Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n = 82; dabigatran, n = 38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p = 0.043), 5.0% (p < 0.001), 8.7% (p < 0.001), and 2.5% (p = 0.043) from their baseline levels after rivaroxaban treatment. Conversely, no significant changes were detected in the dabigatran group. Furthermore, the plasma levels of platelet activation biomarkers (CD40L and sP-selectin) in both LA and LAA groups were significantly lower after anticoagulation with rivaroxaban, as compared to dabigatran treatment (CD40L: 554.62 ± 155.54 vs. 445.02 ± 130.04 for LA p = 0.0013, 578.51 ± 156.28 vs. 480.13 ± 164.37 for LAA p = 0.0052; sP-selectin: 2849.07 ± 846.69 vs. 2225.54 ± 799.96 for LA p = 0.0105, 2915.52 ± 1402.40 vs. 2203.41 ± 1061.67 for LAA p = 0.0022). Notably, the present study suggests that rivaroxaban may be more effective in the prevention of DRT for patients undergoing LAAC.

AMMI and GGE biplot analysis for genotype × environment interactions affecting the yield and quality characteristics of sugar beet.

Sugar beet, an important sugar crop, contributes significantly to the world's sugar production. However, genotype-environment interactions (GEI) often affect the quality characteristics of sugar beet. Hence, understanding the effects of GEI on sugar beet quality can aid in identifying high-quality genotypes that can adapt to different environments. Traditional variance analysis can only be used to examine the yield of a variety and not its specific adaptability to specific conditions. Therefore, more comprehensive analytical methods are required to evaluate the characteristics of the variety under specific environments. Additive main effects and multiplicative interaction (AMMI) and genotype main effect and genotype × environment interaction (GGE) biplot models can be employed to comprehensively evaluate different varieties and address the drawbacks associated with a single evaluation method. Moreover, these models also allow us to explore new varieties more objectively and comprehensively. In this study, the adaptability and stability of 16 sugar beet varieties, in terms of yield and sugar content, were evaluated using AMMI and GGE biplot analysis in seven pilot projects undertaken in 2022. In the assessment of a small but significant proportion of the total GEI variance for the two qualitative traits (yield and sugar content), 80.58% of the variance was explained by the cumulative contribution of IPC1, IPC2, and IPC3. AMMI and GGE biplots clearly highlighted that KWS4207 (G3) exhibited high and stable quality. They also demonstrated that the experiments in Jalaid Banner (Inner Mongolia) (E7) were the most representative. Together, the results suggested that the comprehensive application of AMMI and GGE biplot analysis allowed for a more comprehensive, scientific, and effective evaluation of sugar beet varieties across different regions. The findings offer a theoretical basis for sugar beet breeding and could guide the rational design of experiments for testing new varieties of sugar beet.

Atypical Placental Site Nodules within the Diverticulum of the Uterine Incision, a Rare Gestational Trophoblastic Disease Misdiagnosed as Intrauterine Residue: A Case Report.

Atypical placental site nodule (APSN) is a rare benign gestational trophoblastic disease (GTD). It is a tumor-like transformation that has a certain probability of developing into a placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT). Because of its atypical clinical presentation, it is difficult to diagnose and susceptible to misdiagnosis highly, thus delaying the patient's condition. We report a scarce case of atypical nodules at the placental site of the uterine incision diverticulum in a 35-year-old female, who was irregular vaginal bleeding after a cesarean Sect. 2 years. She was diagnosed by several local hospitals with intrauterine residue and was given a variety of Traditional Chinese Medicine (TCM) orally, but the symptoms of irregular vaginal bleeding have not been alleviated. After being transferred to several hospitals, she went to Hubei Maternal and Child Health Hospital for treatment. Under the condition of excluding the second pregnancy, she underwent hysteroscopic resection of lesions and laparoscopic repair of uterine incision diverticulum. The pathological diagnosis after the operation suggested that the focus at the uterine incision was an atypical placental nodule that invaded the myometrium of the uterus. The operation completely removed the focus, and then the patient was followed up every 3 months in the first postoperative year, then every 6 months up to 3 years, and then annually thereafter up to 5 years, and then maybe every 2 years thereafter. The patient's condition was quickly controlled, and the prognosis was good.

Effectiveness of potato late blight (Phytophthora infestans) forecast by meteorological estimation in mountainous terrain based on CARAH rules.

Potato late blight (PLB) caused by Phytophthora infestans (Mont.) de Bary, its incidence and development are highly dependent on meteorological conditions. To solve the problem of PLB in mountainous terrain under the condition of limited meteorological monitoring capability, the air temperature and humidity was estimated based on the basic meteorological datasets, the forecast effect of the onset period and infection cycle of PLB based on CARAH rules was evaluated. The average MAE, RMSE and CI of the estimated air temperature and observations were 1.17 °C, 1.52 °C and 0.95, respectively. The average MAE, RMSE and CI of the estimated relative humidity and observations were 8.0 %, 10.7 % and 0.53, respectively. The curve of the infection cycle of PLB at different locations were estimated from the basic meteorological datasets based on the CARAH rules, and the false alarm and missing ratios were 8.8 % and 4.6 % respectively. It may be delayed by 1 or 2 fungal generations compared to the observations, and then the protective fungicide should be adjusted to a systemic fungicide. The false alarm of the infection cycle of PLB may increase in dry air conditions, and the missing report may occur in humid condition.

Genome-Wide Identification of B-Box Gene Family and Expression Analysis Suggest Its Roles in Responses to Cercospora Leaf Spot in Sugar Beet (Beta Vulgaris L.).

The B-box (BBX) protein, which is a zinc-finger protein containing one or two B-box domains, plays a crucial role in the growth and development of plants. Plant B-box genes are generally involved in morphogenesis, the growth of floral organs, and various life activities in response to stress. In this study, the sugar beet B-box genes (hereafter referred to as BvBBXs) were identified by searching the homologous sequences of the Arabidopsis thaliana B-box gene family. The gene structure, protein physicochemical properties, and phylogenetic analysis of these genes were systematically analyzed. In this study, 17 B-box gene family members were identified from the sugar beet genome. A B-box domain can be found in all sugar beet BBX proteins. BvBBXs encode 135 to 517 amino acids with a theoretical isoelectric point of 4.12 to 6.70. Chromosome localization studies revealed that BvBBXs were dispersed across nine sugar beet chromosomes except chromosomes 5 and 7. The sugar beet BBX gene family was divided into five subfamilies using phylogenetic analysis. The gene architectures of subfamily members on the same evolutionary tree branch are quite similar. Light, hormonal, and stress-related cis-acting elements can be found in the promoter region of BvBBXs. The BvBBX gene family was differently expressed in sugar beet following Cercospora leaf spot infection, according to RT-qPCR data. It is shown that the BvBBX gene family may influence how the plant reacts to a pathogen infection.

Large-scale analysis of putative Euphorbiaceae R2R3-MYB transcription factors identifies a MYB involved in seed oil biosynthesis.

BACKGROUND: MYB transcription factors are widely distributed in the plant kingdom and play key roles in regulatory networks governing plant metabolism and biochemical and physiological processes. RESULTS: Here, we first determined the R2R3-MYB genes in five Euphorbiaceae genomes. The three Trp (W) residues from the first MYB domain (R2) were absolutely conserved, whereas the first W residue from the second MYB domain (R3) was preferentially mutated. The R2R3-MYBs were clustered into 48 functional subfamilies, of which 34 had both R2R3-MYBs of Euphorbiaceae species and AtMYBs, and four contained only Euphorbiaceae R2R3-MYBs. The whole-genome duplication (WGD) and/or segmental duplication (SD) played key roles in the expansion of the R2R3-MYB family. Unlike paralogous R2R3-MYB family members, orthologous R2R3-MYB members contained a higher selective pressure and were subject to a constrained evolutionary rate. VfMYB36 was specifically expressed in fruit, and its trend was consistent with the change in oil content, indicating that it might be involved in oil biosynthesis. Overexpression experiments showed that VfMYB36 could significantly provide linolenic acid (C18:3) content, which eventually led to a significant increase in oil content. CONCLUSION: Our study first provides insight into understanding the evolution and expression of R2R3-MYBs in Euphorbiaceae species, and also provides a target for the production of biomass diesel and a convenient way for breeding germplasm resources with high linolenic acid content in the future.

Iron oxide nanoparticles inhibit tumor growth by ferroptosis in diffuse large B-cell lymphoma.

Since the approval by the Food and Drug Administration (FDA), ferumoxytol and other iron oxide nanoparticles (IONs) have been widely used as iron supplements for patients with iron deficiency. Meanwhile, IONs have also been used as contrast agents in magnetic resonance imaging and as drug carriers. Importantly, IONs have demonstrated a significant inhibitory effect on the growth of tumors, including hematopoietic and lymphoid tumors, such as leukemia. In this study, we further demonstrated the effect of IONs on inhibiting the growth of diffuse large B-cell lymphoma (DLBCL) cells by enhancing ferroptosis-mediated cell death. IONs treatment caused an accumulation of intracellular ferrous iron and the onset of lipid peroxidation in DLBCL cells as well as the suppressed expression of anti-ferroptosis protein Glutathione Peroxidase 4 (GPX4), thereby leading to increased ferroptosis. Mechanistically, IONs increased cellular lipid peroxidation through the generation of ROS via the Fenton reaction and regulating the iron metabolism-related proteins, such as ferroportin (FPN) and transferrin receptor (TFR), which elevated the intracellular labile iron pool (LIP). Hence, our findings suggest the potential therapeutic effect of IONs on the treatment of patients with DLBCL.

Research Progress of Novel Drug Delivery Systems of Chinese Medicine Monomers based on Natural Silk Fibroin: A Mini-Review.

Traditional Chinese medicine (TCM) has a good curative effect, but its disadvantages include complex components, poor drug stability, potential drug interaction, etc. Therefore, it is particularly important to construct a novel drug delivery system that can load Chinese medicine monomers to solve this problem. Silk fibroin is a kind of natural polymer material with unique properties. It can be used as a carrier material to load Chinese medicine monomers to prepare novel drug delivery systems that significantly affect treating diseases without toxic and side effects. However, there is still a lack of a review on silk fibroin as a carrier material to load Chinese medicine monomers to explore and analyze the current research results and progress. Here, our article focuses on the in-depth excavation and analysis of the recent research on novel drug delivery systems prepared by silk fibroin and TCM monomers. Besides, the characteristics, existing problems, and prospects of silk fibroin are discussed and explained. It is hoped that this research can provide a reference and basis for the modernization of TCM, the design of novel drug delivery systems, the research and development of new drugs in the future, and contribute to the innovation of silk protein.

Burnout, negative emotions, and wellbeing among social workers in China after community lockdowns during the COVID-19 pandemic: Mediating roles of trait mindfulness.

Objective: This study aimed to investigate burnout situation of social workers (SWs) who experienced the COVID-19 pandemic-related community lockdown 1 year before, and to assess the protective value of trait mindfulness (TM) in states of burnout. Method: We surveyed the burnout, trait mindfulness, negative emotions (NEs) and wellbeing (WB) of 182 social workers provided services to Wuhan lockdowns community by COVID-19 one year before. Burnout were measured using the Maslach Burnout Inventory-Human Services Survey; TM using the Mindful Attention Awareness Scale; NEs using the Depression Anxiety and Stress Scale-21; and WB using the General Wellbeing Schedule. We also performed correlation regression analysis and mediation test for burnout, TM, NEs, and WB. Results: Among the 182 respondents, 75 (41.2%) still suffered from severe burnout. TM was negatively correlated with burnout (r = -0.623), negatively correlated with NEs (r = -0.560), and positively correlated with WB (r = 0.617). Burnout had a significantly positive correlation with NEs (r = 0.544) and a significantly negative correlation with WB (r = -0.666). Further, WB had significantly negative correlation with NEs (r = -0.758). After controlling for age, gender, marital status, educational level, and years of employment, burnout had a significantly positive predictive effect on NEs (ß = 0.509), whereas TM had a significantly negative predictive effect on NEs (ß = -0.334). TM played a partial mediating role in the effect of burnout on NEs, with a mediating effect and effect ratio of 0.088 and 39.7%, respectively. Burnout had a significantly negative predictive effect on WB (ß = -0.598), whereas TM had a significantly positive predictive effect on WB (ß = 0.299). TM played a partial mediating role in the effect of burnout on NEs, with a mediating effect and effect ratio of -0.164 and 30.3%, respectively. WB had a significantly negative predictive effect on NEs (ß = -0.711), and it played a partial mediating role in the effect of burnout on NEs, with a mediating effect and effect ratio of 0.185 and 83.3%, respectively. Conclusion: The current levels of burnout among local SWs remained high 1 year after the community lockdowns. TM played a mediating role in the relationship between burnout, NEs, and WB. Concomitantly, WB played a mediating role in the relationship between burnout and NEs. Therefore, in the context of burnout, TM is a protective factor for reducing emotional stress and risks of developing psychiatric disorders through the enhancement of WB.

Safety and efficacy of wrist-ankle acupuncture in treating catheter-related bladder discomfort after transurethral resection of the prostate: a double-blind randomized clinical trial.

Background: Benign prostatic hyperplasia (BPH) is an age-related condition and its prevalence has increased as China's population ages. Transurethral resection of the prostate (TURP) remains the gold standard for treating moderate to severe BPH. Routine placement of a urinary catheter after TURP is often associated with catheter-related bladder discomfort (CRBD). The development of CRBD is related to an increased synthesis of prostaglandin (PG), and wrist-ankle acupuncture (WAA) can inhibit the expression of PG at the site of inflammation, thus alleviating CRBD symptoms. Here we evaluated the efficacy of WAA in alleviating CRBD in patients undergoing TURP. Methods: A total of 46 patients who underwent elective TURP in Hebei Provincial Hospital of Traditional Chinese Medicine from June 2022 to July 2022 were randomly divided into two groups according to the complete randomization method. The WAA group (n=23) and the control group (n=23). The WAA group received WAA, and the needles were retained for 24 h. The control group was treated with sham needles that did not penetrate the skin, and the needles were also retained for 24 h. At T1 (0 h after entering the ward), T2 (0.5 h after entering the ward), T3 (6 h after entering the ward), and T4 (24 h after entering the ward), CRBD severity score, visual analogue scale (VAS) and vital signs monitor were used for assessment. Accidents were recorded in the case report form. Graded data using Wlicoxon signed rank sum test, repeated measures using repeated measures analysis of variance. Results: A total of 46 patients participated in this study, and 44 patients completed the experiment. At T2, T3, and T4, the severity of CRBD in the WAA group was significantly lower than that in the control group (all P<0.05), and the VAS pain score was significantly lower in the WAA group than in the control group (all P<0.05). In contrast, the vital signs, including mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation, showed no statistical significance (all P>0.05). No accident occurred in both groups. Conclusions: WAA can effectively relieve CRBD symptoms after TURP. WAA deserves further research and assessment for clinical practice. Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200061525..

[Relationship between Yingyangbao consumption and anemia status among infants and young children in impoverish areas of Henan Province:a cross-sectional study based on latent class analysis].

OBJECTIVE: To explore latent classes of Yingyangbao(YYB) consumption among infants and young children in impoverished areas of Henan Province, and to analyze the relationship between these classes and anemia status. METHODS: We recruited 4433 children aged 6 to 24 months by multi-stage random sampling in 14 poverty-stricken counties of Henan Province between June and September 2018. We conducted hemoglobin concentration measurement among children and questionnaire survey among their caregivers. Then we used latent class analysis to classify the characteristics of YYB consumption among the children and two-level Logistic regression was used to explore relationship between YYB consumption and anemia status. RESULTS: The prevalence of anemia was 15.1% in poor areas of Henan Province in 2018. There were two latent classes of YYB consumption among children: the one was "effective consumption", latent class probability was 0.889; the other called "ineffective consumption", latent class probability was 0.111. Compared with effective consumption, children who never have consumed YYB(odds ratio(OR)=1.365, P<0.001) or were in "ineffective consumption" class(OR=1.265, P=0.034) were both positive related to anemia. CONCLUSION: Prevalence of anemia among children in impoverished areas has been significantly reduced since the launch of Program of Children's Nutrition Improvement in Impoverished Areas. Effective consumption is a key to ensuring YYB's anemia intervention effect.

Combination effect of azithromycin with TCM preparation Xiyanping injection against Klebsiella pneumoniae infection in rats.

BACKGROUND: Klebsiella pneumoniae is known as one of the most principal opportunistic human pathogens. Although antibiotics such as the first-line agent azithromycin (AZM) usually are efficient for the treatment of K. pneumonia-related infections, growing threat from antibiotic resistance has become a major challenge. Various preparations based on traditional Chinese medicine (TCM) clinical experience have been developed to help combat such a global public health threat, including Xiyanping injection (XYP) that is made from the natural product andrographolide with potent heat-clearing and toxin-resolving functions. PURPOSE: The present study aimed to demonstrate the therapeutic potential, as well as the action of mechanism of AZM in combination with XYP against K. pneumonia infection in rats. METHODS: Pneumonia model of K. pneumoniae infection in rats was established and subjected to various treatments. The lung histopathological lesions were evaluated. ELISA and Griess techniques were used to determine the level of crucial cytokines. The protein expressions of MAPKs and NF-κB pathways were analyzed by Western blotting. RESULTS: The combination in vivo could significantly inhibit the proliferation of K. pneumoniae in lung, improve the pathological changes of lung and reduce inflammatory factors in lung homogenate and bronchoalveolar lavage fluid, mainly by inactivating MAPKs and NF-κB signaling pathways. Combination therapy caused one-fold increase in apparent distribution volume of AZM in rats after multiple dosing, along with a significant increase of AZM level in lungs but obvious decrease in livers. CONCLUSION: The combination therapy of AZM and XYP showed increased antibacterial and anti-inflammatory properties, indicating that it might be used to treat K. pneumoniae infection.

Combination Therapy with TCM Preparation Kumu Injection and Azithromycin against Bacterial Infection and Inflammation: In Vitro and In Vivo.

Background: Azithromycin (AZM) is one of the most common broad-spectrum antibiotics. However, drug resistance is increasing and combination therapy has attracted great attention. AZM is usually combined with traditional Chinese medicine (TCM) preparations with heat-clearing and detoxifying effects, including Kumu injection (KM) made from Picrasma quassioides (D. Don) Benn. Purpose: The present study aimed to investigate synergistic antimicrobial and anti-inflammatory activities of KM plus AZM with the aim of understanding the mechanism of clinical efficacy of combination regimens. Methods: Seven common bacterial clinical isolates and LPS-induced RAW 264.7 cells were used for assay of in vitro potency. The minimum inhibitory concentration (MIC) was determined for each drug, followed by synergy testing through the checkerboard method and fractional inhibitory concentration index (FICI) for quantifying combined antibacterial effects. The rat model of Klebsiella pneumoniae-induced pneumonia was developed and subjected to various drug treatments, namely, AZM, KM, or AZM plus KM, intravenously administered at 75 mg/kg once a day for one week. The combination effects then were evaluated according to pharmacodynamics and pharmacokinetic assessments. Results: KM-AZM combination synergistically inhibits in vitro growth of all the test standard strains except Pseudomonas aeruginosa and also the drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Shigella dysenteriae, Klebsiella pneumoniae, and Escherichia coli. Despite an additive effect against NO, KM plus AZM at an equal dose could synergistically suppress overrelease of the inflammatory cytokines TNF-α and IL-6 by LPS-induced RAW 264.7 cells. The combination significantly inhibited the proliferation of K. pneumoniae in the rat lungs, mainly by inactivating MAPKs and NF-κB signaling pathways. KM-AZM combination caused a onefold increase in apparent distribution volume of AZM, along with a significant decrease of AZM level in the livers and heart for pharmacokinetics. Conclusion: KM-AZM combination displayed synergistic antibacterial and anti-inflammatory effects beneficial to the therapeutic potential against bacterial infection.

AHLs' life in plants: Especially their potential roles in responding to Fusarium wilt and repressing the seed oil accumulation.

Members of the AT-hook motif nuclear localized (AHL) family contain diverse but poorly understood biological functions. We identified 371 AHLs in 20 land plants, varying from the early diverging lycophyte Selagineila moellendorfi to a variety of higher plants. The AHLs were divided into two clades (Clade-A and Clade-B) with three different types (Type-I, Type-II, and Type-III AHLs). The divergence between Clade-A and Clade-B likely occurred before the separation of S. moellendorfi from the vascular plant lineages. Members of the AHLs family expanded with the specific whole-genome duplication (WGD)/segmental duplication in some genomes, such as Hevea brasiliensis. The ortholog (Vf00G1914/Amo018442) exhibited opposite expression patterns between two Vernicia species (V. fordii and V. montana), indicating that it was implicated in resistance to Fusarium wilt disease. The expression of Vf09G2138 exhibited a negative correlation with lipid biosynthesis in V. fordii seeds during different stages of development, suggesting that this gene might repress the seed oil accumulation. The core AT-hook motif and PPC domain were responsible for guiding the localization of AHL in the nucleus. This study helps us to understand the evolution of AHLs in multiple plants, further highlight their functions during V. fordii seed development and response to Fusarium wilt disease.

Copper-Catalyzed Dynamic Kinetic C-P Cross-Coupling/Cyclization for the Concise Asymmetric Synthesis of Six-, Seven- and Eight-Membered P-Stereogenic Phosphorus Heterocycles.

A copper-catalyzed asymmetric aryl C-P cross-coupling/cyclization reaction was successfully developed via dynamic kinetic asymmetric transformation (DYKAT) under mild conditions. This study provides a general and simple method for the catalytic enantioselective synthesis of stable six-, seven- and eight-membered P-stereogenic phosphorus heterocycles with excellent enantioselectivities and moderate to high yields. One-pot gram-scale asymmetric synthesis of the P-stereogenic P-heterocycle from commercially available materials was also successfully accomplished with excellent enantioselectivity and high yield.

Utilizing Bioinformatics Technology to Explore the Potential Mechanism of Danggui Buxue Decoction against NSCLC.

While lung cancer poses a serious threat to human health, non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. Danggui Buxue Decoction (DBD) is a classical traditional antitumor medicine commonly used in China. However, the potential mechanism of DBD against NSCLC has not yet been expounded. Therefore, this study clarified the potential molecular mechanism and key targets of DBD in NSCLC treatment through several technological advances, such as network pharmacology, molecular docking, and bioinformatics. Firstly, the relative active ingredients and key DBD targets were analyzed, and subsequently, a drug-ingredient-target-disease network diagram was constructed for NSCLC treatment with DBD, resulting in the identification of five main active ingredients and ten core targets according to the enrichment degree. The enrichment analysis revealed that DBD can achieve the purpose of treating NSCLC through the AGE-RAGE signaling pathway in diabetic complications. Secondly, the molecular docking approach predicted that quercetin and hederagenin have the best working mechanisms with PDE3A and PTGS1, while the survival analysis results depicted that high PDE3A gene expression has a relatively poor prognosis for NSCLC patients (p < 0.05). Additionally, PDE3A is mainly distributed in the LU65 cell line that originated from Asian population. In summary, our study results showed that DBD can treat NSCLC through the synergistic correlation between multiple ingredients, multiple targets, and multiple pathways, thus effectively improving NSCLC prognosis. This study not only reflected the medicinal value of DBD but also provided a solid structural basis for future new drug developments and targeted therapies.

Identification of miRNAs and their target genes in genic male sterility lines in Brassica napus by small RNA sequencing.

BACKGROUND: Brassica napus is the third leading source of edible oil in the world. Genic male sterility (GMS) lines provide crucial material for harnessing heterosis for rapeseed. GMS lines have been used successfully for rapeseed hybrid production in China. MicroRNAs (miRNAs) play crucial regulatory roles in various plant growth, development, and stress response processes. However, reports on miRNAs that regulate the pollen development of GMS lines in B. napus are few. RESULTS: In this study, 12 small RNA and transcriptome libraries were constructed and sequenced for the flower buds from the fertile and sterile lines of two recessive GMS (RGMS) lines, namely, "6251AB" and "6284AB". At the same time, 12 small RNA and transcriptome libraries were also constructed and sequenced for the flower buds from the fertile and sterile lines of two dominant GMS (DGMS) lines, namely, "4001AB" and "4006AB". Based on the results, 46 known miRNAs, 27 novel miRNAs on the other arm of known pre-miRNAs, and 44 new conserved miRNAs were identified. Thirty-five pairs of novel miRNA-3p/miRNA-5p were found. Among all the identified miRNAs, fifteen differentially expressed miRNAs with over 1.5-fold change between flower buds of sterile and fertile lines were identified, including six differentially expressed miRNAs between "4001A" and "4001B", two differentially expressed miRNAs between "4006A" and "4006B", four differentially expressed miRNAs between "6251A" and "6251B", and ten differentially expressed miRNAs between "6284A" and "6284B". The correlation analysis of small RNA and transcriptome sequencing was conducted. And 257 candidate target genes were predicted for the 15 differentially expressed miRNAs. The results of 5' modified RACE indicated that BnaA09g48720D, BnaA09g11120D, and BnaCnng51960D were cleaved by bna-miR398a-3p, bna-miR158-3p and bna-miR159a, respectively. Among the differentially expressed miRNAs, miR159 was chosen to analyze its function. Overexpression of bna-miR159 in Arabidopsis resulted in decreased seed setting rate, and shortened siliques, illustrating that miR159 may regulate the fertility and silique development in rapeseed. CONCLUSIONS: Our findings provide an overview of miRNAs that are potentially involved in GMS and pollen development. New information on miRNAs and their related target genes are provided to exploit the GMS mechanism and reveal the miRNA networks in B. napus.

Assessment of Mortality-Related Risk Factors and Effective Antimicrobial Regimens for Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Enterobacterales.

Bloodstream infections (BSIs) attributable to carbapenem-resistant Enterobacterales (CRE-BSIs) are dangerous and a major cause of mortality in clinical settings. This study was therefore designed to define risk factors linked to 30-day mortality in CRE-BSI patients and to examine the relative efficacies of different antimicrobial treatment regimens in affected individuals. Data pertaining to 187 CRE-BSI cases from four teaching hospitals in China collected between January 2018 and December 2020 were retrospectively analyzed. For the 187 patients analyzed in this study, the 30-day mortality of CRE-BSI was 41.7% (78/187). Multivariate logistic regression analyses revealed that Pitt bacteremia score, immunocompromised status, meropenem MIC of ≥8 mg/liter,absence of source control of infection, and appropriate empirical therapy were independent predictors of CRE-BSI patient 30-day mortality. After controlling for potential confounding factors relative to ceftazidime-avibactam (CAZ-AVI) treatment, combination therapies including CAZ-AVI (odds ratio [OR], 1.287; 95% confidence interval [CI], 0.124 to 13.403; P = 0.833) were not related to any significant change in patient mortality risk, whereas the 30-day mortality risk was higher for patients administered other antimicrobial regimens (OR, 12.407; 95% CI, 1.684 to 31.430; P = 0.011). When patients were treated with antimicrobial regimens not containing CAZ-AVI, combination therapy (OR, 0.239; 95% CI, 0.077 to 0.741; P = 0.013) was related to a decreased 30-day mortality risk relative to monotherapy treatment. The mortality-related risk factors and relative antimicrobial regimen efficacy data demonstrated in this study may guide the management of CRE-BSI patients.

Artemisia argyi Essential Oil Inhibits Hepatocellular Carcinoma Metastasis via Suppression of DEPDC1 Dependent Wnt/ß-Catenin Signaling Pathway.

The tumor metastasis is the major hurdle for the treatment of advanced hepatocellular carcinoma (HCC), due in part to the lack of effective systemic treatments. DEPDC1, a novel oncoantigen upregulated in HCC, is thought to be a molecular-target for novel therapeutic drugs. Artemisia argyi is a traditional Chinese medicine with anti-inflammatory and anti-tumor activities. This study investigated the potential therapeutic benefits of Artemisia argyi essential oil (AAEO) in suppressing metastasis of HCC by targeting DEPDC1. Assessment of AAEO cytotoxicity was performed by MTT assay. Anti-metastatic effects of AAEO were investigated in vitro using wound healing and transwell assays. The HepG2 cells were transduced with lentiviral vector containing luciferase (Luc). A metastasis model of nude mice was established by tail vein injection of HepG2-Luc cells. The nude mice were treated with AAEO (57.5, 115, and 230 mg/kg) or sorafenib (40 mg/kg). Metastasis of HCC cells was monitored via in vivo bioluminescence imaging. After treatment for 21 days, tissues were collected for histological examination and immunohistochemistry analysis. Gene and protein levels were determined by real-time quantitative PCR and western blotting. The results revealed that AAEO significantly inhibits the migration and invasion in vitro in a concentration-dependent manner. In vivo assays further confirmed that AAEO markedly inhibits HCC metastasis into lung, brain, and femur tissues and exhibits low toxicity. Our results suggested that AAEO significantly downregulates the mRNA and protein expression of DEPDC1. Also, AAEO attenuated Wnt/ß-catenin signaling through reduction of Wnt1 and ß-catenin production. Moreover, AAEO prevented epithelial-mesenchymal transition (EMT) by downregulation of vimentin and upregulation of E-cadherin. Furthermore, we found that DEPDC1 promoted HCC migration and invasion via Wnt/ß-catenin signaling pathway and EMT. These results demonstrate that AAEO effectively inhibits HCC metastasis via attenuating Wnt/ß-catenin signaling and inhibiting EMT by suppressing DEPDC1 expression. Thus, AAEO likely acts as a novel inhibitor of the DEPDC1 dependent Wnt/ß-catenin signaling pathway.

Roles of plant-derived bioactive compounds and related microRNAs in cancer therapy.

Plant-derived bioactive compounds, often called phytochemicals, are active substances extracted from different plants. These bioactive compounds can release therapeutic potential abilities via reducing antitumor drugs side effects or directly killing cancer cells, and others also can adjust cancer initiation and progression via regulating microRNAs (miRNAs) expression, and miRNA can regulate protein-coding expression by restraining translation or degrading target mRNA. A mass of research showed that plant-derived bioactive compounds including tanshinones, astragaloside IV, berberine, ginsenosides and matrine can inhibit tumor growth and metastasis by rescuing aberrant miRNAs expression, which has influence on tumor progression, microenvironment and drug resistance in multifarious cancers. This review aims to provide a novel understanding of plant-derived bioactive compounds targeting miRNAs and shed light on their future clinical applications.