Search

Abstract Aims Myocardial injury after noncardiac surgery (MINS) is common in elderly patients and considered as an independent predictor of 30-day mortality after noncardiac surgery. Dexmedetomidine possesses cardiac-protective profile. Previous clinical studies have found that perioperative application of dexmedetomidine is associated with decreased 1-year mortality in patients undergoing cardiac surgery. The current study protocol aims to investigate the effects of dexmedetomidine on the incidence of MINS, complications, and 30-day mortality in elderly patients subjected to noncardiac surgery. Methods A multicenter, randomized, controlled, double-blind, prospective trial is designed to explore cardiac protection of dexmedetomidine in the elderly patients undergoing noncardiac surgery. A total of 960 patients aged over 65 years will be recruited and randomly assigned to dexmedetomidine group (group Dex) and normal saline placebo group (group NS) in a ratio of 1:1. Patients in group Dex will receive a bolus dose of 0.5 μg/kg dexmedetomidine within 10 min before surgical incision, followed by a consistent infusion at the rate of 0.3–0.5 μg/kg/h throughout the operation. Group NS patients will receive the same volume of normal saline. The primary outcome is the incidence of MINS via detecting the hs-TnT level within 3 days after the operation. The secondary outcome includes myocardial ischemic symptoms, the incidence of major adverse cardiovascular events (MACE) in hospital, length of ICU and postoperative hospital stay, the incidence of inhospital complications, and 30-day all-cause mortality. Discussion The results of the current study will illustrate the effect of dexmedetomidine on myocardial injury for elderly patients undergoing major noncardiac surgery. Trial registration The trial was registered with Chinese Clinical Trial Registry (CHICTR) on Aug 24, 2021 (ChiCTR2100049946, http://www.chictr.org.cn/showproj.aspx?proj=131804 ).

Objective To compare the modified strategy for the right-sided double-lumen tube (R-DLT) placement using a combination of CT measurements and flexible video bronchoscopy guidance with traditional bronchoscopy technique.Trial design, setting and participants Double-blind, parallel randomised control trial at a tertiary care medical centre in China. 100 patients undergoing video-assisted thoracoscopic surgery and requiring R-DLT were randomly allocated to the control group and the intervention group.Intervention The control group used the traditional bronchoscopy-guided technique. In the intervention group, the length and anteroposterior diameter of the right main bronchus (RMB) were measured on CT images to select the side and size of the Rüsch tube, and then a black depth marker was placed on the tube according to the difference between the length of the RMB and the bronchial cuff. Under the guidance of bronchoscopy, the depth marker should be placed parallel to the tracheal carina and a characteristic white line on the tube should be parallel to the midline of the tracheal carina.Main outcomes The primary endpoint was the positioning of right upper lobe (RUL) ventilatory slot and RUL bronchial orifice. The secondary endpoints included intubation data and perioperative adverse events.Results Compared with the control group, our modified strategy significantly increased the optimal and acceptable position rate (76% vs 98%, respectively; p

Light quality is a vital environmental signal used to trigger growth and to develop structural differentiation in plants, and it influences morphological, physiological, and biochemical metabolites. In previous studies, different light qualities were found to regulate the synthesis of anthocyanin. However, the mechanism of the synthesis and accumulation of anthocyanins in leaves in response to light quality remains unclear. In this study, the Loropetalum chinense var. rubrum “Xiangnong Fendai” plant was treated with white light (WL), blue light (BL), ultraviolet-A light (UL), and blue light plus ultraviolet-A light (BL + UL), respectively. Under BL, the leaves were described as increasing in redness from “olive green” to “reddish-brown”. The chlorophyll, carotenoid, anthocyanin, and total flavonoid content were significantly higher at 7 d than at 0 d. In addition, BL treatment also significantly increased the accumulation of soluble sugar and soluble protein. In contrast to BL, ultraviolet-A light increased the malondialdehyde (MDA) content and the activities of three antioxidant enzymes in the leaves, including catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), in varying degrees over time. Moreover, we also found that the CRY-like gene, HY5-like gene, BBX-like gene, MYB-like gene, CHS-like gene, DFR-like gene, ANS-like gene, and UFGT-like gene were significantly upregulated. Furthermore, the SOD-like, POD-like, and CAT-like gene expressions related to antioxidase synthesis were found under ultraviolet-A light conditions. In summary, BL is more conducive to reddening the leaves of “Xiangnong Fendai” and will not lead to excessive photooxidation. This provides an effective ecological strategy for light-induced leaf-color changes, thereby promoting the ornamental and economic value of L. chinense var. rubrum.

Bacterial transcriptomic data have been used to predict antibiotic susceptibility in a species- or antibiotic-specific manner. Here, the authors show that global transcriptional disorder is a common stress response in bacteria with low fitness, and present a general approach that can predict bacterial fitness independently of species or type of stress.

Summary: Legionella pneumophila grows intracellularly within a replication vacuole via action of Icm/Dot-secreted proteins. One such protein, SdhA, maintains the integrity of the vacuolar membrane, thereby preventing cytoplasmic degradation of bacteria. We show here that SdhA binds and blocks the action of OCRL (OculoCerebroRenal syndrome of Lowe), an inositol 5-phosphatase pivotal for controlling endosomal dynamics. OCRL depletion results in enhanced vacuole integrity and intracellular growth of a sdhA mutant, consistent with OCRL participating in vacuole disruption. Overexpressed SdhA alters OCRL function, enlarging endosomes, driving endosomal accumulation of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), and interfering with endosomal trafficking. SdhA interrupts Rab guanosine triphosphatase (GTPase)-OCRL interactions by binding to the OCRL ASPM-SPD2-Hydin (ASH) domain, without directly altering OCRL 5-phosphatase activity. The Legionella vacuole encompassing the sdhA mutant accumulates OCRL and endosomal antigen EEA1 (Early Endosome Antigen 1), consistent with SdhA blocking accumulation of OCRL-containing endosomal vesicles. Therefore, SdhA hijacking of OCRL is associated with blocking trafficking events that disrupt the pathogen vacuole.

Background: Post-operative pain management for patients undergoing thoracoscopy surgery is challenging for clinicians which increase both health and economic burden. The non-selective NMDA receptor antagonist esketamine possesses an analgesic effect twice that of ketamine. The application of esketamine might be beneficial in alleviating acute and chronic pain after thoracic surgery. The current study describes the protocol aiming to evaluate the analgesic effect of esketamine after pulmonary surgery via visual analog scale (VAS) score for acute and chronic pain.Methods: A multi-center, prospective, randomized, controlled, double-blind study is designed to explore the analgesic effect of esketamine in randomized patients undergoing video-assisted thoracoscopic surgery (VATS) with general anesthesia. Patients will be randomly assigned to Esketamine Group (Group K) and Control Group (Group C) in a ratio of 1:1. Group K patients will receive esketamine with a bolus of 0.1 mg/kg after anesthesia induction, 0.1 mg/kg/h throughout the operation and 0.015 mg/kg/h in PCIA after surgery while Group C patients will receive the same volume of normal saline. The primary outcome is to measure the pain intensity through the VAS score at 3 months after the operation. The secondary outcome includes VAS score at 1, 4, 8, 24, and 48 h and on the 7th day and 1 month after the operation, complications, ketamine-related neurological side effects, recovery time of bowel function, and total amount of supplemental analgesics.Discussion: The results of the current study might illustrate the analgesic effect of esketamine for patients undergoing thoracoscopy pulmonary surgery and provide evidence and insight for perioperative pain management.Study Registration: The trial was registered with Chinese Clinical Trial Registry (CHICTR) on Nov 18th, 2020 (ChiCTR2000040012).

Dendrobium officinale Kimura et Migo, a highly valued Chinese herbal medicine, is on the verge of extinction in the wild, and is not cultivated efficiently. In this study, we explored the possibility that orchid mycorrhizal fungi (OMF) might improve the growth and cultivation of D. officinale. Serendipita sp., Tulasnella calospora and Tulasnella asymmetrica isolated from three different orchids were co-cultured with sterile seedlings of D. officinale. The seedlings were found to stably coexist with fungi after 60 days of co-culture. The co-culture of T. calospora with plants upregulated the activity of antioxidant enzymes, stimulated the production of osmoregulatory substances and reduced electrical conductivity. Plants with T. calospora had longer roots (141.2%), thicker leaves (58.3%), increased root number (71.4%) and leaf number (11.1%), and increased weight (155.2%) and photosynthetic pigment content (99.6%), relative to controls. The content of total medicinal polysaccharides increased by 42.69 % due to the addition of T. calospora. T. asymmetrica was less effective, followed by Serendipita sp. When T. calospora established a symbiotic relationship with D. officinale, resistance indicators increased. The content of functional components was significantly increased. This study contributes to the protection and commercial reproduction of endangered orchid plants with mycorrhizal technology.

ABSTRACT The human intestine harbors diverse communities of bacteria and bacteriophages. Given the specificity of phages for their bacterial hosts, there is growing interest in using phage therapies to combat the rising incidence of multidrug-resistant bacterial infections. A significant barrier to such therapies is the rapid development of phage-resistant bacteria, highlighting the need to understand how bacteria acquire phage resistance in vivo. Here we identify novel lytic phages in municipal raw sewage that kill Enterococcus faecalis, a Gram-positive opportunistic pathogen that resides in the human intestine. We show that phage infection of E. faecalis requires a predicted integral membrane protein that we have named PIPEF (for phage infection protein from E. faecalis). We find that PIPEF is conserved in E. faecalis and harbors a 160-amino-acid hypervariable region that determines phage tropism for distinct enterococcal strains. Finally, we use a gnotobiotic mouse model of in vivo phage predation to show that the sewage phages temporarily reduce E. faecalis colonization of the intestine but that E. faecalis acquires phage resistance through mutations in PIPEF. Our findings define the molecular basis for an evolutionary arms race between E. faecalis and the lytic phages that prey on them. They also suggest approaches for engineering E. faecalis phages that have altered host specificity and that can subvert phage resistance in the host bacteria. IMPORTANCE Bacteriophage therapy has received renewed attention as a potential solution to the rise in antibiotic-resistant bacterial infections. However, bacteria can acquire phage resistance, posing a major barrier to phage therapy. To overcome this problem, it is necessary to understand phage resistance mechanisms in bacteria. We have unraveled one such resistance mechanism in Enterococcus faecalis, a Gram-positive natural resident of the human intestine that has acquired antibiotic resistance and can cause opportunistic infections. We have identified a cell wall protein hypervariable region that specifies phage tropism in E. faecalis. Using a gnotobiotic mouse model of in vivo phage predation, we show that E. faecalis acquires phage resistance through mutations in this cell wall protein. Our findings define the molecular basis for lytic phage resistance in E. faecalis. They also suggest opportunities for engineering E. faecalis phages that circumvent the problem of bacterial phage resistance.

ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium that normally inhabits the gastrointestinal tracts of humans and other animals. Although these bacteria are members of our native gut flora, they can cause life-threatening infections in hospitalized patients. Antibiotic resistance genes appear to be readily shared among high-risk E. faecalis strains, and multidrug resistance in these bacteria limits treatment options for infections. Here, we find that CRISPR-Cas and restriction-modification systems, which function as adaptive and innate immune systems in bacteria, significantly impact the spread of antibiotic resistance genes in E. faecalis populations. The loss of these systems in high-risk E. faecalis suggests that they are immunocompromised, a tradeoff that allows them to readily acquire new genes and adapt to new antibiotics.