Percutaneous treatment of type C distal radius fractures using dual-external fixator.

BACKGROUND: This study aimed to introduce a potential alternative percutaneous treatment for AO types C1, C2, and C3 distal radius fractures using dual-external fixator (a no-bridging cemented-pin frame and a conventional wrist-bridging external fixator). MATERIALS AND METHODS: From January 2018 to January 2021, 52 patients (52 distal radius fractures) were treated with dual-external fixator. For comparison, 61 patients (61 distal radius fractures) were treated with a plate and screw system. Wrist function was assessed using the Mayo Wrist Score. Patient satisfaction was assessed using the Short Assessment of Patient Satisfaction. A P < 0.05 was considered statistically significant. RESULTS: Fracture healing was achieved in all patients. At the final follow-up of 29 months (range, 24-34 months) vs 36 months (range, 26-39 months) (P > 0.05), the patients treated with dual-external fixator and a plate and screw system achieved mean ulnar deviations of 31° vs 29° (P < 0.05), mean Mayo Wrist Scores of 91.12 ± 5.98 vs 88.12 ± 7.54 (P < 0.05), and mean patient satisfaction scores of 23.42 ± 2.47 vs 23.04 ± 2.32 (P > 0.05). CONCLUSIONS: AO types C1, C2, and C3 distal radius fractures can be treated successfully using dual-external fixator. The technique is a potential alternative in addition to the conventional treatments. LEVEL OF EVIDENCE: Level IIa.

Palladium/Norbornene Cooperatively Catalyzed Modular Trifunctionalization of 2-Bromoaryl Ketone via a Decarbonylation Process.

Palladium/norbornene cooperatively catalyzed Catellani-type reactions were normally limited to aryl iodides as substrates. The employment of aryl bromides has remained challenging. Herein a Pd/NBE cooperatively catalyzed Catellani-type reaction of 2-bromoaryl ketone is described. The 2-bromoaryl ketone was employed as both substrates and arylation reagents with a Heck acceptor. A decarbonylation process of the ketones also occurred in the reaction, finishing the modular ispo-Heck/ortho,ortho-diarylation in one pot. It provided the functionalized m-triphenyl derivatives with three new C-C bonds in moderate to excellent yields which exhibited good regioselectivities and functional group tolerance.

C(sp)-C(sp) Lever-Based Targets of Orientational Chirality: Design and Asymmetric Synthesis.

In this study, the design and asymmetric synthesis of a series of chiral targets of orientational chirality were conducted by taking advantage of N-sulfinylimine-assisted nucleophilic addition and modified Sonogashira catalytic coupling systems. Orientational isomers were controlled completely using alkynyl/alkynyl levers [C(sp)-C(sp) axis] with absolute configuration assignment determined by X-ray structural analysis. The key structural element of the resulting orientational chirality is uniquely characterized by remote through-space blocking. Forty examples of multi-step synthesis were performed, with modest to good yields and excellent orientational selectivity. Several chiral orientational amino targets are attached with scaffolds of natural and medicinal products, showing potential pharmaceutical and medical applications in the future.

Synthesis, Characterization, and Properties of a Novel Hyperbranched Polymers with Polyacrylamide Side Chains.

A novel hyperbranched polymer with polyacrylamide side chains (HAPAM) was synthesized by aqueous solution polymerization using acrylic acid, acrylamide, 2-acrylamido-2-methyl-1-propanesulfonic acid, hydrophobic monomer of dimethyl octadecyl ammonium chloride, and the homemade skeleton monomer of modified-M2.0 as raw materials and (NH4)2S2O8-NaHSO3 as initiator. The molecular structure, functional groups, and surface morphology of HAPAM were characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, and scanning electron microscopy. It was found that the performance of HAPAM solution was higher than that of ordinary polyacrylamide solution in terms of thickening ability, shearing resistance, thermal endurance, salt-resistance, resistance-coefficient and residual-resistance-coefficient, ability to reduce interfacial tension between polymer solution and crude oil, and oil-displacement-efficiency. In particular, the enhanced oil recovery of the HAPAM solution was 13.03%, and the improvement of shearing resistance and immunity to chromatographic separation were simultaneously achieved by the HAPAM solution. These results indicate that the successful synthesis of the novel HAPAM opens a promising strategy for developing new high-performance oil-displacing polymers.

Microdrop-confined synthesis and regulation of porous hollow Ir-based catalysts for the mass transfer-enhanced electrolysis of pure water.

Maximally exploiting the active sites of iridium catalysts is essential for building low-cost proton exchange membrane (PEM) electrolyzers for green H2 production. Herein, we report a novel microdrop-confined fusion/blasting (MCFB) strategy for fabricating porous hollow IrO1-x microspheres (IrO1-x-PHM) by introducing explosive gas mediators from a NaNO3/glucose mixture. Moreover, the developed MCFB strategy is demonstrated to be general for synthesizing a series of Ir-based composites, including Ir-Cu, Ir-Ru, Ir-Pt, Ir-Rh, Ir-Pd, and Ir-Cu-Pd and other noble metals such as Rh, Ru, and Pt. The hollow structures can be regulated using different organics with NaNO3. The assembled PEM electrolyzer with IrO1-x-PHM as the anode catalyst (0.5 mg/cm2) displays an impressive polarization voltage of 1.593 and 1.726 V at current densities of 1 and 2A/cm2, respectively, outperforming commercial IrOx catalysts and most of the ever-reported iridium catalysts with such low catalyst loading. More importantly, the breakdown of the polarization loss indicates that the improved performance is due to the facilitated mass transport induced by the hollowness. This study offers a versatile platform for fabricating efficient Ir-based catalysts for PEM electrolyzers and beyond.

Multitasking Pharmacophores Support Cabotegravir-Based Long-Acting HIV Pre-Exposure Prophylaxis (PrEP).

Cabotegravir is an integrase strand transfer inhibitor (INSTI) for HIV treatment and prevention. Cabotegravir-based long-acting pre-exposure prophylaxis (PrEP) presents an emerging paradigm for infectious disease control. In this scheme, a combination of a high efficacy and low solubility of anti-infection drugs permits the establishment of a pharmaceutical firewall in HIV-vulnerable groups over a long period. Although the structure-activity-relationship (SAR) of cabotegravir as an INSTI is known, the structural determinants of its low solubility have not been identified. In this work, we have integrated multiple experimental and computational methods, namely X-ray diffraction, solid-state NMR (SSNMR) spectroscopy, solution NMR spectroscopy, automated fragmentation (AF)-QM/MM and density functional theory (DFT) calculations, to address this question. The molecular organization of cabotegravir in crystal lattice has been determined. The combination of very-fast magic-angle-sample-spinning (VF MAS) SSNMR and solution NMR, as supported by AF-QM/MM and DFT calculations, permits the identification of structural factors that contribute to the low aqueous solubility of cabotegravir. Our study reveals the multitasking nature of pharmacophores in cabotegravir, which controls the drug solubility and, meanwhile, the biological activity. By unraveling these function-defining molecular features, our work could inspire further development of long-acting HIV PrEP drugs.

Isochromenylium/Isoquinolinium-Mediated One-Pot Annulation to Hexahydropyrazinoisoquinolines. Synthesis of Quinocarcinol.

A novel annulation protocol has been successfully developed in this work for the quick generation of 1,3,4,6,11,11a-hexahydro-2H-pyrazino[1,2-b]isoquinolines from easily accessible o-alkynylbenzaldehydes. Various hexahydropyrazinoisoquinolines, including those previously unavailable with electron-deficient substituents, have been achieved via the newly developed continuously operational isochromenylium/isoquinolinium-mediated procedure. It also perfectly served as a key step to generate the basic skeleton in the new total synthesis of quinocarcinol, accompanied by the development and application of a direct late-stage stereoselective sp3 C-H hydroxymethylation.

The value of 3D high-resolution IR-prepared fast spoiled gradient-recalled MRI in the diagnosis of meningeal carcinomatosis involving the cranial nerves.

PURPOSE: The purpose of this study was to investigate the clinical utility of three-dimension (3D) high-resolution inversion recovery (IR)-prepared fast spoiled gradient-recalled (SPGR) magnetic resonance imaging (MRI) in the diagnosis of cranial nerve meningeal carcinomatosis (MC). METHODS: A total of 114 patients with MC from January 2015 to March 2020 were enrolled and their MRIs were analyzed retrospectively. All patients underwent MRIs before being administered a contrast agent. Both a 2D conventional MRI sequence and a 3D IR-prepared fast SPGR high-resolution T1-weighted (BRAVO) scan sequence were measured after contrast agent administration. The characteristics of MC and the involved cranial nerves were then examined. RESULTS: Among the 114 MC patients, 81 (71.05%) had cranial nerve enhancement on contrast-enhanced 3D-BRAVO imaging, while only 41 (35.96%) had image enhancement on conventional MRI. The contrast-enhanced 3D-BRAVO displayed stronger image contrast enhancement of the cranial nerves than the conventional MRI (P < 0.001). Furthermore, detection rates for the facial and auditory nerves, trigeminal nerve, oculomotor nerve, sublingual nerve, optic nerve, glossopharyngeal/vagal/accessory nerve, and abductor nerve on contrast-enhanced 3D-BRAVO imaging were 58.77%, 47.37%, 9.65%, 8.77%, 5.26%, 3.51%, and 0.88%, respectively. We found a statistically significant difference between the affected facial and auditory nerves, as well as the trigeminal nerve, oculomotor nerve, sublingual nerve, and optic nerve. CONCLUSION: In MC, contrast-enhanced 3D-BRAVO imaging displayed the cranial nerves more effectively than 2D conventional enhanced MRI. The facial, auditory, and trigeminal nerves are the primary nerves involved in MC, and improved scanning of these nerves would aid in the early detection and treatment of MC.

AgBr nanoparticle surface modified SnO2 enhanced visible light catalytic performance: characterization, mechanism and kinetics study.

In this study, a simple hydrothermal procedure and in situ precipitation method were used to prepare SnO2-AgBr composites, where the molar ratios of SnO2 and AgBr were 1 : 1, 1 : 2 and 2 : 1. Characterization results showed that the composites had excellent dispersion, crystallinity, and purity. A photocatalytic degradation experiment and first-order kinetic model indicate that SnO2-AgBr (1 : 1) had the best photocatalytic performance, and the degradation rates of 30 mg L-1 simulated MO and MG wastewater reached 96.71% and 93.36%, respectively, in 150 min, which were 3.5 times those of SnO2. The degradation rate of MO and MG increases with the dosage. Humic acid inhibited the degradation of MG, while a low concentration of humic acid promoted the degradation of MO, and the composite has good stability with pH. A free radical trapping experiment shows that ·OH and ·O2- were the main active substances, and h+ was the secondary one. According to the results of the characterization and photocatalysis experiments, a Z-scheme mechanism for the SnO2-AgBr composite was proposed, and the degradation pathway of target pollutants was speculated upon. This study has conceived novel methods for the development of a mature Z-scheme mechanism and in doing so has provided new approaches for the development of photocatalysis for water pollution control.

Ag2S Nanoparticles Supported on 3D Flower-Shaped Bi2WO6 Enhanced Visible Light Catalytic Degradation of Tetracycline.

A three-dimensional flower-shaped Bi2WO6 has been prepared by a hydrothermal procedure without the addition of an auxiliary agent and under neutral conditions with ultrapure water serving as solvent, and the Ag2S-Bi2WO6 composite with weight ratios of 5, 10, and 15% was prepared by a hydrothermal method. The crystallinity, morphology, mode of binding, and optical properties of the Ag2S-Bi2WO6 composite were characterized, the results of which showed that the composite had excellent dispersion, crystallinity, and purity. The composite with a weight ratio of 10% had the best photocatalytic performance, and the degradation rate of tetracycline reached 95.51% within 120 min, an increase of 27.35% over Bi2WO6. In experiments, some focus was given to the effect of the initial solution pH and the concentrations of humic acid and inorganic anions on the degradation efficiency. Based on free radical capture experiments and the semiconductor theory, the main active substances and mechanisms in the optical catalytic reaction process were studied, and speculation was given concerning the degradation pathway for the target pollutants. This study has conceived novel methods for the development of dual semiconductor systems consisting of a Ag NP composite and in doing so has provided new approaches for the development and photocatalysis for water pollution control.

Kaposi's sarcoma-associated herpesvirus glycoprotein K8.1 is critical for infection in a cell-specific manner and functions at the attachment step on keratinocytes.

IMPORTANCE: Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of several B cell malignancies and Kaposi's sarcoma. We analyzed the function of K8.1, the major antigenic component of the KSHV virion in the infection of different cells. To do this, we deleted K8.1 from the viral genome. It was found that K8.1 is critical for the infection of certain epithelial cells, e.g., a skin model cell line but not for infection of many other cells. K8.1 was found to mediate attachment of the virus to cells where it plays a role in infection. In contrast, we did not find K8.1 or a related protein from a closely related monkey virus to activate fusion of the viral and cellular membranes, at least not under the conditions tested. These findings suggest that K8.1 functions in a highly cell-specific manner during KSHV entry, playing a crucial role in the attachment of KSHV to, e.g., skin epithelial cells.

Intravenous ketorolac versus metoclopramide in adult patients with migraine headaches: An updated systematic review and meta-analysis.

BACKGROUND: Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide for migraine treatment is an intriguing issue for research and clinical practice. OBJECTIVES: To provide an updated systematic review and meta-analysis of randomized clinical trials (RCTs) to help determine which treatment has better effects for migraine patients. MATERIAL AND METHODS: Intravenous ketorolac and metoclopramide were compared to evaluate whether intravenous ketorolac is associated with significant benefits for pain intensity, short-term headache relief and sustained headache relief among adult patients with migraines. Adverse effects were also analyzed. Five studies with a total of 674 adult patients were included in the analysis, which focused on the outcomes of pain intensity, short-term headache relief, sustained headache relief, and adverse effects. RESULTS: The meta-analysis showed that the only modest but statistically significant difference was present in short-term headache relief when comparing intravenous ketorolac with intravenous metoclopramide. There were no significant differences between intravenous ketorolac and metoclopramide in terms of pain intensity, sustained headache relief or adverse effects. CONCLUSION: The results suggest that there are no significant differences in most treatment effects (aside from short-term headache relief) and adverse effects when comparing intravenous ketorolac with intravenous metoclopramide. However, the paucity of literature on this topic might have limited the interpretation of the current results. Thus, more relevant studies are warranted.

Dinuclear Gold-Catalyzed para-Selective C-H Arylation of Undirected Arenes by Noncovalent Interactions.

The regioselectivity of C-H functionalization is commonly achieved by directing groups, electronic factors, or steric hindrance, which facilitate the identification of reaction sites. However, such strategies are less effective for reactants such as simple monofluoroarenes due to their relatively low reactivity and the modest steric demands of the fluorine atom. Herein, we present an undirected gold-catalyzed para-C-H arylation of a wide array of monofluoroarenes using air-stable aryl silanes and germanes at room temperature. A high para-regioselectivity (up to 98 : 2) can be realized by utilizing a dinuclear dppm(AuOTs)2 (dppm=bis(diphenylphosphino)methane) as the catalyst and hexafluorobenzene as the solvent. This provides a general and practical protocol for the concise construction of structurally diverse para-arylated monofluoroarenes through C-H activation manner. It features excellent functional group tolerance and a broad substrate scope (>80 examples). Besides, this strategy is also robust for other simple monosubstituted arenes and heteroarenes. Our mechanistic studies and theoretical calculations suggest that para-C-H selectivity arises from highly electrophilic and structurally flexible dinuclear Ar-Au(III)-Au(I) species, coupled with noncovalent interaction induced by hexafluorobenzene.

Untargeted Plasma Lipidomics Reveal Perturbed Metabolites of Glycerophospholipids, and Sphingolipids in Moderate-to-Severe Acne.

Background: Acne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. The study aimed to explore the plasma lipidome signatures and identify specific lipid biomarkers in moderate-to-severe acne patients. Patients and Methods: Untargeted plasma lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was employed on 30 moderate-to-severe acne patients aged between 16-25 years and 30 healthy controls. Multivariate data analyses were used to identify the distinguishing lipid metabolites. Results: All 1449 species of 37 lipid subclasses were identified from the MS data. There were apparent differences in plasma lipid profiles between acne groups and control groups. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 26 significantly different lipid metabolites were identified. These metabolites consisted mainly of glycerophospholipids (GPs), sphingolipids (SPs), and glycerolipids (GLs). Combining with AUC≥0.800 as the elected criteria, we obtained five differential lipids with good diagnostic performance for acne severity, including 2 sphingomyelins (SM), 1 phosphatidylglycerol (PG), 1 trihexosylceramide (Hex3Cer), and 1 Phosphatidylcholine (PC). Among them, PG (44:0) had the highest AUC values. Conclusion: Our study revealed the plasma lipidome signature of patients with moderate-to-severe acne. The results will provide a novel light into the perturbed lipid metabolism leading to the development of acne.

Phosphodiesterase 5 and Arginase Inhibitory Activities of the Extracts from Some Members of Nelumbonaceae and Nymphaeaceae Families.

The objectives of this study were (1) to investigate the effect of extracts from some plants in the families Nelumbonaceae and Nymphaeaceae on phosphodiesterase 5 (PDE5) and arginase, which have been used in erectile dysfunction treatment, and (2) to isolate and identify the compounds responsible for such activities. The characterization and quantitative analysis of flavonoid constituents in the active extracts were performed by HPLC. Thirty-seven ethanolic extracts from different parts of plants in the genus Nymphaea and Victoria of Nymphaeaceae and genus Nelumbo of Nelumbonaceae were screened for PDE5 and arginase inhibitory activities. The ethanolic extracts of the receptacles and pollens of Nelumbo nucifera Gaertn., petals of Nymphaea cyanea Roxb. ex G.Don, Nymphaea stellata Willd., and Victoria amazonica (Poepp.) Sowerby and the petals and receptacles of Nymphaea pubescens Willd. showed IC50 values on PDE5 of less than 25 µg/mL while none of the extracts showed effects on arginase. The most active extract, N. pubescens petal extract, was fractionated to isolate and identify the PDE5 inhibitors. The results showed that six flavonoid constituents including quercetin 3'-O-ß-xylopyranoside (1), quercetin 3-methyl ether 3'-O-ß-xylopyranoside (2), quercetin (3), 3-O-methylquercetin (4), kaempferol (5) and 3-O-methylkaempferol (6) inhibited PDE5 with IC50 values at the micromolar level.

The association of carbohydrate antigen 19-9 response with radiologic response and survival in intrahepatic cholangiocarcinoma: A prospective cohort study.

BACKGROUND: The role of carbohydrate antigen 19-9 (CA 19-9) in response assessment among patients with intrahepatic cholangiocarcinoma (iCCA) remains unknown. The authors studied the association of the CA 19-9 response (defined as a reduction >50% from baseline) with the radiologic response and the outcome in patients with unresectable iCCA. METHODS: A prospective cohort of 422 patients who were initially diagnosed with unresectable iCCA, had baseline CA 19-9 levels ≥100 U/mL, and received treatment with systemic therapies at the authors' institution between January 2017 and December 2021 were enrolled in this study. The radiologic response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. A landmark assessment of the CA 19-9 response and the radiologic response was performed. The associations between CA 19-9 response and imaging response, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: Two hundred sixty-seven patients (63.3%) had a CA 19-9 response. A CA 19-9 response was observed in 123 of 132 (93.2%) radiologic responders and in 144 of 290 (49.7%) radiologic nonresponders (p < .001). CA 19-9 responders outperformed nonresponders in median PFS (10.6 vs. 3.6 months; hazard ratio [HR], 4.8 months; 95% confidence interval [CI], 3.8-6.0 months; p < .001) and OS (21.4 vs. 6.3 months; HR, 5.3 months; 95% CI, 4.2-6.7 months; p < .001). The common independent predictors of both OS and PFS included metastasis, CA 19-9 nonresponder status, and radiologic nonresponder status in multivariable analysis. CONCLUSIONS: CA 19-9 response is a valuable addition to assess tumor response and is associated with improved outcomes in patients with iCCA. Achieving a CA 19-9 response should be one of the therapeutic objectives of patients with iCCA after systemic therapies. PLAIN LANGUAGE SUMMARY: A decline in carbohydrate antigen 19-9 levels from elevated baseline levels should be one of the therapeutic aims of patients with intrahepatic cholangiocarcinoma who are managed with systemic therapies.

Quartz Crystal Microbalance Method to Measure Nanoparticle-Receptor Interactions and Evaluate Nanoparticle Design Efficiency.

Conjugation of biomolecules on the surface of nanoparticles (NPs) to achieve active targeting is widely investigated within the scientific community. However, while a basic framework of the physicochemical processes underpinning bionanoparticle recognition is now emerging, the precise evaluation of the interactions between engineered NPs and biological targets remains underdeveloped. Here, we show how the adaptation of a method currently used to evaluate molecular ligand-receptor interactions by quartz crystal microbalance (QCM) can be used to obtain concrete insights into interactions between different NP architectures and assemblies of receptors. Using a model bionanoparticle grafted with oriented apolipoprotein E (ApoE) fragments, we examine key aspects of bionanoparticle engineering for effective interactions with target receptors. We show that the QCM technique can be used to rapidly measure construct-receptor interactions across biologically relevant exchange times. We contrast random adsorption of the ligand at the surface of the NPs, resulting in no measurable interaction with target receptors, to grafted oriented constructs, which are strongly recognized even at lower graft densities. The effects of other basic parameters impacting the interaction such as ligand graft density, receptor immobilization density, and linker length were also efficiently evaluated with this technique. Dramatic changes in interaction outcomes with subtle alterations in these parameters highlight the general importance of measuring the interactions between engineered NPs and target receptors ex situ early on in the construct development process for the rational design of bionanoparticles.

Clinical application of a modified predeposit autologous red blood cell apheresis in multistage spinal fusion: a single-center retrospective study.

Purpose: This study aimed to evaluate the efficacy and safety of predeposit autologous RBC apheresis (PARA) in patients undergoing multilevel spinal fusion surgery. Methods: A total of 112 patients from January 2020 to June 2022 were divided into two groups according to PARA: the PARA group (n = 51) and the control group (n = 61). The baseline characteristics of the patients, outcomes, transfusion cost, hospitalization cost, length of stay, complications, and changes in hemoglobin and hematocrit levels between the two groups were compared. Results: The baseline characteristics were similar in both groups. No significant differences were found in functional outcomes, including VAS score (p = 0.159), ODI score (p = 0.214), JOA score (p = 0.752), and SF-36 score (p = 0.188) between the PARA and control groups. The amount and rate of intraoperative and perioperative allogeneic RBC transfusion were significantly higher in the control group than in the PARA group (p < 0.001). The postoperative (9.04 ± 3.21 vs. 11.05 ± 3.84, p = 0.004) and total length of stay (15.78 ± 3.79 vs. 17.36 ± 4.08, p = 0.038) in the PARA group were significantly lower than those in the control group, respectively. Despite no difference in hospitalization cost (p = 0.737), the total blood transfusion cost in the PARA group was significantly lower, compared with the control group (p < 0.001). For safety evaluation, there were no significant differences in Hb and Hct levels between the two groups at admission, on postoperative day 1, and postoperative day 3, respectively (p > 0.05). Moreover, the number of postoperative infections in the PARA group was significantly lower than that in the control group (p = 0.038). Conclusion: PARA was a novel, safe, and highly efficient technique for mass autologous blood preparation in a quite short preparation time. This method could significantly reduce the amount of allogeneic blood transfusion and length of stay, which could provide a theoretical basis for following clinical practice about the technique.

Acute traumatic coma awakening by right median nerve electrical stimulation: a randomised controlled trial.

PURPOSE: Severe traumatic brain injury (TBI) leads to acute coma and may result in prolonged disorder of consciousness (pDOC). We aimed to determine whether right median nerve electrical stimulation is a safe and effective treatment for accelerating emergence from coma after TBI. METHODS: This randomised controlled trial was performed in 22 centres in China. Participants with acute coma at 7-14 days after TBI were randomly assigned (1:1) to either routine therapy and right median nerve electrical stimulation (RMNS group) or routine treatment (control group). The RMNS group received 20 mA, 300 µs, 40 Hz stimulation pulses, lasting 20 s per minutes, 8 h per day, for 2 weeks. The primary outcome was the proportion of patients who regained consciousness 6 months post-injury. The secondary endpoints were Glasgow Coma Scale (GCS), Full Outline of Unresponsiveness scale (FOUR), Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS) and Glasgow Outcome Scale Extended (GOSE) scores reported as medians on day 28, 3 months and 6 months after injury, and GCS and FOUR scores on day 1 and day 7 during stimulation. Primary analyses were based on the intention-to-treat set. RESULTS: Between March 26, 2016, and October 18, 2020, 329 participants were recruited, of whom 167 were randomised to the RMNS group and 162 to the control group. At 6 months post-injury, a higher proportion of patients in the RMNS group regained consciousness compared with the control group (72.5%, n = 121, 95% confidence interval (CI) 65.2-78.7% vs. 56.8%, n = 92, 95% CI 49.1-64.2%, p = 0.004). GOSE at 3 months and 6 months (5 [interquartile range (IQR) 3-7] vs. 4 [IQR 2-6], p = 0.002; 6 [IQR 3-7] vs. 4 [IQR 2-7], p = 0.0005) and FOUR at 28 days (15 [IQR 13-16] vs. 13 [interquartile range (IQR) 11-16], p = 0.002) were significantly increased in the RMNS group compared with the control group. Trajectory analysis showed that significantly more patients in the RMNS group had faster GCS, CRS-R and DRS improvement (p = 0.01, 0.004 and 0.04, respectively). Adverse events were similar in both groups. No serious adverse events were associated with the stimulation device. CONCLUSION: Right median nerve electrical stimulation is a possible effective treatment for patients with acute traumatic coma, that will require validation in a confirmatory trial.

Protein-Targeted Glycan Editing on Living Cells Disrupts KRAS Signaling.

The frequent mutation of KRAS oncogene in some of the most lethal human cancers has spurred incredible efforts to develop KRAS inhibitors, yet only one covalent inhibitor for the KRASG12C mutant has been approved to date. New venues to interfere with KRAS signaling are desperately needed. Here, we report a "localized oxidation-coupling" strategy to achieve protein-specific glycan editing on living cells for disrupting KRAS signaling. This glycan remodeling method exhibits excellent protein and sugar specificity and is applicable to different donor sugars and cell types. Attachment of mannotriose to the terminal galactose/N-acetyl-D-galactosamine epitopes of integrin αv ß3 , a membrane receptor upstream of KRAS, blocks its binding to galectin-3, suppresses the activation of KRAS and downstream effectors, and mitigates KRAS-driven malignant phenotypes. Our work represents the first successful attempt to interfere with KRAS activity by manipulating membrane receptor glycosylation.