A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses.

Humanized mice are limited in terms of modeling human immunity, particularly with regards to antibody responses. Here we constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated KitW-41J mutant immunodeficient pups with human cord blood CD34+ cells, followed by 17ß-estradiol conditioning to promote immune cell differentiation. THX mice reconstitute a human lymphoid and myeloid immune system, including marginal zone B cells, germinal center B cells, follicular helper T cells and neutrophils, and develop well-formed lymph nodes and intestinal lymphoid tissue, including Peyer's patches, and human thymic epithelial cells. These mice have diverse human B cell and T cell antigen receptor repertoires and can mount mature T cell-dependent and T cell-independent antibody responses, entailing somatic hypermutation, class-switch recombination, and plasma cell and memory B cell differentiation. Upon flagellin or a Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccination, THX mice mount neutralizing antibody responses to Salmonella or severe acute respiratory syndrome coronavirus 2 Spike S1 receptor-binding domain, with blood incretion of human cytokines, including APRIL, BAFF, TGF-ß, IL-4 and IFN-γ, all at physiological levels. These mice can also develop lupus autoimmunity after pristane injection. By leveraging estrogen activity to support human immune cell differentiation and maturation of antibody responses, THX mice provide a platform to study the human immune system and to develop human vaccines and therapeutics.

Intelligent leaching rare earth elements from waste fluorescent lamps.

Rare earth elements (REEs), one of the global key strategic resources, are widely applied in electronic information and national defense, etc. The sharply increasing demand for REEs leads to their overexploitation and environmental pollution. Recycling REEs from their second resources such as waste fluorescent lamps (WFLs) is a win-win strategy for REEs resource utilization and environmental production. Pyrometallurgy pretreatment combined with acid leaching is proven as an efficient approach to recycling REEs from WFLs. Unfortunately, due to the uncontrollable components of wastes, many trials were required to obtain the optimal parameters, leading to a high cost of recovery and new environmental risks. This study applied machine learning (ML) to build models for assisting the leaching of six REEs (Tb, Y, Eu, La, and Gd) from WFLs, only needing the measurement of particle size and composition of the waste feed. The feature importance analysis of 40 input features demonstrated that the particle size, Mg, Al, Fe, Sr, Ca, Ba, and Sb content in the waste feed, the pyrometallurgical and leaching parameters have important effects on REEs leaching. Furthermore, their influence rules on different REEs leaching were revealed. Finally, some verification experiments were also conducted to demonstrate the reliability and practicality of the model. This study can quickly get the optimal parameters and leaching efficiency for REEs without extensive optimization experiments, which significantly reduces the recovery cost and environmental risks. Our work carves a path for the intelligent recycling of strategic REEs from waste.

Potential prediction and coupling relationship revealing for recovery of platinum group metals from spent auto-exhaust catalysts based on machine learning.

As hazardous waste, the massive generation of spent auto-exhaust catalysts (SACs) puts enormous pressure on environmental management, but provides a rare opportunity for platinum group metals (PGMs) recycling. In this study, machine learning (ML) method was firstly applied to accurately predict regional SACs generation in China for 2025-2050 under five shared socio-economic pathways (SSPs) scenarios, based on which economic and carbon emission reduction potential of PGMs recycling were estimated. Population-GDP-GDPII-GDPIII and Random Forest were determined as key variables and the predictive model. Results indicate that SACs will reach 28.15 million sets (1.7 times that of 2020) and PGMs have economic potential of $890 million by 2050 (SSP1). Furthermore, based on environmental impact assessment, the capture enrichment-electrodeposition purification process is proposed as the best low-carbon recycling solution for SACs. And the integrated recovery process based on copper capture can realize 1.51 million tons of carbon emission reduction in China in 2050 (SSP1). This study can provide decision-making guidance for PGMs recovery and environmental management, as well as technical references for SACs recovery program selection.

An environmentally-friendly permeable liquid salt pyrolysis method based on capillary heat transfer for recycling waste insulator materials.

Molten salt pyrolysis technology stands out as a potent approach for achieving efficient degradation and energy recovery of composite organic materials. Nevertheless, challenges such as the high melting point of molten salt, product destruction, and the complexities of treating waste salt pose significant limitations to the widespread application and popularization of this technology. To tackle these issues, this study proposes a salt-assisted pyrolysis method based on capillary heat transfer called permeable liquid salt pyrolysis. Focusing on abandoned power industry insulators, the research delves into the thermal and mass transfer model of cluster-embedded materials under non-molten salt conditions. The investigation reveals that the capillary between glass fiber and resin proves beneficial in enhancing heat transfer conditions by creating a novel phase known as permeate liquid. Results demonstrate that salt-assisted pyrolysis can substantially lower the required temperature and enhance the pyrolysis reaction rate, achieving a maximum degradation efficiency of 98.99 %. Additionally, the pyrolysis products undergo in-situ modification, with a notable reduction in benzene series compounds ranging from 68 % to 85 %. Furthermore, an erosion diffusion capillary mode is established. This study presents an environmentally-friendly approach to recycle and modify products derived from waste resin-based composite materials generated in the electric power industry.

Mechanism of PGMs capture from spent automobile catalyst by copper from waste printed circuit boards with simultaneous pollutants transformation.

The traditional pyrometallurgical recycling of nano-sized platinum group metals (PGMs) from spent automotive catalysts (SACs) is an energy-intensive process that requires the addition of large quantities of copper capture and slag-forming reagents. Similarly, pyro-recycling of valuable metals from waste printed circuit boards (WPCBs) is also an energy- and reagent-intensive process that and carries a risk of pollution emissions. Based on the complementarity of composition and similarity of recycling process, synergistic pyro-recycling of SACs and WPCBs allow copper in WPCBs to capture PGMs in SACs and oxides from two waste form slag jointly, which offers benefits of enhanced metal recovery, reduced reagent and energy consumption, and suppressed pollutant emissions. However, the mechanisms of PGMs capture and pollutant transformation in co-smelting remain unknown. Here, we investigated the sub-processes mechanisms of slag formation, brominates fixation, multi-metal distribution and kinetic settlement. Oxides in both wastes support SiO2-Al2O3-CaO slag formation with low melting point and viscosity, where CaO suppresses the emission of brominated pollutants. Copper (50-100 µm) from WPCBs facilitates nano-sized PGMs in SACs recovery through capture and settlement. The results of demonstration experiments indicated a recovery rate of 94.6 %, 96.8 %, 97.2 %, and 98.1 % for Cu, Pt, Pd, and Rh, respectively, with a debromination efficiency exceeding 98 %. The theoretical analysis provides support for the establishment of a synergistic pyro-recycling process for SACs and WPCBs and provides insights into the potential for a greener and more efficient co-recycling of multi urban mines.

Pollution characteristics and release mechanism of microplastics in a typical end-of-life vehicle (ELV) recycling base, East China.

Microplastics (MPs) is a novel and significant pollution due to its eco-environmental hazards and ubiquity. In end-of-life vehicle (ELV) recycling base, MPs are widely distributed but have rare reported in scientific literature. In this study, a comprehensive analysis of MPs was conducted in a typical ELV recycling base. MPs were found in all samples at different sampling sites and environmental mediums. A total of 34 polymer types were detected by µ-FTIR, and the main polymers include PE-PP, ABS, polyester resin, nylon, and PEU plastic. MPs were released from the crushing, tearing, and breaking of plastic parts in ELVs. They were in high content in ground dust, with the abundance of 737-29,021 p/5 g D (the average abundance of 5552 ± 6435 p/5 g D). The abundance, shape, color, and size of MPs are related with functional areas of ELV recycling. Heavy metals could be adsorbed on MPs, and their contents on MPs have a significant correlation with those in the corresponding dust samples. At last, some specific MPs control measures, such as changing transportation mode, using dust-proof cloths, and equipping dust removal equipment, have been put forward.

Physicochemical reactions in e-waste recycling.

Electronic waste (e-waste) recycling is becoming a global concern owing to its immense quantity, hazardous character and the potential loss of valuable metals. The many processes involved in e-waste recycling stem from a mixture of physicochemical reactions, and understanding the principles of these reactions can lead to more efficient recycling methods. In this Review, we discuss the principles behind photochemistry, thermochemistry, mechanochemistry, electrochemistry and sonochemistry for metal recovery, polymer decomposition and pollutant elimination from e-waste. We also discuss how these processes induce or improve reaction rates, selectivity and controllability of e-waste recycling based on thermodynamics and kinetics, free radicals, chemical bond energy, electrical potential regulation and more. Lastly, key factors, limitations and suggestions for improvements of these physicochemical reactions for e-waste recycling are highlighted, wherein we also indicate possible research directions for the future.

In situ high-valued transformation of nonmetals in waste printed circuit boards into supercapacitor electrodes with excellent performance.

Nonmetals in waste printed circuit boards after metal separation containing brominated resin and fiberglass are considered hazardous and low-recoveryvalue e-waste. However, if these nonmetals are not treated or are improperly treated, they can cause serious environmental pollution. Therefore, there is an urgent and significant need to develop an efficient recycling process for these nonmetals. Based on the concept of high-valued recycling of waste, this study in situ utilized such nonmetals to prepare a porous supercapacitor electrode through a facile carbonization, activation, and carbon thermal reduction process. The results indicated that the activation was a key role in constructing a porous structure. The optimal parameters for activation were a temperature of 800 °C, mass ratio of KOH to pyrolytic residues of 2, and an activation time of 1 h. The electrode materials exhibited a surface area of 589 m2 g-1 and hierarchical porous structures. In addition, the supercapacitors exhibited a capacitance of 77.14 mF cm-2 (62.5 mF cm-2) at 0.5 mA cm-2 (100 mV s-1). Moreover, the supercapacitors had excellent temperature resistance and adaptability. The capacitance retention was 89.36% and 90% at -50 °C and 100 °C after 10 000 cycles, respectively. This study provides a high-valued recycling strategy to utilize the nonmetals in e-waste as energy materials.

A green strategy for upcycling utilization of core parts from end-of-life vehicles (ELVs): Pollution source analysis, technology flowchart, technology upgrade.

The disposal of end-of-life vehicles (ELVs) is an issue of great concern to the society, because of its huge amount, resource value and environmental pollution. A wide variety of pollutants generate and release during the recycling process. However, previous studies are piecemeal and segmentary, the correlation between treatment flowchart and pollution is unknown, and pollution source analysis in ELV recycling and core parts (engine, gear box, etc.) remanufacturing bases is still a challenge. In this study, the aim is to propose a green strategy for upcycling utilization of ELV part based on pollution source analysis, technology flowchart, and technology upgrade. We synthetically analyzed current typical ELV dismantling and core part remanufacturing processes of ELVs. A total of 36 volatile organic compound (VOC) species and 7 heavy metals were found in dismantling process, and 61 VOC species were detected in remanufacturing process. Based on statistical analysis and treatment process characteristics, 18 pollution fingerprints were constructed. At last, an intelligent dismantling and upcycle utilization line for ELVs has been developed to improve production efficiency and reduce pollution release.

Single-cell transcriptomic analyses of tumor microenvironment and molecular reprograming landscape of metastatic laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a malignant tumor with a high probability of metastasis. The tumor microenvironment (TME) plays a critical role in cancer metastasis. To gain insights into the TME of LSCC, we conducted single-cell RNA-seq (scRNA-seq) on samples collected from LSCC patients with or without lymphatic metastasis. The stem and immune cell signatures in LSCC suggest their roles in tumor invasion and metastasis. Infiltration of a large number of regulatory T cells, dysplastic plasma cells, and macrophages that are at the early development stage in the cancerous tissue indicates an immunosuppressive state. Abundant neutrophils detected at the cancer margins reflect the inflammatory microenvironment. In addition to dynamic ligand-receptor interactions between the stromal and myeloid cells, the enhanced autophagy in endothelial cells and fibroblasts implies a role in nutrient supply. Taken together, the comprehensive atlas of LSCC obtained allowed us to identify a complex yet unique TME of LSCC, which may help identify potential diagnostic biomarkers and therapeutic targets for LSCC.

Organophosphate flame retardants in air from formal e-waste recycling workshops in China: Size-distribution, gas-particle partitioning and exposure assessment.

In order to understand the organophosphate flame retardants (OPFRs) pollution and evaluate the inhalation exposure risk in formal e-waste recycling facilities, the air concentrations, particle size distribution and gas-particle partitioning of OPFRs in four typical workshops were investigated. The total Σ15OPFR concentrations inside workshops were in the range of 64.7-682 ng/m3, with 5.80-23.4 ng/m3 in gas phase and 58.8-658 ng/m3 in particle phase. Triphenyl phosphate (TPHP) and tris(2-chloroisopropyl) phosphate (TCIPP) were main analogs, both of which contributed to 49.0-85.7% of total OPFRs. In the waste printed circuit boards thermal treatment workshop, the OPFRs concentration was the highest, and particle-bound OPFRs mainly distributed in 0.7-1.1 µm particles. The proportions of TPHP in different size particles increased as the decrease of particle size, while TCIPP presented an opposite trend. The gas-particle partitioning of OPFR analogs was dominated by absorption process, and did not reach equilibrium state due to continuous emission of OPFRs from the recycling activities. The deposition fluxes of OPFRs in respiratory tract were 65.7-639 ng/h, and the estimated daily intake doses of OPFRs were 8.52-76.9 ng/(kg·day) in four workshops. Inhalation exposure was an important exposure pathway for e-waste recycling workers, and deposition fluxes of size-segregated OPFRs were mainly in head airways region.

Abnormal functional connectivity of white-matter networks and gray-white matter functional networks in patients with NMOSD.

Cognitive impairment (CI) has been reported in 29-70% of patients with neuromyelitis optica spectrum disorder (NMOSD). Abnormal white matter (WM) functional networks that correlate with cognitive functions have not been studied well in patients with NMOSD. The aim of the current study was to investigate functional connectivity (FC), spontaneous activity, and functional covariance connectivity (FCC) abnormalities of WM functional networks in patients with NMOSD and their correlation with cognitive performance. Twenty-four patients with NMOSD and 24 healthy controls (HCs) were included in the study. Participants underwent brain resting-state functional magnetic resonance imaging (fMRI) and the Montreal Cognitive Assessment (MoCA). Eight WM networks and nine gray matter (GM) networks were created. In patients, WM networks, including WM1-4, WM1-8, WM2-6, WM2-7, WM2-8, WM4-8, WM5-8 showed reduced FC (P < 0.05). All WM networks except WM1 showed decreased spontaneous activity (P < 0.05). The major GM networks demonstrated increased/decreased FC (P < 0.05), whereas GM7-WM7, GM8-WM4, GM8-WM6 and GM8-WM8 displayed decreased FC (P < 0.05). The MoCA results showed that two-thirds (16/24) of the patients had CI. FC and FCC in WM networks were correlated negatively with the MoCA scores (P < 0.05). WM functional networks are multi-layered. Abnormal FC of WM functional networks and GM functional networks may be responsible for CI.

Mullite Mineral-Derived Robust Solid Electrolyte Enables Polyiodide Shuttle-Free Zinc-Iodine Batteries.

Zinc dendrite, active iodine dissolution, and polyiodide shuttle caused by the strong interaction between liquid electrolyte and solid electrode are the chief culprits for the capacity attenuation of aqueous zinc-iodine batteries (ZIBs). Herein, mullite is adopted as raw material to prepare Zn-based solid-state electrolyte (Zn-ML) for ZIBs through zinc ion exchange strategy. Owing to the merits of low electronic conductivity, low zinc diffusion energy barrier, and strong polyiodide adsorption capability, Zn-ML electrolyte can effectively isolate the redox reactions of zinc anode and AC@I2 cathode, guide the reversible zinc deposition behavior, and inhibit the active iodine dissolution as well as polyiodide shuttle during cycling process. As expected, wide operating voltage window of 2.7 V (vs Zn2+/Zn), high Zn2+ transference number of 0.51, and low activation energy barrier of 29.7 kJ mol-1 can be achieved for the solid-state Zn//Zn cells. Meanwhile, high reversible capacity of 127.4 and 107.6 mAh g-1 can be maintained at 0.5 and 1 A g-1 after 3 000 and 2 100 cycles for the solid-state Zn//AC@I2 batteries, corresponding to high-capacity retention ratio of 85.2% and 80.7%, respectively. This study will inspire the development of mineral-derived solid electrolyte, and facilitate its application in Zn-based secondary batteries.

Pharmacological inhibition of the LIF/LIFR autocrine loop reveals vulnerability of ovarian cancer cells to ferroptosis.

Of all gynecologic cancers, epithelial-ovarian cancer (OCa) stands out with the highest mortality rates. Despite all efforts, 90% of individuals who receive standard surgical and cytotoxic therapy experience disease recurrence. The precise mechanism by which leukemia inhibitory factor (LIF) and its receptor (LIFR) contribute to the progression of OCa remains unknown. Analysis of cancer databases revealed that elevated expression of LIF or LIFR was associated with poor progression-free survival of OCa patients and a predictor of poor response to chemotherapy. Using multiple primary and established OCa cell lines or tissues that represent five subtypes of epithelial-OCa, we demonstrated that LIF/LIFR autocrine signaling is active in OCa. Moreover, treatment with LIFR inhibitor, EC359 significantly reduced OCa cell viability and cell survival with an IC50 ranging from 5-50 nM. Furthermore, EC359 diminished the stemness of OCa cells. Mechanistic studies using RNA-seq and rescue experiments unveiled that EC359 primarily induced ferroptosis by suppressing the glutathione antioxidant defense system. Using multiple in vitro, ex vivo and in vivo models including cell-based xenografts, patient-derived explants, organoids, and xenograft tumors, we demonstrated that EC359 dramatically reduced the growth and progression of OCa. Additionally, EC359 therapy considerably improved tumor immunogenicity by robust CD45+ leukocyte tumor infiltration and polarizing tumor-associated macrophages (TAMs) toward M1 phenotype while showing no impact on normal T-, B-, and other immune cells. Collectively, our findings indicate that the LIF/LIFR autocrine loop plays an essential role in OCa progression and that EC359 could be a promising therapeutic agent for OCa.

Discovery of fast and stable proton storage in bulk hexagonal molybdenum oxide.

Ionic and electronic transport in electrodes is crucial for electrochemical energy storage technology. To optimize the transport pathway of ions and electrons, electrode materials are minimized to nanometer-sized dimensions, leading to problems of volumetric performance, stability, cost, and pollution. Here we find that a bulk hexagonal molybdenum oxide with unconventional ion channels can store large amounts of protons at a high rate even if its particle size is tens of micrometers. The diffusion-free proton transport kinetics based on hydrogen bonding topochemistry is demonstrated in hexagonal molybdenum oxide whose proton conductivity is several orders of magnitude higher than traditional orthorhombic molybdenum oxide. In situ X-ray diffraction and theoretical calculation reveal that the structural self-optimization in the first discharge effectively promotes the reversible intercalation/de-intercalation of subsequent protons. The open crystal structure, suitable proton channels, and negligible volume strain enable rapid and stable proton transport and storage, resulting in extremely high volumetric capacitance (~1750 F cm-3), excellent rate performance, and ultralong cycle life (>10,000 cycles). The discovery of unconventional materials and mechanisms that enable proton storage of micrometer-sized particles in seconds boosts the development of fast-charging energy storage systems and high-power practical applications.