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Therapeutic bioconjugates are emerging as an essential tool to combat human disease. Site-specific conjugation technologies are widely recognized as the optimal approach for producing homogeneous drug products. Non-natural amino acid (nnAA) incorporation allows the introduction of bioconjugation handles at genetically defined locations. Escherichia coli (E. coli) is a facile host for therapeutic nnAA protein synthesis because it can stably replicate plasmids encoding genes for product and nnAA incorporation. Here, we demonstrate that by engineering E. coli to incorporate high levels of nnAAs, it is feasible to produce nnAA-containing antibody fragments and full-length immunoglobulin Gs (IgGs) in the cytoplasm of E. coli. Using high-density fermentation, it was possible to produce both of these types of molecules with site-specifically incorporated nnAAs at titers > 1 g/L. We anticipate this strategy will help simplify the production and manufacture of promising antibody therapeutics.

ObjectivePleural effusion (PE) is a common pulmonary manifestation in patients with systemic lupus erythematosus (SLE), and is associated with disease activity. However, little is known regarding the additive effects of PE on cardiac function. Therefore, this study aimed to investigate multi-parameter cardiovascular magnetic resonance imaging (CMR) findings in SLE patients with PE and to explore whether cardiac involvement is associated with PE.MethodsPatients with SLE and age-matched/sex-matched healthy controls were included in this study. Patients with SLE were diagnosed according to the 2019 European League Against Rheumatism/American College of Rheumatology classification criteria. Moreover, the PE diagnosis was based on computed tomography, and the height of the effusion was > 5 mm. All enrolled individuals underwent CMR imaging, including cine and late gadolinium enhancement (LGE), T1, and T2 mapping imaging. The left and right ventricular function, LGE, T1, extracellular volume (ECV), and T2 values were evaluated.ResultsA total of 111 patients with SLE were enrolled, of whom 26 (23.42%) had PE. White cell count, hemoglobin, CRP, ESR, and lactate dehydrogenase levels were higher in SLE patients with PE than in SLE patients without PE (P

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

High exhaust temperature is an intrinsic nature of natural gas engines which underlies power de-rating and thermal aging of after-treatment system; therefore, this study integrates an organic Rankine cycle (ORC) system between engine and it's three-way catalyst (TWC) to address these challenges. ORC facilitates power output enhancement through exhaust energy recovery and alleviates thermal aging by reducing exhaust temperature. To estimate the effectiveness of this hypothesized system, a simulation-based investigation is performed. First, simulation models, including engine, TWC, and vehicle dynamic models, are built and validated by experimental data. According to the temperature characteristics of different TWCs, three scenarios, representing old, current, and prospective TWC technology, are formulated to estimate the ORC performance under Worldwide Harmonized Light Vehicles Test Cycle. Results show that ORC system can substantially alleviate the thermal damage caused by high exhaust temperature and extend TWC lifespan. It is estimated that over 98.5 % of thermal damage can be decreased by proper ORC setting, and the average TWC lifespan extension can be at least 55.4, making a reduced noble metal usage and cost of TWC. Meanwhile, with the decrease of the working temperature of TWC, ORC can recover exhaust energy under more road conditions, further improving the net power and shortening the payback period of extra ORC hardware costs. A reduction in the working temperature of TWC from 770.5 K to 618 K yields a 109 % enhancement in maximum power, coupled with a 62.30 % reduction in the payback period. These findings fully reflect the advantage of ORC-TWC coupling and indicate that ORC is supposed to be used more for the TWC with a low working temperature to maximize economic effectiveness. This study provides a novel pathway for thermal aging alleviation of TWC and a valuable reference for prospective studies on matching ORC with TWC under road conditions.

Abstract Background The cardiac magnetic resonance tissue tracking (CMR-TT) technique was used to obtain left atrial strain and strain rate in patients with myocardial infarction (MI) and to evaluate the utility of this technique in the quantitative assessment of myocardial infarction for distinguishing acute from chronic myocardial infarction. Methods We retrospectively analyzed 36 consecutive patients with acute myocardial infarction (AMI) and 29 patients with chronic myocardial infarction (CMI) who underwent CMR and 30 controls. Left atrial (LA) and ventricular functions were quantified by volumetric, and CMR-TT derived strain analysis from long and short left ventricular view cines. Receiver Operating Characteristics (ROC) analysis was used to determine the diagnostic accuracy of CMR-TT strain parameters for discriminating between acute and chronic myocardial infarction. Results AMI and CMI participants had impaired LA reservoir function, conduit function and LA booster pump dysfunction compared to the controls. LA strain was more sensitive than LV global strain for the assessment of the MI stage. Peak late-negative SR yielded the best areas under the ROC curve (AUC) of 0.879, showing differentiation between acute and chronic myocardial infarction of all the LA strain parameters obtained. The highest significant differences between chronic myocardial infarction and normal myocardium were also found in the LV strain (p

The three-point bending fatigue method was used to determine the S-N fatigue curves of smooth specimens and straight-notched specimens to study the fatigue properties of Stellite12 cobalt-based alloy, and the fatigue fracture processes of the cobalt-based alloy were investigated by the observation of fracture morphology.The results show that the fatigue limit of the smooth specimen is 545 MPa, which is about 25.4% of the original bending strength of 1552 MPa. The fatigue limit of the straight-notched specimen is about 101 MPa, which is about 19.1% of static bending strength of 517.6 MPa. The fatigue sensitivity of smooth specimens and straight-notched specimens is 397 and 31, respectively. In addition, it is found that the fatigue cracks can initiate in the carbides aggregated regions in the near surface. Surface defects can also induce the initiation of fatigue cracks. The transgranular fracture of the carbides dominates in the crack propagation. The cobalt base metal presents a lot of tearing ridges under the condition of stress ratio R=0.1, but it also shows a certain degree brittle fracture mode, so the fatigue crack propagation mode is a mixed mode of true fatigue and static fatigue.

Background To investigate whether collateral status could modify the associations between post‐thrombectomy blood pressure (BP) measures and outcomes. Methods and Results Patients with anterior‐circulation large‐vessel‐occlusion successfully recanalized in a multicenter endovascular thrombectomy registry were enrolled. Pretreatment collateral status was graded and dichotomized (good/poor) in angiography. Maximum, minimum, and mean systolic BP (SBP) and BP variability (assessed by the SD, coefficient of variation) during the initial 24 hours after endovascular thrombectomy were obtained. The primary outcome was unfavorable 90‐day outcome (modified Rankin Scale score 3–6). Secondary outcomes included symptomatic intracranial hemorrhage and 90‐day mortality. Adjusted odds ratios (aOR) of BP parameters over the outcomes were obtained in all patients and in patients with good/poor collaterals. Among 596 patients (mean age 66 years; 59.9% males), 302 (50.7%) patients had unfavorable 90‐day outcome. In multivariable analyses, higher mean SBP (aOR, 1.59 per 10 mm Hg increment; 95% CI, 1.26–2.02; P140 mm Hg (versus ≤120 mm Hg; aOR, 4.27; 95% CI, 1.66–10.97; P=0.002), and higher SBP SD (aOR, 1.08 per 1‐SD increment; 95% CI, 1.01–1.16; P=0.02) were respectively associated with unfavorable 90‐day outcome in patients with poor collateral but not in those with good collateral. A marginal interaction between SBP coefficient of variation tertiles and collaterals on 90‐day functional outcome (P for interaction, 0.09) was observed. A significant interaction between SBP coefficient of variation tertiles and collaterals on 90‐day mortality (P for interaction, 0.03) was observed. Conclusions Higher postprocedural BP is associated with 90‐day unfavorable outcomes after successful endovascular thrombectomy in patients with poor collateral. Registration URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Almost all elevated atmospheric CO2 concentrations (eCO2) studies have not addressed the potential responses of plant growth to different CO2 in daytime and nighttime. The present study was to determine the impact of daytime and/or nighttime eCO2 on growth and quality of mulberry (Morus alba L.), a perennial multipurpose cash plant. Six-month-old mulberry seedlings were hence grown in environmentally auto-controlled growth chambers under four CO2 concentrations: (1) ambient CO2 (ACO2, 410 μmol mol–1 daytime/460 μmol mol–1 nighttime), (2) sole daytime elevated CO2 (DeCO2, 710 μmol mol–1/460 μmol mol–1), (3) sole nighttime elevated CO2 (NeCO2, 410 μmol mol–1/760 μmol mol–1), and (4) continuous daytime and nighttime elevated CO2 (D + NeCO2, 710 μmol mol–1/760 μmol mol–1). Plant growth characteristics, nutrient uptake, and leaf quality were then examined after 120 days of CO2 exposure. Compared to control, DeCO2 and (D + N)eCO2 increased plant biomass production and thus the harvest of nutrients and accumulation of leaf carbohydrates (starch, soluble sugar, and fatty acid) and N-containing compounds (free amino acid and protein), though there were some decreases in the concentration of leaf N, P, Mg, Fe, and Zn. NeCO2 had no significant effects on leaf yield but an extent positive effect on leaf nutritional quality due to their concentration increase in leaf B, Cu, starch, and soluble sugar. Meanwhile, (D + N)eCO2 decreased mulberry leaf yield and harvest of nutritious compounds for silkworm when compared with DeCO2. The reason may be associated to N, P, Mg, Fe, and Zn that are closely related to leaf pigment and N metabolism. Therefore, the rational application of mineral nutrient (especially N, P, Fe, Mg, and Zn) fertilizers is important for a sustainable mulberry production under future atmosphere CO2 concentrations.

Objectives: This study aims to investigate whether the machine learning algorithms could provide an optimal early mortality prediction method compared with other scoring systems for patients with cerebral hemorrhage in intensive care units in clinical practice.Methods: Between 2008 and 2012, from Intensive Care III (MIMIC-III) database, all cerebral hemorrhage patients monitored with the MetaVision system and admitted to intensive care units were enrolled in this study. The calibration, discrimination, and risk classification of predicted hospital mortality based on machine learning algorithms were assessed. The primary outcome was hospital mortality. Model performance was assessed with accuracy and receiver operating characteristic curve analysis.Results: Of 760 cerebral hemorrhage patients enrolled from MIMIC database [mean age, 68.2 years (SD, ±15.5)], 383 (50.4%) patients died in hospital, and 377 (49.6%) patients survived. The area under the receiver operating characteristic curve (AUC) of six machine learning algorithms was 0.600 (nearest neighbors), 0.617 (decision tree), 0.655 (neural net), 0.671(AdaBoost), 0.819 (random forest), and 0.725 (gcForest). The AUC was 0.423 for Acute Physiology and Chronic Health Evaluation II score. The random forest had the highest specificity and accuracy, as well as the greatest AUC, showing the best ability to predict in-hospital mortality.Conclusions: Compared with conventional scoring system and the other five machine learning algorithms in this study, random forest algorithm had better performance in predicting in-hospital mortality for cerebral hemorrhage patients in intensive care units, and thus further research should be conducted on random forest algorithm.

Based on Lcr wave acoustoelastic theory, the influence mechanism of blind-hole on stress evaluation with Lcr wave was discussed. Combined with equivalent method, the blind-holes with different diameters were preset, the difference in time of flight between Lcr wave was calculated by cross correlation coefficient function, the Lcr wave acoustoelastic coefficient was determined with linear fitting function, the influence mechanism of blind-hole diameter on Lcr wave acoustoelastic coefficient was clarified based on the elastic plastic deformation theory and stress concentration theory of hole. The results show that when the diameter of blind-hole is different, the change rule of the difference in time of flight between Lcr wave is basically the same as stress increases, the difference in time of flight between Lcr wave increases linearly as stress increases, while the nonlinear feature is also gradually obvious, the maximum stress in linear stage is less than the yield strength of specimen, the Lcr wave acoustoelastic coefficient decreases gradually as blind-hole diameter increases, and it tends to be constant. The analysis shows that the stress concentration is seen as the main reason for above results, anisotropic structure of specimen and blind-hole depth are also the important reasons for that.

The concurrent effect of elevated CO2 (eCO2) concentrations and arbuscular mycorrhizal fungi (AMF) on plant growth, carbon (C), nitrogen (N), phosphorus (P) and potassium (K) accumulations in plant and soil is largely unknown. To understand the mechanisms of eCO2 and mycorrhization on wheat (Triticum aestivum) performance and soil fertility, wheat seedlings were grown under four different CO2 environments for 12 weeks, including (1) ambient CO2 (ACO2, 410/460 ppm, daytime/nighttime), (2) sole daytime eCO2 (DeCO2, 550/460 ppm), (3) sole nighttime eCO2 (NeCO2, 410/610 ppm), and (4) dual or continuous daytime/nighttime eCO2 ((D + N)eCO2, 550/610 ppm), and with or without AMF (Funneliformis mosseae) colonization. DeCO2, NeCO2 and (D + N)eCO2 generally significantly increased shoot and root biomass, plant C, N, P and K accumulation, soil invertase and urease activity, but decreased shoot and root N, P and K concentrations, and soil available N, P and K. Compared with non-AMF, AMF effects on above-mentioned characteristics were significantly positive under ACO2, DeCO2 and (D + N)eCO2, but negative on plant biomass, C, N, P and K accumulation under NeCO2. Overall, AMF colonization alleviated soil nutrient constraints on plant responses to DeCO2, while NeCO2 decreased AMF’s beneficial effects on plants. These results demonstrated that an integration of AMF’s benefits to plants under factual field DeCO2 and/or NeCO2 will be critical for managing the long-term consequence of future CO2 rising on global cropping systems.

A total of two postpartum women with no noteworthy medical history presented with persistent headache. Brain magnetic resonance imaging (MRI) of both revealed extensive cerebral venous thrombosis, concurrently with abnormal signals of the splenium of the corpus callosum (SCC): The splenium appeared hyperintense on T2-weighted sequences, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) imaging, and hypointense on T1 sequences and apparent diffusion coefficient (ADC) map. The patients were given thrombolytic therapy. Clinically, both patients achieved recovery with no neurologic sequelae, and follow-up MRI revealed complete resolution of the lesion in the SCC at day 36 and day 37 after initial presentation, respectively.

Background Studies show tranexamic acid can reduce the risk of death and early neurological deterioration after intracranial haemorrhage. We aimed to assess whether tranexamic acid reduces haematoma expansion and improves outcome in intracerebral haemorrhage patients susceptible to haemorrhage expansion.Methods We did a prospective, double-blind, randomised, placebo-controlled trial at 10 stroke centres in China. Acute supratentorial intracerebral haemorrhage patients were eligible if they had indication of haemorrhage expansion on admission imaging (eg, spot sign, black hole sign or blend sign), and were treatable within 8 hours of symptom onset. Patients were randomly assigned (1:1) to receive either tranexamic acid or a matching placebo. The primary outcome was intracerebral haematoma growth (>33% relative or >6 mL absolute) at 24 hours. Clinical outcomes were assessed at 90 days.Results Of the 171 included patients, 124 (72.5%) were male, and the mean age was 55.9±11.6 years. 89 patients received tranexamic acid and 82 received placebo. The primary outcome did not differ significantly between the groups: 36 (40.4%) patients in the tranexamic acid group and 34 (41.5%) patients in the placebo group had intracranial haemorrhage growth (OR 0.96, 95% CI 0.52 to 1.77, p=0.89). The proportion of death was lower in the tranexamic acid treatment group than placebo group (8.1% vs 10.0%), but there were no significant differences in secondary outcomes including absolute intracranial haemorrhage growth, death and dependency.Conclusions Among patients susceptible to haemorrhage expansion treated within 8 hours of stroke onset, tranexamic acid did not significantly prevent intracerebral haemorrhage growth. Larger studies are needed to assess safety and efficacy of tranexamic acid in intracerebral haemorrhage patients.

Background and purpose Current randomised controlled trials (RCTs) showed an uncertain benefit of haemostatic therapy on preventing haematoma expansion and improving the outcome in patients with intracerebral haemorrhage (ICH). This meta-analysis aims to systematically evaluate the effect of haemostatic agents on the prevention of haemorrhage growth in patients with high-risk spontaneous ICH predicted by CT signs in RCTs.Methods A comprehensive search of PubMed, EMBASE and Cochrane library from 1 January 2005 to 30 June 2021 was conducted. RCTs that compared haemostatic agents with placebo for the treatment of spontaneous patients with ICH with high-risk haemorrhage growth were included. The primary endpoint was haematoma expansion at 24 hours. Other major endpoints of interest included 90-day functional outcome and mortality.Results The meta-analysis included four RCTs that randomised 2666 patients with ICH with high-risk haemorrhage growth. Haemostatic therapy reduced the rate of haematoma expansion at a marginally statistically significant level when compared with placebo (OR 0.84; 95% CI 0.70 to 1.00; p=0.051). Subgroup analysis for patients with black hole sign on CT revealed a significant reduction of haematoma expansion with haemostatic therapy (OR 0.61; 95% CI 0.39 to 0.94; p=0.03). However, both the primary analysis and subgroup analyses showed that haemostatic therapy could not reduce the rate of poor functional outcome (modified Rankin Scale >3) or death.Conclusions Haemostatic therapy showed a marginally significant benefit in reducing early haematoma expansion in patients with high-risk spontaneous ICH predicted by markers on CT scan. However, no significant improvement in functional outcome or reduction of mortality was observed.