Transversus abdominis plane block reduces remifentanil and propofol consumption, evaluated by closed-loop titration guided by bispectral index.

The present prospective, randomized, double-blind study aimed to determine the impact of transversus abdominis plane (TAP) block on propofol and remifentanil consumption, when administered by closed-loop titration guided by processed electroencephalography, i.e., bispectral index (BIS) values. Following institutional review board approval, 60 patients were scheduled for laparoscopic colectomy under general anesthesia. Patients were randomly assigned to receive bilateral TAP block with 20 ml 0.375% ropivacaine (TAP group) or 20 ml 0.9% saline [control (CON) group]. General anesthesia was maintained with propofol and remifentanil administration using closed-loop titration guided by BIS values. The primary outcome was perioperative propofol and remifentanil consumption. The secondary outcomes were hypertensive or hypotensive events requiring treatment, recovery time in PACU and time to first rescue analgesia following surgery. A total of 58 patients participated in the present study. At similar depths of anesthesia, as measured by BIS during the maintenance phase (45-55), patients who received TAP blocks required less propofol (4.2±1.3 vs. 5.5±1.6 mg/kg/h; P<0.001) and remifentanil (0.16±0.05 vs. 0.21±0.05 µg/kg/min; P<0.001). Time to extubation was significantly shorter in the TAP group (9.8±3.2 min) than in the CON group (14.2±4.9 min) (P<0.05). The requirement to treat hemodynamic change was also significantly lower (P<0.05). Pain score at 2 h after surgery was also significantly reduced in the TAP group compared with the CON group (P<0.05), whereas the time to first rescue analgesia was delayed in patients who received TAP block (P<0.05). Postoperative nausea and vomiting occurred at comparable rates in each group (P>0.05). In conclusion, TAP block combined with general anesthesia reduced propofol and remifentanil consumption, shortened time to tracheal extubation and promoted hemodynamic stability in laparoscopic colectomy

Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.

Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3. The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6. However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging4. Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival. Our approach is based on the co-clustering of a self-resistance gene in the natural-product biosynthesis gene cluster7-9, which provides insight into the potential biological activity of the encoded compound. We targeted dihydroxy-acid dehydratase in the branched-chain amino acid biosynthetic pathway in plants; the last step in this pathway is often targeted for herbicide development10. We show that the fungal sesquiterpenoid aspterric acid, which was discovered using the method described above, is a sub-micromolar inhibitor of dihydroxy-acid dehydratase that is effective as a herbicide in spray applications. The self-resistance gene astD was validated to be insensitive to aspterric acid and was deployed as a transgene in the establishment of plants that are resistant to aspterric acid. This herbicide-resistance gene combination complements the urgent ongoing efforts to overcome weed resistance11. Our discovery demonstrates the potential of using a resistance-gene-directed approach in the discovery of bioactive natural products

ProQA: Structural Prompt-based Pre-training for Unified Question Answering

Question Answering (QA) is a longstanding challenge in natural language processing. Existing QA works mostly focus on specific question types, knowledge domains, or reasoning skills. The specialty in QA research hinders systems from modeling commonalities between tasks and generalization for wider applications. To address this issue, we present ProQA, a unified QA paradigm that solves various tasks through a single model. ProQA takes a unified structural prompt as the bridge and improves the QA-centric ability by structural prompt-based pre-training. Through a structurally designed prompt-based input schema, ProQA concurrently models the knowledge generalization for all QA tasks while keeping the knowledge customization for every specific QA task. Furthermore, ProQA is pre-trained with structural prompt-formatted large-scale synthesized corpus, which empowers the model with the commonly-required QA ability. Experimental results on 11 QA benchmarks demonstrate that ProQA consistently boosts performance on both full data fine-tuning, few-shot learning, and zero-shot testing scenarios. Furthermore, ProQA exhibits strong ability in both continual learning and transfer learning by taking the advantages of the structural prompt.Comment: NAACL 202

Structural Basis of Vta1 Function in the Multivesicular Body Sorting Pathway

SummaryThe MVB pathway plays essential roles in several eukaryotic cellular processes. Proper function of the MVB pathway requires reversible membrane association of the ESCRTs, a process catalyzed by Vps4 ATPase. Vta1 regulates the Vps4 activity, but its mechanism of action was poorly understood. We report the high-resolution crystal structures of the Did2- and Vps60-binding N-terminal domain and the Vps4-binding C-terminal domain of S. cerevisiae Vta1. The C-terminal domain also mediates Vta1 dimerization and both subunits are required for its function as a Vps4 regulator. Emerging from our analysis is a mechanism of regulation by Vta1 in which the C-terminal domain stabilizes the ATP-dependent double ring assembly of Vps4. In addition, the MIT motif-containing N-terminal domain, projected by a long disordered linker, allows contact between the Vps4 disassembly machinery and the accessory ESCRT-III proteins. This provides an additional level of regulation and coordination for ESCRT-III assembly and disassembly

Review of quantitative and functional lung imaging evidence of vaping-related lung injury

IntroductionThe pulmonary effects of e-cigarette use (or vaping) became a healthcare concern in 2019, following the rapid increase of e-cigarette-related or vaping-associated lung injury (EVALI) in young people, which resulted in the critical care admission of thousands of teenagers and young adults. Pulmonary functional imaging is well-positioned to provide information about the acute and chronic effects of vaping. We generated a systematic review to retrieve relevant imaging studies that describe the acute and chronic imaging findings that underly vaping-related lung structure-function abnormalities.MethodsA systematic review was undertaken on June 13th, 2023 using PubMed to search for published manuscripts using the following criteria: [(“Vaping” OR “e-cigarette” OR “EVALI”) AND (“MRI” OR “CT” OR “Imaging”)]. We included only studies involving human participants, vaping/e-cigarette use, and MRI, CT and/or PET.ResultsThe search identified 445 manuscripts, of which 110 (668 unique participants) specifically mentioned MRI, PET or CT imaging in cases or retrospective case series of patients who vaped. This included 105 manuscripts specific to CT (626 participants), three manuscripts which mainly used MRI (23 participants), and two manuscripts which described PET findings (20 participants). Most studies were conducted in North America (n = 90), with the remaining studies conducted in Europe (n = 15), Asia (n = 4) and South America (n = 1). The vast majority of publications described case studies (n = 93) and a few described larger retrospective or prospective studies (n = 17). In e-cigarette users and patients with EVALI, key CT findings included ground-glass opacities, consolidations and subpleural sparing, MRI revealed abnormal ventilation, perfusion and ventilation/perfusion matching, while PET showed evidence of pulmonary inflammation.Discussion and conclusionPulmonary structural and functional imaging abnormalities were common in patients with EVALI and in e-cigarette users with or without respiratory symptoms, which suggests that functional MRI may be helpful in the investigation of the pulmonary health effects associated with e-cigarette use