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Background: There is an increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE) infection after liver transplantation (LT). Improved understanding of the risk factors and outcomes of CRE infections can help us to develop effective preventive strategies and even guide early treatment of high-risk LT patients. Methods: This was a retrospective study involving all Chinese adult patients who underwent LT between December 2017 and September 2019 in our center. We analyzed the possible risk factors and outcomes associated with CRE infections in the first 30 days post-LT. Results: A total of 387 patients underwent LT. Among them, 26 patients (6.7%) developed CRE infections within 30 days after transplantation. Patients with CRE infections had significantly lower 30-day and 180-day survival rates (80.8% vs 96.4%, p< 0.001; 51.5% vs 92.4%, p< 0.001). Multivariate analysis identified that intraoperative blood loss equal to or more than 1500 mL (odds ratio [OR], 3.666; 95% confidence interval [CI], 1.407– 9.550; p=0.008), CRE rectal carriage within 30 days post-LT (OR, 5.516; 95% CI, 2.113– 14.399; p=0.000), biliary complications (OR, 3.779; 95% CI, 1.033– 13.831; p=0.045) and renal replacement therapy for more than 3 days (OR, 3.762; 95% CI, 1.196– 11.833; p=0.023) were independent risk factors for CRE infections within 30 days post-LT. Conclusion: CRE infections within 30 days post-LT were associated with worse outcomes. Intraoperative blood loss equal to or more than 1500 mL, CRE rectal carriage within 30 days post-LT, biliary complications and renal replacement therapy for more than 3 days were independent risk factors of CRE infections after LT. [ABSTRACT FROM AUTHOR]

Strawberry cultivation is constantly increasing all over the world thanks to the varietal innovations obtained by numerous breeding and biotechnology projects and to the studies performed to discover new knowledge on plant’s physiology to develop innovative cultivation systems. Genetic resources remain crucial for breeding activities that can now be integrated with new genomic and molecular knowledge and technologies. Several research groups are dominating the development and control of these technologies, but there are also many emerging companies capable of developing innovations that can have important local and even global impacts. These activities are supported by important public research projects, also of international importance, but the link with the companies that must have access to the results to improve their innovation capacity remains important. The ultimate aim is to continue to expand the cultivation of the strawberry with the development of new cultivars with high adaptability to different environments and growing systems (field, greenhouse above ground) with less environmental impact and increased safety and quality for the consumer. [ABSTRACT FROM AUTHOR]

Fragaria orientalis Lozinsk. is valuable germplasm material for cross breeding in Fragaria. In this study, we assembled the complete mitochondrial genome of F. orientalis using a combination of Illumina data and Nanopore data. The mitochondrial genome was 275,143 bp in length, including 29 protein-coding genes, 20 tRNA genes, and three rRNA genes, with a total GC content 45.23%. Seven protein-coding genes contained introns, and three were trans-spliced. Phylogenetic analysis indicated that F. orientalis is making a sister clade to the Amygdaloideae species. The complete mitochondrial genome of F. orientalis reported in this study will improve our understanding of Fragaria evolution. [ABSTRACT FROM AUTHOR]

Reduced sensitivity of prostate cancer (PC) cells to radiation therapy poses a significant challenge in the clinic. Activation of epidermal growth factor receptor (EGFR), type 1 insulin-like growth factor receptor (IGF1R), and crosstalk between these two signaling pathways have been implicated in the development of radiation resistance in PC. This study assessed the effects of targeting both receptors on the regulation of radio-sensitivity in PC cells. Specific inhibitors of EGFR and IGF1R, Erlotinib and AG1024, as well as siRNA targeting EGFR and IGF1R, were used to radio-sensitize PC cells. Our results showed that co-inhibiting both receptors significantly dampened cellular growth and DNA damage repair, and increased radio-sensitivity in PC cells. These effects were carried out through synergistic inhibition of homologous recombination-directed DNA repair (HRR), but not via inhibition of non-homologous end joining (NHEJ). Furthermore, the compromised HRR capacity was caused by reduced phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent interaction with Rad51. The synergistic effect of the EGFR and IGF1R inhibitors was also confirmed in nude mouse xenograft assay. This is the first study testing co-inhibiting EGFR and IGF1R signaling in the context of radio-sensitivity in PC and it may provide a promising adjuvant therapeutic approach to improve the outcome of PC patients to radiation treatment. [ABSTRACT FROM AUTHOR]

Soil ecology plays an important role in the growth and health of plants. Research suggests that long-term monocropping may lead to soil ecological disorders. In this study, we aimed to understand the reasons for the decrease in plant productivity stemming from long-term monoculture cropping. Greenhouse studies were conducted to determine the cause of continuous cropping (CC) obstacles in soils under 12 years of continuous strawberry (Fragaria × ananassa Duch.) production. The data suggested that CC led to three phases of changes in abiotic and biotic soil factors. In phase I (CC for 2–6 years), significant changes were observed only in soil physicochemical properties, such as the pH, total nitrogen (TN), ammonium nitrogen (NH 4 +-N), available phosphorus (AP), available potassium (AK) and soil organic matter (SOM), which obviously changed from the second year to the sixth year. In phase II (CC for 6–8 years), two biotic factors, key fungi such as Fusarium , Humicola and Arthrobotrys and soil nematodes, i.e., populations and communities of nematodes, started to change significantly in terms of their abundance. In phase III (CC for >8 years), the accumulation of phenolic acids, i.e., p-hydroxybenzoic acid (p-HBA), ferulic acid (FA), p-coumaric acid (p-CA) and cinnamic acid (CA), significantly inhibited crop growth, and the abundance of key bacteria, including Bacillus , Sphingomonas and Sphingopyxis , started to change significantly from the eighth CC year. The results in this study provide useful information for solving CC obstacles in strawberry production. Unlabelled Image • Continuous cropping led to changes in abiotic and biotic factors in the soil. • This is the first attempt to comprehensively interpret continuous cropping obstacles. • The continuous cropping soil changes could be divided into three main phases: Phase I, Phase II, and Phase III. • This research provides useful information to solve strawberry continuous cropping problems. [ABSTRACT FROM AUTHOR]

Aim: Novel long-acting drugs for type 2 diabetes mellitus may optimize patient compliance and glycaemic control. Exendin-4-IgG4-Fc (E4F4) is a long-acting glucagon-like peptide-1 receptor agonist. This first-in-human study investigated the safety, tolerability, pharmacokinetic, pharmacodynamic and immunogenicity profiles of a single subcutaneous injection of E4F4 in healthy subjects., Methods: This single-centre, randomized, double-blind, placebo-controlled phase 1 clinical trial included 96 subjects in 10 sequential cohorts that were provided successively higher doses of E4F4 (0.45, 0.9, 1.8, 3.15, 4.5, 6.3, 8.1, 10.35, 12.6 and 14.85 mg) or placebo (ChinaDrugTrials.org.cn: ChiCTR2100049732). The primary endpoint was safety and tolerability of E4F4. Secondary endpoints were pharmacokinetic, pharmacodynamic and immunogenicity profiles of E4F4. Safety data to day 15 after the final subject in a cohort had been dosed were reviewed before commencing the next dose level., Results: E4F4 was safe and well tolerated among healthy Chinese participants in this study. There was no obvious dose-dependent relationship between frequency, severity or causality of treatment-emergent adverse events. C max and area under the curve of E4F4 were dose proportional over the 0.45-14.85 mg dose range. Median T max and t 1/2 ranged from 146 to 210 h and 199 to 252 h, respectively, across E4F4 doses, with no dose-dependent trends. For the intravenous glucose tolerance test, area under the curve of glucose in plasma from time 0 to 180 min showed a dose-response relationship in the 1.8-10.35 mg dose range, with an increased response at the higher doses., Conclusion: E4F4 exhibited an acceptable safety profile and linear pharmacokinetics in healthy subjects. The recommended phase 2 dose is 4.5-10.35 mg once every 2 weeks., (© 2024 John Wiley & Sons Ltd.)

Background: A vaccine for enterovirus 71 (EV71) is needed to address the high burden of disease associated with infection. We assessed the efficacy, safety, immunogenicity, antibody persistence, and immunological correlates of an inactivated alum-adjuvant EV71 vaccine., Methods: We did a randomised, double-blind, placebo-controlled, phase 3 trial. Healthy children aged 6-35 months from four centres in China were randomly assigned (1:1) to receive vaccine or alum-adjuvant placebo at day 0 and 28, according to a randomisation list (block size 30) generated by an independent statistician. Investigators and participants and their guardians were masked to the assignment. Primary endpoints were EV71-associated hand, foot, and mouth disease (HFMD) and EV71-associated disease during the surveillance period from day 56 to month 14, analysed in the per-protocol population. This study is registered with ClinicalTrials.gov, number NCT01508247., Findings: 10,245 participants were enrolled and assigned: 5120 to vaccine versus 5125 to placebo. 4907 (with three cases of EV71-associated HFMD and eight cases of EV71-associated disease) versus 4939 (with 30 cases of EV71-associated HFMD and 41 cases of EV71-associated disease) were included in the primary efficacy analysis. Vaccine efficacy was 90·0% (95% CI 67·1-96·9) against EV71-associated HFMD (p=0·0001) and 80·4% (95% CI 58·2-90·8) against EV71-associated disease (p<0·0001). Serious adverse events were reported by 62 of 5117 (1·2%) participants in the vaccine group versus 75 of 5123 (1·5%) in the placebo group (p=0·27). Adverse events occurred in 3644 (71·2%) versus 3603 (70·3%; p=0·33)., Interpretation: EV71 vaccine provides high efficacy, satisfactory safety, and sustained immunogenicity., Funding: China's 12-5 National Major Infectious Disease Program, Beijing Vigoo Biological., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Enterovirus 71 (EV71) outbreaks are a socioeconomic burden, especially in the western Pacific region. Results of phase 1 clinical trials suggest an EV71 vaccine has a clinically acceptable safety profile and immunogenicity. We aimed to assess the best possible dose and formulation, immunogenicity, and safety profile of this EV71 vaccine in healthy Chinese children., Methods: This randomised, double-blind, placebo-controlled, phase 2 trial was undertaken at one site in Donghai County, Jiangsu Province, China. Eligible participants were healthy boys or girls aged 6–36 months. Participants were randomly assigned (1:1:1:1:1) to receive either 160 U, 320 U, or 640 U alum-adjuvant EV71 vaccine, 640 U adjuvant-free EV71 vaccine, or a placebo (containing alum adjuvant only), according to a blocked randomisation list generated by SAS 9.1. Participants and investigators were masked to the assignment. The primary endpoint was anti-EV71 neutralising antibody geometric mean titres (GMTs) at day 56, analysed according to protocol. The study is registered with ClinicalTrials.gov, number NCT01399853., Findings: We randomly assigned 1200 participants, 240 (120 aged 6–11 months [infants] and 120 aged 12–36 months [children]) of whom were assigned to each dose. 1106 participants completed the study and were included in the according-to-protocol analysis. The main reasons for dropout were withdrawal of consent and refusal to donate a blood sample. Infants who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (742·2 [95% CI 577·3–954·3]), followed by those who received the 320 U formulation (497·9 [383·1–647·0]). For children, those who received the 320 U formulation had the highest GMTs on day 56 (1383·2 [1037·3–1844·5]). Participants who received the vaccine had significantly higher GMTs than did who received placebo (p<0·0001). For the subgroup of participants who were seronegative at baseline, both infants and children who received the 640 U adjuvant vaccine had the highest GMTs on day 56 (522·8 [403·9–676·6] in infants and 708·4 [524·1–957·6] in children), followed by those who received the 320 U adjuvant vaccine (358·2 [280·5–457·5] in infants and 498·0 [383·4–646·9] in children). 549 (45·8%) of 1200 participants (95 CI 42·9–48·6%) reported at least one injection-site or systemic adverse reaction, but the incidence of adverse reactions did not differ significantly between groups (p=0·36). The 640 U alum-adjuvant vaccine group had a significantly higher incidence of induration than did the 640 U adjuvant-free group (p=0·001)., Interpretation: Taking immunogenicity, safety, and production capacity into account, the 320 U alum-adjuvant formulation of the EV71 vaccine is probably the best possible formulation for phase 3 trials., Funding: The National Science and Technology Major Project (2011ZX10004-902) of the Chinese Ministry of Science and Technology, China's 12–5 National Major Infectious Disease Program (2012ZX10002-001), and Beijing Vigoo Biological.

Bladder cancer is the most common malignant urological disease in China. Hydroxycamptothecin (HCPT) is a DNA topoisomerase I inhibitor, which has been utilized in chemotherapy for bladder cancer for nearly 40 years. Previous research has demonstrated that the isoflavone, genistein, can sensitize multiple cancer cell lines to HCPT treatment, such as prostate and cervical cancer. In this study, we investigated whether genistein could sensitize bladder cancer cell lines and bladder epithelial cell BDEC cells to HCPT treatment, and investigated the possible underlying molecular mechanisms. Genistein could significantly and dose-dependently sensitize multiple bladder cancer cell lines and BDEC cells to HCPT-induced apoptosis both in vitro and in vivo. Genistein and HCPT synergistically inhibited bladder cell growth and proliferation, and induced G2/M phase cell cycle arrest and apoptosis in TCCSUP bladder cancer cell and BDEC cell. Pretreatment with genistein sensitized BDEC and bladder cancer cell lines to HCPT-induced DNA damage by the synergistic activation of ataxia telangiectasia mutated (ATM) kinase. Genistein significantly attenuated the ability of HCPT to induce activation of the anti-apoptotic NF-κB pathway both in vitro and in vivo in a bladder cancer xenograft model, and thus counteracted the anti-apoptotic effect of the NF-κB pathway. This study indicates that genistein could act as a promising non-toxic agent to improve efficacy of HCPT bladder cancer chemotherapy.

Aim: To analyze the application significance of ultrasound contrast agent in identification and diagnosis of ocular spaceoccupying lesions, and mainly analyze its advantages and problems., Methods: Thirty-two representative literatures about the application of ultrasound contrast agent in diagnosis of spaceoccupying lesions at home and abroad were collected after focused on sorting the literature reporting the application of ultrasound contrast diagnostic technology in the diagnosis and identification of ocular spaceoccupying lesions in recent years. Its advantages and problems were retrospectively analyzed, and reasonable assessment on existing problems was made and possible solutions to the problems were proposed., Results: As a new imaging diagnostic technique, the contrast-enhanced ultrasound, which can enhance the display of tumor microcirculation vessels and improve the tumor's ultrasound diagnostic capability, was analyzed. Through sorting and comprehensively analyzing the collected literatures, the positive rate of ocular spaceoccupying lesion diagnosis could be significantly improved with ultrasound contrast technology. Thus, the vascular perfusion in normal tissues and lesions was reflected objectively. According to the lesion's perfusion characteristics of the contrast agent plus with the performance features of two-dimensional ultrasound, the ocular spaceoccupying lesions can be accurately diagnosed, and this could provide clinicians with reliable research basis in this field., Conclusion: Ultrasound contrast examination is a new testing method, and ultrasound contrast agent can significantly enhance the ultrasonic detection signal, clearly show the blood perfusion in vessels and tissues, increase the image contrast resolution, and improve the lesion's detection capability in the microcirculation perfusion level, especially its important value in the diagnosis of ocular tumor.

The aim of this study was to explore the mechanism underlying the dual effect of androgen on prostate cancer cells and further explore its correlation with dopa decarboxylase (DDC), an androgen receptor (AR) coactivator and a traditional neuroendocrine differentiation (NED) marker. Cell proliferation and cycling after treatment with synthetic nonmetabolizable androgen R1881 was determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method and flow cytometry. Differential gene expression was analyzed by cDNA microarrays. DDC expression during the dual effect of R1881 was further explored with microarray, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot, and enzyme activity assays. Proliferation of LNCaP cells was inhibited by 1 nM R1881 but stimulated by 0.1 nM R1881. Compared with the untreated cells, 320 (2.26%; 170 up-regulated, 150 down-regulated) and 4608 (32.65%; 2046 up-regulated, 2562 down-regulated) genes were found to be expressed differentially in the 1 nM and 0.1 nM R1881-treated cells, respectively. The results were partially confirmed by RT-PCR and Western blot. The DDC gene was down-regulated in the 1 nM R1881-treated cells and up-regulated in 0.1 nM R1881- and 30 nM hydroxyflutamide-treated cells. The enzymatic activity of DDC in the latter 2 groups was also strengthened. Meanwhile, the NED markers CgA and synaptophysin were not affected by these AR activators. R1881 had a dose-dependent biphasic effect on LNCaP cell proliferation. AR coactivator DDC was respectively down- and up-regulated in high and low concentrations of R1881. DDC up-regulation by exogenous AR activators is not accompanied by up-regulation of definitive NED markers.

Background: Severe acute pancreatitis (SAP) is a serious disease with many complications, high mortality and poor prognosis. It is characterized by rapid deterioration and poses one of the most difficult challenges in clinical practice. Previous investigations suggest that SAP is one of the main causes of intra-abdominal pressure (IAP) increase. The aim of this study was to evaluate the utility of IAP-monitoring in predicting the severity and prognosis of SAP., Methods: Eighty-nine patients with SAP who had been treated from February 2001 to December 2005 were studied. Since bladder pressure accurately reflects IAP, we measured it instead of IAP. Bladder pressure was measured at the time of admission and every 12 hours in the course of the disease, 9 consecutive times in all. The APACHE II scores of all patients were obtained within 24 hours after admission. According to a maximum bladder pressure <10 cmH2O, all patients were divided into two groups, mildly-elevated and severely-elevated. Mortality and mean APACHE II scores in the two groups were calculated. In addition, the mean bladder pressure and APACHE II scores in survivors were compared with those in deaths., Results: Sixty-eight of the 89 patients were in the severely-elevated group. Mortality and mean APACHE II scores in this group were much higher than those in the mildly-elevated group (mortality, 39.71% vs. 9.52%; mean APACHE II score, 23.15+/-7.42 vs. 15.95+/-5.35, P<0.01). The mean bladder pressures and APACHE II scores in deaths were significantly greater than those in survivors (mean bladder pressure, 14.1+/-3.8 vs. 9.2+/-2.3 cmH2O, P<0.01; mean APACHE II score, 27.83+/-4.87 vs. 18.37+/-6.74, P<0.01)., Conclusion: It is suggested that IAP may be used as a marker of the severity and prognosis of SAP.