149 research outputs found
Efficacy and safety of belimumab for the treatment of refractory childhood-onset systemic lupus erythematosus: A single-center, real-world, retrospective study
ObjectiveThis study aimed to investigate the efficacy and safety of belimumab for treating children with refractory childhood-onset systemic lupus erythematosus (cSLE).MethodsTwenty-six cSLE patients who received belimumab treatment in our hospital from January 2020 to September 2021 (23 of them for more than 52 weeks) were enrolled in this study. Their clinical and laboratory data, assessment of disease activity, glucocorticoid dosage, and treatment-emergent adverse events (TEAEs) were retrieved for analysis. The paired samples t-test and the nonparametric test were used to compare the baseline and post-treatment data.ResultsThe mean age of onset was 10.3 ± 2.4 years old; the mean disease duration was 41.6 ± 37.4 months; the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was 10 (P25, P75: 3, 17); and the mean Physicianâs Global Assessment (PGA) score at baseline was 1.9 ± 1.0. Compared with the baseline values, there was a significant decrease in the 24-h urine protein quantifications at 24 and 52 weeks of treatment (P<0.05) as well as an elevated complement (C) 3 and C4 levels at 4, 12, 24, and 52 weeks of treatment. In addition, the SLEDAI-2K and PGA scores as well as the percentage of CD19+ B cells were significantly decreased at 12, 24, and 52 weeks of treatment compared with the baseline values (P<0.05). The dosage of glucocorticoid at 4, 12, 24, and 52 weeks of treatment was significantly less than that at baseline or the previous follow-up (P<0.05). At 52 weeks, 14 subjects (53.8%) achieved Lupus Low Disease Activity State (LLDAS), and 4 subjects (15.4%) reached clinical remission (CR). At the last follow-up, 16 subjects (61.5%) achieved LLDAS, and 10 subjects (38.5%) reached CR.ConclusionsBelimumab treatment can significantly improve laboratory indicators, reduce disease activity, and decrease the dosage of glucocorticoid required in children with cSLE. Moreover, it has a good safety profile
Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38
BackgroundCD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs).MethodsFive suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 âmAb-trapâ platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems.ResultsUsing hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a âmAb-trapâ platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605â26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605â12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605â12C10 efficiently eradicated all established tumors in all mice.ConclusionA panel of BsAbs targeting CD38 and CD47 developed based on the âmAb-tarpâ platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile
Recent progress in low-carbon binders
The development of low-carbon binders has been recognized as a means of reducing the carbon footprint of the Portland cement industry, in response to growing global concerns over CO2 emissions from the construction sector. This paper reviews recent progress in the three most attractive low-carbon binders: alkali-activated, carbonate, and belite-ye'elimite-based binders. Alkali-activated binders/materials were reviewed at the past two ICCC congresses, so this paper focuses on some key developments of alkali-activated binders/materials since the last keynote paper was published in 2015. Recent progress on carbonate and belite-ye'elimite-based binders are also reviewed and discussed, as they are attracting more and more attention as essential alternative low-carbon cementitious materials. These classes of binders have a clear role to play in providing a sustainable future for global construction, as part of the available toolkit of cements
Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study
Summary
Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally.
Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies
have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of
the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income
countries globally, and identified factors associated with mortality.
Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to
hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis,
exomphalos, anorectal malformation, and Hirschsprungâs disease. Recruitment was of consecutive patients for a
minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical
status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary
intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause,
in-hospital mortality for all conditions combined and each condition individually, stratified by country income status.
We did a complete case analysis.
Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital
diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal
malformation, and 517 with Hirschsprungâs disease) from 264 hospitals (89 in high-income countries, 166 in middleincome
countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male.
Median gestational age at birth was 38 weeks (IQR 36â39) and median bodyweight at presentation was 2·8 kg (2·3â3·3).
Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income
countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups).
Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome
countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries;
pâ€0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients
combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88â4·11],
p<0·0001; middle-income vs high-income countries, 2·11 [1·59â2·79], p<0·0001), sepsis at presentation (1·20
[1·04â1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention
(ASA 4â5 vs ASA 1â2, 1·82 [1·40â2·35], p<0·0001; ASA 3 vs ASA 1â2, 1·58, [1·30â1·92], p<0·0001]), surgical safety
checklist not used (1·39 [1·02â1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed
(ventilation 1·96, [1·41â2·71], p=0·0001; parenteral nutrition 1·35, [1·05â1·74], p=0·018). Administration of
parenteral nutrition (0·61, [0·47â0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65
[0·50â0·86], p=0·0024) or percutaneous central line (0·69 [0·48â1·00], p=0·049) were associated with lower mortality.
Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome,
middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will
be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger
than 5 years by 2030
Beyond electrode materials structure design: Binders play a vital role for battery application of micro-size electroactive materials
Micrometre-sized electroactive particles with high tapping density show significant potential for commercial application since they effectively alleviate low Coulombic efficiency and excessive solid electrolyte interphase (SEI) issues brought by nanostructures. Furthermore, optimizing the electrode architecture using novel design concepts can improve the energy density. Beyond the electrode material structure design strategy, binder plays a vital role in providing the mechanical stability and regulating the charge transport. This highlight presents the latest development to design high-capacity batteries by optimizing the binder structures in electrodes and emphasizes the significance of binder design for further commercial application
Synergistically Enhanced Interfacial Interaction to Polysulfide via N,O Dual-Doped Highly Porous Carbon Microrods for Advanced Lithium-Sulfur Batteries
Lithium-sulfur (Li-S) batteries have received tremendous attention because of their extremely high theoretical capacity (1672 mA h g -1 ) and energy density (2600 W h kg -1 ). Nevertheless, the commercialization of Li-S batteries has been blocked by the shuttle effect of lithium polysulfide intermediates, the insulating nature of sulfur, and the volume expansion during cycling. Here, hierarchical porous N,O dual-doped carbon microrods (NOCMs) were developed as sulfur host materials with a large pore volume (1.5 cm 3 g -1 ) and a high surface area (1147 m 2 g -1 ). The highly porous structure of the NOCMs can act as a physical barrier to lithium polysulfides, while N and O functional groups enhance the interfacial interaction to trap lithium polysulfides, permitting a high loading amount of sulfur (79-90 wt % in the composite). Benefiting from the physical and chemical anchoring effect to prevent shuttling of polysulfides, S@NOCMs composites successfully solve the problems of low sulfur utilization and fast capacity fade and exhibit a stable reversible capacity of 1071 mA h g -1 after 160 cycles with nearly 100% Coulombic efficiency at 0.2 C. The N,O dual doping treatment to porous carbon microrods paves a way toward rational design of high-performance Li-S cathodes with high energy density
Mo2C@3D ultrathin macroporous carbon realizing efficient and stable nitrogen fixation
© 2020, Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature. Ammonia is a key feedstock of fertilizers for farming and convenient hydrogen carrier as an emerging clean fuel, but industrial ammonium production process, Haber-Bosch reaction, is an energy-intensive process, consuming 1%â2% of global energy and producing 3% global CO2. Electrochemical nitrogen reduction reaction (NRR) is one of the most promising routes to realize highly efficient NH3 production under ambient conditions. However, up to now, few precious-metal-free electrocatalysts with desirable catalytic performance have been explored. In this work, Mo2C nanodots anchored on three-dimensional ultrathin macroporous carbon (Mo2C@3DUM-C) framework is developed toward significantly enhanced nitrogen reduction reaction. Thanks to the special structural design of 3D ultrathin macroporous carbon and highly active and stable Mo2C toward N2 electrochemical reduction, the Mo2C@3DUM-C framework exhibits a high Faradaic efficiency of 9.5% for NH3 production at â0.20 V and the yield rate reaches 30.4 ”g hâ1mgM02Câ1. Further electrochemical characterizations reveal the enhanced electron transfer and increased electrochemical surface area in the 3D macroporous carbon framework. Moreover, the Mo2C@3DUM-C electrocatalysts hold high catalytic stability after long-term NRR test. The temperature-dependent yield rate of NH3 demonstrates that the activation energy of nitrogen reduction on the employed catalyst was calculated to be 28.1 kJ molâ1. Our proposed earth-abundant Mo2C@3DUM-C demonstrates an alternative insight into developing efficient and stable nitrogen fixation catalysts in acids as alternatives to noble metal catalysts
Tailorable Polypyrrole Nanofilms With Exceptional Electrochemical Performance For All-Solid-State Flexible Supercapacitors
Flexible supercapacitors exhibiting high specific energy (Ë1 mW h cmâ3) and high specific power are of major research interest in energy storage/conversion systems. In this paper, a strategy has been developed for controlled synthesis of polypyrrole (PPy) nanofilms at the ice/alcohol interface through a simple chemical oxidation polymerization method, yielding free-standing PPy nanofilms with decimeter scale. Evidence from molecular dynamics simulations shows monolayer deposition of pyrrole molecules on the ice surface through hydrogen bonding that supports the formation of PPy films at the ice/alcohol interface. Free-standing PPy films can be directly tailored into film electrodes for all-solid-state flexible planar supercapacitor cells (PSCs) and rolled supercapacitor cells (RSCs). Thickness-dependent electrochemical performance for PSCs and RSCs has been constructed in association with PPy nanofilms. The PSCs and RSCs are made from complete PPy films with thickness of 140 ± 5 nm that exhibit specific energy of 0.72 and 2.3 mW h cmâ3 with corresponding specific power of 51.7 and 111.1 mW cmâ3, respectively. After 10,000 cycles at a current density of 2 mA cmâ2, typical RSCs retain a volumetric capacitance of 9.8 F cmâ3 and a specific energy of 1.36 mW h cmâ3, holding great potential in practical applications
Advances in lithium-ion battery recycling: Strategies, pathways, and technologies
The use of lithium-ion batteries in portable electronic devices and electric vehicles has become well-established, and battery demand is rapidly increasing annually. While technological innovations in electrode materials and battery performance have been pursued, the environmental threats and resource wastage posed by the resulting surge in used batteries have been overlooked. Spent batteries are technically inoperable but contain excess metal inside the structure, making recycling essential for environmental protection and recovery of scarce resources. The battery recycling industry has gradually emerged under the influence of government implementation and ecological protection trends. However, the annual recycling volume is still insufficient compared to the output volume of used batteries. Therefore, more recycling plants and advanced technologies are imperative to improve recycling efficiency. This article summarizes pretreatment, pyrometallurgical, and hydrometallurgical processes and technologies in three major parts, analyzes their applicability and environmental friendliness using industrial examples, highlights their technical shortcomings and problems, and emphasizes the bright future of battery recycling
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