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Lignocellulose, the most abundant organic waste on Earth, is of economic value because it can be converted into biofuels like ethanol by enzymes such as ß-glucosidase. This study involved cloning a ß-glucosidase gene named JBG from the rumen fungus Neocallimastix patriciarum J11. When expressed recombinantly in Escherichia coli, the rJBG enzyme exhibited significant activity, hydrolyzing 4-nitrophenyl-ß-d-glucopyranoside and cellobiose to release glucose. Surprisingly, the rJBG enzyme also showed hydrolytic activity against ß-glucan, breaking it down into glucose, indicating that the rJBG enzyme possesses both ß-glucosidase and ß-glucanase activities, a characteristic rarely found in ß-glucosidases. When the JBG gene was expressed in Saccharomyces cerevisiae and the transformants were inoculated into a medium containing ß-glucan as the sole carbon source, the ethanol concentration in the culture medium increased from 0.17 g/L on the first day to 0.77 g/L on the third day, reaching 1.3 g/L on the fifth day, whereas no ethanol was detected in the yeast transformants containing the recombinant plasmid pYES-Sur under the same conditions. These results demonstrate that yeast transformants carrying the JBG gene can directly saccharify ß-glucan and ferment it to produce ethanol. This gene, with its dual ß-glucosidase and ß-glucanase activities, simplifies and reduces the cost of the typical process of converting lignocellulose into bioethanol using enzymes and yeast.
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BACKGROUND: Interscalene catheters (ISC) are considered as the gold standard for perioperative pain control after total shoulder arthroplasty (TSA). Liposomal bupivacaine (LB) for interscalene blocks (ISB) or the addition of dexamethasone to ISBs have both presented as additional options for extended analgesia. We aimed to compare the efficacy of LB to a single shot ISB (SISB) with added dexamethasone to an ISC. We hypothesized that a single injection of LB or an ISB with a dexamethasone will provide non-inferior duration and quality of analgesia compared to ISC. METHODS: A single centered triple blinded randomized controlled trial evaluated patients undergoing elective primary TSA. Patients were randomized to 3 groups, Group A (control): 0.5% bupivacaine 15 ml with a rescue catheter left in situ (0.125% bupivacaine infusion), Group B: 0.5% bupivacaine 14 ml with 4mg (1 ml) dexamethasone with a catheter left in situ (saline infusion), Group C: 10 ml of liposomal bupivacaine (133 mg) with 0.5% bupivacaine 5 ml, with a catheter left in situ (saline infusion). The primary outcome was the worst NRS (numeric rating scale) measured on arrival to PACU, 6 hours, 12 hours, 24 hours, and 36 hours postoperatively. Secondary outcomes recorded were time to first analgesic request, intraoperative opioid consumption, total inpatient opioid consumption, arm weakness, arm numbness, time of analgesia duration, time of motor recovery, sensory testing using pinprick on POD1, Q36, Q48, hand strength assessment using dynamometer POD1, Q36, Q48, PACU and hospital length of stay. RESULTS: We analyzed 72 patients in 3 groups (Group A 24, group B 24, Group C 24). The pre-surgery physical function scores were similar between groups. The change in postoperative pain was not different among the three groups. All 3 groups demonstrated an increase in the postoperative values, a change that was not statistically significant between groups. Likewise, no difference in the mental function score was seen within or between groups. No differences in sleep quality or satisfaction were seen among groups (P values 0.405 and 1.00, respectively). No adverse events were reported in all groups. CONCLUSIONS: No significant difference was demonstrated between a single injection ISB with dexamethasone, a LB injection and an ISC. Given the equivalence in analgesia provided with these three modalities, providers should carefully consider the option that best fits each patient. Thus, a single injection of LB or single injection of bupivacaine with dexamethasone provides similar analgesic efficacy compared to ISC.
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Background: Coronary biomechanical stress contributes to the plaque rupture and subsequent events. This study aimed to investigate the impact of plaque biomechanical stability on the physiological progression of intermediate lesions, as assessed by the radial wall strain (RWS) derived from coronary angiography. Methods: Patients with at least one medically treated intermediate lesion at baseline who underwent follow-up coronary angiography over 6 months were included. The maximal RWS ( RWS max ) of the interrogated lesion was calculated from the baseline angiogram. The primary endpoint was to determine the association between baseline RWS max and the functional progression of coronary lesions, defined as an increase in the lesion-specific â³ quantitative flow ratio (L- â³ QFR, calculated as the absolute change in QFR across the lesion) on serial angiograms. Results: Among 175 lesions in 156 patients, 63 lesions showed an increase in L- â³ QFR during a median follow-up period of 12.4 months. Baseline RWS max values were significantly higher in lesions with increased L- â³ QFR than in those with stabilized or decreased L- â³ QFR (11.8 [10.7, 13.7] vs.10.8 [9.7, 11.7]; p = 0.001). Baseline RWS max presented an area under the curve of 0.658 (95% confidence interval [CI]: 0.572-0.743, p < 0.001) for the prediction of increased L- â³ QFR. After full adjustment for clinical and angiographic factors, a high RWS max ( > 12) was found to be an independent predictor of functional lesion progression (odds ratio: 2.871, 95% CI: 1.343-6.138, p = 0.007). Conclusions: A high RWS max calculated from baseline angiograms was independently associated with the subsequent physiological progression in patients with intermediate coronary lesions.
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PURPOSE: Intermittent hypoxia (IH) is a hallmark of obstructive sleep apnea (OSA), which is related to tumorigenesis and progression. Although micro-ribonucleic acid-210-3p (miR-210-3p) is correlated with hypoxia-induced tumor development, its role in the relationship between IH and tumor function remains poorly understood. The present work focused on elucidating the molecular mechanism through which miR-210-3p drives tumor progression under IH. METHODS: MiR-210-3p levels were quantified within tumor samples from patients with lung adenocarcinoma who had or did not have OSA. Correlations between miR-210-3p and polysomnographic variables were analyzed. For in vitro experiments, miR-210-3p was inhibited or overexpressed via transfection under IH conditions. Cell viability, growth, invasion and migration assays were carried out. For in vivo modeling of IH using mouse xenografts, a miR-210-3p antagomir was intratumorally injected, tumor biological behaviors were evaluated, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry and western blot were carried out for detecting miR-210-3p and E2F transcription factor 3 (E2F3) expression. RESULTS: For patients with lung adenocarcinoma and OSA, high miR-210-3p levels showed positive relation to polysomnographic variables, such as oxygen desaturation index, apnea-hypopnea index, and proportion of total sleep time with oxygen saturation in arterial blood < 90%. IH enhanced tumor viability, proliferation, migration, and invasion, downregulated E2F3 expression, and increased miR-210-3-p levels. miR-210-3p overexpression induced similar changes. These changes were reversed by miR-210-3p inhibition in vitro or miR-210-3p antagomir through intratumoral injection in vivo. CONCLUSIONS: IH-induced tumor development is driven through miR-210-3p by E2F3 suppression. MiR-210-3p represents a potential therapeutic target among patients with concomitant cancer and OSA.
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Plant NLR-type receptors serve as sensitive triggers of host immunity. Their expression has to be well-balanced, due to their interference with various cellular processes and dose-dependency of their defense-inducing activity. A genetic "arms race" with fast-evolving pathogenic microbes requires plants to constantly innovate their NLR repertoires. We previously showed that insertion of the COPIA-R7 retrotransposon into RPP7 co-opted the epigenetic transposon silencing signal H3K9me2 to a new function promoting expression of this Arabidopsis thaliana NLR gene. Recruitment of the histone binding protein EDM2 to COPIA-R7-associated H3K9me2 is required for optimal expression of RPP7. By profiling of genome-wide effects of EDM2, we now uncovered additional examples illustrating effects of transposons on NLR gene expression, strongly suggesting that these mobile elements can play critical roles in the rapid evolution of plant NLR genes by providing the "raw material" for gene expression mechanisms. We further found EDM2 to have a global role in NLR expression control. Besides serving as a positive regulator of RPP7 and a small number of other NLR genes, EDM2 acts as a suppressor of a multitude of additional NLR genes. We speculate that the dual functionality of EDM2 in NLR expression control arose from the need to compensate for fitness penalties caused by high expression of some NLR genes by suppression of others. Moreover, we are providing new insights into functional relationships of EDM2 with its interaction partner, the RNA binding protein EDM3/AIPP1, and its target gene IBM1, encoding an H3K9-demethylase.
Subject(s)
Arabidopsis Proteins/genetics , NLR Proteins/genetics , Receptors, Immunologic/genetics , Transcription Factors/genetics , Arabidopsis , Arabidopsis Proteins/metabolism , Epigenesis, Genetic , Gene Expression , Gene Expression Regulation, Plant , Genes, Plant , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , NLR Proteins/biosynthesis , NLR Proteins/metabolism , PHD Zinc Fingers , Plants, Genetically Modified , Protein Domains , RNA-Binding Proteins/genetics , Transcription Factors/metabolismABSTRACT
The design and synthesis of efficient photocatalysts that promote the degradation of organic pollutants in water have attracted extensive attention in recent years. In this work, CdS nanoparticles are grown in situ on Co@C derived from metal-organic frameworks. The resulting hierarchical CdS/Co@C nanostructures are evaluated in terms of their adsorption and photocatalytic ciprofloxacin degradation efficiency under visible-light irradiation. The results show that, apart from offering a large surface area (55.69 m2·g-1), the prepared material can effectively suppress the self-agglomeration of CdS and enhance the absorption of visible light. The CdS/Co@C-7 composite containing 7% wt Co@C has the highest photodegradation rate, and its activity is approximately 4.4 times greater than that of CdS alone. Moreover, this composite exhibits remarkable stability after three successive cycles of photocatalysis. The enhanced photocatalytic performance is largely ascribed to the rapid separation of electron-hole pairs and the effective electron transfer between CdS and Co@C, which is confirmed via electrochemical experiments and photoluminescence spectra. The active substance capture experiment and the electron spin resonance technique show that h+ is the main active entity implicated in the degradation of CIP, and accordingly, a possible mechanism of CIP photocatalytic degradation over CdS/Co@C is proposed. In general, this work presents a new perspective on designing novel photocatalysts that promote the degradation of organic pollutants in water.
Subject(s)
Ciprofloxacin , Nanoparticles , Ciprofloxacin/chemistry , Photolysis , Carbon , Adsorption , Cobalt , Catalysis , Nanoparticles/chemistry , WaterABSTRACT
Trichloroethylene (TCE) was once a widely applied industrial solvent, but is now an infamous contaminant in groundwater. Although anaerobic reductive dechlorination is considered a greener remediation approach, the accumulation of toxic intermediates, such as vinyl chloride (VC), and a longer remediation period are highly concerning. Biostimulation and bioaugmentation have been developed to solve these problems. The former method may not be effective, and the latter may introduce foreign genes. Here, we propose a new approach by applying environmental stresses to reshape the indigenous microbiome. In this study, by using the Taguchi method, the effects of heating, pH, salinity, and desiccation were systematically examined. The optimum conditions were defined as 50 °C, pH 9, 3.50% salinity (w/v), and 21% volumetric water content (θW). The top performing group, G7, can complete the conversion of 11.81 mg/L TCE into ethene in 3.0 days with a 1.23% abundance of Dehalococcoides mccartyi 195 (Dhc 195). Redundancy analysis confirmed that temperature and salinity were the predominant factors in reorganizing the microbiomes. The microbiome structure and its effectiveness can last for at least 90 d. The repetitive selection conditions and sustainable degradation capability strongly supported that microbiome reengineering is feasible for the rapid bioremediation of TCE-contaminated environmental matrices.
Subject(s)
Microbiota , Trichloroethylene , Vinyl Chloride , Biodegradation, Environmental , SalinityABSTRACT
Background and Aims: Social media provides a platform for physicians helping them change the practice in anaesthesiology as it promotes both personal and professional growth. In this cross-sectional study, we identify social media presence and engagement of Accreditation Council for Graduate Medical Education (ACGME)-accredited Regional Anesthesia and Acute Pain Medicine (RAAPM) fellowship programs, specifically on Twitter (Twitter Inc., San Francisco, CA) and Instagram (Meta Platforms Inc., Menlo Park, CA). This article presents current evidence about social media presence and engagement of ACGME-accredited RAAPM fellowship programs on Twitter and Instagram. These findings could potentially help cultivate greater social media engagement in the RAAPM community and improve recruitment of prospective applicants. Material and Methods: The list of ACGME-accredited RAAPM fellowship programs for the academic year 2020-2021 was obtained from the ACGME website. Accounts were searched by reviewing each program's website for profile links and by querying for the name of the program directly on Twitter and Instagram. Department of Anesthesiology, Perioperative and Pain Medicine accounts were analysed for posts pertaining to RAAPM elements, and RAAPM fellowship-specific accounts were investigated. Accounts that were solely focused on an anaesthesiology residency were excluded. All posts over the academic year period of 1 July 2020 to 30 June 2021 were analyzed. Results: While many programs had active departmental social media accounts during our study, there was a dearth of RAAPM-related output (3.4% of tweets and 2.7% Instagram posts). Furthermore, only 10% of programs had RAAPM fellowship-specific Twitter accounts, of which only 5% of programs were active. Finally, there were no RAAPM fellowship-specific Instagram accounts. Conclusions: While there is robust use of social media by departmental accounts, there is a paucity of RAAPM-related content and RAAPM fellowship-specific social media accounts. The current gap provides valuable opportunities for future investigations into the cyber footprint and innovative engagement strategies for the RAAPM community.
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OBJECTIVES: To study the left heart structure and functional characteristics of term neonates with intrauterine growth restriction (IUGR). METHODS: This study included 86 term neonates with IUGR admitted to the Neonatal Ward of Beijing Friendship Hospital, Capital Medical University from January 2019 to January 2022 as the IUGR group, as well as randomly selected 86 term neonates without IUGR born during the same period as the non-IUGR group. The clinical data and echocardiographic data were compared between the two groups. RESULTS: The analysis of left heart structure and function showed that compared with the non-IUGR group, the IUGR group had significantly lower left ventricular mass, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left atrial diameter, end-diastolic interventricular septal thickness, left ventricular posterior wall thickness, left ventricular end-diastolic volume, left ventricular end-systolic volume, and stroke volume (P<0.05) and significantly higher ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness, proportion of neonates with a mitral peak E/A ratio of ≥1, and cardiac index (P<0.05). The Spearman correlation analysis suggested that stroke volume was positively correlated with birth weight and body surface area (rs=0.241 and 0.241 respectively; P<0.05) and that the ratio of end-diastolic interventricular septal thickness to left ventricular posterior wall thickness was negatively correlated with birth weight and body surface area (rs=-0.229 and -0.225 respectively; P<0.05). CONCLUSIONS: The left ventricular systolic function of neonates with IUGR is not significantly different from that of neonates without IUGR. However, the ventricular septum is thicker in neonates with IUGR. This change is negatively correlated with birth weight and body surface area. The left ventricular diastolic function may be impaired in neonates with IUGR.
Subject(s)
Fetal Growth Retardation , Heart , Humans , Infant, Newborn , Birth Weight , Echocardiography , Heart Ventricles/diagnostic imaging , Ventricular Function, LeftABSTRACT
CRISPR-associated (Cas) protein systems have been increasingly incorporated in nucleic-acid diagnosis. CRISPR/Cas12a can cleave single-stranded DNA (ssDNA) after being guided to the target double-stranded DNA (dsDNA) with crRNA, making it a specific tool for dsDNA detection. Assisted by nucleic acid preamplification, CRISPR/Cas12a enables dsDNA detection at the attomolar level. However, such mandatory preamplification in CRISPR/Cas12a also accompanies the extra step of transferring preamplification products into the CRISPR/Cas12a system, which is not only cumbersome and time-consuming but also induces the risk of cross-contamination. Herein, we demonstrate a multiplex-crRNA strategy to enhance the sensitivity of the CRISPR/Cas12a system without any preamplification. This multiplex-crRNA strategy harnesses multiple sequences of crRNA which target different regions of the same dsDNA substrate in the same CRISPR/Cas12a system. Therefore, detection signals are accumulated without amplification, which augments the conventional detection limit. For application demonstration, the B646L gene from the African swine fever virus (ASFV), which is a dsDNA virus, is exemplified. The detection limit of the multiplex-crRNA system can be improved to â¼1 picomolar (pM) without amplification, which is â¼64 times stronger than the conventional single-crRNA system. The multiplex-crRNA system presented in this study, with slight modifications, can be generalized to other biosensing settings where preamplification is not readily available.
Subject(s)
African Swine Fever Virus , African Swine Fever Virus/genetics , Animals , CRISPR-Cas Systems/genetics , DNA/genetics , DNA, Single-Stranded , Nucleic Acid Amplification Techniques , SwineABSTRACT
OBJECTIVES: Patients undergoing robotic video-assisted thoracoscopic surgery (rVATS) report significant postoperative pain. Both the serratus anterior plane block (SAPB) and the surgical intercostal block (IB) (performed by a surgeon from within the thorax), along with incision infiltration (II), are distinct modalities that target the lateral cutaneous branches of intercostal nerves and are acceptable analgesic modalities in an enhanced recovery after rVATS surgery. DESIGN: Prospective, double-blinded, randomized, controlled pilot trial with 65 patients to assess the difference in analgesia quality between the SAPB and IB+II in rVATS. SETTING: Major academic teaching hospital. PARTICIPANTS: The inclusion criteria included ASA physical status I-IV, ages 18-to-75 undergoing an elective, unilateral rVATS procedure. INTERVENTIONS: Patients were randomized to receive either an ultrasound-guided SAPB at the end of their surgery, using a 20-mL mixture consisting of 10 mL of liposomal bupivacaine (133 mg) and 10 mL 0.25% bupivacaine, or IB+II, using a 20-mL mixture consisting of 10 mL of liposomal bupivacaine (133 mg) and 10 mL 0.5% bupivacaine prior to skin closure by the surgeon. RESULTS: The primary outcome was the amount of postoperative opioid consumption in morphine milliequivalents [MME] during the first 24 hours after surgery. Secondary outcomes were time to first analgesic request, VAS scores at zero, two, six, 18, or 24 hours at rest, and PACU, ICU, or hospital lengths of stay (LOS). There were no differences in any outcomes between the groups. CONCLUSIONS: Both SAPB and IB+II are comparable analgesic modalities for rVATS procedures.
Subject(s)
Robotic Surgical Procedures , Adolescent , Adult , Aged , Bupivacaine , Humans , Middle Aged , Pain Measurement , Pain, Postoperative/prevention & control , Pilot Projects , Prospective Studies , Thoracic Surgery, Video-Assisted/methods , Young AdultABSTRACT
ABSTRACT: The analgesic efficacy of bilateral low thoracic erector spinae blocks for combined major breast and abdominal surgery has not been reported. The aim of this case series was to assess the feasibility and efficacy of T8 thoracic preincisional erector spinae blocks in patients undergoing total radical mastectomies with axillary lymph node dissections in addition to reconstruction with abdominal deep inferior epigastric flaps. The aim was to supply dermatomal coverage to provide analgesia for T2-L1 that formed the basis for an opioid-sparing multimodal technique in the context of our early recovery after breast surgery with deep inferior epigastric flap program.
Subject(s)
Breast Neoplasms , Nerve Block , Perforator Flap , Humans , Female , Mastectomy, Simple , Mastectomy , Breast Neoplasms/surgery , Feasibility Studies , Mastectomy, Radical , Nerve Block/methods , Ultrasonography, InterventionalABSTRACT
STUDY OBJECTIVE: TXA is an antifibrinolytic medication widely used to reduce perioperative blood loss, but it has been seldom used during foot and ankle surgery. Our study evaluates the impact of TXA use on blood loss, post-operative pain, peri-operative opioid consumption, and wound healing in ambulatory outpatient foot and ankle procedures. DESIGN: Prospective, triple-blinded, randomized controlled trial. SETTING: Peri-operative environment of a major academic health centre in New York City. PATIENTS: A total of 100 participants who were scheduled for ambulatory foot and ankle surgery with a single surgeon. INTERVENTIONS: Patients receive either 10 mg/kg TXA (TXA group) or 10 ml/kg of normal saline (placebo group) intravenously prior to skin incision. MEASUREMENTS: Primary outcome was intra-operative blood loss. Secondary outcomes were peri-operative opioid consumption and wound complications between post-operative days 14 and 21. MAIN RESULTS: We found no difference between TXA and placebo groups in terms of intra-operative blood loss, p value 0.71, 95% CI (63.13-19.80). There was no difference between the two groups in terms of post-operative morphine milliequivalents (MME). The incidence of wound complications was 16.3% in the TXA group compared to 15.7% in the placebo group with OR 1.04, p value 0.93, 95% CI (0.32-2.77). No adverse events associated with TXA were reported. CONCLUSIONS: The use of TXA during foot and ankle surgery was not associated with any benefits in perioperative outcomes in our outpatient ambulatory surgical population. Considering potential risks, we do not support the routine use of TXA in this surgical model.
Subject(s)
Antifibrinolytic Agents , Blood Loss, Surgical , Tranexamic Acid , Ankle/surgery , Blood Loss, Surgical/prevention & control , Foot/surgery , Humans , Prospective StudiesABSTRACT
Osteosarcoma is the most common type of primary malignant bone cancer, and it is associated with high rates of pulmonary metastasis. Integrin αvß3 is critical for osteosarcoma cell migratory and invasive abilities. Chemokine (C-C motif) ligand 4 (CCL4) has diverse effects on different cancer cells through its interaction with its specific receptor, C-C chemokine receptor type 5 (CCR5). Analysis of mRNA expression in human osteosarcoma tissue identified upregulated levels of CCL4, integrin αv and ß3 expression. Similarly, an analysis of records from the Gene Expression Omnibus (GEO) dataset showed that CCL4 was upregulated in human osteosarcoma tissue. Importantly, the expression of both CCL4 and integrin αvß3 correlated positively with osteosarcoma clinical stages and lung metastasis. Analysis of osteosarcoma cell lines identified that CCL4 promotes integrin αvß3 expression and cell migration by activating the focal adhesion kinase (FAK), protein kinase B (AKT), and hypoxia inducible factor 1 subunit alpha (HIF-1α) signaling pathways, which can downregulate microRNA-3927-3p expression. Pharmacological inhibition of CCR5 by maraviroc (MVC) prevented increases in integrin αvß3 expression and cell migration. This study is the first to implicate CCL4 as a potential target in the treatment of metastatic osteosarcoma.
Subject(s)
Biomarkers, Tumor/metabolism , Cell Movement , Chemokine CCL4/metabolism , Gene Expression Regulation, Neoplastic , Integrin alphaVbeta3/metabolism , MicroRNAs/genetics , Osteosarcoma/pathology , Apoptosis , Biomarkers, Tumor/genetics , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cell Proliferation , Chemokine CCL4/genetics , Humans , Integrin alphaVbeta3/genetics , Osteosarcoma/genetics , Osteosarcoma/metabolism , Tumor Cells, CulturedABSTRACT
The NLR-receptor RPP7 mediates race-specific immunity in Arabidopsis. Previous screens for enhanced downy mildew (edm) mutants identified the co-chaperone SGT1b (EDM1) and the PHD-finger protein EDM2 as critical regulators of RPP7. Here, we describe a third edm mutant compromised in RPP7 immunity, edm3. EDM3 encodes a nuclear-localized protein featuring an RNA-recognition motif. Like EDM2, EDM3 promotes histone H3 lysine 9 dimethylation (H3K9me2) at RPP7. Global profiling of H3K9me2 showed EDM3 to affect this silencing mark at a large set of loci. Importantly, both EDM3 and EDM2 co-associate in vivo with H3K9me2-marked chromatin and transcripts at a critical proximal polyadenylation site of RPP7, where they suppress proximal transcript polyadeylation/termination. Our results highlight the complexity of plant NLR gene regulation, and establish a functional and physical link between a histone mark and NLR-transcript processing.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolismABSTRACT
OBJECTIVES: To characterize the genetic environment of the carbapenem resistance determinant in Proteus vulgaris of swine origin. METHODS: The carbapenem-resistant P. vulgaris strain BC22 was isolated from a faecal swab from a diseased pig with diarrhoea in Sichuan Province of China in 2018. The presence of carbapenemase genes was screened by PCR. WGS and bioinformatics analysis were performed to analyse the genetic environment of the carbapenem resistance determinant. RESULTS: P. vulgaris strain BC22 was found to harbour the carbapenemase gene blaNDM-1. WGS data revealed that blaNDM-1 was located in a truncated ISAba125 composite transposon. The carbapenem resistance gene blaNDM-1 and 20 other resistance genes, including the multiresistance gene cfr and the bifunctional aminoglycoside/quinolone resistance gene aac(6')-lb-cr, were located in a novel SXT/R391 integrative and conjugative element (ICE). This new SXT/R391 ICE of 148.7 kb was chromosomally located, and could be transferred to Escherichia coli. CONCLUSIONS: Here, we report a carbapenemase gene, blaNDM-1, integrated into an SXT/R391 ICE. Our study highlights that this SXT/R391 ICE may facilitate the dissemination of clinically important resistance genes such as blaNDM-1, cfr and aac(6')-lb-cr.
Subject(s)
Proteus vulgaris , beta-Lactamases , Animals , Bacterial Proteins/genetics , China , Conjugation, Genetic , Swine , beta-Lactamases/geneticsABSTRACT
BACKGROUND: Over-stimulation of dopamine signaling is thought to underlie the pathophysiology of a list of mental disorders, such as psychosis, mania and attention-deficit/hyperactivity disorder. These disorders are frequently associated with cognitive deficits in attention or learning and memory, suggesting that persistent activation of dopamine signaling may change neural plasticity to induce cognitive or emotional malfunction. METHODS: Dopamine transporter knockdown (DAT-KD) mice were used to mimic a hyper-dopamine state. Novel object recognition (NOR) task was performed to assess the recognition memory. To test the role of dopamine D3 receptor (D3R) on NOR, DAT-KD mice were treated with either a D3R antagonist, FAUC365 or by deletion of D3R. Total or phospho-GSK3 and -ERK1/2 signals in various brain regions were measured by Western blot analyses. To examine the impact of GSK3 signal on NOR, wild-type mice were systemically treated with GSK3 inhibitor SB216763 or, micro-injected with lentiviral shRNA of GSK3ß or GSK3α in the medial prefrontal cortex (mPFC). RESULTS: We confirmed our previous findings that DAT-KD mice displayed a deficit in NOR memory, which could be prevented by deletion of D3R or exposure to FAUC365. In WT mice, p-GSK3α and p-GSK3ß were significantly decreased in the mPFC after exposure to novel objects; however, the DAT-KD mice exhibited no such change in mPFC p-GSK3α/ß levels. DAT-KD mice treated with FAUC365 or with D3R deletion exhibited restored novelty-induced GSK3 dephosphorylation in the mPFC. Moreover, inhibition of GSK3 in WT mice diminished NOR performance and impaired recognition memory. Lentiviral shRNA knockdown of GSK3ß, but not GSK3α, in the mPFC of WT mice also impaired NOR. CONCLUSION: These findings suggest that D3R acts via GSK3ß signaling in the mPFC to play a functional role in NOR memory. In addition, treatment with D3R antagonists may be a reasonable approach for ameliorating cognitive impairments or episodic memory deficits in bipolar disorder patients.
Subject(s)
Bipolar Disorder/genetics , Cognitive Dysfunction/genetics , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3/genetics , Receptors, Dopamine D3/genetics , Animals , Bipolar Disorder/pathology , Cognitive Dysfunction/pathology , Dopamine/genetics , Dopamine/metabolism , Dopamine Plasma Membrane Transport Proteins/genetics , Gene Knockdown Techniques , Humans , MAP Kinase Signaling System/genetics , Memory, Episodic , Mice , Prefrontal Cortex/metabolismABSTRACT
The aim of this paper was to investigate the effect of Faeces Bombycis(FB) on the intestinal microflora in rats with syndrome of damp retention in middle-jiao, and to explore its mechanism in regulating intestinal microflora from the perspective of microorganisms contained in FB. The contents of antidiuretic hormone(ADH) and C-reactive protein(CRP) in serum and aquaporin 3(AQP3) in jejunum were determined by enzyme-linked immunosorbent assay(ELISA). Illumina Miseq platform was used for high-throughput sequencing of the rat feces and FB. The ELISA results showed that as compared with the normal control group, the contents of ADH and CRP in the model group were significantly increased(P<0.05), and the content of AQP3 was significantly decreased(P<0.05). After drug administration, the ADH, CRP and AQP3 contents were recovered. Sequencing of rat feces showed that the ACE, Chao1 and Shannon indexes of the intestinal microflora were the lowest in the model group. As compared with the normal control group, the levels from phylum to genus were all significantly changed in model group, and Proteobacteria, Acinetobacter, Anaerobacter, Pseudomonas, and Parabacteroides levels were significantly increased(P<0.05), while Marvinbryantia level was significantly decreased(P<0.05). As compared with the model group, Proteobacteria was significantly decreased in the FB low and high dose groups(P<0.05), and Acinetobacter, Anaerobacter, Pseudomonas, Parabacteroides levels were significantly decreased in the low, medium and high dose groups(P<0.05), while Lachnoanaerobaculum, Intestinimonas and Marvinbryantia were increased significantly in the high dose group(P<0.05). Sequencing analysis of FB showed that the relative abundance of Leclercia, Pantoea, Brachybacterium, Shimwellia, Hartmannibacter, Klebsiella, Serratia, Aurantimonas, Paenibacillus and Bacillus was high in the FB, but they were basically not present or little in the rat feces. In conclusion, FB may play a role in the treatment of "syndrome of damp retention in middle-jiao" by balancing the intestinal microflora, and this effect may be related to the metabolites of microorganisms in the FB.
Subject(s)
Bombyx/chemistry , Feces/chemistry , Gastrointestinal Microbiome , Animals , Aquaporin 3/analysis , C-Reactive Protein/analysis , High-Throughput Nucleotide Sequencing , Medicine, Chinese Traditional , Rats , Vasopressins/bloodABSTRACT
OBJECTIVE: To use optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in assessing myocardial bridging (MB) vessel size and wall thickness. BACKGROUND: During stent implantation, MB is associated with complications, especially perforation. METHODS: OCT and IVUS were performed in 56 patients with typical angiographic "milking" from November 2016 to May 2017. The vessel area and thickness in the MB segments and adjacent proximal and distal reference segments were measured and compared with eight normal left anterior descending (LAD) segment (no atherosclerosis in a segment that was at least 20 mm long and that began ~40 mm distal to the LAD ostium). RESULTS: Compared with the reference vessel size distal to the MB segment (6.3 ± 1.8 mm2 ), the IVUS-measured size of the tunneled vessel during diastole was significantly smaller (6.0 ± 1.9 mm2 , p < 0.05) (remodeling index = 0.79 ± 0.18). The minimum intramyocardial arterial wall thickness was 0.16 ± 0.02 mm, significantly thinner than that of the mean reference (0.22 ± 0.03 mm, p < 0.001). The location of the thinnest arterial wall was in the distal and middle MB segments in 45 (80.4%) and 11 (19.6%) patients, respectively, and was not related to the degree of systolic compression or remodeling index. The walls of the middle and distal MB subsegments, but not of the proximal MB subsegment, were thinner than that of the comparison group of normal LADs. CONCLUSION: The coronary vessel involved in an MB is both smaller and thinner than that of the adjacent non-MB segment. This may explain the increased frequency and severity of coronary perforation during stent implantation.
Subject(s)
Coronary Vessels/diagnostic imaging , Myocardial Bridging/diagnostic imaging , Tomography, Optical Coherence , Ultrasonography, Interventional , Aged , Coronary Angiography , Coronary Vessels/injuries , Female , Heart Injuries/etiology , Humans , Male , Middle Aged , Myocardial Bridging/complications , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , Predictive Value of Tests , Risk Factors , StentsABSTRACT
INTRODUCTION: Recruitment is an important aspect of clinical research, as poor recruitment could undermine the scientific value of a trial or delay the development process of new treatments. The development of electronic medical records provides a new way to identify potential participants for trials by matching the eligibility criteria with patients' data within electronic medical records. METHODS: A literature search was performed to examine the effectiveness and efficiency of the electronic medical record recruitment method using MEDLINE, PubMed, PubMed Central, CINAHL Plus with Full Text, ScienceDirect and Cochrane Library databases. These searches generated 11 articles that met the eligibility criteria, and handsearching reference lists generated two additional articles bringing the total number of articles to 13. These articles were subjected to critical appraisal utilising the Effective Public Health Practice Project tool. RESULTS: Out of the 13 included articles, 11 provided quantitative data on recruitment effectiveness while seven articles provided quantitative data on recruitment efficiency. The automation in screening and patient identification by using alerts, a notification system, to notify research staff of a potential participant, was observed to contribute to higher recruitment yield and reduced workload due to its specificity on participant screening. The use of electronic medical record alerts was found to be associated with better recruitment outcomes when they were sent to dedicated research staff rather than physicians. Using electronic medical records for recruitment was found to be effective due to its capability for patient identification outside working hours and fast processing time, which was particularly useful for clinical trials in acute conditions. Several challenges may hinder the impact of the electronic medical record recruitment method, including the lack of conformity of clinical trial eligibility criteria and electronic medical record data structure and missing data. 'Alert fatigue' could also impact on the effectiveness of this method in the long term. CONCLUSION: The results from this review supports electronic medical record being an effective and efficient method for clinical trial recruitment. Recommendations were made in order to maximise the potential of the electronic medical record recruitment method and also for future research in order to improve the quality of evidence to support this strategy for recruitment.