Modulating effector immune cells via monoclonal antibodies (mAbs) and facilitating the co-engagement of T cells and tumor cells via chimeric antigen receptor- T cells or bispecific T cell-engaging ...antibodies are two typical cancer immunotherapy approaches. We speculated that immobilizing two types of mAbs against effector cells and tumor cells on a single nanoparticle could integrate the functions of these two approaches, as the engineered formulation (immunomodulating nano-adaptor, imNA) could potentially associate with both cells and bridge them together like an 'adaptor' while maintaining the immunomodulatory properties of the parental mAbs. However, existing mAbs-immobilization strategies mainly rely on a chemical reaction, a process that is rough and difficult to control. Here, we build up a versatile antibody immobilization platform by conjugating anti-IgG (Fc specific) antibody (αFc) onto the nanoparticle surface (αFc-NP), and confirm that αFc-NP could conveniently and efficiently immobilize two types of mAbs through Fc-specific noncovalent interactions to form imNAs. Finally, we validate the superiority of imNAs over the mixture of parental mAbs in T cell-, natural killer cell- and macrophage-mediated antitumor immune responses in multiple murine tumor models.
•Satisfactory degradation efficiency of pollutants was achieved by FeS/PAA system.•S(-II) and H2S (aq) played a significant role in Fe(II) regeneration.••OH played a dominant role in pharmaceuticals ...degradation.•The R-O• generated was supposed to be quickly consumed by sulfur specie.•Degradation products of three pharmaceuticals were successfully detoxified.
As peracetic acid (PAA) is being increasingly used as an alternative disinfectant, efficient activation of PAA by low-cost and environmentally friendly catalysts over a wide pH range is potentially useful for simultaneous sterilization and pharmaceutical degradation in wastewater, such as hospital wastewater. In this study, peracetic acid (PAA) was successfully activated by low-cost and environmental-friendly FeS (25 mg/L) for efficient oxidative removal of three pharmaceuticals over a wide pH range (3.0∼9.0) as indicated by 80∼100% removal rate within 5 min. As expected, Fe(II) rather than sulfur species was the primary reactive site for PAA activation, while unlike the homogeneous Fe2+/PAA system with organic radicals (R-O·) and ·OH as the dominant reactive oxidized species (ROS), ·OH is the key reactive species in the FeS/PAA system. Interestingly and surprisingly, in-depth investigation revealed the dual role of sulfur species in regulating the reactive oxidized species: (1) S(-II) and its conversion product H2S (aq) played a significant role in Fe(II) regeneration with a result of accelerated PAA activation; (2) however, the R-O· generated in the initial seconds of the FeS/PAA process was supposed to be quickly consumed by sulfur species, resulting in ·OH as the dominant ROS over the whole process. The selective reaction of sulfur species with R-O· instead of ·OH was supported by the obviously lower Gibbs free energy of CH3COO· and sulfur species than ·OH, suggesting the preference of CH3COO· to react with sulfur species with electron transfer. After treatment with the FeS/PAA system, the products obtained from the three pharmaceuticals were detoxified and even facilitated the growth of E. coli probably due to the supply of numerous carbon sources by activated PAA. This study significantly advances the understanding of the reaction between PAA and sulfur-containing catalysts and suggests the practical application potential of the FeS/PAA process combined with biotreatment processes.
Display omitted
As a new kind of water pollutant, antibiotics have encouraged researchers to develop new treatment technologies. Electrospun fiber membrane shows excellent benefits in antibiotic removal in water due ...to its advantages of large specific surface area, high porosity, good connectivity, easy surface modification and new functions. This review introduces the four aspects of electrospinning technology, namely, initial development history, working principle, influencing factors and process types. The preparation technologies of electrospun functional fiber membranes are then summarized. Finally, recent studies about antibiotic removal by electrospun functional fiber membrane are reviewed from three aspects, namely, adsorption, photocatalysis and biodegradation. Future research demand is also recommended.
•S-ZVI exhibited superior activity for PAA activation and micropollutants removal.•Enhancement of the electron donating ability of ZVI by sulfidation was the key.•HO• was the main contributor ...responsible for micropollutants degradation.•Simple strategy for extending the applicability of S-ZVI/PAA is proposed.•Fe(III) slowed Fe° consumption and elevated electron utilization of S-ZVI.
In this study, mechanically sulfidated microscale zero valent iron (S-ZVI) was found to effectively activate the peracetic acid (PAA) with a result of almost complete degradation of six micropollutants within 10 min under neutral conditions, and > 95% sulfamethoxazole (SMX) removal after six cycles. Reactive oxidized species (ROS) including HO•, carbon-centered radicals, and Fe(IV) were generated in the S-ZVI/PAA system, while HO• was the main contributor towards micropollutants degradation. This study clearly revealed that enhancement of the electron donating ability of ZVI by the formed conductive iron sulfides was crucial for promoted Fe(II) generation and subsequent PAA activation over several cycles, rather than the ability of sulfides to reduce Fe(III) for Fe(II) regeneration as reported previously. Interestingly, it's discovered that co-existence of Fe(III) would dramatically improve the contaminants removal efficiency of the S-ZVI/PAA system; transform the surfaced Fe(II) dominated ROS generation process to aqueous Fe(II) one; enhance the tolerance of the proposed system to water matrix. The promoting effect of predosed Fe(III) on PAA activation by S-ZVI should be mainly associated with: the greater ability of Fe(III) than H2O to accept electron from Fe0 for obtaining more active sites; slower Fe0 consumption and solid sulfur species release for elevated electron utilization efficiency and PAA activation. Considering the convenient and cost-effective access of Fe(III), the decrease of acute toxicity of treated SMX, excellent stability and good removal of various micropollutants fully demonstrate the superiority of S-ZVI/PAA system for practical application.
Display omitted
Objective
Intertrochanteric fracture is one type of hip fracture, which is the most serious consequence of osteoporosis. Along with the growing elderly population, intertrochanteric fracture is ...expected to rise increasingly. The aim of this study was to assess excess mortality after intertrochanteric fractures and to identify the predictors of long‐term mortality by therapy among patients aged 50 years and older in Tianjin.
Methods
This is a retrospective cohort study on mortality for 3029 patients aged 50 years and older in Tianjin experiencing an intertrochanteric fracture between December 26, 2014 and December 31, 2018. Data were from Tianjin Hospital Hip Fracture (THHF) cohort. Follow‐up period was until March 31, 2022. Mortality, excess mortality, and comorbidities were analyzed and stratified by therapy and gender. Time dependent Cox models were performed to estimate the effects of the variables.
Results
Absolute mortality for all the patients was 5.90% at 3 months, 12.55% at 12 months, 19.92% at 24 months and 27.28% at 36 months. Absolute mortality for surgical group was 1.57% at 3 months, 4.77% at 12 months, 8.49% at 24 months and 12.07% at 36 months, significantly lower than conservative group: 10.50% at 3 months, 20.73% at 12 months, 31.96% at 24 months and 43.04% at 36 months. We found a substantially lower mortality (hazard ratio HR 0.34, 95% confidence internal, CI: 0.23–0.52, p = 0.000) among patients undergoing surgical therapy than those undergoing conservative therapy, even when controlled for gender, age, the length of hospital stay, and all the comorbidities. Female patients (HR 0.68, 95% CI: 0.58–0.79, p = 0.000) were less likely to die than male patients after an intertrochanteric fracture. Patients treated by the two methods were both found to have excess mortality rates compared to the general population, although in different levels. The excess mortality rates for patients in the conservative therapy group were 14.46% in males and 17.93% in females, while in the surgical therapy group, 2.78% in females and 4.37% in males. The comorbidities moderate or severe renal disease (HR 2.19, 95% CI: 1.61–2.98, p = 0.000), metastatic solid tumor (HR 6.35, 95% CI: 1.56–25.85, p = 0.010), hypoproteinemia (HR 1.22, 95% CI: 1.01–1.47, p = 0.034), and older age (HR 1.89, 95% CI: 1.73–2.08, p = 0.000) were also risk factors on mortality. A worse‐case analysis for the primary outcome were performed as sensitivity analysis and it was consistent with the original conclusion.
Conclusion
Intertrochanteric factures for people aged 50 years older were found to have excess mortality compared to the general population in Tianjin city, and preventing the fractures in the hip for elderly people was imperative. After controlling tfor comorbidities and age, female gender and surgical therapy were protective factors for the death after fractures, which could provide strong evidence for patients and surgeons to make decisions.
Elderly patients with femoral intertrochanteric fracture treated with two methods were both found to have an excess mortality rate compared to the general population, although in different levels. The excess mortality rates for patients in the conservative therapy group were 14.46% in males and 17.93% in females, while in the surgical therapy group, it was 2.78% in females and 4.37% in males. After controlling other covariates, surgical therapy could greatly reduce the excess mortality after intertrochanteric fracture.
Visual Simultaneous Localization and Mapping (VSLAM) estimates the robot's pose in three-dimensional space by analyzing the depth variations of inter-frame feature points. Inter-frame feature point ...mismatches can lead to tracking failure, impacting the accuracy of the mobile robot's self-localization and mapping. This paper proposes a method for removing mismatches of image features in dynamic scenes in visual SLAM. First, the Grid-based Motion Statistics (GMS) method was introduced for fast coarse screening of mismatched image features. Second, an Adaptive Error Threshold RANSAC (ATRANSAC) method, determined by the internal matching rate, was proposed to improve the accuracy of removing mismatched image features in dynamic and static scenes. Third, the GMS-ATRANSAC method was tested for removing mismatched image features, and experimental results showed that GMS-ATRANSAC can remove mismatches of image features on moving objects. It achieved an average error reduction of 29.4% and 32.9% compared to RANSAC and GMS-RANSAC, with a corresponding reduction in error variance of 63.9% and 58.0%, respectively. The processing time was reduced by 78.3% and 38%, respectively. Finally, the effectiveness of inter-frame feature mismatch removal in the initialization thread of ORB-SLAM2 and the tracking thread of ORB-SLAM3 was verified for the proposed algorithm.
Biological ethylene production is a promising sustainable alternative approach for fossil-based ethylene production. The high glucose utilization of
Z. mobilis
makes it as a promising bioethylene ...producer. In this study,
Zymomonas mobilis
has been engineered to produce ethylene through the introduction of the synthetic ethylene-forming enzyme (EFE). We also investigated the effect of systematically knocking out the competitive metabolic pathway of pyruvate in an effort to improve the availability of pyruvate for ethylene production in
Z. mobilis
expressing EFE. Guided by these results, we tested a number of conjectures that could improve the α-ketoglutarate supply. Optimization of these pathways and different substrate supplies resulted in a greater production of ethylene (from 1.36 to 12.83 nmol/OD
600
/mL), which may guide future engineering work on ethylene production using other organisms. Meanwhile, we achieved an ethylene production of 5.8 nmol/OD
600
/mL in the ZM532-
efe
strain using enzymatic straw hydrolysate of corn straw as the sole carbon source. As a preferred host in biorefinery technologies using lignocellulosic biomass as feedstock, heterologous expression of EFE in
Z. mobilis
converts the non-ethylene producing strain into an ethylene-producing one using a metabolic engineering approach, which is of great significance for the utilization of cellulosic biomass in the future.
Key points
•
Heterologous expression of EFE in Z. mobilis successfully converted the non-ethylene producing strain into an ethylene producer (1.36 nmol/OD
600
/mL). Targeted modifications of the central carbon metabolism can effectively improve ethylene production (peak production: 8.3 nmol/OD
600
/mL).
•
The addition of nutrients to the medium can further increase the production of ethylene (peak production: 12.8 nmol/OD
600
/mL).
•
The ZM532-efe strain achieved an ethylene production of 5.8 nmol/OD
600
/mL when enzymatic hydrolysate of corn straw was used as the sole carbon source.
Iron-based PAA activation process is a promising advanced oxidation process for water decontamination which depends on Fe(II) as the main reactive site for PAA activation, resulting in various ...reactive oxidative species (ROSs) generation. For practical application, the impact of water matrix chloride ion (Cl-) on ROSs production and contaminants removal should be carefully considered. In this study, it's found that the introduction of Cl- (0.1-10 mM) could significantly enhance the reaction rate of the rapid stage (kobs1) up to 2.15 times at the initial pH of 4.25 in the Fe(II)/PAA system. Further studies demonstrated that the improved removal capacity of NAP resulted from Cl- induced R-O• generation as indicated by the exposure dose of R-O• increasing from 7.74 × 10-11 M•s to 1.44 × 10-10 M•s, rather than chlorine-containing radicals' generation. DFT calculation results suggested that the formed Fe(II)-Cl- complexes could easily activate PAA to generate more ROSs for NAP removal. Moreover, Fe(II)/PAA treatment can alleviate the biological toxicity of pollutants via both the Escherichia coli test and toxicity assessment. The obtained new knowledge manifested that Cl- can boost ROSs generation and conversion in iron-based PAA systems, providing guidance for the efficient decontamination of chlorine-containing sewage with PAA-based AOPs.
Display omitted
•The adsorption of three kinds of antibiotics onto vivianite following the order: tetracycline > ciprofloxacin > sulfamethoxazole.•The presence of fulvic acid (FA) greatly enhanced ...the adsorption of CIP and SMX onto vivianite.•New adsorption pathway will be created by the non-bond interaction between FA molecules and antibiotics.•Presence of FA and/or antibiotics makes the vivianite form better crystal.•Adsorption efficiency of three antibiotics onto vivianite was affected by the molecular weight of dissolved organic matter.
Formation of vivianite is a promising strategy to recover phosphorus from urban sewage and livestock wastewater, in which both various antibiotics and dissolved organic matters are contained. In this study, the interaction relationship and mechanism between vivianite, antibiotics and DOM were analyzed through the variations of DOM and antibiotics concentrations in supernatant, combined with characterization analysis and theoretical calculation. It’s found that the adsorption of three kinds of antibiotics onto vivianite following the order: tetracycline (TC) (∼90%) > ciprofloxacin (CIP) (∼15%) > sulfamethoxazole (SMX) (∼5%). The presence of fulvic acid (FA) greatly enhanced the adsorption of CIP, SMX to about 90%, 17% respectively, while there was no significant change in the adsorption of TC probably due to its good adsorption in the absence of FA. Interestingly, further analysis demonstrated that the FA will enhance the adsorption of antibiotics to vivianite because of the non-bonding interaction between FA molecules adsorbed on the surface of vivianite and antibiotics, and make the vivianite form better crystal without significant influences on phosphorus recovery. In addition, this study found that the adsorption of different kinds of antibiotics by vivianite was significantly related to the molecular weight of dissolved organic matter (DOM) in the actual livestock wastewater. Interestingly, the promotion of SMX adsorption is more likely to occur in the presence of DOM with small molecular weight (<5 kDa), while the introduction of DOM with larger molecular weight has greater promotion effect on CIP adsorption. The results gained in this study will expand the knowledge about the fate of antibiotics and recovery of phosphorus from urban sewage and livestock wastewater in the formation of vivianite.
K+ channels regulate morphogens to scale adult fins, but little is known about what regulates the channels and how they control morphogen expression. Using the zebrafish pectoral fin bud as a model ...for early vertebrate fin/limb development, we found that K+ channels also scale this anatomical structure, and we determined how one K+-leak channel, Kcnk5b, integrates into its developmental program. From FLIM measurements of a Förster Resonance Energy Transfer (FRET)-based K+ sensor, we observed coordinated decreases in intracellular K+ levels during bud growth, and overexpression of K+-leak channels in vivo coordinately increased bud proportions. Retinoic acid, which can enhance fin/limb bud growth, decreased K+ in bud tissues and up-regulated regulator of calcineurin (rcan2). rcan2 overexpression increased bud growth and decreased K+, while CRISPR-Cas9 targeting of rcan2 decreased growth and increased K+. We observed similar results in the adult caudal fins. Moreover, CRISPR targeting of Kcnk5b revealed that Rcan2-mediated growth was dependent on the Kcnk5b. We also found that Kcnk5b enhanced depolarization in fin bud cells via Na+ channels and that this enhanced depolarization was required for Kcnk5b-enhanced growth. Lastly, Kcnk5b-induced shha transcription and bud growth required IP3R-mediated Ca2+ release and CaMKK activity. Thus, we provide a mechanism for how retinoic acid via rcan2 can regulate K+-channel activity to scale a vertebrate appendage via intercellular Ca2+ signaling.
PDF
