Quantification of Charge Transport and Mass Deprivation in Solid Electrolyte Interphase for Kinetically-Stable Low-Temperature Lithium-Ion Batteries.

Graphite (Gr)-based lithium-ion batteries with admirable electrochemical performance below -20 °C are desired but are hindered by sluggish interfacial charge transport and desolvation process. Li salt dissociation via Li+-solvent interaction enables mobile Li+ liberation and contributes to bulk ion transport, while is contradictory to fast interfacial desolvation. Designing kinetically-stable solid electrolyte interphase (SEI) without compromising strong Li+-solvent interaction is expected to compatibly improve interfacial charge transport and desolvation kinetics. However, the relationship between physicochemical features and temperature-dependent kinetics properties of SEI remains vague. Herein, we propose four key thermodynamics parameters of SEI potentially influencing low-temperature electrochemistry, including electron work function, Li+ transfer barrier, surface energy, and desolvation energy. Based on the above parameters, we further define a novel descriptor, separation factor of SEI (SSEI), to quantitatively depict charge (Li+/e-) transport and solvent deprivation processes at Gr/electrolyte interface. A Li3PO4-based, inorganics-enriched SEI derived by Li difluorophosphate (LiDFP) additive exhibits the highest SSEI (4.89×103) to enable efficient Li+ conduction, e- blocking and rapid desolvation, and as a result, much suppressed Li-metal precipitation, electrolyte decomposition and Gr sheets exfoliation, thus improving low-temperature battery performances. Overall, our work originally provides visualized guides to improve low-temperature reaction kinetics/thermodynamics by constructing desirable SEI chemistry.

Scavenging Radionuclide by Shapeable Porous Materials.

Nuclear energy is a competitive and environmentally friendly low-carbon energy source. It is seen as an important avenue for satisfying energy demands, responding to the energy crisis, and mitigating global climate change. However, much attention has been paid to achieving the effective treatment of radionuclide oxoanions produced in nuclear waste. Initially, advanced adsorbents were mainly available in powder form, which meant that additional purification processes were usually required for separation and recovery in industrial applications. Therefore, to meet the practical requirements of industrial applications, materials need to be molded and processed into forms such as beads, membranes, gels, and resins. Here, we summarize the fabrication of porous materials used for capturing typical radionuclide oxoanions, including UO22+, TcO4-, IO3-, SeO32-, and SeO4-.

IKZF1 and UBR4 gene variants drive autoimmunity and TH2 polarization in IgG4-related disease.

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated' fibroinflammatory disease. The pathomechanisms remain poorly understood. Here, we identified gene variants in familial IgG4-RD and determined their functional consequences. All three affected members shared mutations of the transcription factor IKAROS, encoded by IKZF1, and the E3 ubiquitin ligase UBR4. The IKAROS mutation increased binding to the FYN promoter resulting in higher transcription of FYN in T cells. The UBR4 mutation prevented the lysosomal degradation of the phosphatase CD45. In the presence of elevated FYN, CD45 functioned as a positive regulatory loop, lowering the threshold for T cell activation. Consequently, T cells from affected family members were hyperresponsive to stimulation. When transduced with a low avidity, autoreactive T cell receptor, they responded to the autoantigenic peptide. In parallel, the high expression of FYN in T cells biased their differentiation towards TH2 polarization by stabilizing the transcription factor JunB. This bias is consistent with the frequent atopic manifestations in IgG4-RD patients including our afflicted family members. Building on the functional consequences of these two mutations, we propose a disease model that is not only instructive for IgG4-RD but also for atopic diseases for autoimmune diseases associated with an IKZF1 risk haplotype.

A reliable fluorescence "turn-on" aptasensor based on dual-emitting europium metal-organic frameworks for ultrasensitive and selective detection of sulfamethazine.

A high-performance fluorescent "turn-on" aptasensor (Eu-MOFs@SMZ-Apt) for sulfamethazine (SMZ) determination was designed using dual-emitting europium metal-organic frameworks (Eu-MOFs) as a signal transducer and an amplifier. Eu-MOFs featuring dual emission peaks (430 nm and 620 nm) were first prepared via a facile self-assembly strategy employing Eu (III) ions and 2-aminoterephthalic acid as precursors. The high-affinity aptamer was bonded with Eu-MOFs to form Eu-MOFs@SMZ-Apt through the amidation reaction. Benefiting from the integration of inherent virtues from Eu-MOFs and aptamer, the Eu-MOFs@SMZ-Apt-based sensor allowed sensitive and selective determination of SMZ with good linear relationships in a range of 1.4-40 ng mL-1 and a low detection line (0.379 ng mL-1). This sensor was successfully applied to the determination of trace SMZ in real samples with satisfactory recoveries (86.47-113.52%) and a relative standard deviation (<6.51). Consequently, the Eu-MOFs@SMZ-Apt ratiometric fluorescence sensor furnishes new possibilities for the accurate detection of various pollutants in food.

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome.

Background: Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood. Methods: A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration. Results: A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46±4.40 vs 11.65±6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand-receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS. Conclusion: MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.

Mendelian Randomization and Transcriptomic Analysis Reveal the Protective Role of NKT Cells in Sepsis.

Background: Sepsis is a life-threatening clinical syndrome caused by dysregulated host response to infection. The mechanism underlying sepsis-induced immune dysfunction remains poorly understood. Natural killer T (NKT) cells are cytotoxic lymphocytes that bridge the innate and adaptive immune systems, the role of NKT cells in sepsis is not entirely understood, and NKT cell cluster differences in sepsis remain unexplored. Methods: Mendelian randomization (MR) analyses were first conducted to investigate the causal relationship between side scatter area (SSC-A) on NKT cells and 28-day mortality of septic patients. A prospective and observational study was conducted to validate the relationship between the percentage of NKT cells and 28-day mortality of sepsis. Then, the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from healthy controls and septic patients were profiled. Results: MR analyses first revealed the protective roles of NKT cells in the 28-day mortality of sepsis. Then, 115 septic patients were enrolled. NKT percentage was significantly higher in survivors (n = 84) compared to non-survivors (n = 31) (%, 5.00 ± 3.46 vs 2.18 ± 1.93, P < 0.0001). Patients with lower levels of NKT cells exhibited a significantly increased risk of 28-day mortality. According to scRNA-seq analysis, NKT cell clusters exhibited multiple distinctive characteristics, including a distinguishing cluster defined as FOS+NKT cells, which showed a significant decrease in sepsis. Pseudo-time analysis showed that FOS+NKT cells were characterized by upregulated expression of crucial functional genes such as GZMA and CCL4. CellChat revealed that interactions between FOS+NKT cells and adaptive immune cells including B cells and T cells were decreased in sepsis compared to healthy controls. Conclusion: Our findings indicate that NKT cells may protect against sepsis, and their percentage can predict 28-day mortality. Additionally, we discovered a unique FOS+NKT subtype crucial in sepsis immune response, offering novel insights into its immunopathogenesis.

Sustainable Recycling of Selenium-Based Optoelectronic Devices.

Selenium (Se), the world's oldest optoelectronic material, has been widely applied in various optoelectronic devices such as commercial X-ray flat-panel detectors and photovoltaics. However, despite the rare and widely-dispersed nature of Se element, a sustainable recycling of Se and other valuable materials from spent Se-based devices has not been developed so far. Here a sustainable strategy is reported that makes use of the significantly higher vapor pressure of volatile Se compared to other functional layers to recycle all of them from end-of-life Se-based devices through a closed-space evaporation process, utilizing Se photovoltaic devices as a case study. This strategy results in high recycling yields of ≈ 98% for Se and 100% for other functional materials including valuable gold electrodes and glass/FTO/TiO2 substrates. The refabricated photovoltaic devices based on these recycled materials achieve an efficiency of 12.33% under 1000-lux indoor illumination, comparable to devices fabricated using commercially sourced materials and surpassing the current indoor photovoltaic industry standard of amorphous silicon cells.

A real-time field bus architecture for multi-smart-motor servo system.

The multi-motor servo system (MMSS) is an electro-mechanical system widely used in various fields, including electric vehicles, robotics, and industrial machinery. Depending on the application, the number of motors in the system can range from several dozens to tens of thousands, which imposes additional communication demands. Thus, ensuring synchronization and control precision of the system requires addressing the challenge of guaranteeing the performance and reliability of communication among motors in the MMSS. In this paper, we design a smart servo motor (SSM) to upgrade the system to the multi-smart-motor servo system (MSMSS) based on a distributed real-time field bus architecture, namely, Multi-Motor Bus (MMB) architecture. The proposed MMB architecture is lightweight and stable, providing real-time support for Control Area Network connections to a central user computer and inter-integrated circuit connections to SSM units. This MMB architecture facilitates the synchronization of command transmission across SSMs and ensures the consistency of motors in the MSMSS. Additionally, a serial experiments to examine 3 key system performance and reliability characteristics are conducted, including command transmission time, transmission jitters, and rotation consistency. The analysis of these characteristics demonstrates the system's potential and feasibility to be applicable in industry.

Multifunctionality promotes the prosperity of riverine planktonic diatoms in plateau.

Interpreting the biogeographic distribution and underlying mechanisms of functional traits not only contributes to revealing the spatiotemporal dynamics of species biodiversity but also helps to maintain ecological stability during environmental variations. However, little is known about the functional profiles of diatom communities over large river systems. Herein, we provided the first blueprints about the spatiotemporal distributions and driving forces of functional traits for both planktonic and sedimentary diatoms over the 6030 km continuum of the Yangtze River, with the help of the high-throughput sequencing and functional identification. By investigating the 28 functional traits affiliated into five categories, we found that planktonic diatom functions showed clearer landform-heterogeneity patterns (ANOSIM R = 0.336) than sedimentary functions (ANOSIM R = 0.172) along the river, represented by life-forms and ecological-guilds prominent in water-plateau as well as cell-sizes and life-forms particularly in sediment-plateau. Planktonic diatom functions also displayed higher richness and network complexity in plateau (richness: 58.70 ± 9.30, network edges: 65) than in non-plateau regions (23.82 ± 13.16, 16), promoting the stability and robustness of diatom functions against the high-radiation and low-temperature plateau environment. Environmental selection (mainly exerted by PAR, UV, and Tw) played crucial roles in determining the functional variations of planktonic diatoms (explaining 80.5%) rather than sedimentary diatoms (14.5%) between plateau and non-plateau regions. Meanwhile, planktonic diatom traits within life-forms were identified to be well responsive to the ecological environment quality (r = 0.56-0.60, P < 0.001) in the Yangtze. This study provided comprehensive insights into the multifunctionality of diatoms and their responses to environmental disturbance and environment quality, which helps to develop effective strategies for maintaining ecological stability in changing river environments.

Evaluating the Field Emission Properties of N-Type Black Silicon Cold Cathodes Based on a Three-Dimensional Model.

Black silicon (BS), a nanostructured silicon surface containing highly roughened surface morphology, has recently emerged as a promising candidate for field emission (FE) cathodes in novel electron sources due to its huge number of sharp tips with ease of large-scale fabrication and controllable geometrical shapes. However, evaluating the FE performance of BS-based nanostructures with high accuracy is still a challenge due to the increasing complexity in the surface morphology. Here, we demonstrate a 3D modeling methodology to fully characterize highly disordered BS-based field emitters randomly distributed on a roughened nonflat surface. We fabricated BS cathode samples with different morphological features to demonstrate the validity of this method. We utilize parametrized scanning electron microscopy images that provide high-precision morphology details, successfully describing the electric field distribution in field emitters and linking the theoretical analysis with the measured FE property of the complex nanostructures with high precision. The 3D model developed here reveals a relationship between the field emission performance and the density of the cones, successfully reproducing the classical relationship between current density J and electric field E (J-E curve). The proposed modeling approach is expected to offer a powerful tool to accurately describe the field emission properties of large-scale, disordered nano cold cathodes, thus serving as a guide for the design and application of BS as a field electron emission material.

Establishment and application of the BRP prognosis model for idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease. Clinical models to accurately evaluate the prognosis of IPF are currently lacking. This study aimed to construct an easy-to-use and robust prediction model for transplant-free survival (TFS) of IPF based on clinical and radiological information. METHODS: A multicenter prognostic study was conducted involving 166 IPF patients who were followed up for 3 years. The end point of follow-up was death or lung transplantation. Clinical information, lung function tests, and chest computed tomography (CT) scans were collected. Body composition quantification on CT was performed using 3D Slicer software. Risk factors in blood routine examination-radiology-pulmonary function (BRP) were identified by Cox regression and utilized to construct the "BRP Prognosis Model". The performance of the BRP model and the gender-age-physiology variables (GAP) model was compared using time-ROC curves, calibration curves, and decision curve analysis (DCA). Furthermore, histopathology fibrosis scores in clinical specimens were compared between the different risk stratifications identified by the BRP model. The correlations among body composition, lung function, serum inflammatory factors, and profibrotic factors were analyzed. RESULTS: Neutrophil percentage > 68.3%, pericardial adipose tissue (PAT) > 94.91 cm3, pectoralis muscle radiodensity (PMD) ≤ 36.24 HU, diffusing capacity of the lung for carbon monoxide/alveolar ventilation (DLCO/VA) ≤ 56.03%, and maximum vital capacity (VCmax) < 90.5% were identified as independent risk factors for poor TFS among patients with IPF. We constructed a BRP model, which showed superior accuracy, discrimination, and clinical practicability to the GAP model. Median TFS differed significantly among patients at different risk levels identified by the BRP model (low risk: TFS > 3 years; intermediate risk: TFS = 2-3 years; high risk: TFS ≈ 1 year). Patients with a high-risk stratification according to the BRP model had a higher fibrosis score on histopathology. Additionally, serum proinflammatory markers were positively correlated with visceral fat volume and infiltration. CONCLUSIONS: In this study, the BRP prognostic model of IPF was successfully constructed and validated. Compared with the commonly used GAP model, the BRP model had better performance and generalization with easily obtainable indicators. The BRP model is suitable for clinical promotion.

Immune aging - A mechanism in autoimmune disease.

Evidence is emerging that the process of immune aging is a mechanism leading to autoimmunity. Over lifetime, the immune system adapts to profound changes in hematopoiesis and lymphogenesis, and progressively restructures in face of an ever-expanding exposome. Older adults fail to generate adequate immune responses against microbial infections and tumors, but accumulate aged T cells, B cells and myeloid cells. Age-associated B cells are highly efficient in autoantibody production. T-cell aging promotes the accrual of end-differentiated effector T cells with potent cytotoxic and pro-inflammatory abilities and myeloid cell aging supports a low grade, sterile and chronic inflammatory state (inflammaging). In pre-disposed individuals, immune aging can lead to frank autoimmune disease, manifesting with chronic inflammation and irreversible tissue damage. Emerging data support the concept that autoimmunity results from aging-induced failure of fundamental cellular processes in immune effector cells: genomic instability, loss of mitochondrial fitness, failing proteostasis, dwindling lysosomal degradation and inefficient autophagy. Here, we have reviewed the evidence that malfunctional mitochondria, disabled lysosomes and stressed endoplasmic reticula induce pathogenic T cells and macrophages that drive two autoimmune diseases, rheumatoid arthritis (RA) and giant cell arteritis (GCA). Recognizing immune aging as a risk factor for autoimmunity will open new avenues of immunomodulatory therapy, including the repair of malfunctioning mitochondria and lysosomes.

Isolation and Genome-Based Characterization of Biocontrol Potential of Bacillus siamensis YB-1631 against Wheat Crown Rot Caused by Fusarium pseudograminearum.

Fusarium crown rot (FCR) caused by Fusarium pseudograminearum is one of the most serious soil-borne diseases of wheat. Among 58 bacterial isolates from the rhizosphere soil of winter wheat seedlings, strain YB-1631 was found to have the highest in vitro antagonism to F. pseudograminearum growth. LB cell-free culture filtrates inhibited mycelial growth and conidia germination of F. pseudograminearum by 84.14% and 92.23%, respectively. The culture filtrate caused distortion and disruption of the cells. Using a face-to-face plate assay, volatile substances produced by YB-1631 inhibited F. pseudograminearum growth by 68.16%. In the greenhouse, YB-1631 reduced the incidence of FCR on wheat seedlings by 84.02% and increased root and shoot fresh weights by 20.94% and 9.63%, respectively. YB-1631 was identified as Bacillus siamensis based on the gyrB sequence and average nucleotide identity of the complete genome. The complete genome was 4,090,312 bp with 4357 genes and 45.92% GC content. In the genome, genes were identified for root colonization, including those for chemotaxis and biofilm production, genes for plant growth promotion, including those for phytohormones and nutrient assimilation, and genes for biocontrol activity, including those for siderophores, extracellular hydrolase, volatiles, nonribosomal peptides, polyketide antibiotics, and elicitors of induced systemic resistance. In vitro production of siderophore, ß-1, 3-glucanase, amylase, protease, cellulase, phosphorus solubilization, and indole acetic acid were detected. Bacillus siamensis YB-1631 appears to have significant potential in promoting wheat growth and controlling wheat FCR caused by F. pseudograminearum.

Modulation of virus-induced neuroinflammation by the autophagy receptor SHISA9 in mice.

Microglia and astrocytes are subgroups of brain glia cells that support and protect neurons within the central nervous system (CNS). At early stages of viral infection in the CNS, they are predominant responding cells and lead to recruitment of peripheral immune cells for viral clearance. Inhibitor of nuclear factor κB kinase subunit epsilon (IKKi) is critical for type I interferon signalling and inflammation, which modulate heterogenic immune responses during CNS infection. Balanced autophagy is vital to maintain brain integrity, yet regulation of autophagy and immune activity within brain glia cells is poorly understood. Here we identify SHISA9 as an autophagy cargo receptor that mediates the autophagy-dependent degradation of IKKi during herpes simplex virus type 1 infection. IKKi is recognized by SHISA9 through unanchored K48-linked poly-ubiquitin chains and bridged to autophagosome membrane components GABARAPL1. Single-cell RNA sequencing analysis shows that SHISA9 has temporal characteristics while modulating both antiviral and inflammatory responses in microglia and astrocytes at different stages during viral infection. We found that Shisa9-/- mice are highly susceptible to herpes simplex virus encephalitis, have pathogenic astrocytes and display more severe neuroinflammation compared with wild-type mice. Taken together, our study unravels a critical role of selective autophagy by orchestrating immune heterogeneity of different CNS resident cells through the SHISA9-IKKi axis.

Preparation of a Tetra-Imidazolium Salt and Sensing for p-Dinitrobenzene.

A macrocyclic tetra-imidazolium salt (2) based on quinoxaline was prepared and characterized. The recognition of 2 to nitro compounds was investigated by fluorescence spectroscopy, 1H NMR titrations, MS, IR spectroscopy, and UV/vis spectroscopy. The results displayed that 2 was able to effectively differentiate p-dinitrobenzene from other nitro compounds via the fluorescence method.

T cell aging as a risk factor for autoimmunity.

Immune aging is a complex process rendering the host susceptible to cancer, infection, and insufficient tissue repair. Many autoimmune diseases preferentially occur during the second half of life, counterintuitive to the concept of excess adaptive immunity driving immune-mediated tissue damage. T cells are particularly susceptible to aging-imposed changes, as they are under extreme proliferative pressure to fulfill the demands of clonal expansion and of homeostatic T cell repopulation. T cells in older adults have a footprint of genetic and epigenetic changes, lack mitochondrial fitness, and fail to maintain proteostasis, diverging them from host protection to host injury. Here, we review recent progress in understanding how the human T-cell system ages and the evidence detailing how T cell aging contributes to autoimmune conditions. T cell aging is now recognized as a risk determinant in two prototypic autoimmune syndromes; rheumatoid arthritis and giant cell arteritis. The emerging concept adds susceptibility to autoimmune and autoinflammatory disease to the spectrum of aging-imposed adaptations and opens new opportunities for immunomodulatory therapy by restoring the functional intactness of aging T cells.

Expression of PD-1 on Memory T Lymphocytes Predicts 28-Day Mortality of Patients with Sepsis: A Prospective Observational Study.

Background: PD-1 is an important immune checkpoint expressed on T lymphocytes and is associated with T-cell function in sepsis. However, the role of PD-1 in naive and memory T-cell responses in sepsis is not well understood. We aimed to determine the expression of PD-1 induced on naive and memory T lymphocytes in patients with sepsis and its association with clinical outcome. Methods: A prospective observational study was conducted at a general intensive care unit (ICU). Whole blood samples were collected from patients within 48 h after sepsis diagnosis. PD-1 expression on naive and memory T cells was measured by flow cytometry. The levels of IFN-γ, IL-2 and TNF-α released by memory T cells were also determined. All patients were followed up to 28 days, and 28-day mortality was recorded. Results: PD-1 expression showed no difference in naive CD4+ T cells (P=0.617) or naive CD8+ T cells (P=0.079) between survivors (n = 21) and nonsurvivors (n = 9). Increased PD-1 expression on memory CD4+ T cells was found in nonsurvivors (P=0.030) and memory CD8+ T cells (P=0.006) in comparison with survivors. According to the cutoff value of the percentage of PD-1 on memory CD8+ T cells in predicting 28-day mortality of patients with sepsis, patients were divided into two groups. The 28-day mortality rates between the two groups were significantly different (P=0.009). A Kaplan Meier curve was constructed to derive a hazard ratio of 9.33 (95% CI: 2.52-34.60) for the percentage of PD-1 on memory CD8+ T cells regarding 28-day mortality. In addition, the IFN-γ secretion of memory CD4+ T cells (P=0.046) and IL-2 secretion of memory CD8+ T cells (P=0.014) were significantly greater in survivors than nonsurvivors. Conclusion: Flow cytometric assessment of PD-1 expression on memory CD8+ T cells identifies patients with poor outcomes during sepsis.

Commutability Assessment of Processed Human Plasma Samples for Normetanephrine and Metanephrine Measurements Based on the Candidate Reference Measurement Procedure.

Background: To identify candidate external quality assessment (EQA) materials for normetanephrine and metanephrine measurements, we assessed the commutability of eight processed human plasma samples. The agreement between routine assays and the candidate reference measurement procedure (cRMP) was also evaluated. Methods: Fifty-three clinical samples and eight processed plasma samples were prepared. The processed samples included pooled and individual plasma samples spiked with pure normetanephrine and metanephrine and non-spiked pooled and individual plasma samples. The clinical and processed samples were subjected to four routine isotope dilution tandem mass spectrometry assays and cRMP. Commutability was assessed based on two approaches recommended by the CLSI and International Federation of Clinical Chemistry (IFCC). Passing-Bablok regression and Bland-Altman analysis were used to evaluate the agreement between the routine assays and cRMP. Results: The commutability results of the CLSI approach were better than those of the IFCC approach. For the CLSI approach, spiked individual plasma samples and spiked high-concentration pooled plasma samples were commutable for all routine assays for both analytes. The non-spiked pooled plasma sample was commutable for two out of four routine assays for metanephrine and three out of four routine assays for normetanephrine. The agreement between the routine assays and the cRMP was satisfactory, except for one routine assay showing significant bias. Conclusions: High-concentration spiked pooled plasma samples and spiked individual plasma samples are candidate EQA materials for normetanephrine and metanephrine measurements.

Facile discovery of surrogate cytokine agonists.

Cytokines are powerful immune modulators that initiate signaling through receptor dimerization, but natural cytokines have structural limitations as therapeutics. We present a strategy to discover cytokine surrogate agonists by using modular ligands that exploit induced proximity and receptor dimer geometry as pharmacological metrics amenable to high-throughput screening. Using VHH and scFv to human interleukin-2/15, type-I interferon, and interleukin-10 receptors, we generated combinatorial matrices of single-chain bispecific ligands that exhibited diverse spectrums of functional activities, including potent inhibition of SARS-CoV-2 by surrogate interferons. Crystal structures of IL-2R:VHH complexes revealed that variation in receptor dimer geometries resulted in functionally diverse signaling outputs. This modular platform enabled engineering of surrogate ligands that compelled assembly of an IL-2R/IL-10R heterodimer, which does not naturally exist, that signaled through pSTAT5 on T and natural killer (NK) cells. This "cytokine med-chem" approach, rooted in principles of induced proximity, is generalizable for discovery of diversified agonists for many ligand-receptor systems.

Vertical distribution and river-sea transport of microplastics with tidal fluctuation in a subtropical estuary, China.

The river-sea transport of microplastic with complex environmental conditions and diverse driving factors has received growing attention in the estuary. This research investigated the vertical distribution of microplastics in the water column and surface sediments and explored the effect of tidal variation on the transport of microplastics in Jiulong Estuary and Xiamen Bay, China. Results show that the microplastics in the estuary (630 ± 515 µm) was significantly larger than that in the bay (344 ± 420 µm, p < 0.01). Low-density microplastics are present in the whole water column, while high-density microplastics was apt to accumulate in the bottom water and surface sediment suggesting biofouling and material density of microplastics synergistic affect its vertical distribution. Every 1-2 h high-frequency samples collected in a whole tide found the increase of fine size (45-300 µm) and decrease of large size (>300 µm) in the flood tide, which implied fine microplastics were easily driven into the estuary from the bay at flood tide than large microplastics. The abundance of microplastics in the sediments decreased in the fast-rising and fast-falling period implies the tide influences the fragmentation and resuspension of microplastics in the estuary. Finally, the flux of microplastics entering Xiamen Bay was 53.5 t/month in the moderate flow month were estimated based on the abundance of different water layers instead of floating microplastics in the surface water.