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We aimed to assess the accuracy of BD Phoenix for determining carbapenem susceptibility because we observed a decline in carbapenem susceptibility rate from the biannual cumulative data, after we transitioned to the BD Phoenix form Vitek 2 system. Between October 2021 and May 2022, we collected 82 non-duplicated Enterobacterales showing non-susceptible to at least one of the three carbapenems by BD Phoenix. We performed the broth microdilution (BMD) and disk diffusion (DD) according to the CLSI guideline. Compared to BMD, the categorical agreements for ertapenem (ERT), imipenem (IPM) and meropenem (MEPM) was 58.8%, 56.8% and 91.5% for BD Phoenix and it was 85.4%, 89.0%, and 97.6%, respectively, for DD (p value; 0.0001 for ERT and IPM, p value; 0.17 for MEPM). The major errors/minor errors for ERT, IPM, and MEPM were 14.0%/31.7%, 2.94%/40.7%, and 2.56%/6.10%, respectively for BD Phoenix, compared to 0%/14.6%, 0%/9.8%, and 0%/2.5%, for DD. While errors in the BD Phoenix showed tendency towards resistance, those in DD displayed no tendency towards either resistance or susceptibility. With DD, 21 out of the 27 isolates showing susceptible/intermediate/susceptible pattern (ERT/IPM/MEPM) and 13 out of the 16 isolates showing intermediate/susceptible/susceptible pattern (ERT/IPM/MEPM), were correctly categorized by DD. However, for 22 isolates showing resistant/susceptible/susceptible pattern (ERT/IPM/MEPM), only 13 isolates were correctly categorized by DD. In conclusion, to mitigate the risk of overcalling carbapenem non-susceptibility with BD Phoenix, it will be helpful to perform a complementary test using DD and to provide comments on the DD results to clinicians., Competing Interests: Declaration of competing interest No potential conflicts of interest relevant to this paper were reported., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Vancomycin variable Enterococcus (VVE) bacteria are phenotypically susceptible to vancomycin, but they harbor the vanA gene. We aimed to ascertain the prevalence of VVE among clinically isolated vancomycin-susceptible Enterococcus faecium (VSE) isolates, as well as elucidate the molecular characteristics of the vanA gene cluster within these isolates. Notably, we investigated the prevalence and structure of the vanA gene cluster of VVE. Between June 2021 and May 2022, we collected consecutive, non-duplicated vancomycin-susceptible Enterococcus faecium (VSE) samples. Real-time PCR was performed to detect the presence of vanA , vanB , and vanC . Overlapping PCR with sequencing and whole-genome sequencing were performed for structural analysis. Sequence types (STs) were determined by multilocus sequence typing. Exposure testing was performed to assess the ability of the isolates to acquire vancomycin resistance. Among 282 VSE isolates tested, 20 isolates (7.1%) were VVE. Among them, 17 isolates had partial deletions in the IS 1216 or IS 1542 sequences in vanS (N=10), vanR (N=5), or vanH (N=2). All VVE isolates belonged to the CC17 complex and comprised five STs, namely ST17 (40.0%), ST1421 (25.0%), ST80 (25.0%), ST787 (5.0%), and ST981 (5.0%). Most isolates were related to three hospital-associated clones (ST17, ST1421, and ST80). After vancomycin exposure, 18 of the 20 VVEs acquired vancomycin resistance. Considering the high reversion rate, detecting VVE by screening VSE for vanA is critical for appropriate treatment and infection control.

Background: Endobronchial metastases (EBMs) are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi, and are visible under a bronchofibrescope. Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours, such as lung cancer, oesophageal cancer or mediastinum tumours. Renal cell carcinoma (RCC), accounting for 2% to 3% of all tumours, is a common malignant tumour of the urinary system. Renal clear cell carcinoma (RCCC) constitutes the predominant pathological subtype of RCC, comprising approximately 70% to 80% of all RCC cases. RCCC can spread and metastasise through arterial, venous and lymphatic circulation to almost all organs of the body. Moreover, lung, bone, liver, brain and local recurrence are the most common metastatic neoplasms of RCCC. However, EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer., Case Summary: A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough. The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung, and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe. Therefore, the patient underwent thoracoscopic left superior lobe wedge resection, and pathology confirmed EBM from the RCCC., Conclusion: EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage. If a bronchial tumour is found in a patient with RCCC, the possibility of bronchial metastatic cancer should be considered., Competing Interests: Conflict-of-interest statement: All authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aims: The impact of macrovascular and microvascular complications, the common vascular complications of type 2 diabetes, on long-term mortality has been well evaluated, but the impact of different complications of newly diagnosed type 2 diabetes (diagnosed within the past 2 years) on long-term mortality has not been reported. We aimed to investigate the relationship between all-cause mortality and vascular complications in U.S. adults (aged ≥ 20 years) with newly diagnosed type 2 diabetes., Methods: We used data from the 1999-2018 National Health and Nutritional Examination Surveys (NHANES). Cox proportional hazard models was used to assess hazard ratios (HR) and 95% confidence intervals for all-cause mortality., Results: A total of 928 participants were enrolled in this study. At a mean follow-up of 10.8 years, 181 individuals died. In the fully adjusted model, the hazard ratio (HR) (95% confidence interval [CI]) of all-cause mortality for individuals with any single complication compared with those with newly diagnosed type 2 diabetes without complications was 2.24 (1.37, 3.69), and for individuals with two or more complications was 5.34 (3.01, 9.46).Co-existing Chronic kidney disease (CKD) and diabetic retinopathy (DR) at baseline were associated with the highest risk of death (HR 6.07[2.92-12.62]), followed by CKD and cardiovascular disease (CVD) (HR 4.98[2.79-8.89]) and CVD and DR (HR 4.58 [1.98-10.57])., Conclusion: The presence of single and combined diabetes complications exerts a long-term synergistic adverse impact on overall mortality in newly diagnosed U.S. adults with type 2 diabetes, underscoring the importance of comprehensive complication screening to enhance risk stratification and treatment., (© 2024. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Immune dysfunction is a primary culprit behind spontaneous miscarriage (SM). To address this, immunosuppressive agents have emerged as a novel class of tocolytic drugs, modulating the maternal immune system's tolerance towards the embryo. Rapamycin (PubChem CID:5284616), a dual-purpose compound, functions as an immunosuppressive agent and triggers autophagy by targeting the mTOR pathway. Its efficacy in treating SM has garnered significant research interest in recent times. Autophagy, the cellular process of self-degradation and recycling, plays a pivotal role in numerous health conditions. Research indicates that autophagy is integral to endometrial decidualization, trophoblast invasion, and the proper functioning of decidual immune cells during a healthy pregnancy. Yet, in cases of SM, there is a dysregulation of the mTOR/autophagy axis in decidual stromal cells or immune cells at the maternal-fetal interface. Both in vitro and in vivo studies have highlighted the potential benefits of low-dose rapamycin in managing SM. However, given mTOR's critical role in energy metabolism, inhibiting it could potentially harm the pregnancy. Moreover, while low-dose rapamycin has been deemed safe for treating recurrent implant failure, its potential teratogenic effects remain uncertain due to insufficient data. In summary, rapamycin represents a double-edged sword in the treatment of SM, balancing its impact on autophagy and immune regulation. Further investigation is warranted to fully understand its implications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Androgen receptor (AR) has been extensively established as a potential therapeutic target for nearly all stages of prostate cancer (PCa). However, acquired resistance to AR-targeted drugs inevitably develops and severely limits their clinical efficacy. Particularly, there currently exists no efficient treatment for patients expressing the constitutively active AR splice variants, such as AR-V7. Herein, we report the structure-activity relationship studies of 55 N -heterocycle-substituted hydantoins, which identified the structural motifs required for AR/AR-V7 degradation. Among them, the most potent compound 27c exhibited selective AR/AR-V7 degradation over other hormone receptors and excellent antiproliferative activities in LNCaP and 22RV1 cells. RNA sequence analysis confirmed that 27c effectively suppressed transcriptional activity of the AR signaling pathway. Importantly, 27c demonstrated potent antitumor efficacy in an enzalutamide-resistant 22RV1 xenograft model. These results highlight the potential of 27c as a promising dual AR/AR-V7 degrader for overcoming drug resistance in advanced PCa expressing AR splice variants.

DNA polymerase theta (Polθ) has recently emerged as a new attractive synthetic lethal target involved in DNA damage repair. Inactivating Polθ alone or in combination with PARP inhibitors has demonstrated substantial therapeutic potential against tumors with homologous recombination (HR) defects such as alternation of BRCA genes. Herein, we report the design and proof of concept of a highly potent dual Polθ/PARP inhibitor 25d , which exhibited low nanomolar inhibitory activities against both Polθ and PARP1. Compared to combination treatment, 25d demonstrated superior antitumor efficacy in both MDA-MB-436 cells and xenografts by inducing more DNA damage and apoptosis. Importantly, 25d retained sensitivity in PARP inhibitor-resistant MDA-MB-436 cells with 53BP1 defect. Altogether, these findings illustrate the potential advantages of 25d , a first-in-class dual Polθ/PARP inhibitor, over monotherapy in treating HR-deficient tumors, including those with acquired PARP inhibitor resistance.

Though firstly identified in cerebral folate deficiency, autoantibodies against folate receptors (FRAbs) have been implicated in pregnancy complications such as miscarriage; however, the underlying mechanism needs to be further elaborated. FRAbs can be produced via sensitization mediated by folate-binding protein as well as gene mutation, aberrant modulation, or degradation of folate receptors (FRs). FRAbs may interfere with folate internalization and metabolism through blocking or binding with FRs. Interestingly, different types of FRs are expressed on trophoblast cells, decidual epithelium or stroma, and macrophages at the maternal-fetal interface, implying FRAbs may be involved in the critical events necessary for a successful pregnancy. Thus, we propose that FRAbs may disturb pregnancy establishment and maintenance by modulating trophoblastic biofunctions, placental development, decidualization, and decidua homeostasis as well as the functions of FOLR2 + macrophages. In light of these findings, FRAbs may be a critical factor in pathological pregnancy, and deserve careful consideration in therapies involving folic acid supplementation for pregnancy complications., Competing Interests: The authors declare no conflicts of interest.

The aim of this study is to optimize the performance conditions used for maximum anti-inflammatory activity and to clarify in vitro anti-inflammatory properties of fermented C. tricuspidata fruit. Based on the single-factor experiment and Box-Behnken design, the optimized fermentation conditions of C. tricuspidata fruit for maximum anti-inflammatory activity were 3.8 d fermentation period, 8.4% (v/w) inoculation concentration, and 29.2°C fermentation temperature. Under optimal conditions, anti-inflammatory activity-based nitric oxide of fermented C. tricuspidata fruit reached 93.9%. Moreover, this study provides a theoretical basis and experimental data containing β -hexosaminidase and reactive oxygen species for the medical use and industrialization of C. tricuspidata fruit fermentation. Interestingly, the results of GC-MS analysis confirmed that fermented C. tricuspidata fruits detect volatile components different from unfermented C. tricuspidata fruits. We suggested that this volatile component may have been involved in the anti-inflammatory reaction, but scientific verification of this is needed later. Therefore, an in-depth study of volatile components detected from fermented C. tricuspidata fruits will need to be conducted later., Competing Interests: The authors declare that they have no conflicts of interest regarding this article., (Copyright © 2023 Si Young Ha et al.)

This study evaluated the effects of supplementing solubles from shredded, steam-exploded pine particles (SSPP) on growth performances, plasma biochemicals, and microbial composition in broilers. The birds were reared for 28 days and fed basal diets with or without the inclusion of SSPP from 8 days old. There were a total of three dietary treatments supplemented with 0% (0% SSPP), 0.1% (0.1% SSPP) and 0.4% (0.4% SSPP) SSPP in basal diets. Supplementation of SSPP did not significantly affect growth or plasma biochemicals, but there was a clear indication of diet-induced microbial shifts. Beta-diversity analysis revealed SSPP supplementation-related clustering (ANOSIM: r = 0.31, p < 0.01), with an overall lower (PERMDISP: p < 0.05) individual dispersion in comparison to the control group. In addition, the proportions of the Bacteroides were increased, and the relative abundances of the families Vallitaleaceae, Defluviitaleaceae, Clostridiaceae, and the genera Butyricicoccus and Anaerofilum ( p < 0.05) were significantly higher in the 0.4% SSPP group than in the control group. Furthermore, the linear discriminant analysis effect size (LEfSe) also showed that beneficial bacteria such as Ruminococcus albus and Butyricicoccus pullicaecorum were identified as microbial biomarkers of dietary SSPP inclusion ( p < 0.05; | LDA effect size | > 2.0). Finally, network analysis showed that strong positive correlations were established among microbial species belonging to the class Clostridia , whereas Erysipelotrichia and Bacteroidia were mostly negatively correlated with Clostridia . Taken together, the results suggested that SSPP supplementation modulates the cecal microbial composition of broilers toward a "healthier" profile., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2023 Korean Society of Animal Science and Technology.)

The study investigated the antioxidant effects of roasted Cudrania tricuspidata ( C. tricuspidata ) fruits by comparing them with unroasted C. tricuspidata fruits. The results showed that the roasted C. tricuspidata fruits (150 °C, 120 min) exhibited significantly higher antioxidant activity, especially in terms of anti-inflammatory effects, than the unroasted fruits. Interestingly, there is a high correlation between the color of the roasted fruit and the antioxidant activity. Heating disrupts cells and deactivates endogenous oxidative enzymes, leading to an increase in flavonoid content. Moreover, heat treatment may also interfere with plant metabolism, thereby influencing flavonoid content. Moreover, an HPLC analysis of roasted fruits in our study showed that the increase in antioxidant activity was attributed to the increase in flavan-3-ols and phenolic acids in the roasted C. tricuspidata fruits. To the best of our knowledge, this is the first time the antioxidant activity and anti-inflammation of roasted C. tricuspidata fruits was studied. The study concluded that roasted C. tricuspidata fruits could be a valuable natural source of antioxidants for various food and medicinal applications.

This study was conducted to investigate the effect of supplementing solubles from steam-exploded pine particles (SSPP) on mitigating the adverse effects of cyclic heat stress (CHS) in broilers which were distributed into 3 dietary treatment groups and 2 temperature conditions. Heat stress (HS) exposure for 6 h daily for 7 d adversely affected performance parameters and rectal temperature of chickens. The absolute and relative weights of the liver and bursa of Fabricius decreased in the CHS group while the relative lengths of the jejunum and ileum increased, which was rescued by dietary supplementation with SSPP. The expression of mucin2 (MUC2) and occludin (OCLN) genes was decreased in CHS birds. The expression of heat shock protein -70 and -90 increased in 0% HS compared to that in 0% NT. Birds supplemented with 0.4% SSPP had higher NADPH oxidase -1 expression than birds in the 0% and 0.1% SSPP treatments. Beta diversity of gut microbiota evaluated through unweighted UniFrac distances was significantly different among treatments. Bacteroidetes was among the 2 most abundant phyla in the cecum, which decreased with 0.1% NT and increased with 0.1% HS in comparison to 0% NT. A total of 13 genera were modified by HS, 5 were altered by dose, and nine showed an interaction effect. In conclusion, CHS adversely affects performance and gut health which can be mitigated with dietary SSPP supplementation that modifies the cecal microbiota in broilers., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Bruton's tyrosine kinase (BTK) is a promising drug target for the treatment of B-cell related malignancies. Irreversible inhibition of BTK by a covalent inhibitor has been proved to be a clinically effective therapy. However, most irreversible BTK inhibitors also inhibit other kinases including JAK3 and EGFR, leading to some adverse events. Herein, we reported the structure-based design and optimization of a series of irreversible BTK inhibitors bearing the 6-amino-1,3,5-triazine scaffold. Most of the synthesized compounds demonstrated considerable BTK inhibition and improved anti-proliferative activity against Raji and Ramos cells. Among them, compound C11 exhibited potent BTK inhibition (BTK IC 50  = 17.0 nM) and a desirable selectivity profile especially over EGFR. Moreover, C11 effectively blocked activation of BTK and downstream signaling, arrested the cell cycle in G0/G1 phase and induced apoptosis in Raji cells. Its irreversible binding mode was further investigated by both molecular modeling and a washout experiment. Collectively, C11 is a novel selective irreversible BTK inhibitor worthy of further in-depth research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Prostate cancer (PC), the second most prevalent malignancy in men worldwide, has been proven to depend on the aberrant activation of androgen receptor (AR) signaling. Long-term androgen deprivation for the treatment of PC inevitably leads to castration-resistant prostate cancer (CRPC) in which AR remains a crucial oncogenic driver. Thus, there is an urgent need to develop new strategies to address this unmet medical need. Targeting AR for degradation has recently been in a vigorous development stage, and accumulating clinical studies have highlighted the benefits of AR degraders in CRPC patients. Herein, we provide a comprehensive summary of small-molecule AR degraders with diverse mechanisms of action including proteolysis-targeting chimeras (PROTACs), selective AR degraders (SARDs), hydrophobic tags (HyT), and other AR degraders with distinct mechanisms. Accordingly, their structure-activity relationships, biomedical applications, and therapeutic values are also dissected to provide insights into the future development of promising AR degradation-based therapeutics for CRPC.

Marine oil spill pollution have increased recent years, threatening the safety of the marine environment. This paper proposes a coupling technique: Fast Mapping & Addressing(FMA) that integrates the oil spill model with oceanographic model. The FMA technique is based on hash function and spatial quadtree algorithm to achieve efficient addressing from an unstructured to a structured grid. The oil spill model simulates the oil spill process, while the ocean model simulates the ocean currents. The efficiency is improved about ten times compared to the interpolation algorithm. Results reveal the difference between the simulation results of the ocean model and the measured data is minimal, with an MAE(Mean Absolute Error) and RMSE(Root Mean Square Error) of about 0.06 m. Moreover, two oil spill events in China's nearshore were selected to simulate and verify the results. Indeed, our model's results agree with the observed data, demonstrating that our model can achieve a satisfied simulation of oil spill., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Improving the availability of underutilized waste for the economic use of livestock feed can be important in countries where feed grain production is scarce. Modulating the gut microbiota through the fibrous content present in these wastes may help mitigate the adverse effects of heat stress (HS). Here, we investigated the effects of dietary steam-exploded pine particle (SPP), a value-added waste product, on the performance, gut health, and cecum microbiota in heat-stressed broilers. Ross 308 broilers (n = 180) at 29 days of age were distributed into three dietary treatment groups (0%, 1%, and 2% SPP) and two temperature conditions (NT: 21 °C; CHS: 31 °C) and grown for seven days. CHS, but not SPP, adversely affected performance parameters, but SPP did not interactively modulate these results. On the contrary, both differently affected other parameters. CHS resulted in increased rectal temperature, total protein in serum, and Nox4 gene expression, whereas 2% SPP increased GLP-2 and the Nox4 gene expression in the duodenum in comparison to 0% and 1% SPP. CHS significantly modified the beta-diversity of cecal microbiota while 1% SPP supplementation in diets increased the abundance of the favorable bacterial genera in chicken. Concludingly, CHS adversely affects growth performances, gut health, stress-related genes, and cecal microbiota while dietary 1% SPP may facilitate the proliferation of beneficial microorganisms in the cecum of broilers., (© 2022. The Author(s).)

Heat stress (HS) negatively influences livestock productivity, but it can be, at least in part, mitigated by nutritional interventions. One such intervention is to use byproducts from various sources that are likely to be included in the consumer chain. Thus, the present study investigated the effects of dietary supplementation of solubles from shredded, steam-exploded pine particles (SSPPs) on the performance and cecum microbiota in broilers subjected to acute HS. One-week-old Ross 308 broilers (n = 108) were fed 0%, 0.1%, or 0.4% SSPP in their diets. On the 37th day, forty birds were allocated to one of four groups; namely, a group fed a control diet without SSPPs at thermoneutral temperature (NT) (0% NT) and acute heat-stressed birds with 0% (0% HS), 0.1% (0.1% HS), and 0.4% (0.4% HS) SSPP-supplemented diets. The NT was maintained at 21.0 °C, while the HS room was increased to 31 °C. The final BW, percent difference in body weight (PDBW), and feed intake (FI) were lower in HS birds, but PDBW was reversely associated with dietary SSPP. Similarly, HS birds had a higher rectal temperature (RT) and ΔT in comparison to birds kept at NT. The FI of SSPP-supplemented birds was not significant, indicating lower HS effects. Plasma triglyceride was decreased in HS birds but not affected in 0.1% HS birds in comparison to 0% NT birds. OTUs and Chao1 were increased by 0.1% HS compared to 0% NT. Unweighted Unifrac distances for 0.1% HS were different from 0% NT and 0.4% HS. The favorable bacterial phylum ( Tenericutes ) and genera ( Faecalibacterium and Anaerofustis ) were increased, while the pathogenic genus ( Enterococcus ) was decreased, in SSPP-supplemented birds. In sum, production performances are negatively affected under acute HS. Dietary supplementation of SSPPs is beneficial for improving community richness indices and unweighted Unifrac distances, and it enhanced the advantageous bacterial phyla and reduced virulent genera and triglyceride hydrolysis in acute HS broilers. Our results indicate that dietary SSPPs modulates the microbial profile of the cecum while resulting in relatively less weight loss and lower rectal temperature compared to control.

We compared the performance of 2 automated systems for detection of carbapenemase-producing Enterobacteriaceae, BD MAX Check-Points CPO (CPO assay) and Xpert Carba-R assay, with culture confirmed by polymerase chain reaction as the reference method. Using 867 samples from 627 patients, the overall sensitivity, specificity, total positive predictive value, and negative predictive value of the CPO assay were 95.7%, 96.5%, 60.8% and 99.8% and for the Xpert assay were 97.9%, 99.8%, 95.8%, and 99.9%, respectively. The cycle threshold values (Ct value) of the false-positive CPO assay results were significantly higher than those of true-positive cases (P < 0.001). By applying a modified cut-off Ct value of 37.3 for klebsiella pneumoniae carbapenemases (KPC), the positive predictive value for KPC was improved from 52.9% to 89.5%. The CPO assay will be useful when handling many specimens, as tests are conducted in batches. However, positive cases showing high Ct values should be confirmed by another assay to rule out false positivity., Competing Interests: Declaration of competing interest The authors declare the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Osteosarcoma (OS) is a malignant tumor that occurs in children and adolescents. Previous studies reported a low expression of miR-148b-3p in OS, but its biological function in OS remains obscure. This study aimed to explore the role of miR-148b-3p in OS progression. Herein, the expression of miR-148b-3p and son of sevenless homolog 1 (SOS1) both in OS tissues and cells were examined using quantitative real-time polymerase chain reaction and Western blotting assay. miR-148b-3p mimic or inhibitor, pcDH-SOS1 plasmid or si-SOS1 and agomir-miR-148b-3p were constructed for cell transfection. In vitro , the biological effect of miR-148b-3p was determined employing MTT, EdU, colony formation, flow cytometry, transwell and wound healing assay, separately. The target relationship between SOS1 3'-untranslated region (3'-UTR) and miR-148b-3p was analyzed using dual-luciferase reporter gene. In vivo , the inhibition of agomir-miR-148b-3p in mice was evaluated via a xenograft mouse model. miR-148b-3p was noticeably low-expressed in OS tissues and cells, and miR-148b-3p over-expression in OS cells suppressed the growth, migration and invasion, induced apoptosis. The effect of miR-148b-3p-inhibitor on cell biological behavior is opposite to that of miR-148b-3p over-expression. Conversely, The expression of SOS1 was significant higher in OS tissues and cells, miR-148b-3p targeted and was negatively associated with the expression level of SOS1. In addition, the anti-tumor effect of miR-148b-3p was reversed by SOS1. Importantly, we demonstrated that the tumor growth of stably over-expressed miR-148b-3p human MG-63 cells was obviously reduced in tumor-bearing mice. These data highlighted that miR-148b-3p might be as a promising therapeutic target for OS.

The conditions for sex reversal in vertebrate species have been extensively studied, and the results highlighted numerous key factors involved in sex differentiation. However, the transcriptomes in hypothalamic and pituitary tissues from intersex goats have rarely been studied. The aim of this study was to screen candidate genes and signalling pathways related to sex reversal in Huai goats by analyzing gene expression in hypothalamic and pituitary tissues via transcriptome sequencing and bioinformatics analyses. In total, 612 and 139 differentially expressed genes (DEGs) were identified between the intersex and non-intersex groups in the hypothalamus and pituitary, respectively. The DEGs in the hypothalamus and pituitary were significantly enriched in 41 and 16 signalling pathways, respectively, including the calcium signalling pathway, neuroactive ligand-receptor interaction signalling pathway, and oestrogen signalling pathway, which might be related to intersex sex development disorders. A candidate gene from the tachykinin family (TACR1) was significantly enriched in the calcium signalling pathway. Thirty-one DEGs were shared between these two comparisons and were enriched in several acetyl-CoA-related processes and the oestrogen signalling pathway. The results of the real-time PCR analysis show that the transcriptome sequencing results were reliable. The transcriptome data indicate that the regulation of various physiological systems is involved in intersex goat development. Therefore, these results provide helpful data enhancing our understanding of the molecular mechanisms underlying intersex syndrome in goats., (© 2021 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Essential oils are aromatic oils extracted from the leaves, stems, peels, petals, and roots of aromatic plants grown in nature or grown in organic methods and have various medical effects as natural substances. The essential oil extracted from Camellia japonica seeds exhibits various functional properties; however, its tyrosinase inhibitory activity has not been investigated extensively. This study is performed to investigate the chemical composition and tyrosinase inhibitory activity of Camellia japonica seed essential oil (CJS-EO). Hexamethylcyclotrisiloxane (42.36%) and octamethylcyclotetrasiloxane (23.28%) are the two primary components of CJS-EO, as identified via gas chromatography-mass spectrometry. The inhibitory activities of CJS-EO and positive control arbutin are further evaluated against mushroom tyrosinase. The results show that CJS-EO and arbutin inhibit tyrosinase activity. Moreover, CJS-EO significantly inhibits melanogenesis in the α -melanocyte-stimulating hormone-treated group, and a significant amount of melanin is suppressed. To ascertain the cause of the CJS-EO tyrosinase inhibitory effect and melanin reduction effect, genetic and protein analyses are performed. Based on our results, we tentatively conclude that CJS-EO can inhibit melanocytes from harmful factors such as tyrosinase-related protein. These results demonstrate that CJS-EO possesses potent antityrosinase activity and may be a good skin-whitening agent., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Si Young Ha et al.)

Objectives: To compare cardiac function and systolic dyssynchrony of fetuses not exposed to and those exposed to maternal autoimmune antibodies using two-dimensional speckle tracking echocardiography (2DSTE)., Methods: An observational study of 52 fetuses, 18 from mothers with autoimmune antibodies (anti-SSA/Ro60, anti-Ro52 or/and anti-SSB/La) and 34 from healthy mothers without antibodies, was conducted. Maternal baseline characteristics, fetoplacental Doppler parameters, and conventional echocardiographic data were prospectively collected. Systolic global and regional longitudinal strain of left and right ventricle (LV and RV) and the time to peak strain of regional myocardium were measured using 2DSTE. We also calculated the differences in time to peak strain between the LV free wall and RV free wall (two-chamber dyssynchrony, 2C-DYS) and the LV dyssynchrony between the septum and LV free wall (one-chamber dyssynchrony, 1C-DYS)., Results: There were no significant differences in conventional systolic and diastolic functional parameters for the LV and RV. No effect modification was demonstrated in a myocardial deformation analysis. However, 1C-DYS was significantly more prolonged in the maternal autoimmune disease group (19.50 [8.00 to 29.25] vs. 28.50 [13.50 to 39.25], P = 0.042)., Conclusions: LV systolic mechanical dyssynchrony in fetuses of mothers with autoimmune antibodies suggests in-utero subclinical damage of the cardiac conduction system. Key points • The left ventricular systolic dyssynchrony was significantly more prolonged in the maternal autoimmune disease (AD) fetuses. • Subclinical damage to the left ventricular conduction system of the fetal heart in maternal AD was observed. • Systolic and diastolic functional of the left and right ventricle were preserved in fetuses exposed to maternal autoimmune disease., (© 2021. The Author(s).)

The gut microbiome stimulates nutrient metabolism and could effectively generate heat tolerance in chickens. This study investigates the effects of dietary steam-exploded pine particle (SPP) supplementation and subsequent acute heat stress on productive performance and cecum microbiome in broilers. Eight-day Ross 308 broilers were distributed in three groups with 0%, 1%, and 2% SPP in diets. On the 41st day, forty birds were allocated to four groups with ten birds each. The treatments were control diet at thermoneutral temperature (0% NT) and acute heat-stressed (HS) birds fed control (0% HS), 1% (1% HS), and 2% (2% HS) SPP. Parameters recorded were body weight (BW), feed intake (FI), rectal temperature (RT), relative organ weight, and metagenome analysis from cecum samples. Percent difference in BW, FI, and RT was decreased in HS birds. Metagenome analysis revealed similar richness and diversity in microbial communities. The relative abundance of the bacterial genus such as Limosilactobacillus , Drancourtella , and Ihubacter was increased while that of Alistipes , Alkalibacter , Lachnotalea , and Turicibacter was decreased in SPP supplemented HS birds. Concludingly, the production performance of broilers is negatively influenced during HS, and 2% dietary SPP supplementation may reduce the adverse effects of HS by modifying the microbiota in chickens.

Accurate long-term streamflow and flood forecasting have always been an important research direction in hydrology research. Nowadays, climate change, floods, and other anomalies occurring more and more frequently and bringing great losses to society. The prediction of streamflow, especially flood prediction, is important for disaster prevention. Current hydrological models based on physical mechanisms can give accurate predictions of streamflow, but the effective prediction period is only about 1 month in advance, which is too short for decision making. The artificial neural network (ANN) has great potential for predicting runoff and is not only good at handling non-linear data but can also make long-period forecasts. However, most of ANN models are unstable in their predictions when faced with raw flow data, and have excessive errors in predicting extreme flows. Previous studies have shown a link between the El Niño-Southern Oscillation (ENSO) and the streamflow of the Yangtze River. In this paper, we use ENSO and the monthly streamflow data of the Yangtze River from 1952 to 2018 to predict the monthly streamflow of the Yangtze River in two extreme flood years and a small flood year by using deep neural networks. In this paper, three deep neural network frameworks are used: stacked long short-term memory, Conv long short-term memory encoder-decoder long short-term memory and Conv long short-term memory encoder-decoder gate recurrent unit. The results show that the use of ConvLSTM improves the stability of the model and increases the accuracy of the flood prediction. Besides, the introduction of ENSO to the experimental data resulted in a more accurate prediction of the time of the occurrence of flood peaks and flood flows. Furthermore, the best results were obtained on the convolutional long short-term memory + encoder-decoder gate recurrent unit model.

Background: Rapid and accurate microbial identification and antimicrobial susceptibility testing (AST) are essential for timely use of appropriate antimicrobial agents for bloodstream infection. To shorten the time for isolating colonies from the positive blood culture, various preparation methods for direct identification using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system were developed. Here, we evaluated the SepsiPrep kit (ASTA Corp.) for direct identification of microorganisms and AST from positive blood cultures using MicroIDSys Elite MALDI-TOF MS system (ASTA Corp.) and VITEK-2 system (bioMérieux)., Methods: For direct identification, a total of 124 prospective monomicrobial positive blood culture bottles were included. For direct identification, the pellet was prepared by centrifugation and washing twice. For direct AST, the pellet was suspended in 0.45% saline and adjusted to McFarland 0.5. The results from the direct identification and AST using MicroIDSys Elite and VITEK-2 system were compared to those from the conventional method performed with pure colony subcultured on agar plate., Results: Compared to the conventional method using pure colony, correct direct identification rate was 96.5% and 98.5% for 57 gram-positive isolates and 67 gram-negative isolates, respectively. For direct AST, among the 55 gram-positive isolates, the categorical agreement (CA) for staphylococci, streptococci, and enterococci was 96.7%, 98.4%, and 94.1%, respectively. For 66 gram-negative isolates, the CA for Enterobacterales and non-fermentative gram-negative rods was 99.0% and 96.6%, respectively., Conclusions: The SepsiPrep kit was easy to use combined with MicroIDSys Elite and VITEK-2 system and also, the correct identification and AST rate were very high., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

The ASTA MicroIDSys system (ASTA, Suwon, Korea) is a newly developed Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system for identification of microorganisms. We compared the performance of the ASTA MicroIDSys system with that of the VITEK MS system (bioMérieux, Marcy l'Etoile, France) for identifying clinical microorganisms. A total 2055 isolates including 1910 bacteria and 145 yeasts were tested. Among them, the VITEK MS correctly identified 1999 (97.3%) isolates to species level and 26 (1.3%) to the genus level. The ASTA MicroIDSys correctly identified 1988 (96.7%) isolates to species level and 28 (1.4%) to the genus level. The VITEK MS and ASTA MicroIDSys misidentified one isolate and four (0.2%) isolates, respectively, and provided no identification for 29 (1.4%) and 35 (1.7%) isolates, respectively. The performance of the ASTA MicroIDSys was comparable to that of the VITEK MS for identification of clinically relevant bacterial and yeast isolates., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Huang-huai sheep are a new multiparous mutton sheep breed that has been cultivated by domestic scientific research institutes, governments, and sheep farms in China. Huang-huai sheep were bred using Dorper sheep as a sire and Small-tailed Han sheep as a dam. The breeding of Huang-huai sheep started in 2003, and three stages have been carried out: crossbreeding innovation, fixation in a two-way-crossbred closed flock, and herd propagation. A pilot test of Huang-huai sheep was conducted on 6 sheep farms from 2017 to 2018, and hereditary properties and production performance were evaluated in 2019. Huang-huai sheep were identified on site by the National Livestock and Poultry Resources Committee of China in December 2019 and approved as a new multiparous mutton sheep breed in China. The genetic distance showed that Huang-huai sheep are most closely related to Dorper sheep, Luxi black-headed sheep, and Small-tailed Han sheep, but the genetic distances are subspecies (0.02-0.20) each other. The body weights of adult Huang-huai sheep are 98.1 ± 5.2 kg (♂) and 71.7 ± 3.5 kg (♀), and those of 6-month-old Huang-huai sheep are 58.50 ± 6.55 kg (♂) and 52.45 ± 5.67 kg (♀). The slaughter rates of 6-month-old sheep are 56.02 ± 1.25% (♂) and 53.19 ± 1.19% (♀). The estrus cycle of Huang-huai sheep is 19.32 ± 2.8 days, the first estrus cycle occurs at 168 ± 12 days, the annual lambing rate of ewes is 252.82% ± 10.69%, the survival rate of lambs is 95.79 ± 0.95%, and the number of weaned lambs per ewe per year is 2.38 ± 0.14. The growth performance, carcass quality, and reproductive performance of Huang-huai sheep have been improved, resulting in considerable economic and social benefits and broader market prospects. This breed represents a new multiparous mutton sheep breed adapted for industrial sheep farms in China.

Problem: Endometrial hyperplasia (EH) is characterized by an endometrial gland-to-stroma ratio >1 and is one of the most common gynecological diseases in the world. The role of immunocyte subsets in the development of EH remains unknown., Methods: Patients who underwent dilatation and curettage due to abnormal uterine bleeding were recruited in the present study. Alterations in the numbers of different types of immune cell subsets in the endometrium of patients were analyzed by flow cytometry., Results: The present study included 48 patients who were divided into three groups, based on the pathological results: (a) proliferative period (PP, n = 12); (b) simple EH (SEH, n = 30); and (c) complex EH (CEH, n = 6). The results showed that immune cell subpopulations were significantly different between these three groups. Compared with the PP group, the proportion of CD45 + cells and neutrophils and the subtypes of T cells and macrophages were significantly increased in the SEH patients. Compared with the PP and SEH groups, subsets of immunocytes in the CEH group were significantly decreased, including the population of CD45 + cells and the subtypes of T cells and natural killer cells; in contrast, the proportion of macrophages was significantly increased. There were no significant differences between the other cell subsets in each group., Conclusion: The changes in immune cell subsets may be closely associated with the progression of EH. Although the specific role of different immune cell subsets in the development of the diseases requires further study, the changes in the proportions of immune cell subsets should not be ignored., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of a series of cytokines and immune cells. Chemokines are a type of special cytokine those were originally described as having a role in leukocyte trafficking. CXC chemokine ligand (CXCL) 16 is a member of the chemokine family, and CXC chemokine receptor (CXCR) 6 is its sole receptor. Emerging evidence has shown that CXCL16/CXCR6 is expressed at the maternal-fetal interface, by cell types that include trophoblast cells, decidual stroma cells, and decidual immune cells (eg, monocytes, γδT cells, and natural killer T (NKT) cells). The regulation of expression of CXCL16 is quite complex, and this process involves a multitude of factors. CXCL16 exerts a critical role in the establishment of a successful pregnancy through a series of molecular interactions at the maternal-fetal interface. However, an abnormal expression of CXCL16 is associated with certain pathological states associated with pregnancy, including recurrent miscarriage, pre-eclampsia, and gestational diabetes mellitus (GDM). In the present review, the expression and pleiotropic roles of CXCL16 under conditions of physiological and pathological pregnancy are systematically discussed., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Immune cells and cytokines have important roles in the pathogenesis of endometriosis. However, the production and role of cytokines of T helper type 1 (Th1) and Th2 cells in the progress of endometriosis have remained to be fully elucidated. The present study reported that the interferon (IFN)-γ levels and the percentage of IFN-γ+CD4+ cells were significantly increased in the peritoneal fluid (PF) at the early stage and maintained at a higher level at the advanced stage of endometriosis; furthermore, interleukin (IL)-10 and IL-10+CD4+ cells were elevated in the advanced stage of endometriosis. In addition, IL-2 levels in the PF at the advanced stage of endometriosis were elevated and negatively associated with IFN-γ expression. In a co-culture system of ectopic endometrial stromal cells (ESCs) and macrophages, elevated IL-2 was observed, and treatment with cytokines IL-2 and transforming growth factor-β led to upregulation of the ratio of IL-2+ macrophages. IL-27-overexpressing ESCs and macrophages were able to induce a higher ratio of IL-10+CD4+ T cells. Blocking of IL-2 with anti-IL-2 neutralizing antibody led to upregulation of the ratio of IFN-γ+CD4+ T cells in the co-culture system in vitro. Recombinant human IL-10 and IFN-γ promoted the viability, invasiveness and transcription levels of matrix metalloproteinase (MMP)2, MMP9, and prostaglandin-endoperoxide synthase 2 of ESCs, particularly combined treatment with IL-10 and IFN-γ. These results suggest that IL-2 and IL-27 synergistically promote the growth and invasion of ESCs by modulating the balance of IFN-γ and IL-10 and contribute to the progress of endometriosis.

During gestation, excess palmitate (PA) is enriched in decidua. Both excess PA and decidual dysfunctions are associated with numerous adverse pregnancy outcomes such as gestational diabetes, preeclampsia and preterm birth and intrauterine growth restriction. Here, mRNA data about the effects of PA were collected from multiple databases and analyzed. Human decidual tissues were obtained from clinically normal pregnancies, terminated for non-medical reasons, during the first trimester, and decidual stromal cells (DSCs) were isolated and exposed to PA, alone or together with the inhibitors of Toll-like receptor 4 (TLR4), Jun N-terminal kinase (JNK), nuclear factor-kappa-gene binding (NF-kB) or glutamine (GLN) oxidation. Furthermore, DSCs were transfected with lentiviral particles overexpressing human TLR4. We demonstrate that excess PA interacting with its receptor TLR4 disturbs DSC hemostasis during the first trimester. Specifically, high PA signal induced DSC apoptosis and formed an inflammatory program (elevated interleukin-1 beta and decreased interleukin-10) via the activation of TLR4/JNK/NF-kB pathways. A complexed cross-talk was found between TLR4/JNK/NF-kB signals and PA deposition in DSCs. Besides, under an excess PA environment, GLN oxidation was significantly enhanced in DSCs and the suppression of GLN oxidation further augmented PA-mediated DSC apoptosis and inflammatory responses. In conclusion, excess PA induces apoptosis and inflammation in DSCs via the TLR4/JNK/NF-kB pathways, which can be augmented by the suppression of GLN oxidation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Problem: Decidual natural killer (dNK) cells play key roles in maternal-fetal immune regulation, trophoblast invasion, and vascular remodeling, and most dNK cell populations are CD56 bright CD16 - NK cells. However, the enrichment and redistribution of dNK cells in the local decidua have not been clarified yet., Method of Study: A total of 45 women with normal pregnancies and 8 unexplained recurrent spontaneous abortion (RSA) patients were included. We isolated primary human dNK (n = 53) and peripheral blood NK (pNK) cells (n = 5) from specimen and analyzed CD56, CD82, and CD29 by flow cytometry (FCM). We assessed their adhesion ability by cell counts of NK cells adhered to decidual stromal cells (DSCs) in a co-culture system., Results: We found that RSA patients had more CD56 dim dNK cells with lower CD82 and higher CD29 than women with normal pregnancies. There were negative correlations of CD82 to CD29 on CD56 dim and CD56 + dNK cells. In normal pregnancies, dNK cells had lower CD82 and higher CD29 expression with a stronger adhesion ability than pNK cells. Blocking CD82 on dNK cells increased the adhesive ability and CD29 expression, while blocking CD29 decreased the adhesive ability. Co-culturing dNK cells with trophoblast cells decreased CD82 expression and increased the adhesive ability of dNK cells and the percentage of CD56 bright NK cells, while blocking trophoblast-derived CXCL12 increased CD82 expression, decreased CD29 expression, and impaired the adhesive ability of NK cells., Conclusion: Trophoblast cells enhance the adhesive ability of NK cells to DSCs via the CXCL12/CD82/CD29 signaling pathway and contribute to CD56 bright NK cell enrichment in the uterus., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Indocyanine green (ICG) video angiography has been widely used in cerebrovascular surgery. ICG injection is generally safe, with a low incidence of complications. ICG-related anaphylactic reactions during neurosurgery have been rarely reported. We report the cases of 2 patients who had experienced anaphylactic shock in response to intravenous ICG injection (DID Indocyanine Green [Dongindang, Inc., Gyeonggi-do, Republic of Korea]) during intracranial aneurysm (IA) surgery., Case Description: The first patient, a 69-year-old woman with an unruptured IA, had been undergoing clipping surgery under general anesthesia. Immediately after ICG injection, her blood pressure suddenly decreased from 140/80 mm Hg to 50/30 mm Hg and she developed a skin rash on her abdomen and all extremities. Chest compression was initiated, and her vital signs gradually recovered to their pre-ICG levels within 10 minutes. The second patient was a 58-year-old woman with an unruptured IA who had been undergoing clipping surgery. After ICG injection, her blood pressure had decreased from 130/80 mm Hg to 60/40 mm Hg, and a rash-like skin lesion was observed on her abdomen. After intravenous injection of norepinephrine and dexamethasone, her blood pressure recovered to its pre-ICG level within 30 minutes and remained stable thereafter. The postoperative ICG skin provocation test findings were positive for both patients; however, only 1 patient showed markedly increased serum tryptase levels., Conclusion: Despite the rarity of ICG-related anaphylaxis, clinicians should be aware of this unexpected, but potentially life-threatening, drug reaction in patients undergoing cerebrovascular surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Endometriosis (EMS) is the most common gynecological disease in women of reproductive age, and it is associated with chronic pelvic pain, dyspareunia and infertility. As a consequence of genetic, immune and environmental factors, endometriotic lesions have high cyclooxygenase (COX)-2 and COX-2-derived prostaglandin E 2 (PGE 2 ) biosynthesis compared with the normal endometrium. The transcription of the PTGS2 gene for COX-2 is associated with multiple intracellular signals, which converge to cause the activation of mitogen-activated protein kinases (MAPKs). COX-2 expression can be regulated by several factors, such as estrogen, hypoxia, proinflammatory cytokines, environmental pollutants, metabolites and metabolic enzymes, and platelets. High concentrations of COX-2 lead to high cell proliferation, a low level of apoptosis, high invasion, angiogenesis, EMS-related pain and infertility. COX-2-derived PGE 2 performs a crucial function in EMS development by binding to EP2 and EP4 receptors. These basic findings have contributed to COX-2-targeted treatment in EMS, including COX-2 inhibitors, hormone drugs and glycyrrhizin. In this review, we summarize the most recent basic research in detail and provide a short summary of COX-2-targeted treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Problem: Decidual stromal cells (DSCs) are important origins of cytokines to modulate maternal-fetal immunotolerance and provide a feasible environment for embryo implantation and development. Interleukin (IL)-24 is a multifunctional cancer killing cytokine and a pleiotropic immunoregulator with complex potency according to tissue or cell types. Its role in establishment and maintenance of normal pregnancy is largely unknown. The aim of our study was to investigate the function and significance of IL-24 and its receptor in the coordination between DSCs and natural killer cells (NK) in early pregnancy., Method of Study: The levels of IL-24 in DSC, endometrial stromal cell (ESC), peripheral blood NK cells (pNK), or decidual NK cells (dNK) culture supernatants were detected by enzyme-linked immunosorbent assay (ELISA), and the levels of IL-24 receptors were determined by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry assays. The effect of IL-24 on the functions of decidual NK cells was analyzed by flow cytometry assays in vitro., Results: The concentration of IL-24 in culture supernatant of DSCs was significantly higher than that of ESCs. Both eNK (endometrial NK cells) and dNK highly expressed IL-24 receptors (IL-20R1 and IL-22R1), especially on CD56 dim eNK. However, there were extremely low levels of IL-20R1 and IL-22R1 on pNK. Recombinant human IL-24 or DSCs-secreted IL-24 downregulated the levels of CD16, Granzyme B, perforin, and interferon (IFN)-γ and upregulated the levels of inhibitory receptors killer-cell immunoglobulin-like receptor (KIR)2DL1 and KIR3DL1, or immunotolerant or angiogenic cytokines (eg, transforming growth factor (TGF)-β, IL-10, and IL-8), and elevated the percentage of CD56 bright CD16 - dNK in vitro., Conclusion: These data suggest that DSCs promote the differentiation of CD56 bright CD16 - NK with high levels of inhibitory receptors, immunotolerant, and angiogenic cytokines by secreting IL-24 during decidualization in early pregnancy., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: We aim to investigate whether C21, a selective angiotensin type 2 receptor agonist, can exert protective effects on pancreatic β-cells through activation of antiapoptosis and autophagy., Methods: The high-fat diet-induced obese rats (HFDs) were under C21 treatment for 4 weeks., Results: C21 treatment decreased the fasting glucose levels and improved β-cell insulin secretory function in the HFD group. Hematoxylin and eosin staining and electron microscopy indicated that the islet morphology was improved in the C21-treated obese rats, which was associated with increased levels of the key transcription factor PDX1, glucose sensing, and uptaking protein GCK and GLUT2, respectively. C21 treatment exerted antiapoptotic effects through decreasing the levels of apoptotic marker Caspase-3 while increasing the levels of antiapoptotic markers AKT, p-AKT, and BCL2. C21 treatment also induced autophagosome formation in the mitochondria of the β-cells in the HFD group accompanied by increased levels of autophagy markers, LC-3B and Beclin-1., Conclusions: The results suggested C21 treatment decreased the fasting glucose level and protected β-cell function in the HFD-induced obese rat model, which in part through activation of antiapoptotic and autophagy processes. This study provided preclinical evidence for the utilization of C21 in the treatment of type 2 diabetes.

Heat shock protein 70 (Hsp70) family members play important roles in protecting plants against abiotic stresses, including salt, drought, heat, and cold. In this study, 20 putative StHsp70 genes were identified in potato (Solanum tuberosum L.) through the integration of the gene structures, chromosome locations, phylogenetic relationships, and expression profiles. These StHsp70 genes were classified into five sub-families based on phylogenetic analysis. Chromosome mapping revealed that they were unevenly and unequally distributed on 10 of the 12 chromosomes. Furthermore, segmental and tandem duplication events contributed to the expansion of the StHsp70 genes. Phylogenetic tree of the HSP70 genes from potato and other plant species revealed multiple sub-families. These findings indicated a common ancestor which had generated diverse sub-families prior to a mono-dicot split. In addition, expression analysis using RNA-seq revealed that the majority of these genes were expressed in at least one of the tested tissue, and were induced by Phytophthora infestans. Then, based on qRT-PCR analysis, the results showed that the transcript levels of some of the StHsp70 genes could be remarkably induced by such abiotic and hormone stresses, which indicated their potential roles in mediating the responses of potato plants to both abiotic and biotic stress conditions.

Endometriosis (EMS) is a female hormone‑ dependent disease with controversial reports of its etiology and pathogenesis. Apoptosis is particularly important in the human endometrium due to the dynamic cycles of proliferation and shedding. Estrogen possessed antiapoptotic effects on endometrial stromal cells (ESCs), which appears to be exacerbated in women with EMS; however, the underlying mechanism of the antiapoptotic effects of estrogen on ESC remains unknown. The present study aimed to determine whether estrogen regulates the apoptosis of ESCs via thymic stromal lymphopoietin (TSLP) and the associated mechanism. An ELISA was conducted to detect TSLP content in the ESC culture medium treated with estrogen. Subsequently, the early apoptotic rate and expression of B‑cell lymphoma (Bcl‑2) of ESCs were analyzed by flow cytometry in the presence of recombinant human TSLP, anti‑human TSLP neutralizing antibody or estrogen. In the present study, it was reported that ESCs exhibited basal TSLP secretion in the absence of estrogen as reported in previous studies, and that estrogen promoted TSLP secretion of ESCs in a dose‑dependent manner. The results demonstrated that estrogen suppressed the apoptosis of ESCs associated with the promotion of Bcl‑2 expression, which may be partly reversed by inhibiting TSLP. Therefore, the findings of the present study revealed a novel mechanism of estrogen‑dependent apoptotic suppression of ESCs associated with TSLP secretion and Bcl‑2 regulation. Endogenous and estrogen‑induced endometrial TSLP may promote the initiation and development of EMS via the inhibition of apoptosis.

Background: We evaluated the two in-house sample preparation methods (saponin method (SAP) and [saponin + Sputazyme] method (SSPZ)) for direct identification of microorganisms using MALDI-TOF MS from positive blood culture bottles. Also, we evaluated the [saponin + Sputazyme] method for direct antimicrobial susceptibility testing (AST) using Vitek 2 system., Methods: For direct identification, 163 prospective, monomicrobial positive blood culture bottles and 25 contrived blood culture bottles spiked with 25 infrequently isolated bacterial strains were included. For direct AST, pellets obtained by SSPZ method from 102 prospective blood culture bottles were tested. The results from the direct identification and AST were compared with those from the routine diagnostic method performed with colonies sub cultured on solid media., Results: In 163 prospective specimens, SAP method correctly identified 132/163 (81.0%) isolates and SSPZ method correctly identified 148/163 (90.8%) isolates (P = .018). Among the 92 Gram-positive isolates, the correct identification rate was significantly higher with the SSPZ method than the SAP method (92.4% vs. 81.5%), respectively (P = .041). However, the SSPZ method failed to identify Streptococcus pneumoniae. Among the 64 Gram-negative isolates, the correct identification rate was 82.8% (53/64) and 87.5% (56/64) for the former and the latter method, respectively (P = .491). Compared with standard methods direct AST showed 98.5% (1523/1547) agreement., Conclusion: The addition of Sputazyme improved the identification of commonly isolated bacteria, especially for Gram-positive isolates and yeasts and can be applied for direct antimicrobial susceptibility testing of bacteria. Although SAP method showed better results for Campylobacter spp. and anaerobic bacteria, considering their very low incidence, routine use of SSPZ will be more practical., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The dysfunction of NK cells in women with endometriosis (EMS) contributes to the immune escape of menstrual endometrial fragments refluxed into the peritoneal cavity. The reciprocal communications between endometrial stromal cells (ESCs) and lymphocytes facilitate the development of EMS. However, the mechanism of these communications on cytotoxicity of natural killer (NK) cells in endometriotic milieus is still largely unknown. To imitate the local immune microenvironment, the co-culture systems of ESCs from patients with EMS and monocyte-derived macrophages or of ESCs, macrophages and NK cells were constructed. The cytokine levels in the co-culture unit were evaluated by ELISA. The expression of functional molecules in NK cells was detected by flow cytometry (FCM). The NK cell behaviors in vitro were analyzed by cell counting kit-8 and cytotoxic activation assays. After incubation with ESCs and macrophages, the expression of CD16, NKG2D, perforin and IFN-γ, viability and cytotoxicity of NK cells were significantly downregulated. The secretion of interleukin (IL)-1β, IL-10 and transforming growth factor (TGF)-β in the co-culture system of ESCs and macrophages was increased. Exposure with anti-IL-10 receptor β neutralizing antibody (αhIL-10Rβ) or αTGF-β could partly reverse these effects of ESCs and macrophages on NK cells in vitro These results suggest that the interaction between macrophages and ESCs downregulates cytotoxicity of NK cells possibly by stimulating the secretion of IL-10 and TGF-β, and may further trigger the immune escape of ectopic fragments and promote the occurrence and the development of EMS., (© 2017 Society for Reproduction and Fertility.)

Purpose: After oesophagectomy, anatomical changes and loss of function induce various symptoms that may affect quality of life (QoL) in oesophageal cancer patients. The purpose of this study was to identify the factors influencing QoL in Korean patients who have undergone oesophageal cancer surgery., Method: This was a cross-sectional study of a convenience sample consisting of 120 surgery patients with oesophageal cancer. We used the EORTC QLQ-C30 and EORTC QLQ-OES18 to measure participants' oesophageal cancer-related symptoms and QoL. Multiple regression analyses were applied to analyse to the relationship between cancer-related symptoms and QoL., Results: The average score of oesophageal cancer-related symptoms was 19.28 points, and the most common symptom was reflux. The mean score for global health status/QoL was 60.55. There were significant differences in the functional and symptom subscales according to financial burden, operation type (procedure), and treatment period. Dysphagia most affected global health status/QoL, and eating problems most affected the functional and symptom subscales., Conclusion: Dysphagia and eating problems were confirmed to be the most common symptoms affecting the QoL of patients who had undergone oesophageal cancer surgery. These results can be used to aid in the development of strategies to better manage symptoms in these patients., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False-negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery.

The recently developed CRISPR/Cas9 system is a promising technology for targeted genome editing in a variety of species including plants. However, the first generation systems were designed to target one or two gene loci at a time. We designed a new multiplex CRISPR/Cas9 system that allows the co-expression of six sgRNA modules in one binary vector using a simple (three steps) cloning strategy in Arabidopsis. The transcription of the sgRNA modules is under the control of three different RNA Polymerase III-dependent promoters. We tested the efficiency of the new multiplex system by targeting six of the fourteen PYL families of ABA receptor genes in a single transformation experiment. One line with mutations in all six targeted PYLs was identified from 15 T1 plants. The mutagenesis frequency for the six individual PYL targets in the T1 lines ranged from 13 to 93 %. In the presence of ABA, the transgenic line identified as containing mutations in all six PYL genes produced the highest germination rate in the T2 progeny (37 %). Among these germinated seedlings, half of the analyzed plants (15/30) were homozygous mutants for at least four targeted genes and two plants (6.7 %) contained homozygous mutations in five of the targeted PYLs and the other targeted PYL had biallelic mutations. Homozygous sextuple mutants were identified in the T3 progeny and characterized together with previously described triple and sextuple PYL mutants. We anticipate that the application of this multiplex CRISPR/Cas9 system will strongly facilitate functional analysis of genes pathways and families.

Background: The ideal alternative airway device should be intuitive to use, yielding proficiency after only a few trials. The Clarus Video System (CVS) is a novel optical stylet with a semi-rigid tip; however, the learning curve and associated orodental trauma are poorly understood., Methods: Two novice practitioners with no CVS experience performed 30 intubations each. Each trial was divided into learning (first 10 intubations) and standard phases (remaining 20 intubations). Total time to achieve successful intubation, number of intubation attempts, ease of use, and orodental trauma were recorded., Results: Intubation was successful in all patients. In 51 patients (85%), intubation was accomplished in the first attempt. Nine patients required two or three intubation attempts; six were with the first 10 patients. Learning and standard phases differed significantly in terms of success at first attempt, number of attempts, and intubation time (70% vs. 93%, 1.4 ± 0.7 vs. 1.1 ± 0.3, and 71.4 ± 92.3 s vs. 24.6 ± 21.9 s, respectively). The first five patients required longer intubation times than the subsequent five patients (106.8 ± 120.3 s vs. 36.0 ± 26.8 s); however, the number of attempts was similar. Sequential subgroups of five patients in the standard phase did not differ in the number of attempts or intubation time. Dental trauma, lip laceration, or mucosal bleeding were absent., Conclusions: Ten intubations are sufficient to learn CVS utilization properly without causing any orodental trauma. A relatively small number of experiences are required in the learning curve compared with other devices.

Cardiac resynchronization therapy (CRT) is a proven therapy for selected patients with heart failure, it has been shown to improve symptoms and left ventricular (LV) function and prolong survival. Despite proven benefit of CRT, a significant proportion of patients fail to respond to CRT. Multiple factors contribute to the non-response such as patient selection and device implantation including LV lead placement. Speckle tracking echocardiography (STE) derived strain imaging offers detailed characterization of LV function and provides indices of mechanical dyssynchrony, in addition, STE systolic strain could be used to identify area of scar, therefore applications of STE-derived strain imaging in CRT warrant a closer inspection. This review considers and summarizes different indices of mechanical dyssynchrony generated by STE-derived strain imaging and their relevance in patient selection for CRT and their prognostic values in predicting response to CRT. This review further examines applications of STE-derived strain imaging in optimizing LV lead position by detecting site of latest mechanical activation and presence or absence of transmural scar in a particular segment.

Objectives: The noninvasive and accurate evaluation of vessel characteristics in mouse models has become an intensive focus of vascular medicine. This study aimed to apply ultrasound biomicroscopy to evaluate aortic atherosclerotic progression in a low-density lipoprotein receptor (LDL-R) knockout mouse model of atherosclerosis., Methods: Ten male LDL-R(-/-)C57BL/6 mice aged 16 and 24 weeks and 8 male wild-type C57BL/6 mice aged 16 and 24 weeks were used as experimental and control groups, respectively. Ultrasound biomicroscopy was applied to detect the morphologic characteristics of the aortic root, ascending aorta, aortic arch, and carotid artery and to measure the aortic root intima-media thickness and carotid artery bifurcation., Results: Ultrasound biomicroscopy showed a significant increase in the aortic root intima-media thickness from 0.10 ± 0.03 mm in 16-week-old mice to 0.16 ± 0.04 mm in 24-week-old mice (P < .01). The ultrasound biomicroscopically measured intima-media thickness was highly correlated with the histologic measurement (r = 0.81)., Conclusions: Ultrasound biomicroscopy could be used for a noninvasive, accurate, and dynamic analysis of aortic atherosclerosis in LDL-R knockout mice., (© 2015 by the American Institute of Ultrasound in Medicine.)

Background: Rapid evaluation and management of intracranial pressure (ICP) can help to early detection of increased ICP and improve postoperative outcomes in neurocritically-ill patients. Sonographic measurement of optic nerve sheath diameter (ONSD) is a non-invasive method of evaluating increased intracranial pressure at the bedside. In the present study, we hypothesized that sonographic ONSD, as a surrogate of ICP change, can be dynamically changed in response to carbon dioxide change using short-term hyperventilation., Methods: Fourteen patients were enrolled. During general anesthesia, end-tidal carbon dioxide concentration (ETCO2) was decreased from 40 mmHg to 30 mmHg within 10 minutes. ONSD, which was monitored continuously in the single sonographic plane, was repeatedly measured at 1 and 5 minutes with ETCO2 40 mmHg (time-point 1 and 2) and measured again at 1 and 5 minutes with ETCO2 30 mmHg (time-point 3 and 4)., Results: The mean ± standard deviation of ONSD sequentially measured at four time-points were 5.0 ± 0.5, 5.0 ± 0.4, 3.8 ± 0.6, and 4.0 ± 0.4 mm, respectively. ONSD was significantly decreased at time-point 3 and 4, compared with 1 and 2 (P < 0.001)., Conclusions: The ONSD was rapidly changed in response to ETCO2. This finding may support that ONSD may be beneficial to close ICP monitoring in response to CO2 change.