber, low retrieving accuracy, high equipment costs, and transportation inconvenience. This study proposed a novel method for collecting tree canopy samples using a portable mini-drone. The mini-drone is operated to pull a traction line across the target branch, drag the retrieving rope to the selected cutting point of the branch, and carry the equipped wire saw or chain saw to cut the canopy sample off. Through on-site testing and field trials, this method was feasible for lower- and middle-canopy sampling (up to 30 meters tall) across most temperate broad-leaved and coniferous tree species. This technique would have great potential in plantation and old-growth forests. Adopting this low-cost mini-drone technique, researchers can collect tree canopy samples safely and efficiently, leading to improvements in relevant physiological and ecological studies focusing on functional traits of branches, leaves, and seeds.

Abstract Background Since ovarian cancer leads to the poor prognosis in women all over the world, we aim to construct an immune-related lncRNAs signature to improve the survival of ovarian cancer patients. Methods Normal and cancer patient samples and corresponding clinical data of ovarian were obtained from The Genotype-Tissue Expression (GTEx) portal and The Cancer Genome Atlas (TCGA) database. The predictive signature was constructed by the lasso penalty Cox proportional hazard regression model. The division of different risk groups was accounting for the optimal critical value of the time-dependent Receiver Operating Characteristic (ROC) curve. Finally, we validated and evaluated the application of this prognostic signature based on the clinical factors, chemo-sensitivity and immune status of different risk groups. Results The signature was established from 145 DEirlncRNAs and can be shown as an independent prognostic risk factor with accurate prediction on overall survival in ovarian cancer patients. Further analysis on the application of the prognostic signature showed that patients with low-risk had a better sensitivity to chemotherapy and a higher immunogenicity. Conclusion We constructed and verified an effective signature based on DEirlncRNA pairs, which could predict the prognosis, drug sensitivity and immune status of ovarian cancer patients and promote the prognostic estimation and individualized treatment.

SEP genes are famous for their function in the morphological novelty of bisexual flowers. Although the diverse functions of SEP genes were reported, only the regulatory mechanisms underlying floral organ development have been addressed. In this study, we identified SEP-like genes in Gossypium and found that SEP3 genes were duplicated in diploid cotton varieties. GhSEP4.1 and GhSEP4.2 were abundantly transcribed in the shoot apical meristem (SAM), but only GhSEP4.2 was expressed in the leaf vasculature. The expression pattern of GhSEPs in floral organs was conserved with that of homologs in Arabidopsis, except for GhSEP2 that was preponderantly expressed in ovules and fibers. The overexpression and silencing of each single GhSEP gene suggested their distinct role in promoting flowering via direct binding to GhAP1 and GhLFY genomic regions. The curly leaf and floral defects in overexpression lines with a higher expression of GhSEP genes revealed the concentration-dependent target gene regulation of GhSEP proteins. Moreover, GhSEP proteins were able to dimerize and interact with flowering time regulators. Together, our results suggest the dominant role of GhSEP4.2 in leaves to promote flowering via GhAP1-A04, and differently accumulated GhSEP proteins in the SAM alternately participate in forming the dynamic tetramer complexes to target at the different loci of GhAP1 and GhLFY to maintain reproductive growth. The regulatory roles of cotton SEP genes reveal their conserved and diversified functions.

The phenotypic switch in tumor-associated macrophages (TAMs) mediates immunity escape of cancer. However, the underlying mechanisms in the TAM phenotypic switch have not been systematically elucidated. In this study, long noncoding RNA (lncRNA)-Xist, CCAAT/enhancer-binding protein (C/EBP)α, and Kruppel-like factor 6 (KLF6) were upregulated, whereas microRNA (miR)-101 was downregulated in M1 macrophages-type (M1). Knockdown of Xist or overexpression of miR-101 in M1 could induce M1-to-M2 macrophage-type (M2) conversion to promote cell proliferation and migration of breast and ovarian cancer by inhibiting C/EBPα and KLF6 expression. Furthermore, miR-101 could combine with both Xist and C/EBPα and KLF6 through the same microRNA response element (MRE) predicted by bioinformatics and verified by luciferase reporter assays. Moreover, we found that miR-101 knockdown restored the decreased M1 marker and the increased M2 marker expression and also reversed the promotion of proliferation and migration of human breast cancer cells (MCF-7) and human ovarian cancer (OV) cells caused by silencing Xist. Generally, the present study indicates that Xist could mediate macrophage polarization to affect cell proliferation and migration of breast and ovarian cancer by competing with miR-101 to regulate C/EBPα and KLF6 expression. The promotion of Xist expression in M1 macrophages and inhibition of miR-101 expression in M2 macrophages might play an important role in inhibiting breast and ovarian tumor proliferation and migration abilities.

Abstract Background Dirigent (DIR) proteins mediate regioselectivity and stereoselectivity during lignan biosynthesis and are also involved in lignin, gossypol and pterocarpan biosynthesis. This gene family plays a vital role in enhancing stress resistance and in secondary cell-wall development, but systematical understanding is lacking in cotton. Results In this study, 107 GbDIRs and 107 GhDIRs were identified in Gossypium barbadense and Gossypium hirsutum, respectively. Most of these genes have a classical gene structure without intron and encode proteins containing a signal peptide. Phylogenetic analysis showed that cotton DIR genes were classified into four distinct subfamilies (a, b/d, e, and f). Of these groups, DIR-a and DIR-e were evolutionarily conserved, and segmental and tandem duplications contributed equally to their formation. In contrast, DIR-b/d mainly expanded by recent tandem duplications, accompanying with a number of gene clusters. With the rapid evolution, DIR-b/d-III was a Gossypium-specific clade involved in atropselective synthesis of gossypol. RNA-seq data highlighted GhDIRs in response to Verticillium dahliae infection and suggested that DIR gene family could confer Verticillium wilt resistance. We also identified candidate DIR genes related to fiber development in G. barbadense and G. hirsutum and revealed their differential expression. To further determine the involvement of DIR genes in fiber development, we overexpressed a fiber length-related gene GbDIR78 in Arabidopsis and validated its function in trichomes and hypocotyls. Conclusions These findings contribute novel insights towards the evolution of DIR gene family and provide valuable information for further understanding the roles of DIR genes in cotton fiber development as well as in stress responses.

The unprecedented coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious threat to global public health. Development of effective therapies against SARS-CoV-2 is urgently needed. Here, we evaluated the antiviral activity of a remdesivir parent nucleotide analog, GS441524, which targets the coronavirus RNA-dependent RNA polymerase enzyme, and a feline coronavirus prodrug, GC376, which targets its main protease, using a mouse-adapted SARS-CoV-2 infected mouse model. Our results showed that GS441524 effectively blocked the proliferation of SARS-CoV-2 in the mouse upper and lower respiratory tracts via combined intranasal (i.n.) and intramuscular (i.m.) treatment. However, the ability of high-dose GC376 (i.m. or i.n. and i.m.) was weaker than GS441524. Notably, low-dose combined application of GS441524 with GC376 could effectively protect mice against SARS-CoV-2 infection via i.n. or i.n. and i.m. treatment. Moreover, we found that the pharmacokinetic properties of GS441524 is better than GC376, and combined application of GC376 and GS441524 had a synergistic effect. Our findings support the further evaluation of the combined application of GC376 and GS441524 in future clinical studies.

Gossypium hirsutum is most broadly cultivated in the world due to its broader adaptation to the environment and successful breeding of early maturity varieties. However, how cotton responds to environmental cues to adjust flowering time to achieve reproductive success is largely unknown. SOC1 functions as an essential integrator for the endogenous and exogenous signals to maximize reproduction. Thus we identified six SOC1-like genes in Gossypium that clustered into two groups. GhSOC1-1 contained a large intron and clustered with monocot SOC1s, while GhSOC1-2/3 were close to dicot SOC1s. GhSOC1s expression gradually increased during seedling development suggesting their conserved function in promoting flowering, which was supported by the early flowering phenotype of 35S:GhSOC1-1 Arabidopsis lines and the delayed flowering of cotton silencing lines. Furthermore, GhSOC1-1 responded to short-day and high temperature conditions, while GhSOC1-2 responded to long-day conditions. GhSOC1-3 might function to promote flowering in response to low temperature and cold. Taken together, our results demonstrate that GhSOC1s respond differently to light and temperature and act cooperatively to activate GhLFY expression to promote floral transition and enlighten us in cotton adaptation to environment that is helpful in improvement of cotton maturity.

Most of the time-sensitive networking standards are based on a high precise and reliability time reference, which is accomplished by IEEE 802.1 AS. However, the accuracy and reliability of clock synchronization could be affected in practice. To conquer the inaccuracy resulting from the collision between different packets, an algorithm that combines time-slot-based synchronization and priority scheduling is proposed. To improve the reliability, an abnormal recovery strategy of the master clock is proposed. The proposed algorithms are implemented on the OMNet++ simulation platform with an typical in-vehicle network topology. The simulation results show that the clock synchronization accuracy could achieve sub-microsecond level even if there are interference flows, and the abnormal recovery mechanism can maintain the stable state of the clock.

Albendazole (ABZ), an effective benzimidazole antiparasitic drug is limited by its poor solubility and oral bioavailability. In order to overcome its disadvantages, ABZ nanocrystals were prepared using a novel bottom-up method based on acid-base neutralization recrystallization with high-speed mixing and dispersing. The cosolvent, stabilizer and preparation temperature were optimized using single factor tests. The physicochemical properties, solubility and pharmacokinetics of the optimal ABZ nanocrystals were evaluated. The high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD) showed that ABZ had no structural and crystal phase change after nanocrystallization. The saturated solubility of ABZ nanocrystals in different solvents was increased by 2.2–118 fold. The oral bioavailability of the total active ingredients (ABZ and its metabolites of albendazole sulfoxide (ABZSO) and albendazole sulfone (ABZSO2)) of the nanocrystals in rats was enhanced by 1.40 times compared to the native ABZ. These results suggest that nanocrystals might be a promising way to enhance the solubility and oral bioavailability of ABZ and other insoluble drugs.

Abstract Background Ovarian cancer is the leading cause of death in gynecological cancer. Cancer stem cells (CSCs) contribute to the occurrence, progression and resistance. Small nucleolar RNAs (SnoRNAs), a class of small molecule non-coding RNA, involve in the cancer cell stemness and tumorigenesis. Methods In this study, we screened out SNORNAs related to ovarian patient’s prognosis by analyzing the data of 379 cases of ovarian cancer patients in the TCGA database, and analyzed the difference of SNORNAs expression between OVCAR-3 (OV) sphere-forming (OS) cells and OV cells. After overexpression or knockdown SNORD89, the expression of Nanog, CD44, and CD133 was measured by qRT-PCR or flow cytometry analysis in OV, CAOV-3 (CA) and OS cells, respectively. CCK-8 assays, plate clone formation assay and soft agar colony formation assay were carried out to evaluate the changes of cell proliferation and self-renewal ability. Scratch migration assay and trans-well invasion analysis were used for assessing the changes of migration and invasion ability. Results High expression of SNORD89 indicates the poor prognosis of ovarian cancer patients and was associated with patients’ age, therapy outcome. SNORD89 highly expressed in ovarian cancer stem cells. The overexpression of SNORD89 resulted in the increased stemness markers, S phase cell cycle, cell proliferation, invasion and migration ability in OV and CA cells. Conversely, these phenomena were reversed after SNORD89 silencing in OS cells. Further, we found that SNORD89 could upregulate c-Myc and Notch1 expression in mRNA and protein levels. SNORD89 deteriorates the prognosis of ovarian cancer patients by regulating Notch1-c-Myc pathway to promote cell stemness and acts as an oncogene in ovarian tumorigenesis. Consequently, SNORD89 can be a novel prognostic biomarker and therapeutic target for ovarian cancer.

Abstract Background Triple negative breast cancer (TNBC) is a specific subtype of breast cancer with a poor prognosis due to its aggressive biological behaviour and lack of therapeutic targets. We aimed to explore some novel genes and pathways related to TNBC prognosis through bioinformatics methods as well as potential initiation and progression mechanisms. Methods Breast cancer mRNA data were obtained from The Cancer Genome Atlas database (TCGA). Differential expression analysis of cancer and adjacent cancer, as well as, triple negative breast cancer and non-triple negative breast cancer were performed using R software. The key genes related to the pathogenesis were identified by functional and pathway enrichment analysis and protein–protein interaction network analysis. Based on univariate and multivariate Cox proportional hazards model analyses, a gene signature was established to predict overall survival. Receiver operating characteristic curve was used to evaluate the prognostic performance of our model. Results Based on mRNA expression profiling of breast cancer patients from the TCGA database, 755 differentially expressed overlapping mRNAs were detected between TNBC/non-TNBC samples and normal tissue. We found eight hub genes associated with the cell cycle pathway highly expressed in TNBC. Additionally, a novel six-gene (TMEM252, PRB2, SMCO1, IVL, SMR3B and COL9A3) signature from the 755 differentially expressed mRNAs was constructed and significantly associated with prognosis as an independent prognostic signature. TNBC patients with high-risk scores based on the expression of the 6-mRNAs had significantly shorter survival times compared to patients with low-risk scores (P

Ovarian cancer stem cells (OCSCs) are sources of tumor chemoresistance and recurrence. A hypoxic microenvironment contributes to the chemoresistance of cancer stem cells (CSCs), but the underlying mechanism is not fully understood yet. Here, we show that increased HIF‐2α expression is associated with enhanced stemness of OCSCs and poor outcomes in ovarian cancer patients. OVCAR‐3 and CAOV‐3 sphere‐forming (OVCAR‐3 S and CAOV‐3 S) cells with OCSC‐like properties showed strong resistance to adriamycin (ADR). Hypoxia (1% O2) induced high expression of both HIF‐1α and especially HIF‐2α, and increased the resistance of OVCAR‐3 S and CAOV‐3 S cells to ADR. Notably, treatment with ADR further increased the expression of HIF‐2α, but not that of HIF‐1α. Knockdown of HIF‐2α expression substantially attenuated the resistance of OVCAR‐3 S and CAOV‐3 S cells to ADR, and the HIF‐2α overexpression had the opposite effect. Furthermore, in mouse models xenografted with OCSCs, HIF‐2α depletion significantly inhibited tumor growth and sensitized OCSCs to ADR in vivo. Mechanistically, HIF‐2α directly promotes transcription/expression of BCRP, a gene encoding a transporter protein responsible for pumping drugs (e.g., ADR) out of cells, which in turn increases drug resistance due to increased drug transportation. Collectively, our studies reveal a novel drug‐resistant mechanism in ovarian cancer by which hypoxia (and ADR treatment)‐induced HIF‐2α overexpression endows OCSCs with resistance to ADR by promoting BCRP expression and ADR transportation. Therefore, targeting the HIF‐2α/BCRP axis holds therapeutic potential for treating drug‐resistant ovarian cancer.

Abstract Background Maize is one of the primary crops of genetic manipulation, which provides an excellent means of promoting stress resistance and increasing yield. However, the differences in induction and regeneration capacity of embryonic callus (EC) among various genotypes result in genotypic dependence in genetic transformation. Results In this study, embryonic calli of two maize inbred lines with strong redifferentiation capacity and two lines with weak redifferentiation capability were separately subjected to transcriptome sequencing analysis during the early redifferentiation stages (stage I, 1–3 d; stage II, 4–6 d; stage III, 7–9 d) along with their corresponding controls. A total of ~ 654.72 million cDNA clean reads were yielded, and 62.64%~ 69.21% clean reads were mapped to the reference genome for each library. In comparison with the control, the numbers of differentially expressed genes (DEGs) for the four inbred lines identified in the three stages ranged from 1694 to 7193. By analyzing the common and specific DEGs of the four materials, we found that there were 321 upregulated genes and 386 downregulated genes identified in the high-regeneration lines (141 and DH40), whereas 611 upregulated genes and 500 downregulated genes were specifically expressed in the low-regeneration lines (ZYDH381–1 and DH3732). Analysis of the DEG expression patterns indicated a sharp change at stage I in both the high- and low-regeneration lines, which suggested that stage I constitutes a crucial period for EC regeneration. Notably, the specific common DEGs of 141 and DH40 were mainly associated with photosynthesis, porphyrin and chlorophyll metabolism, ribosomes, and plant hormone signal transduction. In contrast, the DEGs in ZYDH381–1 and DH3732 were mainly related to taurine and hypotaurine metabolism, nitrogen metabolism, fatty acid elongation, starch and sucrose metabolism, phenylpropanoid biosynthesis, and plant circadian rhythm. More importantly, WOX genes, which have an ancestral role in embryo development in seed plants and promote the regeneration of transformed calli, were specifically upregulated in the two high-regeneration lines. Conclusions Our research contributes to the elucidation of molecular regulation during early redifferentiation in the maize embryonic callus.

Well-developed maize reference genomes and genotyping technology along with fast decreasing detection costs have enabled the chance of shifting essentially derived varieties (EDV) identification to high-throughput SNP genotyping technology. However, attempts of using high-throughput technologies such as SNP array on EDV identification and the essential baseline parameters such as genetic homozygosity and/or stability in EDV practices have not been characterized. Here, we selected 28 accessions of 21 classical maize inbreds, which definitely form a pedigree network from initial founders to derivatives that had made huge contribution to corn production, to demonstrate these fundamental analyses. Our data showed that average residual heterozygosity (RH) rate of these 28 accessions across genome was about 1.03%. However, the RH rate of some accessions was higher than 3%. In addition, some inbreds were found to have an overall RH rate lower than 2% but over 8% level at certain chromosomes. Genetic drift (GD) between two accessions from different years or breeding programs varied from 0.13% to 13.16%. Accessions with low GD level showed cluster distribution pattern and compared with RH distributions indicated that RH was not the only resource of GD. Both RH and GD data suggested that genetic purity analysis is an essential procedure before determining EDV. Eleven derivative lines were characterized with regard to their genome compositions and were inferred as their breeding histories. The backcross, bi-parental recycling, and mutation breeding records could be identified. The data provide insights of underlining fundamental parameters for defining EDV threshold and the results demonstrate the EDV identification process.

Reductive soil disinfestation (RSD) is an effective practice to eliminate plant pathogens and improve the soil microbial community. However, little is known about how RSD treatment affects microbial interactions and functions. Previous study has shown that RSD-regulated microbiomes may degenerate after re-planting with former crops, while the effect of planting with different crops is still unclear. Here, the effects of both RSD treatment and succession planting with different crops on microbial community composition, interactions, and functions were investigated. Results showed that RSD treatment improves the soil microbial community, decreases the relative abundance of plant pathogens, and effectively enhances microbial interactions and functions. The microbial network associated with RSD treatment was more complex and connected. The functions of hydrocarbon (C, H), nitrogen (N), and sulfur (S) cycling were significantly increased in RSD-treated soil, while the functions of bacterial and fungal plant pathogens were decreased. Furthermore, the bacterial and fungal communities present in the RSD-treated soil, and soil succession planted with different crops, were found to be significantly different compared to untreated soil. In summary, we report that RSD treatment can improve soil quality by regulating the interactions of microbial communities and multifunctionality.

Cancer stem cells (CSCs) are responsible for the migration and recurrence of cancer progression. Small nucleolar RNAs (snoRNAs) play important roles in tumor development. However, how snoRNAs contribute to the regulation of the stemness of ovarian CSCs (OCSCs) remains unclear. In the present study, we found that SNORA72 was significantly upregulated in OVCAR-3 spheroids (OS) and CAOV-3 spheroids (CS) with the OCSC characteristics attained by serum-free culture in a suspension of OVCAR-3 (OV) and CAOV-3 (CA) cells. The overexpression of SNORA72 increased self-renewal abilities and migration abilities in OV and CA cells and upregulated the expressions of the stemness markers Nanog, Oct4, and CD133. In addition, the ectopic expression of SNORA72 can elevate the messenger RNA (mRNA) and protein expression levels of Notch1 and c-Myc in parental cells. The opposite results were observed in SNORA72-silenced OCSCs. Moreover, we found that Notch1 knockdown inversed the migration abilities and self-renewal abilities raised by overexpressing SNORA72. In summary, stemness transformation of ovarian cancer cells can be activated by SNORA72 through the Notch1/c-Myc pathway. This study introduces a novel therapeutic strategy for improving the treatment efficiency of ovarian cancer.

Drug resistance is a major obstacle in the treatment of tumors, which easily lead to relapse or poor prognosis. Cancer stem cells (CSCs) are regarded as one of the important targets that mediate tumor resistance. Increasing evidence shows that the tumor hypoxia microenvironment is closely related to the resistance of CSCs to chemotherapy and radiotherapy. In this review, we intend to review the articles that have described how the hypoxic microenvironment affects CSC stemness and mediates tumor resistance and provide new directions and methods in the clinical treatment of tumors. Here, we also discuss the feasibility and development prospects of using hypoxia-inducible factors (HIFs) that regulate the hypoxic microenvironment of tumors as targeted agents to treat tumors, as well as to reduce or even reverse the resistance of tumors to chemotherapy and radiotherapy.

The present study involves the use of Gnidia glauca (G.glauca) leaf extract in the fabrication of gold nanoparticles (Au NPs), dip-coated onto the surface of gloves and their antimicrobial properties were studied for use in nursing care. The prepared Au NPs were studied by various spectroscopic and microscopic techniques. Au NPs were Purple in color with a characteristic plasmon resonance peak on the surface at a wavelength of 532 nm. The images of transmission electron microscopy (TEM) showed the Au NPs with size ranging from 22–35 nm. The crystalline size and nature of Au NPs was demonstrated by x-ray diffraction (XRD) and Energy dispersive x-ray spectroscopy (EDS) analysis. Further, antimicrobial results showed that the AuNPs-coated gloves demonstrated good antibacterial effect, notably against multidrug-resistant bacteria. Hence, the highly effective AuNPs-coated gloves may be ideal candidates for preventing or minimising indirect microbial transmission and cross-contamination in nursing care.

Abstract Background Hypoxic tumor microenvironment and maintenance of stemness contribute to drug resistance in breast cancer. However, whether Hypoxia-inducible factor-2α (HIF-2α) in hypoxic tumor microenvironment mediates conversion to a stem cell phenotype and chemoresistance of breast tumors has not been elucidated. Methods The mRNA and protein expressions of HIF-1α, HIF-2α, Wnt and Notch pathway were determined using qRT-PCR and western blot. Cell viability and renew ability were assessed by MTT, Flow cytometric analysis and soft agar colony formation. Results In our study, acute hypoxia (6–12 h) briefly increased HIF-1α expression, while chronic hypoxia (48 h) continuously enhanced HIF-2α expression and induced the resistance of breast cancer cells to Paclitaxel (PTX). Furthermore, HIF-2α overexpression induced a stem cell phenotype, the resistance to PTX and enhanced protein expression of stem cell markers, c-Myc, OCT4 and Nanog. Most importantly, Wnt and Notch signaling, but not including Shh, pathways were both activated by HIF-2α overexpression. Dickkopf-1 (DKK-1), a Wnt pathway inhibitor, and L685,458, an inhibitor of the Notch pathway, reversed the resistance to PTX and stem phenotype conversion induced by HIF-2α overexpression. In addition, HIF-2α overexpression enhanced tumorigenicity and resistance of xenograft tumors to PTX, increased activation of the Wnt and Notch pathways and induced a stem cell phenotype in vivo. Conclusion In conclusion, HIF-2α promoted stem phenotype conversion and induced resistance to PTX by activating Wnt and Notch pathways.

Branched chain fatty acids (BCFA) are components of common food fats but little is known about their positional distribution on triacylglycerols (TAG). Human milk fat, mature milk of cows and goats, and several fish oil products available in China were evaluated for BCFA content in the sn-2 position. Compared to the sn-1/sn-3 (α) positions, BCFA are enriched in sn-2 (β) position of human milk (68% of BCFA), but randomly distributed among the sn-2 and sn-1/sn-3 positions of cow and goat milk. Fish oil TAG sn-2 BCFA were consistently depleted compared to the sn-1/sn-3 positions (5.2–11.9% of BCFA). Human intestinal epithelial cells were incubated with human milk sn-2 MAG, or fatty acids liberated from human milk sn-2 MAG. Cells incorporated more BCFA as sn-2 MAG than as FFA. The stereochemical positioning of BCFA in human milk fat may be unique compared to other BCFA sources, and mediate selective absorption of BCFA.

Zipper hydraulic fracturing in multiple wells with long horizontal sections is a primary solution means to increase the shale gas production rate and efficiency and to reduce the cost in Southern Sichuan Basin. Microseismic based fracturing monitoring can be used for real-time imaging of hydraulic fractures, so it has been widely used to evaluate the fracturing effect of shale gas reservoirs and to direct the optimization and adjustment of fracturing parameters. In China, however, the microseismic fracturing monitoring on fracturing of shale gas reservoirs cannot be used to evaluate the fracturing results until the fracturing operation in the pad wells is completed according to the parameters which are designed prior to the fracturing monitoring. Its evaluation results can merely provide a guidance for the fracturing parameters of the next pad wells instead of the wells in operation. As a result, the real-time effect of microseismic fracturing monitoring is out of work. In view of this, the fractures induced by zipper hydraulic fracturing in multiple shale gas wells with long horizontal sections in the southern Sichuan Basin, was real-time imaged by using the combined technology of radially arranged microseismic surface monitoring and microseismic well monitoring on the basis of real-time positioning method. The fracturing results were assessed and used in real time for the optimization of prepad fluid parameter, perforation and temporary plugging additive releasing time, so as to effectively avoid repeated fracturing and uneven fracturing effects and improve fracturing stimulation effects. This method is applied in two well groups. It is shown that the average shale gas production rate is increased by 2–5 times. Furthermore, microseismic fracturing real-time monitoring plays a vital role in real-time evaluation of fracturing effect and real-time optimization of fracturing parameters, so it can be used as the reference and should be popularized further.

Rapid emergence of antibiotic-resistant bacteria has brought huge threat to global healthcare systems. Alternative strategies are urgently needed to fight against these superbugs. In this study, we synthesized a series of cobalt phosphide nanoarchitectures and characterized their physicochemical properties as well as their antibacterial activities. We found that all nanomaterials showed an impressive photothermal property as indicated by their strong near-infrared (NIR) absorption capacity. In particular, 1D-CoP nanowires exhibited the optimal photothermal efficiency due to their higher aspect ratio. Under NIR light illumination, the temperature of the 1D-CoP nanowires suspension was increased by 45.4 °C within 20 min. In contrast, the temperatures of 2D-CoP nanoplates and 3D-CoP nanocubes were increased by 25.5 °C and 26.9 °C, respectively. The growth of planktonic bacteria can be effectively inhibited by 99% within 30 min under NIR irradiation with the presence of 1D-CoP nanowires in suspension. In comparison, up to 60% of the bacteria could be killed when treated with 2D-CoP nanoplates and 3D-CoP nanocubes. Moreover, all nanomaterials displayed high cytocompatibility. This work emphasizes that the anisotropy plays an important role in governing the photothermal properties of NIR-driven materials. Furthermore, the application of CoP nanowires is a promising strategy to treat antibiotic-resistant bacteria.

Developing a targeted oral delivery system to improve the efficacy of veterinary antibiotics and reduce their consumption and environmental risks is urgent. To achieve the duodenum-targeted release of tilmicosin, the enteric granule containing tilmicosin-loaded solid lipid nanoparticles (TIL-SLNs) was prepared based on its absorption site and transport characteristics. The in vitro release, release mechanisms, stability, palatability, and pharmacokinetics of the optimum enteric granules were studied. The intestine perfusion indicated that the main absorption site of tilmicosin was shifted to duodenum from ileum by TIL-SLNs, while, the absorption of TIL-SLNs in the duodenum was hindered by P-glycoprotein (P-gp). In contrast with TIL-SLNs, the TIL-SLNs could be more effectively delivered to the duodenum in intact form after enteric coating. Its effective permeability coefficient was enhanced when P-gp inhibitors were added. Compared to commercial premix, although the TIL-SLNs did not improve the oral absorption of tilmicosin, the time to reach peak concentration (Tmax) was obviously shortened. After the enteric coating of the granules containing SLNs and P-gp inhibitor of polysorbate-80, the oral absorption of tilmicosin was improved 2.72 fold, and the Tmax was shortened by 2 h. The combination of duodenum-targeted release and P-gp inhibitors was an effective method to improve the oral absorption of tilmicosin.

Periprosthetic joint infection (PJI) is one of the most pivotal issues accounting for clinical failure of titanium (Ti)-based implants. Therefore, it is of great significance to develop an antibacterial coating with high biocompatibility on the Ti implant surface. In this article, a novel zinc-doped strontium phosphate coating, denoted as Sr-Zn-PCC, was deposited on Ti substrates by phosphate chemical conversion (PCC) method. The texture characterizations indicated that continuous coatings containing SrHPO _4 , Sr _3 (PO _4 ) _2 and SrZn _2 (PO _4 ) _2 phases were formed on the Ti surface. It is found that the doping of Zn could tune the surface microstructure, roughness, wettability and corrosion resistance of the coatings. The Sr-Zn-PCC coating showed the same bacterial adhesion property at short time (2 h), but tended to hinder biofilm formation on coatings after incubation for up to 24 h. Up to 80% of Staphylococcus aureus ( S. aureus ) were killed within 24 h by contact with the Sr-Zn-PCC surface. Moreover, cytocompatibility assay indicated that MC-3T3 cells had good adhesion, spreading properties on the coatings, suggesting that it is a promising alloy with both excellent antibacterial ability and high biocompatibility for the applications on orthopedic implants.

Non-specific lipid transfer proteins (nsLTPs) had been previously isolated from cotton fiber but their functions were unclear so far. Bioinformatic analysis of the tetraploid cotton genome database identified 138 nsLTP genes, falling into the 11 groups as reported previously. Different from Arabidopsis, cacao, and other crops, cotton type XI genes were considerably expanded and diverged earlier on chromosome At11, Dt11, and Dt08. Corresponding to the type XI genes, the type XI proteins (GhLtpXIs) all contained an extra N-terminal cap resulting in larger molecular weight. The research revealed that the expression of type XI genes was dramatically increased in fibers of tetraploid cotton compared with the two diploid progenitors. High-level of GhLtpXIs expression was observed in long-fibered cotton cultivars during fiber elongation. Ectopic expression of GhLtpXIs in Arabidopsis significantly enhanced trichome length, suggesting that GhLtpXIs promoted fiber elongation. Overall, the findings of this research provide insights into phenotypic evolution of Gossypium species and regulatory mechanism of nsLTPs during fiber development.HIGHLIGHTA specific group, type XI nsLTPs, was identified with predominant expression in elongating fibers of Gossypium hirsutum based on evolutionary, transcriptional, and functional analyses.

The regenerative capacity of the embryonic callus, a complex quantitative trait, is one of the main limiting factors for maize transformation. This trait was decomposed into five traits, namely, green callus rate (GCR), callus differentiating rate (CDR), callus plantlet number (CPN), callus rooting rate (CRR), and callus browning rate (CBR). To dissect the genetic foundation of maize transformation, in this study multi-locus genome-wide association studies (GWAS) for the five traits were performed in a population of 144 inbred lines genotyped with 43,427 SNPs. Using the phenotypic values in three environments and best linear unbiased prediction (BLUP) values, as a result, a total of 127, 56, 160, and 130 significant quantitative trait nucleotides (QTNs) were identified by mrMLM, FASTmrEMMA, ISIS EM-BLASSO, and pLARmEB, respectively. Of these QTNs, 63 QTNs were commonly detected, including 15 across multiple environments and 58 across multiple methods. Allele distribution analysis showed that the proportion of superior alleles for 36 QTNs was

The Staphylococcus aureus (S. aureus) cow mastitis causes great losses to the cow industry. In order to improve the treatment effect of tilmicosin against cow mastitis, the combination of solid lipid nanoparticle (SLN) technology with in situ hydrogel technology was used to prepare the self-assembly tilmicosin nanogel (TIL-nanogel). The physicochemical characteristics, in vitro release, antibacterial activity and in vivo treatment efficacy of TIL-SLNs and TIL-nanogel were studied, respectively. The results showed the loading capacity (LC), encapsulation efficiency (EE), size, zeta potential and poly dispersion index (PDI) of TIL-nanogel were 23.33 ± 0.77%, 67.89 ± 3.01%, 431.57 ± 12.87 nm, 8.3 ± 0.06 mv and, 0.424 ± 0.032, respectively. The TIL-nanogel showed stronger sustained release in vitro than TIL-SLNs and commercial injection. The cure rate of half dosage and normal dosage of TIL-nanogel was 58.3% and 75.0%, which was higher than that of commercial injection (50.0%) at normal dosage. The results suggest that the treatment dosage of tilmicosin for cow mastitis could be reduced by TIL-nanogel. The novel TIL-nanogel will be beneficial by decreasing the usage of tilmicosin and the treatment costs of cow mastitis.