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Background: Huangqi Guizhi Wuwu decoction (HQGZWW) exhibits good effects when administered to treat multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Understanding the precise mechanism of this decoction is thus important. Based on the findings of our previous study, the aim of the present study was to understand the role of antigen-specific CD8+ T-cells on the pathogenesis of MS/EAE when HQGZWW is administered as treatment. Methods: Myelin oligodendrocyte glycoprotein (MOG) 35-55-induced mice were administered distilled water, prednisone, and high dose or low dose HQGZWW. After purified CD4+ and CD8+ T-cells were stimulated with the MOG35-55 peptide, proliferation and cytokine secretion assays were performed. To establish the adoptive transfer EAE model, naïve mice were injected with MOG35-55 -CD8+ or CD4+ T-cells. Results: Significant improvements in EAE score and pathology were observed in the high dose HQGZWW and prednisone groups. Compared to the low dose HQGZWW and distilled water groups, lower antigen-specific responses, lower levels of interferon-gamma, and higher levels of interleukin (IL)-4 and IL-10 from CD8+ and CD4+ T cells were observed in the high dose HQGZWW and prednisone groups. Finally, the EAE score was observed to be similar between the high dose HQGZWW group and prednisone group; however, this finding was not observed in the low dose HQGZWW group. Conclusion: Our findings suggest that high dose HQGZWW has similar effects on cell proliferation, cytokine secretion, and EAE score to prednisone, while low dose HQGZWW does not have such effect. The protective role of HQGZWW against EAE might thus depend on the Th2 cytokine secretion profile induced by either MOG35-55 specific CD8+ or CD4+ T-cells.

Background: Pasteurella multocida is an important and old zoonotic pathogen worldwide which has an impressive host spectrum including numerous domestic and wild animals as well as birds, causing specific diseases or outbreak with great economic impact. It has never been reported that P. multocida can cause an epidemic in wild rodents. In June 5–17, 2016, more than 1000 rodent deaths of an unknown cause quickly spread in the PuEr City, Yunnan province, southwestern China. Methods: The rodents in affected areas and outside of the epidemic areas were collected and screened for possible known pathogens including Yersinia pestis, rabies virus and hantavirus as well as other bacteria. The possible bacterial pathogens were isolated both by culture medium and by mouse inoculation in parallel. The isolates were identified by the Vitek GNI card and PCR assays for 16S rRNA genes. The pathogen strains were selected for whole genome sequencing analysis. Results: A total of 123 rodents were collected from 25 sample sites at affected area, among of which, all 119 dead rodents were negative for the pathogen under consideration except P. multocida, and all four live rodents were negative for P. multocida. In addition, 480 rodents collected from other 23 counties outside of the epidemic area in Yunnan were negative for with P. multocida. A total of 14 strains of P. multocida (six directly isolated from the field rodents and eight from the experimental mice that were injected with the organ substrates from the dead rodents) belonged to serogroup A and serogroup F represented by 9 N and 20 N were identified in these epidemic areas. Whole genome sequencing revealed that the serogroup F strain shared 99% similarity to P. multocida Pm70 from chicken, but contained a 50 k bp insertion sequence. The serogroup A strain shared 95% similarity to P. multocida FDAARGOS_385 from a human patient, but contained four large structural differences. Histological abnormalities were identified in the livers, lungs, hearts and brains of the inoculated mice. Conclusions: The simultaneous occurrence of both serotypes of P. multocida may have caused this sudden onset of mortality across the local rodent population in Yunnan Province, China. Further attention should be paid to this old bacterium in the world.

Colorectal carcinoma (CRC) is a kind of malignant tumor closely related to ulcerative colitis. Xanthone derivatives are one of the most promising therapeutic drugs which have been used in phase I/II clinical trials for cancer therapy. Our previous study indicated that the aerial parts of Gentianella acuta Michx. Hulten (GA) was rich in xanthones and showed a good therapeutic effect on ulcerative colitis in mice, suggesting that GA xanthones might have some therapeutic or ameliorative effects on CRC. However, no relevant study has been reported. This study aims to find the effective substances of GA inhibiting CRC and clarify their mechanism. Solvent extraction, column chromatographic separation, and LC-MS analysis were used to characterize the 70% EtOH extract of GA and track xanthones abundant fraction XF. MTT assay was carried out to clarify the activity of GA fractions; the result showed XF to be the main active fraction. LC-MS analysis was executed to characterize XF, 38 xanthones were identified. Network pharmacology prediction, in vitro activity screening, and molecular docking assay were combined to predict the potential mechanism; the PI3K/Akt/mTOR signaling pathway was found to be most important. Western blot assay on the main active xanthones 1,3,5-trihydroxyxanthone (16), 1,3,5,8-tetrahydroxyxanthone (17), 1,5,8-trihydroxy-3-methoxyxanthone (18), and 1,7-dihydroxy-3,8-dimethoxyxanthone (19) was used to verify the above prediction; these xanthones were found to inhibit the PI3K/Akt/mTOR signaling pathway, and 17 played a significant role among them through Western blot assay using PI3K/AKT/mTOR agonist IGF-1. In conclusion, this study demonstrated that GA xanthones were effective compounds of GA inhibiting CRC by regulating PI3K/Akt/mTOR signaling pathway transduction, at least. Importantly, 1,3,5,8-tetrahydroxyxanthone (17), the most abundant active xanthone in GA, might be a candidate drug for CRC.

Considering that the state transfer rules between nodes in existing rumor propagation models are mostly based on a single propagation mechanism, and most of the models have a single way of refuting rumors, in this paper, a new SEIOR rumor propagation model (ignorant (S), hesitators (E), spreaders (I), rumor debunkers (O), immunizers (R)) is proposed by introducing hesitators and rumor debunkers and combining different rumor-refuting ways of rumor debunkers. Firstly, the dynamics process of the propagation model is described by using the mean-field equations. Secondly, the equilibrium point and the basic regeneration number of the model are solved, and the existence and stability of the equilibrium point are discussed. Then, numerical simulations are used to analyze the effects of different factors on rumor propagation patterns. The results show that the rumor-spreading rate α2 has the greatest effect on rumor propagation. With the increase in α2, the degree of influence of the hesitator-converting rate α1 on the scale of rumor propagation first increases and then decreases. Different rumor-refuting ways have different inhibiting effects on the spread of rumors. Finally, based on the results of the theoretical proving and numerical analysis, some targeted measures to control the spread of rumors are proposed.

Virtual reality (VR), a rapidly evolving technology that simulates three-dimensional virtual environments for users, has been proven to activate brain functions. However, the continuous alteration pattern of the functional small-world network in response to comprehensive three-dimensional stimulation rather than realistic two-dimensional media stimuli requires further exploration. Here, we aimed to validate the effect of VR on the pathways and network parameters of a small-world organization and interpret its mechanism of action. Fourteen healthy volunteers were selected to complete missions in an immersive VR game. The changes in the functional network in six different frequency categories were analyzed using graph theory with electroencephalography data measured during the pre-, VR, and post-VR stages. The mutual information matrix revealed that interactions between the frontal and posterior areas and those within the frontal and occipital lobes were strengthened. Subsequently, the betweenness centrality (BC) analysis indicated more robust and extensive pathways among hubs. Furthermore, a specific lateralized channel (O1 or O2) increment in the BC was observed. Moreover, the network parameters improved simultaneously in local segregation, global segregation, and global integration. The overall topological improvements of small-world organizations were in high-frequency bands and exhibited some degree of sustainability.

Objective: To investigate the protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) against chronic alcoholic liver injury. C57BL/6J mice were fed with the Lieber–DeCarli alcohol diet to induce chronic alcoholic liver injury. DNLA (20 mg/kg/day) was gavaged along with the alcohol diet for 28 days. Liver injury was evaluated by serum enzymes. Triglyceride levels, histopathology, and transcriptome changes were examined by RNA-Seq and qPCR. DNLA decreased serum triglyceride levels in mice receiving alcohol. Hepatocyte degeneration and steatosis were ameliorated by DNLA, as evidenced by H&E and Oil-red O staining. DNLA brought the alcohol-induced aberrant gene expression pattern towards normal. Alcohol induced 787 differentially expressed genes (padj < 0.01). DNLA induced 280 differentially expressed genes to a much less extent. Ingenuity pathway analysis showed that DNLA ameliorated alcohol-induced oxidative stress and xenobiotic metabolism disruption. qPCR verified that DNLA alleviated over-activation of Cyp2a4, Cyp2b10, and Abcc4; attenuated oxidative stress (Hmox1, Gstm3, Nupr1), reduced the expression of Nrf2 genes (Nqo1, Gclc, Vldlr); and rescued some metabolic genes (Insig1, Xbp1, Socs3, Slc10a2). In conclusion, DNLA was effective against alcohol-induced fatty liver disease, and the protection may be attributed to alleviated oxidative stress and restored metabolism homeostasis, probably through modulating nuclear receptor CAR-, PXR-, and Nrf2-mediated gene expression pathways.

Fruit ripening is controlled by internal factors such as hormones and genetic regulators, as well as external environmental factors. However, the impact of redox regulation on fruit ripening remains elusive. Here, we explored the effects of L-cysteine hydrochloride (LCH), an antioxidant, on tomato fruit ripening and elucidated the underlying mechanism. The application of LCH effectively delayed tomato fruit ripening, leading to the suppression of carotenoid and lycopene biosynthesis and chlorophyll degradation, and a delayed respiration peak. Moreover, LCH-treated fruit exhibited reduced hydrogen peroxide (H2O2) accumulation and increased activities of superoxide dismutase (SOD), catalase (CAT), and monodehydroascorbate reductase (MDHAR), compared with control fruit. Furthermore, transcriptome analysis revealed that a substantial number of genes related to ethylene biosynthesis (ACS2, ACS4, ACO1, ACO3), carotenoid biosynthesis (PSY, PDS, ZDS, CRTISO), cell wall degradation (PG1/2, PL, TBG4, XTH4), and ripening-related regulators (RIN, NOR, AP2a, DML2) were downregulated by LCH, resulting in delayed ripening. These findings suggest that the application of LCH delays the ripening of harvested tomato fruit by modulating the redox balance and suppressing the expression of ripening-related genes. [ABSTRACT FROM AUTHOR]

The metallurgical quality control of magnesium (Mg) and Mg alloys in melting process is required to ensure a satisfied mechanical and corrosion performance, while the typical used steel crucible introduces impurities and interfacial interaction during melting process. Therefore, a systematic study about impurities diffusion and interfacial interaction between molten Mg and steel is necessary. In the present study, the interfacial reaction between molten AZ91D Mg alloy and mild steel during melting process was investigated with the melting temperatures of 700 °C, 750 °C and 800 °C. The results show that Al(Fe, Mn) intermetallic layer is the intermetallic primarily formed at the interfaces of AZ91D melt and mild steel. Meanwhile, Al8(Mn, Fe)5 is indexed between Al(Fe, Mn) and AZ91D. AlFe3C appears between the mild steel and Al(Fe, Mn) at 700 °C and 750 °C, but absent at 800 °C due to the increased solubility of carbon in Mg matrix. It is found that the growth of the intermetallic layer is controlled by diffusion mechanism, and Al and Mn are the dominant diffusing species in the whole interfacial reaction process. By measuring the thickness of different layers, the growth constant was calculated. It increases from 1.89(±0.03)×10-12 m² ·s-1 at 700 °C to 3.05(±0.05)×10-12 m² ·s-1 at 750 °C, and 5.18(±0.05)×10-12 m² ·s-1 at 800 °C. Meanwhile, the content of Fe is linearly increased in AZ91D with the increase of holding time at 700 °C and 750 °C, while it shows a significantly increment after holding for 8 h at 800 °C, indicating holding temperature is more crucial to determine the Fe content of AZ91D than holding time. [ABSTRACT FROM AUTHOR]

Isoflavones are predominantly found in legumes and play roles in plant defense and prevention of estrogen-related diseases. Genistein is an important isoflavone backbone with various biological activities. In this paper, we describe how a cell factory that can de novo synthesize genistein was constructed in Saccharomyces cerevisiae. Different combinations of isoflavone synthase, cytochrome P450 reductase, and 2-hydroxyisoflavone dehydratase were tested, followed by pathway multicopy integration, to stably de novo synthesize genistein. The catalytic activity of isoflavone synthase was enhanced by heme supply and an increased intracellular NADPH/NADP+ ratio. Redistribution of the malonyl-CoA flow and balance of metabolic fluxes were achieved by adjusting the fatty acid synthesis pathway, yielding 23.33 mg/L genistein. Finally, isoflavone glycosyltransferases were introduced into S. cerevisiae, and the optimized strain produced 15.80 mg/L of genistin or 10.03 mg/L of genistein-8-C-glucoside. This is the first de novo synthesis of genistein-8-C-glucoside in S. cerevisiae, which is advantageous for the green industrial production of isoflavone compounds. [ABSTRACT FROM AUTHOR]

(2S)-eriodictyol (ERD) is a flavonoid widely found in citrus fruits, vegetables, and important medicinal plants with neuroprotective, cardioprotective, antidiabetic, and anti-obesity effects. However, the microbial synthesis of ERD is limited by complex metabolic pathways and often results in a low production performance. Here, we engineered Saccharomyces cerevisiae by fine-tuning the metabolism of the ERD synthesis pathway. The results showed that the ERD titer was effectively increased, and the intermediate metabolites levels were reduced. First, we successfully reconstructed the de novo synthesis pathway of p-coumaric acid in S. cerevisiae and fine-tuned the metabolic pathway using promoter engineering and terminator engineering for the high-level production of (2S)-naringenin. Subsequently, the synthesis of ERD was achieved by introducing the ThF3′H gene from Tricyrtis hirta. Finally, by multiplying the copy number of the ThF3′H gene, the production of ERD was further increased, reaching 132.08 mg L−1. Our work emphasizes the importance of regulating the metabolic balance to produce natural products in microbial cell factories. [ABSTRACT FROM AUTHOR]

Anthocyanins are the main phenolic active components in blueberry, which have attracted much attention due to their excellent antioxidant, anti-inflammatory, anti-tumor and eye protection functions. However, anthocyanins in blueberry are easily affected by light, oxygen, pH value, metal ions and other factors, and their absorption and utilization rate are low in the human body, which limits their application. This review summarized the functional activities, extraction and purification methods, and stabilization technology of anthocyanins in blueberry, and hope to provide reference for the application of anthocyanins in food industry. [ABSTRACT FROM AUTHOR]

To explore the effects of calcium ion, pectin and NFC citrus juice addition on the sensory and nutritional quality of fruit juice-type canned yellow peach, the processing technology of juice-type canned yellow peach was opti¬mized by using Dangshan yellow peach NJ83 as raw material and the combination of yellow peach pulp and NFC citrus juice through evaluation indexes such as chromaticity, texture characteristics and sensory level. The results of visual anal-ysis and variance analysis showed that the adding amount of calcium ion had the greatest impact on the sensory quality of juice-type canned yellow peach, followed by NFC orange juice, and the last was pectin. The optimal process was as follows: The mass fraction of calcium ion was 0.4%, the mass fraction of pectin was 0.35%, the mass fraction of NFC fruit juice was 8%. In the final product, fruit juice was transparent, the pulp was golden yellow, the color was uniform, the block shape was complete without burrs, the taste was sweet and sour, the hardness was moderate. HPLC was further used to detect the flavonoids in canned foods under the optimal process and found that the content of hesperidin in juice-type canned yellow peach was 70.665 mg/kg, which was 22 times higher than 3.149 mg/kg in water-type. The content of narirutin (9.193 mg/kg) and didymin (6.807 mg/kg) were 161 times and 33 times higher in juice-type can than in water-type can, respectively. Therefore, juice-type canned yellow peach is a new canned product with both taste and nutrition. [ABSTRACT FROM AUTHOR]

Current yeast metabolic engineering in isoprenoids production mainly focuses on rewiring of cytosolic metabolic pathway. However, the precursors, cofactors and the enzymes are distributed in various sub-cellular compartments, which may hamper isoprenoid biosynthesis. On the other side, pathway compartmentalization provides several advantages for improving metabolic flux toward target products. We here summarize the recent advances on harnessing sub-organelle for isoprenoids biosynthesis in yeast, and analyze the knowledge about the localization of enzymes, cofactors and metabolites for guiding the rewiring of the sub-organelle metabolism. This review may provide some insights for constructing efficient yeast cell factories for production of isoprenoids and even other natural products.

Abstract Background Transurethral resection of the prostate (TURP) is the first choice for the treatment of benign prostatic hyperplasia. However, Transurethral split of prostate (TUSP) also seems to have clear clinical efficacy and clinical promotion value. To better clarify the potential and limitations of this treatment of prostate hyperplasia. This study objectively evaluated the clinical efficacy and safety of TUSP. Methods The Pubmed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Database for Chinese Technical Periodicals (VIP), Wanfang (Wanfang data), and SinoMed databases were searched for relevant studies. We then used Revman Manager 5.3 to perform a meta-analysis of all randomized controlled trials that evaluated the efficacy and safety of TUSP versus the classic surgical procedures commonly used in the clinic. Results A total of 7 studies involving 592 patients were included. The combined data showed that TUSP can shorten the operation time [MD: -33.68; 95% CI: − 38.45 to − 28.91; P

Autophagy is associated with the cytoprotection of physiological processes against inflammation and oxidative stress. Salvia miltiorrhiza possesses cardiovascular protective actions and has powerful anti-oxidative and anti-inflammatory effects; however, whether and how Salvia miltiorrhiza-derived microRNAs (miRNAs) protect vascular smooth muscle cells (VSMCs) by inducing autophagy across species are unknown. We first screened and identified Sal-miR-58 from Salvia miltiorrhiza as a natural autophagy inducer. Synthetic Sal-miR-58 suppresses chronic angiotensin II (Ang II) infusion-induced abdominal aortic aneurysm (AAA) formation in mice, as well as induces autophagy in VSMCs and attenuates the inflammatory response elicited by Ang II in vivo and in vitro. Mechanistically, Sal-miR-58 downregulates Krüppel-like factor 3 (KLF3) expression through direct binding to the 3′ UTR of KLF3, which in turn relieves KLF3 repression of E3 ubiquitin ligase neural precursor cell-expressed developmentally downregulated 4-like (NEDD4L) expression, whereas NEDD4L upregulation increases the ubiquitination and degradation of the platelet isoform of phosphofructokinase (PFKP), subsequently leading to a decrease in the activation of Akt/mammalian target of rapamycin (mTOR) signaling and facilitating VSMC autophagy induced by Sal-miR-58 in the context of chronic Ang II stimulation and aneurysm formation. Our results provide the first evidence that plant-derived Sal-miR-58 induces autophagy and attenuates inflammation in VSMCs through cross-species modulation of the KLF3/NEDD4L/PFKP regulatory pathway.

Abstract Background miRNAs regulate a multitude of cellular processes and their aberrant regulation is linked to human cancer. However, the role of miR-425-5p in lung cancer (LCa) is still largely unclear. Here, we explored the role of miR-425-5p during LCa tumorigenesis. Methods Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and real-time PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-425-5p and PTEN. Results We demonstrate that miR-425-5p is overexpressed in LCa tissue and enhances the proliferative and colony formation capacity of the LCa cell lines A549 and NCI-H1299. Through predictive binding assays, PTEN was identified as a direct gene target and its exogenous expression inhibited the pro-cancer effects of miR-425-5p. Through its ability to down-regulate PTEN, miR-425-5p activated the PI3K/AKT axis. Conclusion We conclude that miR-425-5p promotes LCa tumorigenesis through PTEN/PI3K/AKT signaling.

When the government decides to use the public-private partnership (PPP) in projects, such as infrastructure construction, selecting a private-sector partner that meets the project's needs is one of the key factors for successful implementation, but this is ignored in existing research. On this basis, this paper proposes a GRA-VIKOR method based on the combined weight of the improved CRITIC-entropy weight method (EWM). The traditional CRITIC method is improved by combining it with EWM. The combined weights are measured, which reduces the limitations of the single weight. Considering the inherent correlation of evaluation indicators, the VIKOR method is combined with the grey relational analysis (GRA), which makes the results of the selection assessment more reasonable. This paper carries out a case study of the first inland navigation PPP project in China. Through preliminary tracking studies, it tests the effectiveness of the proposed method, the superiority of which is demonstrated by comparing the evaluation results with those of the traditional GRA methods, VIKOR, and TOPSIS.

Background: We determined the effect of prostate-specific antigen velocity (PSAV) on the surgical outcome of thulium laser enucleation of the prostate (ThuLEP) in patients with benign prostatic hyperplasia (BPH).Methods: A retrospective review was performed of prospectively collected data of patients with BPH who underwent ThuLEP at any time from 2017 to 2019. Patients who had undergone BPH surgery or had prostate cancer previously were excluded, and patients with prostate-specific antigen (PSA) > 4 ng/ml were examined through transrectal ultrasound-guided prostate biopsy to rule out prostatic malignancy. Furthermore, patients were excluded if prostatic malignancy was diagnosed during postsurgery follow-up.Results: The PSA level, International Prostate Symptom Score (IPSS), and quality of life (QoL) of 27 male patients at 3 and 15 months postsurgery differed significantly from those at presurgery; the maximum flow rate (Qmax) and postvoid residual (PVR) significantly differed between 3 months postsurgery and presurgery; and 22 and 5 patients had good to excellent and fair to poor outcomes, respectively, at 15 months postsurgery. Patients were divided into two groups (fair and poor vs. good and excellent outcomes at 15 months postsurgery), which significantly differed with respect to PSAV at 3 months postsurgery (P = 0.04), IPSS presurgery (P < 0.02), surgical length (P = 0.01), and hospitalization duration (P = 0.04). In a receiver operating characteristic (ROC) analysis, the optimal cutoff value of PSAV of −0.52 ng/ml characterized effectiveness at 15 months after ThuLEP, and the area under the curve (AUC), sensitivity, and specificity were 0.82 (P < 0.02), 0.80, and 0.82, respectively. For PSAV < -0.52 and ≥-0.52 ng/ml, the percentages of reduction for IPSS, QoL, Qmax, and PVR were −78.6 and −71.4%, −33.3 and 0.0%, 94.4 and 40.0%, and −85.1 and −38.7%, respectively.Conclusions: Postsurgical PSAV was positively correlated with surgical success, and the PSAV cutoff was −0.52 ng/ml. PSAV can, thus, be used to guide the postsurgical follow-up treatment at 3 months after BPH surgery.

BackgroundAtrial fibrillation (AF) has been linked to left atrial (LA) enlargement. Whereas most studies focused on 2D-based estimation of static LA volume (LAV), we used a fully-automatic convolutional neural network (CNN) for time-resolved (CINE) volumetry of the whole LA on cardiac MRI (cMRI). Aim was to investigate associations between functional parameters from fully-automated, 3D-based analysis of the LA and current classification schemes in AF.MethodsWe retrospectively analyzed consecutive AF patients who underwent cMRI on 1.5T systems including a stack of oblique-axial CINE series covering the whole LA. The LA was automatically segmented by a validated CNN. In the resulting volume-time curves, maximum, minimum and LAV before atrial contraction were automatically identified. Active, passive and total LA emptying fractions (LAEF) were calculated and compared to clinical classifications (AF Burden score (AFBS), increased stroke risk (CHA2DS2VASc≥2), AF type (paroxysmal/persistent), EHRA score, and AF risk factors). Moreover, multivariable linear regression models (mLRM) were used to identify associations with AF risk factors.ResultsOverall, 102 patients (age 61±9 years, 17% female) were analyzed. Active LAEF (LAEF_active) decreased significantly with an increase of AFBS (minimal: 44.0%, mild: 36.2%, moderate: 31.7%, severe: 20.8%, pConclusionsFully-automatic morphometry of the whole LA derived from cMRI showed significant relationships between LAEF_active with increased stroke risk and severity of AFBS. Furthermore, higher age, higher AFBS and presence of heart failure were independent predictors of reduced LAEF_active, indicating its potential usefulness as an imaging biomarker.

This study investigated and compared the surgical outcomes of using endoscopic enucleation (thulium: YAG laser and bipolar plasma; ThuLEP) with robotic-assisted simple prostatectomy (RASP) in the treatment of prostates larger than 80 cm 3 . Records were obtained for the period from January 2014 to December 2020 for selected patients with BPO who underwent RASP, ThuLEP, or bipolar transurethral enucleation of the prostate (B-TUEP). Patients were excluded if they had active malignant disease, neurogenic bladder, lower urinary tract syndrome for reasons other than BPO, and a history of prostate surgery. Data of 396 patients who underwent B-TUEP, ThuLEP, and RASP were examined. A total of 112 patients met the including criteria, 85 of whom (B-TUEP: 29; ThuLEP: 41; RASP: 15) completed the final visit. The mean operation time and duration of postoperative hospital stays in the RASP group were significantly longer than those of the B-TUEP and ThuLEP groups. Only 1 patient in the RASP group required blood transfusion. The RASP group was superior to the other groups in voiding improvement including Qmax and IPSS voiding score. The pain score of the ThuLEP group after surgery was significantly lower than that of the other two groups during hospitalization, whereas the QoL scores were identical between the three groups at 2 weeks, 3 months, and 6 months post operation. The rates of returning to ER within the first postoperative month did not differ significantly between the three groups, and all the reasons for return involved minor complications that required no additional invasive treatment. These three surgical methods (B-TUEP, ThuLEP, and RASP) are all effective and safe for treating prostates larger than 80 cm3, with each having its particular advantages. B-TUEP requires the shortest operation time, ThuLEP causes the lowest postoperative pain, and RASP results in superior voiding function improvement.

Increasing cases related to the pathogenicity of Enterovirus D68 (EV-D68) have made it a growing worldwide public health concern, especially due to increased severe respiratory illness and acute flaccid myelitis (AFM) in children. There are currently no vaccines or medicines to prevent or treat EV-D68 infections. Herein, we performed genome-wide transcriptional profiling of EV-D68-infected human rhabdomyosarcoma (RD) cells to investigate host-pathogen interplay. RNA sequencing and subsequent experiments revealed that EV-D68 infection induced a profound transcriptional dysregulation of host genes, causing significantly elevated inflammatory responses and altered antiviral immune responses. In particular, triggering receptor expressed on myeloid cells 1 (TREM-1) is involved in highly activated TREM-1 signaling processes, acting as an important mediator in EV-D68 infection, and it is related to upregulation of interleukin 8 (IL-8), IL-6, IL-12p70, IL-1β, and tumor necrosis factor alpha (TNF-α). Further results demonstrated that NF-κB p65 was essential for EV-D68-induced TREM-1 upregulation. Moreover, inhibition of the TREM1 signaling pathway by the specific inhibitor LP17 dampened activation of the p38 mitogen-activated protein kinase (MAPK) signaling cascade, suggesting that TREM-1 mainly transmits activation signals to phosphorylate p38 MAPK. Interestingly, treatment with LP17 to inhibit TREM-1 inhibited viral replication and infection. These findings imply the pathogenic mechanisms of EV-D68 and provide critical insight into therapeutic intervention in enterovirus diseases.

Abstract Background Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor prognosis in patients with cervical cancer. In our present study, we further studied the effects of DLL4 on the biological behavior and radiosensitivity of cervical cancer cells. Methods The expression of DLL4 and epithelial–mesenchymal transition (EMT) phenotype markers in cervical cancer cell lines or tissues were detected using Western blotting, and the expression of DLL4 mRNA in cervical cancer cell lines or tissues was detected using Quantitative real-time PCR. The effect of DLL4 on cell proliferation, migration, and radiosensitivity was evaluated using the CCK8 assay, flow cytometry, Transwell assays for cell invasion and migration, and Immunofluorescence staining in vitro. Results The expression of DLL4 in radiotherapy-resistant SiHa cells was significantly higher than that in radiotherapy-sensitive Me-180 cells. Furthermore, downregulation of DLL4 enhanced the radiosensitivity of SiHa and Caski cells via the inhibition of cell proliferation, promotion of radiation-induced apoptosis, and inhibition of the DNA damage repair. Moreover, downregulation of DLL4 inhibited the EMT and reduced the proliferation, invasion, and migration ability in SiHa and Caski cells. Consistent with the DLL4 expression in the cell lines, the expression of DLL4 in the tissues of the radioresistant group was also higher than that of the radiosensitive group. Conclusions Downregulation of DLL4 inhibited the progression and increased the radiosensitivity in cervical cancer cells by reversing EMT. These results indicated the promising prospect of DLL4 against the radioresistance and metastasis of cervical cancer and its potential as a predictive biomarker for radiosensitivity and prognosis in patients with cervical cancer patients receiving concurrent chemoradiotherapy (cCRT).

Abstract Background To understand the gene expression networks controlling flower color formation in alfalfa, flowers anthocyanins were identified using two materials with contrasting flower colors, namely Defu and Zhongtian No. 3, and transcriptome analyses of PacBio full-length sequencing combined with RNA sequencing were performed, across four flower developmental stages. Results Malvidin and petunidin glycoside derivatives were the major anthocyanins in the flowers of Defu, which were lacking in the flowers of Zhongtian No. 3. The two transcriptomic datasets provided a comprehensive and systems-level view on the dynamic gene expression networks underpinning alfalfa flower color formation. By weighted gene coexpression network analyses, we identified candidate genes and hub genes from the modules closely related to floral developmental stages. PAL, 4CL, CHS, CHR, F3’H, DFR, and UFGT were enriched in the important modules. Additionally, PAL6, PAL9, 4CL18, CHS2, 4 and 8 were identified as hub genes. Thus, a hypothesis explaining the lack of purple color in the flower of Zhongtian No. 3 was proposed. Conclusions These analyses identified a large number of potential key regulators controlling flower color pigmentation, thereby providing new insights into the molecular networks underlying alfalfa flower development.

Abstract Background The key to modern drug discovery is to find, identify and prepare drug molecular targets. However, due to the influence of throughput, precision and cost, traditional experimental methods are difficult to be widely used to infer these potential Drug-Target Interactions (DTIs). Therefore, it is urgent to develop effective computational methods to validate the interaction between drugs and target. Methods We developed a deep learning-based model for DTIs prediction. The proteins evolutionary features are extracted via Position Specific Scoring Matrix (PSSM) and Legendre Moment (LM) and associated with drugs molecular substructure fingerprints to form feature vectors of drug-target pairs. Then we utilized the Sparse Principal Component Analysis (SPCA) to compress the features of drugs and proteins into a uniform vector space. Lastly, the deep long short-term memory (DeepLSTM) was constructed for carrying out prediction. Results A significant improvement in DTIs prediction performance can be observed on experimental results, with AUC of 0.9951, 0.9705, 0.9951, 0.9206, respectively, on four classes important drug-target datasets. Further experiments preliminary proves that the proposed characterization scheme has great advantage on feature expression and recognition. We also have shown that the proposed method can work well with small dataset. Conclusion The results demonstration that the proposed approach has a great advantage over state-of-the-art drug-target predictor. To the best of our knowledge, this study first tests the potential of deep learning method with memory and Turing completeness in DTIs prediction.

C-C bond scission of unstrained cycloketones with high regioselectivity is a challenging synthetic task. Here, the authors show a facile C-C cleavage of cyclohexanones and cyclopentanones with unusual selectivity under mild conditions with the aid of an in situ formed side-chain aryl radical.

Abstract The thermal‐hydraulic performance of printed circuit heat exchanger (PCHE) through an experimental vaporization process of supercritical nitrogen was investigated. The inlet temperature of supercritical nitrogen was controlled between 113 K and 129 K, while its pressure was controlled between 4.5 MPa and 6 MPa. The mass of supercritical nitrogen corresponds to the turbulent state on the cold side of PCHE, which was maintained at 299.94 kg/h. A numerical processing of the same supercritical nitrogen flow through a single channel of PCHE cold side was presented. The numerical results were validated by comparison with the experimental data. Both experimental and numerical results showed that the increased inlet supercritical nitrogen pressure improved the heat transfer performance and pressure drop decreased with increasing the pressure at the PCHE cold side. Furthermore, the Fanning friction coefficient (f) and the Nusselt number (Nu) of supercritical nitrogen flow obtained by numerical simulation and empirical correlation were compared.