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Byline: Kuan-Jen. Chen, Ming-Hui. Sun, Pei-Lun. Sun A 54-year-old diabetic man with acute myeloid leukemia underwent chemotherapy. He was diagnosed with uveitis and underwent a vitreous biopsy. Two weeks later, [...]

The electrochemical reduction of nitrogen to produce ammonia is pivotal in modern society due to its environmental friendliness and the substantial influence that ammonia has on food, chemicals, and energy. However, the current electrochemical nitrogen reduction reaction (NRR) mechanism is still imperfect, which seriously impedes the development of NRR. In situ characterization techniques offer insight into the alterations taking place at the electrode/electrolyte interface throughout the NRR process, thereby helping us to explore the NRR mechanism in-depth and ultimately promote the development of efficient catalytic systems for NRR. Herein, we introduce the popular theories and mechanisms of the electrochemical NRR and provide an extensive overview on the application of various in situ characterization approaches for on-site detection of reaction intermediates and catalyst transformations during electrocatalytic NRR processes, including different optical techniques, X-ray-based techniques, electron microscopy, and scanning probe microscopy. Finally, some major challenges and future directions of these in situ techniques are proposed.

Hollow zeolite microspheres have recently attracted much attention for their applications in catalysis, microreactors and biomedicine. Herein, we present hierarchically structured zeolite ZSM-5 microspheres with unique, abundant macropores that allow more efficient use for catalysis. The hierarchically macroporous zeolite ZSM-5 microspheres are synthesized under the assistance of water/oil emulsions and using polystyrene nanospheres as templates. The zeolite microsphere is assembled by uniform hollow zeolite nanospheres. Their large inner cavities and thin zeolite shells lead to smaller diffusion channel and higher improved accessibility to active sites, contributing to high catalytic performance in the catalytic conversion of benzyl alcohol in mesitylene. Such novel zeolite microspheres with impressive performance will be applied to numerous other industrial catalytic reactions.

Characterized by their pivotal roles in cell-to-cell communication, cell proliferation, and immune regulation during tissue repair, exosomes have emerged as a promising avenue for “cell-free therapy” in clinical applications. Hydrogels, possessing commendable biocompatibility, degradability, adjustability, and physical properties akin to biological tissues, have also found extensive utility in tissue engineering and regenerative repair. The synergistic combination of exosomes and hydrogels holds the potential not only to enhance the efficiency of exosomes but also to collaboratively advance the tissue repair process. This review has summarized the advancements made over the past decade in the research of hydrogel-exosome systems for regenerating various tissues including skin, bone, cartilage, nerves and tendons, with a focus on the methods for encapsulating and releasing exosomes within the hydrogels. It has also critically examined the gaps and limitations in current research, whilst proposed future directions and potential applications of this innovative approach.

Developing ultrasensitive lateral flow immunoassays (LFIAs) has garnered significant attention in the field of point-of-care testing. In this study, a trimetallic dendritic nanozyme (Pd@Pt–Ru) was synthesized through Ru deposition on a Pd@Pt core and utilized to enhancing the sensitivity of LFIAs. Pd@Pt–Ru exhibited a Kmvalue of 5.23 mM for detecting H2O2, which indicates an H2O2affinity comparable with that of horseradish peroxidase. The Ru surface layer reduces the activation energy barrier, which increases the maximum reaction rate. As a proof of concept, the proposed Pd@Pt–Ru nanozyme was incorporated into LFIAs (A–Pd@Pt–Ru–LFIAs) for detecting human chorionic gonadotropin (hCG). Compared with conventional gold nanoparticle (AuNP)–LFIAs, A–Pd@Pt–Ru–LFIAs demonstrated 250-fold increased sensitivity, thereby enabling a visible detection limit as low as 0.1 IU/L. True positive and negative rates both reached 100%, which renders the proposed Pd@Pt–Ru nanozyme suitable for detecting hCG in clinical samples.

The South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), has invaded most Afro-Eurasian countries. Since its first detection in China in late 2017, this pest has been now present in nearly 20 provinces/prefectures in China and is threating tomato and other Solanaceous crops such as potato, eggplants, and tobacco. Here, we provide a timely review on the current distribution, damage, management, and research in China. A standard survey form was designed and 30 answered surveys from 25 provinces have been received. The data showed that the damage has been witnessed in most of the regions despite that the severities vary among the regions. The management is chemical-control biased, and more efforts are needed to increase the adoption of non-chemical alternatives in the Integrated Pest Management packages. An Integrated Pest Management (IPM) package called “CAMEFA” was developed and demonstrated in Yunnan and Xinjiang, the two earliest regions for the invasion. Yet, the adoption by local growers is still limited. Besides T. absoluta, we suggest a multi-pest approach by combing IPM tactics coping with other major insect pests sharing the crop. Lastly, international projects are deemed to serve as a key lever for promoting IPM of T. absoluta and other invasive insect pests.

Cannibalism, an act of killing and consuming conspecific individuals, is a common behavior among various insect taxa. This study investigated the effects of food limitation and larval health status on cannibalistic behavior in the South American tomato pinworm, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), a devastating insect pest on solanaceous crops. In “no-choice” trials, where either a healthy versus weak conspecific larva was provided, T. absoluta larvae exhibited a significantly higher cannibalism rate toward weak conspecific individuals compared with healthy ones. This pattern was further confirmed in “choice” trials where T. absoluta larvae significantly preferred to consume weak larvae to healthy ones when both targets were supplied. When plant food was supplied as an alternative to a healthy or a weak conspecific larva, cannibalism was observed only when weak conspecific individuals were available, despite a significant preference for tomato leaflets. Therefore, cannibalism in T. absoluta is largely opportunistic and is significantly influenced by plant food limitation and larval health status. These findings enhance our understanding of conspecific interactions in herbivorous insects.

Vitellogenin (Vg) is a glycolipid complex protein produced by the fat body of female insects. It plays vital roles in oocyte development and helps regulate reproductive development. In this study, we determined the grading criteria for ovarian development and identified a Vg gene (designated TaVg) from the devastating invasive pest, Tuta absoluta (Meyrick). TaVg contains a 5208 bp open reading frame encoding a protein of 1735 amino acids that includes conserved domain structures of insect Vg. Phylogenetic analysis indicated that TaVg was clustered into a clade with the Vg of other Lepidoptera species, suggesting this gene has been conserved during evolution. Spatiotemporal expression analyses showed that TaVg was highly expressed in the female pupae and adults. There was increased expression during sexual maturation, and the high expression level was found in the ovary and fat body. RNAi-mediated silencing of TaVg resulted in significant downregulation of vitellogenin contents and severely affected ovarian development. Females injected with dsTaVg had shorter ovarian tubes and fewer oocytes compared with the untreated individuals. The number of oocytes and the amount of yolk deposition in the egg chambers also reduced. Depletion of TaVg significantly reduced the number of eggs laid and the hatching rate. Co-silencing of TaVg and TaVgR had a more significant effect on inhibiting the ovarian development and reducing female fecundity of T. absoluta, showing that the two genes play important role in regulating the reproduction. Our results provide potential targets for developing RNAi-based pest management tractic on T. absoluta.

Harmine (HAM) is a natural product with neuroprotective and antitumor activity. Its poor aqueous solubility is the major factor limiting its clinical application. In this work, seven new organic acid salts of HAM were prepared and systematically characterized. Their single crystals were obtained, and the structures were identified by a single-crystal X-ray diffractometer. The corresponding solubilities in water were determined in the temperature range of 20–35 °C by the HPLC method. All HAM salts showed significantly improved powder solubility profiles compared with the free base. The relationship between the aqueous solubility and the single-crystal structures of HAM organic salts was explored from several perspectives, including the basic properties of acidic counterions, the intermolecular force in crystals (type of lattice force, cohesive energy density, and lattice energy), the factors affecting the dissolution process (hydration energy and sublimation energy), and the external environmental factors (chemical hardness). The aqueous solubility of different HAM salts was dependent on the type of charge assistant hydrogen bonds; that is, the salts with N+–H···O and O–H···O–hydrogen bonds exhibited better solubility than the other salts with N+–H···O–hydrogen bonds. In addition, the results revealed that HAM salts with higher acidic counterion intrinsic solubility (SACID) showed smaller cohesive energy density of the crystal; the larger the absolute value of hydration energy (ΔGhyd0), the greater the chemical hardness (η) of acidic anions in the crystal and ultimately the better the equilibrium solubility in water. The rank order of the linear fitting accuracy of these four parameters regarding solubility was as follows: Δη > CED > ΔGhyd0. The solubility of HAM organic acidic salts is associated with several factors, even though the chemical hardness seems to play a central role.

Converting CO2into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO2reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO2@Bi2WO6heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO2@Bi2WO6photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi(3–x)+sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 μmol h–1g–1, which is 15 and 4.7 times higher than that of pure Bi2WO6and that of physically mixed TiO2/Bi2WO6, respectively. An in situ study shows that the pathway for the transformation of CO2into CO over our TiO2@Bi2WO6proceeds via two important intermediates, including COO–and COOH–. Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO2conversion.

Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories.

ABSTRACTPYCARD (PYD and CARD domain containing), a pivotal adaptor protein in inflammasome assembly and activation, contributes to innate immunity, and plays an essential role in the pathogenesis of atherosclerosis and restenosis. However, its roles in microRNA biogenesis remain unknown. Therefore, this study aimed to investigate the roles of PYCARD in miRNA biogenesis and neointima formation using pycardknockout (pycard−/−) mice. Deficiency of Pycardreduced circulating miRNA profile and inhibited Mir17seed family maturation. The systemic pycardknockout also selectively reduced the expression of AGO2 (argonaute RISC catalytic subunit 2), an important enzyme in regulating miRNA biogenesis, by promoting chaperone-mediated autophagy (CMA)-mediated degradation of AGO2, specifically in adipose tissue. Mechanistically, pycardknockout increased PRMT8 (protein arginine N-methyltransferase 8) expression in adipose tissue, which enhanced AGO2 methylation, and subsequently promoted its binding to HSPA8 (heat shock protein family A (Hsp70) member 8) that targeted AGO2 for lysosome degradation through chaperone-mediated autophagy. Finally, the reduction of AGO2 and Mir17family expression prevented vascular injury-induced neointima formation in Pycard-deficient conditions. Overexpression of AGO2 or administration of mimic of Mir106b(a major member of the Mir17family) prevented Pycarddeficiency-mediated inhibition of neointima formation in response to vascular injury. These data demonstrate that PYCARD inhibits CMA-mediated degradation of AGO2, which promotes microRNA maturation, thereby playing a critical role in regulating neointima formation in response to vascular injury independently of inflammasome activity and suggest that modulating PYCARD expression and function may represent a powerful therapeutic strategy for neointima formation.Abbreviations:6-AN: 6-aminonicotinamide; ACTB: actin, beta; aDMA: asymmetric dimethylarginine; AGO2: argonaute RISC catalytic subunit 2; CAL: carotid artery ligation; CALCOCO2: calcium binding and coiled-coil domain 2; CMA: chaperone-mediated autophagy; CTSB: cathepsin B; CTSD: cathepsin D; DGCR8: DGCR8 microprocessor complex subunit; DOCK2: dedicator of cyto-kinesis 2; EpiAdi: epididymal adipose tissue; HSPA8: heat shock protein family A (Hsp70) member 8; IHC: immunohistochemical; ISR: in-stent restenosis; KO: knockout; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; miRNA: microRNA; NLRP3: NLR family pyrin domain containing 3; N/L: ammonium chloride combined with leupeptin; PRMT: protein arginine methyltransferase; PVAT: peri-vascular adipose tissues; PYCARD: PYD and CARD domain containing; sDMA: symmetric dimethylarginine; ULK1: unc-51 like kinase 1; VSMCs: vascular smooth muscle cells; WT: wild-type.

ABSTRACTBackgroundAnti-IL-5 monoclonal antibodies (mAbs) targeting IL-5 or IL-5 R α (including mepolizumab, benralizumab, and reslizumab) are widely used for inflammatory diseases such as asthma, eosinophilia, and polyangiitis. However, real-world data regarding its safety in a large sample population are incomplete. So, we evaluated the safety of anti-IL-5 mAbs by pharmacovigilance analyzes based on related adverse events (AEs) from the FDA Adverse Event Reporting System (FAERS).MethodsIn disproportionality analysis, four algorithms were employed to detect the signals of anti-IL-5 mAbs from the FAERS between 2016 and 2022. In addition, we also used MYSQL 8.0, Navicat Premium 15, and Microsoft EXCEL 2019 to analyze the signals of anti-IL-5 mAbs systematically.ResultsThere are 9,476,351 reports collected from the FAERS database, of which 22,174 reports listed anti-IL-5 mAbs as the ‘primary suspected (PS)’ drug. A total of 59 (20 new signals, mepolizumab) and 62 (19 new signals, benralizumab) significant disproportionality preferred terms (PTs) conforming to the four algorithms were retained synchronously. Finally, we detected that the anti-IL-5 mAbs-induced AEs occurred in 31 organ systems (mepolizumab) and 30 organ systems (benralizumab). For mepolizumab and reslizumab, unexpected and new significant PTs of AEs were found, such as asthmatic crisis, chronic obstructive pulmonary disease (COPD), pneumonia, COVID-19, pneumothorax, adrenal insufficiency and so on. Notably, the risk signal of asthmatic crisis for mepolizumab was stronger than benralizumab (ROR 108.04 [95%CI, 96.09–121.47] vs 26.83 [95%CI, 18.91–38.06]). Comparing with mepolizumab and benralizumab, we found the proportion of serious adverse events in mepolizumab was both greater than benralizumab in each age group (≤20, 20–65, and ≥ 65). The median onset time of mepolizumab was 280 days (interquartile range [IQR] 1–367 days).ConclusionAnalysis of FAERS data identified anti-IL-5 mAbs-associated AEs, and our findings supported continuous clinical monitoring, pharmacovigilance, and further studies of anti-IL-5 mAbs. In addition, clinicians may be more aware of the limitations of use in package inserts of anti-IL-5 mAbs: Not for relief of acute bronchospasm or status asthmaticus. Because of some limitations in the FAERS such as self-reports from patients and other confounding factors, the safety of anti-IL-5 mAbs needed more studies in different dimensions, especially the risk of cancer.

This contribution presents a novel and comparative study on the relationship between the crystal structure and the property diversity of a complex polymorph system of nicorandil oxalate (NIC-OA) salts. Single-crystal structures of four salt polymorphs with 1:1 stoichiometry were prepared, and crystal structure analysis revealed the difference of configuration and tautomer structure among those polymorphs. Bulk samples of three polymorphs (S1, S3 and S4) were successfully isolated from ethanol/water solution, while the metastable form S2 could not be obtained. Detailed property studies including solvent-mediated polymorph transformation, physical-chemical stability, and intrinsic dissolution of those polymorphs were conducted. Phase transformation from S3 to S4 in high-humidity conditions and accelerated conditions was driven by lowering of lattice energy. High hygroscopicity would accelerate the process. All polymorphs showed better chemical stability and greater dissolution rate compared to NIC. The binding energy between NIC and oxalate acid and crystal-solvent interaction were studied to investigate the correlation between polymorph packing and bulk property. The chemical stability of NIC was affected by the diversity in cation–anion binding modes, while the dissolution process of the polymorphs was influenced by the crystal face differences and the interaction between the crystal and solvent. It is the first time that four crystalline forms of NIC-OA are reported, and the structure and property diversity among these salt polymorphs are revealed with experiments and the quantum chemistry method, which provided new insights into the NIC-OA polymorphs in the crystal engineering field and might contribute to the property research of the complex pharmaceutical polymorphism system.

In the eukaryotic cell nucleus, chromatin and its associated macromolecules must be organized into a higher-ordered conformation to function normally. However, mechanisms underlying the organization and dynamics of the nucleus remain unclear. Long noncoding RNAs (lncRNAs), i.e., transcripts longer than 200 nucleotides with little or no protein-coding capacity, are increasingly recognized as important regulators in diverse biological processes. Recent studies have shown that some lncRNAs are involved in various aspects of genome organization, including the facilitation of chromosomal interactions and establishment of nuclear bodies, suggesting that lncRNAs act as general organizers of the nuclear architecture. Here, we discuss recent advances in this emerging and intriguing field.

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18–66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P= 0.007; HR 3.937, 95% CI: 1.456–9.804) and baseline lung involvement (P= 0.028; HR 2.976, 95% CI: 1.126–7.874) as poor prognostic factors for EFS. The most common grade 3–4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.

Purpose: A piezoelectric vibration energy harvester (PVEH), as a self-power device that can convert ambient vibration energy into electric energy, has extensive application prospects in power supply for microsensors used in Internet of Things (IoT). How to match the ambient vibration frequencies, which are always random and broadband, is a key point to design a PVEH. In this study, a tuning fork-shaped PVEH with pendulum impact-driven enhancement is proposed for energy harvesting from broadband low-frequency vibration. Methods: The impact-driven tuning fork-shaped PVEH with adjustable mechanisms is first designed, and the working principle is introduced in detail. Dynamic equations are established, and the vibration characteristics are analyzed by comparing the results of the finite element analysis (FEA) and numerical simulation, where the natural frequencies and modes are studied, and the effects of pendulum impact-driven enhancement on the energy harvesting performance are analyzed in detail. Results: The results show that the proposed PVEH can obtain 0.6 mW and 6.4 mW output powers when the excitation frequencies are 5 Hz and 34 Hz with 0.5 g excitation amplitude and the optimum load resistance, respectively. Finally, experimental investigations are carried out to verify the energy harvesting performance, and 19 light-emitting diodes (LEDs) are lit up to assess the prospective applications of the proposed impact-driven PVEH. Conclusions: The investigation demonstrates that the pendulum impact-driven could enhance the low-frequency responses, which helps the PVEH achieve the energy harvesting from broadband low-frequency ambient vibration.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals’ responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADAcircuit. Furthermore, the LHbGlu-VTADAexcitatory inputs were dampened via GABABreceptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADAinhibition in depressive behavioral regulation.

Levamisole hydrochloride cocrystallizes with hydroquinone in different solvates (methanol, ethanol, water, acetonitrile, and n-propanol), forming the changing Z″ cocrystal solvates from 23 to 3.33. These cocrystals were characterized by using single-crystal and powder X-ray diffraction and thermal analysis. All cocrystal solvates consist of different 2D planar sheets, which influence the Z″ value and melting point. The findings suggest a method for obtaining high Zcrystals through suitable solvents. Topology analysis and Hirshfeld surface analysis were conducted to understand the Z″ transformation. Further, quantum chemistry was demonstrated as a significant tool to explain the extremely low melting point and the change of the melting point in different solid forms.

Plant stomatal phenotype traits play an important role in improving crop water use efficiency, stress resistance and yield. However, at present, the acquisition of phenotype traits mainly relies on manual measurement, which is time-consuming and laborious. In order to obtain high-throughput stomatal phenotype traits, we proposed a real-time recognition network SLPA-Net for stomata localization and phenotypic analysis. After locating and identifying stomatal density data, ellipse fitting is used to automatically obtain phenotype data such as apertures. Aiming at the problems of small stomata and high similarity to background, we introduced ECANet to improve the accuracy of stoma and aperture location. In order to effectively alleviate the unbalance problem in bounding box regression, we replaced the Loss function with a more effective Focal EIoU Loss. The experimental results show that SLPA-Net has excellent performance in the migration generalization and robustness of stomata and apertures detection and identification, as well as the correlation between stomata phenotype data obtained and artificial data.

Microstructure evolution and mechanical properties of Ti-1023 alloy during cooling from single-phase region to dual-phase region with the cooling rate of 1 °C/min were systematically investigated. As the final cooling temperature decreased, grain boundary α′martensite (α′GB), grain boundary αphase (αGB), Widmanstatten grain boundary αphase (αWGB), and Widmanstatten intragranular αphase (αWI) were sequentially precipitated. Correspondingly, mechanical properties and deformation mechanisms of Ti-1023 alloy changed significantly. When the final cooling temperature was higher than 700 °C, tensile curve showed an obvious double-yielding phenomenon with elongation >20%. Whereas the final cooling temperature was lower than 700 °C, and the double-yielding phenomenon disappeared. This was mainly attributed to the fact that βstability of Ti-1023 alloys was enhanced with the increase of α(α′) precipitated phases. And the room temperature deformation mechanism gradually changed from stress-induced α″martensitic phase transformation to dislocation slip. Furthermore, strengthening mechanism of Ti-1023 alloy was analyzed in combination with grain size and precipitated phase effects.

Anti-glomerular basement membrane (anti-GBM) disease is an organ-specific autoimmune disorder characterized by autoantibodies against GBM components. Evidence from human inherited kidney diseases and animal models suggests that the α, β, and γ chains of laminin-521 are all essential for maintaining the glomerular filtration barrier. We previously demonstrated that laminin-521 is a novel autoantigen within the GBM and that autoantibodies to laminin-521 are present in about one-third of patients. In the present study, we investigated the pathogenicity of autoantibodies against laminin-521 with clinical and animal studies. Herein, a rare case of anti-GBM disease was reported with circulating autoantibodies binding to laminin-521 but not to the NC1 domains of α1-α5(IV) collagen. Immunoblot identified circulating IgG from this patient bound laminin α5 and γ1 chains. A decrease in antibody levels was associated with improved clinical presentation after plasmapheresis and immunosuppressive treatments. Furthermore, immunization with laminin-521 in female Wistar-Kyoto rats induced crescentic glomerulonephritis with linear IgG deposits along the GBM, complement activation along with infiltration of T cells and macrophages. Lung hemorrhage occurred in 75.0% of the rats and was identified by the presence of erythrocyte infiltrates and hemosiderin-laden macrophages in the lung tissue. Sera and kidney-eluted antibodies from rats immunized with laminin-521 demonstrated specific IgG binding to laminin-521 but not to human α3(IV)NC1, while the opposite was observed in human α3(IV)NC1-immunized rats. Thus, our patient data and animal studies imply a possible independent pathogenic role of autoantibodies against laminin-521 in the development of anti-GBM disease.

Aluminum hydride (AlH3) has attracted much attention due to its potential to replace aluminum (Al) as a novel energetic material in solid propellants. In this research, ammonium perchlorate (AP) and perfluoropolyether (PFPE) as functionalized coatings and a combination of acoustic resonance and spray drying technology have been employed to prepare AlH3@Al@AP (AHAPs) and AlH3@Al@AP@PFPE (AHAPs-F) energetic composite particles. The formulations of composite propellants and modified AlH3particles were designed and fabricated. Their thermal reactivity, reaction heat, density, vacuum stability, combustion performance, and condensed combustion products (CCPs) have been systematically investigated. The results show that the solid propellants containing AHAPs (SP13) and AHAPs-F (SP14) composites can significantly enhance the reactivity and energy output compared to conventional solid propellants with the mechanical mixture Al/AlH3(SP12). In particular, the total heat releases of SP13 and SP14 are almost 1.2 and 1.7 times higher than those of conventional ones (SP12, 1442 J g–1), respectively. Among the AlH3-based propellants, SP14 propellants exhibit the highest reaction heat of 5887 J g–1, the most intensive flame radiation of 31.4 × 103, and the highest combustion wave temperature of 2495 °C. Moreover, the particle size distribution of CCPs from SP14 propellants is much narrower and smaller than that of SP12, resulting in higher combustion efficiency.

We developed and externally validated a machine learning model capable of outperforming well-established tools in predicting lymph node involvement in patients with prostate cancer referred for pelvic lymph node dissection.

To overcome the clinical limitations of oxaliplatin (OXA), such as side effects and toxicity, increasing attention was paid to the use of OXA-based Pt(IV) complexes as oral administration prodrugs. In this study, we prepared trans-[Pt(R,R-DACH)(oxalate)(OH)2] (DHOXA) as a model of OXA-based Pt(IV) complexes and synthesized six cocrystals of DHOXA to investigate their stability in pH 1.2 and 7.4 buffer and the reduction rate of producing OXA. Six cocrystals of DHOXA with oxalic acid, hydroquinone (HYD), benzoic acid, salicylic acid, 3,5-difluorobenzoic acid, and 3-hydroxy-2-naphthoic acid were characterized by single-crystal X-ray diffraction, powder X-ray diffraction, and thermal analysis. Further contrastive analysis of the dissolution behavior and reduction test of the six cocrystals of DHOXA showed that DHOXA-HYD dihydrate (DHOXA-HYD-DH) significantly improved the performances of the stability in hydrochloric acid (pH 1.2) and the reduction rate. Besides, the cytotoxicity studies showed that DHOXA-HYD-DH increased cytotoxicity to cancer cells and possessed higher safety. The study provides a new method to develop the OXA-based Pt(IV) complexes as prodrugs.

Owing to their facile reactants migration channels, large surface area, maximized exposure of reaction sites and efficient light utilization, three-dimensionally ordered macroporous (3DOM) materials have been extensively adopted in environmental fields such as pollutants removal, environmental detection as well as bacterial disinfection. In this review, the up-to-date 3DOM materials, the corresponding synthesis protocols and the related environmental applications involving photo electrocatalytic pollutants decomposition, thermocatalytic volatile organic compounds (VOCs) elimination, hazardous substances sensing and bacteria inactivation are completely presented. Simultaneously, the inherent advantages and mechanisms of 3DOM materials in different environmental utilization are thoroughly demonstrated and summarized. Furthermore, the improved performance of environmental applications and the methods of fabricating 3DOM materials are correlated in depth, being favorable for readers to obtain the fundamental knowledge and to motivate some innovative thoughts for modifying 3DOM materials with further elevated environmental remediation capability. Finally, the current difficulties and prospects of 3DOM materials for large-scale and commercial applications are outlooked. This critical review is anticipated to promote the optimization of 3DOM materials and to ripen the related environmental remediation techniques.

To illuminate the spatio-temporal variation characteristics and geochemical driving mechanism of soil pH in the Nenjiang River Basin, the National Multi-objective Regional Geochemical Survey data of topsoil, the Second National Soil Survey data and Normalized Difference Vegetation Index (NDVI) were analyzed. The areas of neutral and alkaline soil decreased by 21100 km2and 30500 km2, respectively, while that of strongly alkaline, extremely alkaline, and strongly acidic soil increased by 19600 km2, 18200 km2, and 15500 km2, respectively, during the past 30 years. NDVI decreased with the increase of soil pH when soil pH > 8.0, and it was reversed when soil pH < 5.0. There were significant differences in soil pH with various surface cover types, which showed an ascending order: Arbor < reed < maize < rice < high and medium-covered meadow < low-covered meadow

Co-carbonization of weakly caking coal and zinc-containing dust to prepare highly reactive ferro-coke and collaboratively recover zinc powder is one of the feasible ways for steel enterprises to recycle zinc-containing dust. The pyrolysis mass loss behavior of adding blast furnace dust with different zinc contents to different ferro-coke materials was systematically studied by thermogravimetry and differential thermogravimetry analysis, and the kinetic mechanism of pyrolysis-reduction reaction of hybrid briquette was explored. The results of thermogravimetric curve analysis show that the addition of zinc oxide to the sample has no significant effect on the mass loss rate of the sample below 580 °C, and the pyrolysis mass loss of zinc oxide mainly occurs between 800 and 1000 °C. Kinetic analysis results show that the pyrolysis of zinc-containing samples is controlled by chemical reactions below 580 °C. The reaction at 580–700 °C is controlled by the nucleation and growth model, and that above 700 °C is mainly controlled by diffusion. The results of X-ray diffraction analysis show that the pyrolysis process can effectively remove zinc oxide from ferro-coke.

Background:Hyperoxaluria is a major cause of oxalate nephropathy, which can lead to impaired renal function presenting as acute kidney injury, acute on chronic kidney disease, or chronic kidney disease. The Chronic Renal Insufficiency Cohort study showed that higher urinary oxalate is associated with renal outcome in patients with chronic kidney disease, supporting the nephrotoxicity of oxalate. Therefore, a better understanding of the role of oxalate in kidney injury is needed. This review describes the metabolism of oxalate and the clinical and pathology presentation of oxalate nephropathy. It also summarizes the available evidence for the underlying pathogenic mechanism and the development of treatments for oxalate-induced kidney injury. Summary:Disruption to any key step in the oxalate pathway including abnormal endogenous generation, ingestion of abnormally high dose of oxalate, increased absorption or attenuation of oxalate degradation in the gut, and reduced excretion through the kidney may lead to disrupted oxalate homeostasis. Oxalate nephropathy is mainly caused by hyperoxaluria. Oxalate crystal deposition in the kidney is usually accompanied with tubular toxicity, obstruction, interstitial fibrosis, and tubular atrophy. The mechanism of oxalate-induced renal injury has not been fully clarified. Evidence from both in vivo and in vitro studies shows that NLRP3 inflammasome activation and macrophage infiltration are involved in the processes of crystal adhesion, aggregation, and elimination and promote intrarenal inflammation and renal fibrosis. Novel treatment strategies have been developed and targeted therapies tested for oxalate nephropathy. Key Messages:Prompt diagnosis and management may help to reduce the deposition of calcium oxalate crystals in the kidney. Further studies are needed to clarify the underlying mechanisms to help develop more targeted therapies for oxalate nephropathy.

Light and sound are the most ubiquitous forms of waves, associated with a variety of phenomena and physical effects such as rainbows and echoes. Light and sound, both categorized as classical waves, have lately been brought into unexpected connections with exotic topological phases of matter. We are currently witnessing the onset of a second wave of active research into this topic. The past decade has been marked by fundamental advances comprising two-dimensional quantum Hall insulators and quantum spin and valley Hall insulators, whose topological properties are characterized using linear band topology. Here, going beyond these conventional topological systems, we focus on the latest frontiers, including non-Hermitian, nonlinear and non-Abelian topology as well as topological defects, for which the characterization of the topological features goes beyond the standard band-topology language. In addition to an overview of the current state of the art, we also survey future research directions for valuable applications.

Wafer-scale monolayer two-dimensional (2D) materials have been realized by epitaxial chemical vapor deposition (CVD) in recent years. To scale up the synthesis of 2D materials, a systematic analysis of how the growth dynamics depend on the growth parameters is essential to unravel its mechanisms. However, the studies of CVD-grown 2D materials mostly adopted the control variate method and considered each parameter as an independent variable, which is not comprehensive for 2D materials growth optimization. Herein, we synthesized a representative 2D material, monolayer hexagonal boron nitride (hBN), on single-crystalline Cu (111) by epitaxial chemical vapor deposition and varied the growth parameters to regulate the hBN domain sizes. Furthermore, we explored the correlation between two growth parameters and provided the growth windows for large flake sizes by the Gaussian process. This new analysis approach based on machine learning provides a more comprehensive understanding of the growth mechanism for 2D materials.

Plant essential oils have good antimicrobial properties, but their poor stability and compatibility in aqueous solutions greatly limit their practical application. To address this issue, a dynamically crosslinked nanoemulsion based on host–guest assembly was developed in this study. First, a β-cyclodextrin-functionalized quaternary ammonium surfactant (β-CD-QA) and adamantane-terminated polyethylene glycol (APA) crosslinker were first synthesized. Then, the oil-in-water host–guest crosslinked nanoemulsions (HGCTNs) were formed by incorporating tea tree essential oils (TTO) as a natural antimicrobial agent. The results showed that HGCTNs significantly improved the stability of the essential oil nanoemulsions and extended their shelf life. Furthermore, HGCTNs demonstrated effective antimicrobial properties against both Gram-negative/positive bacterioplankton and bacterial biofilms. The results of antibacterial experiments showed that the dynamically crosslinked HGCTNs exhibit superior antibacterial efficacy, with a minimum inhibitory concentration (MIC) of 12.5 v/v % (0.13 μL/mL TTO) and could eradicate the biofilms. The electrical conductivity of the bacterial solution gradually increased within 5 h of treatment with the nanoemulsions, indicating that the HGCTNs have a slow-release effect of TTO and sustainable antibacterial ability. The antimicrobial mechanism can be attributed to the synergistic antibacterial action of the β-CD-QA surfactant containing a quaternary ammonium moiety and TTO, which are stabilized by nanoemulsions.

IMPORTANCE: Mesial temporal lobe epilepsy (MTLE) is the most common focal epilepsy subtype and is often refractory to antiseizure medications. While most patients with MTLE do not have pathogenic germline genetic variants, the contribution of postzygotic (ie, somatic) variants in the brain is unknown. OBJECTIVE: To test the association between pathogenic somatic variants in the hippocampus and MTLE. DESIGN, SETTING, AND PARTICIPANTS: This case-control genetic association study analyzed the DNA derived from hippocampal tissue of neurosurgically treated patients with MTLE and age-matched and sex-matched neurotypical controls. Participants treated at level 4 epilepsy centers were enrolled from 1988 through 2019, and clinical data were collected retrospectively. Whole-exome and gene-panel sequencing (each genomic region sequenced more than 500 times on average) were used to identify candidate pathogenic somatic variants. A subset of novel variants was functionally evaluated using cellular and molecular assays. Patients with nonlesional and lesional (mesial temporal sclerosis, focal cortical dysplasia, and low-grade epilepsy–associated tumors) drug-resistant MTLE who underwent anterior medial temporal lobectomy were eligible. All patients with available frozen tissue and appropriate consents were included. Control brain tissue was obtained from neurotypical donors at brain banks. Data were analyzed from June 2020 to August 2022. EXPOSURES: Drug-resistant MTLE. MAIN OUTCOMES AND MEASURES: Presence and abundance of pathogenic somatic variants in the hippocampus vs the unaffected temporal neocortex. RESULTS: Of 105 included patients with MTLE, 53 (50.5%) were female, and the median (IQR) age was 32 (26-44) years; of 30 neurotypical controls, 11 (36.7%) were female, and the median (IQR) age was 37 (18-53) years. Eleven pathogenic somatic variants enriched in the hippocampus relative to the unaffected temporal neocortex (median [IQR] variant allele frequency, 1.92 [1.5-2.7] vs 0.3 [0-0.9]; P = .01) were detected in patients with MTLE but not in controls. Ten of these variants were in PTPN11, SOS1, KRAS, BRAF, and NF1, all predicted to constitutively activate Ras/Raf/mitogen-activated protein kinase (MAPK) signaling. Immunohistochemical studies of variant-positive hippocampal tissue demonstrated increased Erk1/2 phosphorylation, indicative of Ras/Raf/MAPK activation, predominantly in glial cells. Molecular assays showed abnormal liquid-liquid phase separation for the PTPN11 variants as a possible dominant gain-of-function mechanism. CONCLUSIONS AND RELEVANCE: Hippocampal somatic variants, particularly those activating Ras/Raf/MAPK signaling, may contribute to the pathogenesis of sporadic, drug-resistant MTLE. These findings may provide a novel genetic mechanism and highlight new therapeutic targets for this common indication for epilepsy surgery.

AbstractThis study examines how maximum emotional intelligence (EI) members can contribute to the emergence of team-level organizational citizenship behaviors (OCB). Based on integrating a strategic core role and multilevel theory, we developed and tested a model in which the maximum EI score in teams results in intrateam trust and consequently impacts team OCB and examined whether the indirect effect of maximum EI on team OCB through intrateam trust would be moderated by EI diversity and trust divergence in teams. The results from 129 project teams showed that the relationship of maximum EI with team OCB is mediated by intrateam trust and this relationship is stronger for lower levels of EI diversity and trust divergence than for higher levels of diversity and divergence. The findings advance our understanding of the role of EI in team settings. Our research has important implications for organizations attempting to develop the applied value of EI.

Electrocatalytic carbon dioxide reduction (CO2R) in neutral electrolytes can mitigate the energy and carbon losses caused by carbonate formation but often experiences unsatisfied multicarbon selectivity and reaction rates because of the kinetic limitation to the critical carbon monoxide (CO)–CO coupling step. Here, we describe that a dual-phase copper-based catalyst with abundant Cu(I) sites at the amorphous–nanocrystalline interfaces, which is electrochemically robust in reducing environments, can enhance chloride-specific adsorption and consequently mediate local *CO coverage for improved CO–CO coupling kinetics. Using this catalyst design strategy, we demonstrate efficient multicarbon production from CO2R in a neutral potassium chloride electrolyte (pH ∼6.6) with a high Faradaic efficiency of 81% and a partial current density of 322 milliamperes per square centimeter. This catalyst is stable after 45 h of operation at current densities relevant to commercial CO2electrolysis (300 mA per square centimeter).

Background:Lupus nephritis is characterized by multiple autoantibodies production. However, there are few autoantibodies associated with disease activity and prognosis. CRP exists in at least two conformationally distinct forms: native pentameric C-reactive protein (pCRP) and modified/monomeric CRP (mCRP). Autoantibodies against mCRP are prevalent in sera of patients with lupus nephritis and are reported to be pathogenic. Summary:The levels of serum anti-mCRP autoantibodies are associated with clinical disease activity, tubulointerstitial lesions, treatment response, and prognosis in patients with lupus nephritis. The key epitope of mCRP was amino acid 35–47. Furthermore, emerging evidence indicated that anti-mCRP autoantibodies could participate in the pathogenesis of lupus nephritis by forming in situ immune complexes or interfering with the biological functions of mCRP, such as binding to complement C1q and factor H. Key Messages:Here, we review the recent advances in the prevalence, clinical-pathological associations, and potential pathogenesis of anti-mCRP autoantibodies in lupus nephritis, which may provide a promising novel therapeutic strategy for lupus nephritis.

The epoxidation reaction over titanium silicalite-1 (TS-1) zeolites is a green way to produce epoxides that are important intermediates for chemicals. Nevertheless, the conventional microporous TS-1 zeolite shows limited diffusion ability for bulky molecules, leading to poor activity and low selectivity. Constructing hierarchical porosity in microporous materials is an effective strategy to enhance the diffusion properties of catalysts. However, there are few reports on the design and synthesis of TS-1 zeolites with hierarchical structure featuring multilevels, interconnectivity, and regularity for efficient diffusion and epoxidations. Herein, hierarchical TS-1 zeolites with ordered macro–meso–microporosity (OMMM-TS-1) are obtained by a method combining a templated effect of ordered macro–mesoporous matrices and a confined in situ crystallization process. The OMMM-TS-1 possesses ordered macropores with tunable size (∼200–600 nm), ordered mesopores (∼8 nm), and intact micropores (∼0.5 nm). The OMMM-TS-1 achieves a cyclooctene conversion as 3.6 times and 1.8 times and a selectivity to epoxy product as 1.6 times and 1.3 times higher than the conventional TS-1 (C-TS-1) and nanosized TS-1 (Nano-TS-1) zeolites, respectively. The OMMM-TS-1 also outperforms the C-TS-1 and Nano-TS-1 zeolites in epoxidations of a series of alkenes. Such a novel hierarchical structure can be applied in the design and synthesis of many other catalysts.

ZrO2catalysts with different crystal structures show different catalytic performance in isobutene synthesis from CO hydrogenation reaction. Although monoclinic ZrO2has the best catalytic performance in isobutene synthesis from syngas, its isosynthesis active sites are still not well understood. To better understand the critical parameters that influence syngas to isobutene reactions over ZrO2catalysts, we prepared a series of ZrO2catalysts with distinct crystal structures and investigated their catalytic performance of CO hydrogenation to isobutene. Compared with tetragonal and amorphous ZrO2catalysts, there are more coordinatively unsaturated Zr and O sites on the surface of monoclinic ZrO2catalyst. The coordinatively unsaturated Zr sites are the active sites of CO adsorption and activation, which is beneficial to CO conversion. The coordinatively unsaturated O sites provide more basic sites for isobutene formation. Furthermore, the coordinatively unsaturated Zr and O sites on monoclinic ZrO2catalyst surface may inhibit electron transfer to formate species formed during reaction, resulting in weak adsorption on catalyst surface of formate species. The weakly adsorbed formate species on the surface of monoclinic ZrO2catalyst is favorable for the synthesis of isobutene from CO hydrogenation reaction.

The present study aims to plumb blockage of the deep-sea mining pump transporting large particles with different shapes. A numerical work was performed through combining the computational fluid dynamics (CFD) technique and the discrete element method (DEM). Six particle shapes with sphericity ranging from 0.67 to 1.0 were selected. A velocity triangle is built with the absolute, relative, and circumferential velocities of particles. Velocity triangles with absolute velocity angles ranging from 90° to 180° prevail in the first-stage impeller. With declining sphericity, more particles follow the velocity triangle with absolute velocity angles ranging from 0° to 90°, which weakens the ability of particles to pass through the flow passage. Furthermore, the forces acting on the particles traveling in the impeller passage are analyzed. Large particles, especially non-spherical ones, suffer from high centrifugal force and therefore move along the suction surface of the impeller blades. Non-spherical particles undergo great drag force as a result of large surface area. The distribution of drag force angles is featured by two peaks, and one vanishes due to blockage. As particle sphericity declines, both magnitude and angle of the pressure gradient force decrease. Variation of the drag force and the pressure gradient force causes clockwise deflection of the centripetal force, resulting in deflection and elongation of particle trajectory, which increases the possibility of blockage.

The exploration of virology knowledge was limited by the optical technology for the observation of virus. Previously, a three-dimensional multi-resolution real-time microscope system (3D-MRM) was developed to observe the uptake of HIV-1-tat peptide-modified nanoparticles in cell membrane. In this study, we labeled HIV-1 virus-like particles (VLPs) with passivated giant quantum dots (gQDs) and recorded their interactive trajectories with human Jurkat CD4 cells through 3D-MRM.

ABSTRACT The strength of concrete will be developed as the age increases. When a sustained load is applied on the concrete, the development rules will be changed. Research on these [...]

Plant chlorophyll biosynthesis and chloroplast development are two complex processes that are regulated by exogenous and endogenous factors. In this study, we identified OsDXR, a gene encoding a reductoisomerase that positively regulates chlorophyll biosynthesis and chloroplast development in rice. OsDXRknock-out lines displayed the albino phenotype and could not complete the whole life cycle process. OsDXRwas highly expressed in rice leaves, and subcellular localization indicated that OsDXR is a chloroplast protein. Many genes involved in chlorophyll biosynthesis and chloroplast development were differentially expressed in the OsDXRknock-out lines compared to the wild type. Moreover, we found that the RNA editing efficiencies of ndhA-1019 and rpl2-1 were significantly reduced in the OsDXRknock-out lines. Furthermore, OsDXR interacted with the RNA editing factor OsMORF1 in a yeast two-hybrid screen and bimolecular fluorescence complementation assay. Finally, disruption of the plastidial 2-C-methyl-derythritol-4-phosphate pathway resulted in defects in chloroplast development and the RNA editing of chloroplast genes.