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Background: Microsporidia is an obligate intracellular eukaryote, which is capable of parasitizing vertebrates and invertebrates. Nosema ceranae, which can infect both Apis mellifera and Apis cerana, poses a serious threat and causes heavy losses to the worldwide apiculture. During infection, polar tube, a highly specialized invasion structure, ejected from the spore to deliver the sporoplasm into host cells to cause infection. Although seven different polar tube proteins (PTP1 ~ 7) have been reported from various microsporidia and showed key functions associated with spore invasion and proliferation, no systematic analysis on identification and characterization of polar tube proteins from N. ceranae was found., Methods and Results: The polar tube proteins 2 (NcPTP2) was identified from the total polar tube proteins of N. ceranae by LC_MS/MS and the transcriptional profile was performed by RT-PCR. Sequence characterization analysis revealed that NcPTP2 was rich in lysine and had a signal peptide at the N-terminal. It had 3 potential O-glycosylation sites and 6 potential N-glycosylation sites. 25 phosphorylation sites were found on serine, tyrosine and threonine sites. Sequence alignment analysis revealed that NcPTP2 was homologous and had conserved cysteine residues with PTP2 proteins from other microsporidia. Indirect immunofuorescence analysis (IFA) and Immunoelectron Microscopy analysis (IEM) confirmed that NcPTP2 was localized on the polar tube of the germinated spores. The interaction between NcPTP2 and spore wall protein in N. ceranae indicated its potential function in anchoring and coiling of polar tube in spore., Conclusion: NcPTP2 was the first subcellular localized polar tube protein in N. ceranae and this work could provide an important basis for further analyzing the biological functions of polar tube proteins and uncovering the infection mechanism of N. ceranae to the host cells., Competing Interests: Declarations Conflict of interest No conflicts of interest, financial or otherwise, are declared by the authors. Ethical approval It is not applicable., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

The concepts of origami and kirigami have often been presented separately. Here, we put forth a synergistic approach-the folded kirigami-in which kirigami assemblies are complemented by means of folding, typical of origami patterns. Besides the emerging patterns themselves, the synergistic approach also leads to topological mechanical metamaterials. While kirigami metamaterials have been fabricated by various methods, such as 3D printing, cutting, casting, and assemblage of building blocks, the "folded kirigami" claim their distinctive properties from the universal folding protocols. For a target kirigami pattern, we design an extended high-genus pattern with appropriate sets of creases and cuts, and proceed to fold it sequentially to yield the cellular structure of a 2D lattice endowed with finite out-of-plane thickness. The strategy combines two features that are generally mutually exclusive in canonical methods: fabrication involving a single piece of material and realization of nearly ideal intercell hinges. We test the approach against a diverse portfolio of triangular and quadrilateral kirigami configurations. We demonstrate a plethora of emerging metamaterial functionalities, including topological phase-switching reconfigurability between polarized and nonpolarized states in kagome kirigami, and availability of nonreciprocal mechanical response in square-rhombus kirigami., Competing Interests: Competing interests statement:The authors declare no competing interest.

The integration of multiple functions within a single fluorescent molecule provides a promising platform for developing versatile, efficient, and cost-effective materials with enhanced performance across diverse applications. In this study, we introduce TPEC, an aggregation-induced emission (AIE) molecule derived from tetraphenylethylene-based tetracarboxylate, which demonstrates multifunctional capabilities, including metal ion sensing and self-erasable writing. TPEC exhibits amphiphilicity in water, self-assembling into single-layer nanosheets with robust blue fluorescence. Notably, the aqueous solution of TPEC displays a fluorescence colorimetric response to Al 3+ ions and fluorescence quenching in the presence of Fe 3+ ions. Additionally, TPEC powders undergo fluorescence colorimetric changes under mechanical stimulation, enabling self-erasable writing on prepared paper. This study presents a straightforward strategy for the development of multifunctional luminescent materials based on the self-assembly of a single-component fluorophore., (© 2024 Wiley-VCH GmbH.)

Chemical oxygen demand (COD) is a critical criterion for the analytical assessment of the degree of organic contaminants in an aqueous system. Typically, toxic and expensive reagents are employed in standardized COD analysis methods, leading to secondary pollution. In this work, we developed a rapid electrochemical method for COD detection based on the oxidation of hydroxyl radicals for organics in water by using oxygen vacancy doped anatase/rutile-TiO 2 nanoparticles as electrooxidation catalysts. Homojunction interface generated increasing oxygen vacancies for enhancing electron-transfer rate and accelerating H 2 O oxidation to substantially improve ·OH yield. Oxygen vacancy further increased the oxygen evolution potential of the material. Initially, glucose was chosen as a standard analyte to evaluate electrochemical responses, and water from urban wastewater treatment plants was assessed as real samples subsequently. Excellent analytical characteristics were achieved with the A/R-TiO 2 sensor under the optimal conditions, exhibiting a linear range from 1 to 300 mg L -1 and detection limit of 0.1 mg L -1 COD. The estimated COD values obtained from the samples were highly consistent with those determined using the conventional standard dichromate method. We have presented a fast, cost-effective, and ecologically sustainable method that outperforms the standard COD analysis method and holds great potential for the accurate determination of COD and boasts high detection sensitivity and a broad linear range.

In this study, three samples were randomly selected from corn, wheat, and broken rice before and after extrusion for electron microscope scanning, Fourier transform infrared spectral analysis, and in vitro digestion to investigate the impact of extrusion on physicochemical characteristics and starch digestion kinetics of cereals. The cereals used for extrusion were sourced identically before and after the process, with each analysis conducted in triplicate. The results showed that the extrusion compromised the physical structure of cereal, resulting in loose structure arrangement, and the ratio of Fourier transform infrared spectral absorbance at wavelength 1047 cm -1 and 1022 cm -1 , which characterized the short-range order of starch, was significantly reduced ( p < 0.05). In addition, the proportion of rapidly digestible starch (RDS), the velocity parameter k of digestive kinetics and the predicted glycemic index of cereals were significantly increased by extrusion ( p < 0.05). Digestibility kinetics showed a total increase of 10.7%, 7.3%, and 5.4% for cereals, along with a sharp rise in digestion rate within the first 15 minutes. The findings revealed that the compromising of starch's structural integrity and the increase in proportion of RDS not only enhanced overall starch digestibility, but also significantly accelerated its digestion, particularly during the initial 15 min of intestinal digestion.

Transcriptomic analysis plays a vital role in investigating Systemic Lupus Erythematosus (SLE), a complex autoimmune disease characterized by diverse clinical manifestations. This approach has yielded valuable insights into gene expression patterns and molecular regulatory mechanisms involved in SLE pathogenesis. Notably, interferon-stimulated gene (ISG) signatures are significantly upregulated in immune cells, skin, and kidney. Although a correlation with serological parameters and clinical symptoms has been proposed, the association with global disease activities remains controversial. Key findings in the field include an upregulated plasmablast signature, which positively correlates with disease activity; a neutrophil signature associated with lupus nephritis; and a decreased lymphocyte signature, reflecting lymphopenia. Tissue-level studies highlight the critical role of infiltrating immune cells in organ damage. Future research should leverage advanced technologies and integrate multi-omics data to deepen our understanding of SLE's molecular underpinnings, facilitating the development of targeted therapies., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To explore whether differences in diffusional kurtosis imaging (DKI) between therapy-naïve high-grade gliomas (HGGs) and low-grade gliomas (LGGs) are related to the cellularity and/or the nuclear-to-cytoplasmic (N/C) ratio., Methods: We analyzed 44 and 40 diffuse glioma samples that were pathologically confirmed as HGGs and IDH1-mutant LGGs, respectively. The DKI parameters included kurtosis metrics (mean kurtosis [MK], axial kurtosis [K // ], and radial kurtosis [K ⊥ ]), and the diffusional metrics (fractional anisotropy [FA], mean diffusion [MD], axial diffusion [λ // ], and radial diffusion [λ ⊥ ]). The cellularity and the N/C ratio were compared within LGGs and HGGs using the Mann-Whitney U test (significant level, p < 0.007 [0.05/7]); Bonferroni correction). Spearman's correlation analysis was used to calculate the correlation coefficients among DKI metrics, cellularity, and the N/C ratio at a significant level of p = 0.05., Results: Excluding FA, all DKI metrics showed significant differences between HGGs and LGGs (all p ≤ 0.001). The N/C ratio of HGGs was significantly higher than that of LGGs; however, differences in cellularity were not significant between the two glioma groups (p = 0.525). Similarly, excluding FA, all DKI metrics were significantly correlated with the N/C ratio in LGGs, with correlation coefficients of - 0.365 (MD), - 0.313 (λ // ), - 0.376 (λ ⊥ ), 0.859 (MK), 0.772 (K // ), and 0.842 (K // ). There was a non-significant correlation between any DKI parameters and the cellularity in LGGs. Additionally, the cellularity and N/C ratios in HGGs did not correlate with any DKI metrics., Conclusions: DKI differentiate LGGs from HGGs associated with their different N/C ratios., Clinical Relevance Statement: This study shows that DKI differentiates LGGs from HGGs may correlated with their different N/C ratios, this could provide a possible histopathological mechanism about why DKI can DKI differentiate LGGs from HGGs., Key Points: • Excluding FA, all DKI metrics showed a significant difference between high-grade gliomas and IDH1-mutant low-grade gliomas. • The nuclear-to-cytoplasm ratios in high-grade gliomas were significantly more extensive than that in IDH1-mutant low-grade gliomas, but not the cellularity. • Significant associations were seen between DKI measures and the N/C ratio; a non-significant correlation was noted between any DKI metric and cellularity in glioma specimens., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Background: China has faced barriers to implementation of a population-based mammographic screening program. Breast ultrasound provides an alternative screening modality to mammography in low-resource settings. Objective: To evaluate the performance of ABUS with remote reading as the primary screening modality for breast cancer. Methods: This prospective study enrolled asymptomatic women 35-69 years old from 46 community health centers across 18 provinces representing all six regions of China from January 2021 to December 2021. Participants underwent screening ABUS as the sole breast cancer screening modality, with images acquired by a technologist at the community health center. The 3D volumetric data were transferred via cloud-based software to a single remote reading center, where examinations were interpreted independently in batches by two subspecialized breast radiologists using BI-RADS; a third radiologist at the remote reader center resolved discrepancies. Diagnostic reports were returned to the community centers, and patients sought follow-up care at local hospitals. The reference standard incorporated a combination of histopathology and 24-month follow-up. Outcomes measures included cancer detection rate, abnormal interpretation rate (AIR), sensitivity, specificity, biopsy rate, and PPV. Results: The final analysis included 5978 enrolled participants (median age, 46 years [IQR 40-52 years]) who underwent screening ABUS at the community health centers with subsequent remote reading. A total of 24 ABUS-detected cancers and two interval cancers were diagnosed. The cancer detection rate was 4.0 per 1000 women (95% CI: 2.7-5.9), and the AIR was 11.9% (95% CI: 11.1-12.7). A total of 95.8% (23/24) of ABUS-detected cancers were invasive. The 23 invasive cancers had a median diameter of 10.0 mm; 73.9% (17/23) were node-negative. Sensitivity was 92.3% (95% CI: 75.9-97.9), and specificity was 88.4% (95% CI: 87.6-89.2). The biopsy rate was 1.7% (95% CI: 1.4-2.0), and the PPV of biopsy was 24.0% (95% CI: 16.7-33.2). Conclusion: ABUS screening with remote reading met benchmark performance for cancer detection in comparison to mammography, with infrequent interval cancers. Clinical Impact: ABUS with remote reading holds promise in enhancing access to breast cancer screening and early detection in low-resource settings or underserved regions where mammographic screening is not established.

Osteomyelitis is a severe bone condition caused by bacterial infection that can lead to lifelong disabilities or fatal sepsis. Given that the infection is persistent and penetrates deep into the bone tissue, targeting and rapidly treating osteomyelitis remain a significant challenge. Herein, a triblock targeting peptide featuring ROS-cleavable linkage/antibacterial/bone-targeting unit was grafted onto the macrophage-derived exosomes (RAB-EXO). In vitro , the effective eradication of osteomyelitis pathogens MRSA / E. coli and induction of M2 macrophage differentiation were triggered by RAB-EXO. In vivo , after the intravenous administration of RAB-EXO, it can target the bone tissue and release antimicrobial peptides in the high ROS environment of osteomyelitis. The released antimicrobial peptides markedly inhibit bacterial growth at the infection sites. Moreover, M2 differentiation of the bone tissue macrophages are facilitated by EXO, thereby decreasing the inflammatory factors and achieving the anti-inflammatory effect. Finally, the complete healing of osteomyelitis without adverse effects associated with traditional treatments is achieved within 28 days in rat models. Our findings confirm that RAB-EXO, as a targeted treatment for osteomyelitis, offers promising directions for addressing other bacterial infection diseases, such as periodontitis and rheumatoid arthritis, through similar mechanisms.

Background: Systemic Lupus Erythematosus (SLE) is a complex autoimmune disorder, and transposable elements (TEs) have been hypothesized to play a significant role in its development. However, limited research has explored this connection. Our study aimed to examine the relationship between TE expression and SLE pathogenesis., Methods: We analyzed whole blood RNA-seq datasets from 198 SLE patients and 84 healthy controls. The REdiscoverTE pipeline was employed to quantify TE and other gene expressions, identifying differentially expressed TEs. A TE score was calculated to measure overall TE expression for each sample. Gene ontology and gene set enrichment analyses were conducted to explore the functional implications of TE upregulation. Independent datasets were utilized to replicate the results and investigate cell type-specific TE expression., Results: Our analysis identified two distinct patient groups: one with high TE expression and another with TE expression comparable to controls. Patients with high TE expression exhibited upregulation of pathways involving nucleic acid sensors, and TE expression was strongly correlated with interferon (IFN) signatures. Furthermore, these patients displayed deregulated cell composition, including increased neutrophils and decreased regulatory T cells. Neutrophils were suggested as the primary source of TE expression, contributing to IFN production., Conclusions: Our findings suggest that TE expression may serve as a crucial mediator in maintaining the activation of interferon pathways, acting as an endogenous source of nucleic acid stimulators in SLE patients., (© 2024. The Author(s).)

Key Message: A stable QTL, GW3, controlling grain width was identified in two populations. Its causal gene LOC&#95;Os03g04680 was verified by gene-based haplotype analysis, expression analysis, gene knockout and complementation transgenic tests. Grain width (GW) is one of the key traits affecting grain size and determines grain yield and appearance quality in rice. Mining gene loci and elite alleles controlling GW is necessary. The GW phenotypes of the two populations were investigated in three environments, which showed abundant phenotypic variation. GW3, encoding a P450 subfamily protein, was identified and validated as a causal gene by gene-based haplotype analysis, expression analysis, gene knockout and complementation transgenic tests. The accessions with large GW values had high gene expression levels. In addition, the GW of the accessions with the GG allele was significantly greater than that of the accessions with the AA allele. The Hap 1 and Hap 3 were identified as elite haplotypes, which can increase GW. The expression levels of OsKO1, OsGA3ox1, OsGA20ox1 and OsGA20ox2 in the young panicle of A7444 were significantly greater than those in the young panicle of the mutants, indicating that GW3 may be involved in the gibberellins (GA) biosynthesis pathway to regulate GW. GA 4 content detection and electron scanning analysis revealed that GA 4 regulates GW by affecting glume cell size. These results provide new insights for studying the genetic mechanism of rice GW and provide a material basis for breeding high-yield rice varieties., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Based on a self-controlled case, this study evaluated the finite element analysis (FEA) results of a single missing molar with wide mesiodistal length (MDL) restored by a single or double implant-supported crown., Methods: A case of a missing bilateral mandibular first molar with wide MDL was restored using a single or double implant-supported crown. The implant survival and peri-implant bone were compared. FEA was conducted in coordination with the case using eight models with different MDLs (12, 13, 14, and 15 mm). Von Mises stress was calculated in the FEA to evaluate the biomechanical responses of the implants under increasing vertical and lateral loading, including the stress values of the implant, abutment, screw, crown, and cortical bone., Results: The restorations on the left and right sides supported by double implants have been used for 6 and 12 years, respectively, and so far have shown excellent osseointegration radiographically.The von Mises stress calculated in the FEA showed that when the MDL was >14 mm, both the bone and prosthetic components bore more stress in the single implant-supported strategy. The strength was 188.62-201.37 MPa and 201.85-215.9 MPa when the MDL was 14 mm and 15 mm, respectively, which significantly exceeded the allowable yield stress (180 MPa)., Conclusions: Compared with the single implant-supported crown, the double implant-supported crown reduced peri-implant bone stress and produced a more appropriate stress transfer model at the implant-bone interface when the MDL of the single missing molar was ≥14 mm.

The rise of polymer materials in modern life has drawn attention to renewable, easily biodegradable, environmentally-friendly bio-based polymers. Notably, significant research has been dedicated to creating green antimicrobial functional materials for the biomedical field using natural polymer materials. Cellulose is a rich natural biomass organic polymer material. Given its favorable attributes like film-forming capability, biodegradability, and biocompatibility, it is extensively employed to tackle a wide range of challenges confronting humanity today. However, its inherent drawbacks, such as insolubility in water and most organic solvents, hygroscopic nature, difficulty in melting, and limited antimicrobial properties, continue to pose challenges for realizing the high-value applications of cellulose. Achieving multifunctionality and more efficient application of cellulose still poses major challenges. In this regard, the current development status of cellulose materials was reviewed, covering the classification, preparation methods, and application status of cellulose-based antimicrobial materials. The application value of cellulose-based antimicrobial materials in biomedicine, textiles, food packaging, cosmetics and wastewater treatment was summarised. Finally, insights were provided into the developing prospects of cellulose-based antimicrobial materials were provided., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The worldwide transmission of infectious respiratory pathogens has caused innumerable deaths and suffering, while wearing a face mask is still the most effective way to terminate the respiratory infections spread. However, the frequent mask replacement as a result of the lack of pathogen sterilization ability not only increases the cross-contamination risk but also, even worse, produces a large amount of medical waste. In this work, we report on a ketonized carbonitride functionalized bioprotective face mask with pathogen sterilization activity that can effectively produce biocidal singlet oxygen triggered by light irradiation. Ketonized carbonitride loading on the outer layer of the mask is found to be capable of generating singlet oxygen, enabling the mask with antibacterial ability. Thanks to its high pathogen inactivation activity, the as-prepared mask exhibits long-term light triggered health protection performance, which, in return, reduces medical waste production as a result of the decreased mask replacement frequency. The synthesis of a fascinating bioprotective mask provides a new viewpoint into the development of personal bioprotective devices for health protection.

Enhancing data privacy security in medical data sharing is crucial for the informatization development in the healthcare sector. This paper proposes a healthcare data sharing scheme based on two-dimensional chaotic mapping and blockchain (2DCM-DS). Specifically, a new two-dimensional chaotic mapping is proposed, which demonstrates superior chaotic performance. Then, by incorporating biometric audio information as an identity credential and integrating it with the proposed two-dimensional chaotic mapping, we design a data encryption method that establishes a strongly coupled and bi-directionally verifiable data ownership relationship in healthcare data sharing. Finally, we employ blockchain as the underlying network and design corresponding smart contracts to support 2DCM-DS. This approach addresses potential issues of unauthorized access, malicious tampering, and single points of failure in centralized data sharing. Experimental results demonstrate that 2DCM-DS effectively protects data security under the specified attack models. The results validate the security and efficiency of the 2DCM-DS, proving its application potential in healthcare insurance data sharing scenarios., (© 2024. The Author(s).)

Pluripotent stem cell (PSC) technologies have been widely used in drug discovery, disease modeling, and regenerative medicine. However, available PSC-to-functional cell differentiation systems are impeded by problems of severe line-to-line and batch-to-batch variability. Precise control of cell differentiation in real time is therefore important. In this protocol, we describe a non-invasive and intelligent strategy that overcomes the variability in cell differentiation by using bright-field image-based machine learning. Taking PSC-to-cardiomyocyte differentiation as an example, this methodology provides detailed information for control of the initial PSC state, early assessment and intervention in differentiation conditions, and elimination of the misdifferentiated cell contamination, together realizing consistently high-quality differentiation from PSCs to functional cells. In principle, this strategy can be extended to other cell differentiation or reprogramming systems with multiple steps to support cell manufacturing, as well as to further our understanding of the mechanisms during cell fate conversion.

Objectives: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with varying symptoms and multi-organ damage. Relapse-remission cycles often persist for many patients for years with the current treatment. Improved understanding of molecular changes caused by SLE flare and intensive treatment may result in more targeted therapies., Methods: RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from 65 SLE patients in flare, collected both before (SLE1) and after (SLE2) in-hospital treatment, along with 15 healthy controls (HC). Differentially expressed genes (DEGs) were identified among the three groups. Enriched functions and key molecular signatures of the DEGs were analysed and scored to elucidate the transcriptomic changes during treatment., Results: Few upregulated genes in SLE1 vs HC were affected by treatment (SLE2 vs SLE1), mostly functional in interferon signalling (IFN), plasmablasts and neutrophils. IFN and plasmablast signatures were repressed, but the neutrophil signature remained unchanged or enhanced by treatment. The IFN and neutrophil scores together stratified the SLE samples. IFN scores correlated well with leukopenia, while neutrophil scores reflected relative cell compositions but not cell counts., Conclusions: In-hospital treatment significantly relieved SLE symptoms with expression changes of a small subset of genes. Notably, IFN signature changes matched SLE flare and improvement, while enhanced neutrophil signature upon treatment suggested the involvement of low-density granulocytes (LDG) in disease development., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The reliable operation of scroll compressors is crucial for the efficiency of rotating machinery and refrigeration systems. To address the need for efficient and accurate fault diagnosis in scroll compressor technology under varying operating states, diverse failure modes, and different operating conditions, a multi-branch convolutional neural network fault diagnosis method (SSG-Net) has been developed. This method is based on the Swin Transformer, the Global Attention Mechanism (GAM), and the ResNet architecture. Initially, the one-dimensional time-series signal is converted into a two-dimensional image using the Short-Time Fourier Transform, thereby enriching the feature set for deep learning analysis. Subsequently, the method integrates the window attention mechanism of the Swin Transformer, the 2D convolution of GAM attention, and the shallow ResNet's two-dimensional convolution feature extraction branch network. This integration further optimizes the feature extraction process, enhancing the accuracy of fault feature recognition and sensitivity to data variability. Consequently, by combining the global and local features extracted from these three branch networks, the model significantly improves feature representation capability and robustness. Finally, experimental results on scroll compressor datasets and the CWRU dataset demonstrate diagnostic accuracies of 97.44% and 99.78%, respectively. These results surpass existing comparative models and confirm the model's superior recognition precision and rapid convergence capabilities in complex fault environments.

Toll-like receptor (TLR) activation converts immunologically inactive tumors into immunologically active tumors by activating tumor residing antigen-presenting cells and recruitment of cytotoxic T lymphocytes. Targeted immune agonists (TIAs) are antibody drug conjugates with small-molecule TLR agonist payloads. The mechanism of action of TIAs involves tumor antigen recognition, Fcγ-receptor-dependent phagocytosis, and TLR-mediated activation to drive tumor killing by myeloid cells. Several new low DAR anti-HER2 TIAs conjugated with novel TLR7 or dual-TLR7/8 agonists with cleavable and noncleavable linkers were synthesized and profiled. In vitro studies demonstrated that these TIAs activate myeloid cells only in the presence of antigen-expressing cancer cells. Evaluation in ELISpot-based assays confirmed the low immunogenicity of these constructs. Systemic administration of the novel TIAs in tumor-bearing mice resulted in tumor reduction at low doses. These results provide a strong rationale for further development of the TIAs as a novel class of immunotherapeutics.

The photoredox electron donor-acceptor (EDA) complex-mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application in two-component coupling reactions. However, EDA complex-promoted multi-component reactions are not well developed with only a limited number of examples have been reported. Herein, we report a photoinduced and EDA complex-promoted highly chemoselective three-component radical arylalkylation of [1.1.1]propellane, which allows the direct functionalization of C(sp 3 )-H with bicyclo[1.1.1]pentanes (BCP)-aryl groups under mild conditions. A variety of unnatural α-amino acids, featuring structurally diversified 1,3-disubstituted BCP moieties, were synthesized in a single-step process. Notably, leveraging the high tension release of [1.1.1]propellane, the highly unstable transient aryl radical undergoes rapid conversion into a relatively stable tertiary alkyl transient radical, and consequently, the competing side-reaction of two-component coupling was entirely suppressed. The strategic use of this transient radical conversion approach would be useful for the design of diverse EDA complex-mediated multi-component reactions. It is noteworthy that the highly chemoselective late-stage incorporation of the 1,3-disubstituted BCP pharmacophores into peptides was achieved both in liquid-phase and solid-phase reactions. This advancement is anticipated to have significant application potential in the future development of peptide drugs., (© 2024 Wiley-VCH GmbH.)

Objective: Bipolar disorder (BD) is a debilitating neuropsychiatric disorder, which is associated with genetic variation through "vast but mixed" Genome-Wide Association Studies (GWAS). Transcriptome-Wide Association Study (TWAS) is more effective in explaining genetic factors that influence complex diseases and can help identifying risk genes more reliably. So, this study aims to identify potential BD risk genes in pedigrees with TWAS., Methods: We conducted a TWAS analysis with expression quantitative trait loci (eQTL) analysis on extended BD pedigrees, and the BD genome-wide association study (GWAS) summary data acquired from the Psychiatric Genomics Consortium (PGC). Furthermore, the BD-associated genes identified by TWAS were validated by mRNA expression profiles from the Gene Expression Omnibus (GEO) Datasets (GSE23848 and GSE46416). Functional enrichment and annotation analysis were implemented by RStudio (version 4.2.0)., Results: TWAS identified 362 genes with P value < 0.05, and 18 genes remain significant after Bonferroni correction, such as SEMA3G (P TWAS =1.07 × 10 -11 ), ALOX5AP (P TWAS =3.12 × 10 -8 ), and PLEC (P TWAS =1.27 × 10 -7 ). Further 6 overlapped genes were detected in integrative analysis, such as UQCRB (P TWAS =0.0020, P mRNA =0.0000), TMPRSS9 (P TWAS =0.0405, P mRNA =0.0032), and SNX10 (P TWAS =0.0104, P mRNA =0.0015). Using genes identified by TWAS, Gene Ontology (GO) enrichment analysis identified 40 significant GO terms, such as mitochondrial ATP synthesis coupled electron transport, mitochondrial respiratory, aerobic electron transport chain, oxidative phosphorylation, mitochondrial membrane proteins, and ubiquinone activity. The Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway enrichment analysis identified significant 15 pathways for BD, such as Oxidative phosphorylation, endocannabinoids signaling, neurodegeneration, and reactive oxide species., Conclusions: We found a set of BD-associated genes and pathways, validating the important role of neurodevelopmental abnormalities, inflammatory responses, and mitochondrial dysfunction in the pathology of BD, offering novel information for comprehending the genetic basis of BD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Efficient utilization of light energy is crucial for various technological applications ranging from solar energy conversion to optoelectronic devices. Supramolecular light-harvesting systems (LHS) have emerged as promising platforms for enhancing light absorption and energy transfer process. In this Feature Article, we highlight the utilization of tetraphenylethylene (TPE) chromophores as antennas in supramolecular assemblies for light harvesting applications. TPE, as an archetypal aggregation-induced emission (AIE) chromophore, offers unique advantages such as high photostability and efficient light-harvesting capabilities upon self-assembly. We discuss the design principles and synthetic strategies employed to construct supramolecular assemblies incorporating TPE chromophores, elucidating their roles as efficient light-harvesting antennas. Furthermore, we delve into the mechanisms governing energy transfer processes within these assemblies, such as Förster resonance energy transfer (FRET). The potential applications of these TPE-based supramolecular systems in various fields, including photocatalysis, reactive oxygen species generation, optoelectronic devices and sensing, are explored. Finally, we provide insights into future directions and challenges in the development of next-generation supramolecular LHSs utilizing TPE chromophores.

Background: Patients with knee osteoarthritis (OA) who receive unilateral total knee arthroplasty (TKA) often report reduced pain and enhanced function in the untreated knee, yet the kinematic mechanisms are not fully understood. Our study aimed to clarify these effects through a gait analysis of the untreated knee following unilateral TKA., Methods: This study enrolled 118 end-stage OA patients with varus deformity scheduled for TKA, categorized into the contralateral osteoarthritis group (Contra-OA), consisting of patients with end-stage OA in both knees requiring surgical treatment, and the contralateral TKA group (Contra-TKA), which included patients who had undergone TKA on one knee and had end-stage OA in the untreated knee awaiting surgery. Kinematic data of the knee joint during treadmill walking were collected using the Opti&#95;Knee gait analysis system, and a comparative analysis was conducted., Results: The Contra-TKA group exhibited improvements in step length, anterior-posterior translation, range of motion, vertical translation, and internal-external rotation compared to the Contra-OA group ( p -values ranging from 0.0013 to 0.0463). Notable differences in flexion-extension angles and abduction/adduction rotation were also observed ( p = 0.0013 and 0.0166, respectively). At the initial contact (IC), obvious differences in internal-external rotation, anterior/posterior translation, and vertical translation were noted. At the opposite toe-off (OT), significant differences in internal-external rotation. At the tibia vertical (TV) moment, significant differences were observed in all three translation indicators of joint translation. At other pivotal gait cycle points, vertical and anterior/posterior translations in Contra-TKA group continued to exhibit more meaningful decrease. Collectively, these findings underscore the protective kinematic effects of TKA on the untreated contralateral knee, indicating an improved biomechanical adaptation following TKA surgery., Conclusion: In summary, the study's findings indicate that unilateral TKA imparts kinetic effects on the untreated contralateral knee, as evidenced by significant improvements in key gait parameters. These enhancements, observed at both initial contacts and throughout the gait cycle, suggest a positive biomechanical support post-TKA, might contribute to better gait efficiency and reduced load on the contralateral untreated knee., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Duan, Dang, Chen, Peng, Yao, Zhang and Ma.)

Since the birth of cognitive science, researchers have used reaction time and accuracy to measure cognitive ability. Although recognition of these two measures is often based on empirical observations, the underlying consensus is that most cognitive behaviors may be along two fundamental dimensions: cognitive processing speed (CPS) and cognitive processing accuracy (CPA). In this study, we used genomic-wide association studies (GWAS) data from 14 cognitive traits to show the presence of those two factors and revealed the specific neurobiological basis underlying them. We identified that CPS and CPA had distinct brain phenotypes (e.g. white matter microstructure), neurobiological bases (e.g. postsynaptic membrane), and developmental periods (i.e. late infancy). Moreover, those two factors showed differential associations with other health-related traits such as screen exposure and sleep status, and a significant causal relationship with psychiatric disorders such as major depressive disorder and schizophrenia. Utilizing an independent cohort from the Adolescent Brain Cognitive Development (ABCD) study, we also uncovered the distinct contributions of those two factors on the cognitive development of young adolescents. These findings reveal two fundamental factors underlying various cognitive abilities, elucidate the distinct brain structural fingerprint and genetic architecture of CPS and CPA, and hint at the complex interrelationship between cognitive ability, lifestyle, and mental health., (© 2024. The Author(s).)

Schizophrenia (SCZ) is a severe neuropsychiatric disorder characterized by cognitive, affective, and social dysfunction, resulting in hallucinations, delusions, emotional blunting, and disordered thinking. In recent years, proteomics has been increasingly influential in SCZ research. Glycosylation, a key post-translational modification, can alter neuronal stability and normal signaling in the nervous system by affecting protein folding, stability, and cellular signaling. Recent research evidence suggests that abnormal glycosylation patterns exist in different brain regions in autopsy samples from SCZ patients, and that there are significant differences in various glycosylation modification types and glycosylation modifying enzymes. Therefore, this review explores the mechanisms of aberrant modifications of N-glycosylation, O-glycosylation, glycosyltransferases, and polysialic acid in the brains of SCZ patients, emphasizing their roles in neurotransmitter receptor function, synaptic plasticity, and neural adhesion. Additionally, the effects of antipsychotic drugs on glycosylation processes and the potential for glycosylation-targeted therapies are discussed. By integrating these findings, this review aims to provide a comprehensive perspective to further understand the role of aberrant glycosylation modifications in the pathophysiology of SCZ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Feng, Sun, Dang, Liu, Liao, Yao, Zhang, Deng, Li, Zhao and Liu.)

Immunosuppressive tumor-associated macrophages (TAMs) account for a high proportion of the tumor tissue and significantly impede immunoefficacy. Furthermore, the signal regulatory protein α (SIRPα) expressed in TAMs adversely correlates with macrophage activation and phagocytosis, resulting in immunosurveillance escape. To address these difficulties, a mannose-modified, pH-responsive nanoplatform with resiquimod (R848) and 2', 3'-cyclic GMP-AMP (cGAMP) co-encapsulation (named M-PNP@R@C) is designed to polarize TAMs and lower SIRPα expression. The co-delivery of R848 and cGAMP synergistically facilitates the polarization of TAMs from the anti-inflammatory M2 phenotype into the pro-inflammatory M1 phenotype, thereby enhancing antitumor immunotherapy. Remarkably, activation of the cGAMP-mediated stimulator of interferon genes (STING) in TAMs significantly downregulates the expression of SIRPα, which synergizes with the cluster of differentiation 47 (CD47) antibody for the dual blockade of the CD47-SIRPα axis. Further analysis of single-cell RNA sequencing indicates that STING activation downregulates SIRPα by regulating intracellular fatty acid oxidation metabolism. In vivo studies indicate that M-PNP@R@C significantly inhibits tumor growth with a potent antitumor immune response in melanoma graft tumor models. After synergy with anti-CD47, the double blockade strategies of the SIRPα/CD47 axis result in a notable inhibition of lung metastasis. A prolonged survival rate is observed after combination treatment with CD47 and programmed death ligand-1 antibodies for the triple immune checkpoint blockade. In summary, our study provides original insights into the potential role of the STING pathway in macrophage-based immunotherapy, thus offering a potential combinatorial strategy for cancer therapy., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: The objective of this study is to compare and assess the efficacy and safety of low-molecular-weight heparin calcium (LMWH-Ca), followed by either warfarin or rivaroxaban, as treatment options for portal vein thrombosis (PVT) in patients with cirrhosis., Methods: In this pilot study, cirrhotic (with liver function score of Child-Pugh A) patients diagnosed with PVT who were not on anticoagulant therapy received 2 weeks of subcutaneous injections of LMWH-Ca. They were then randomized to either warfarin (a full course of oral warfarin for 6 months) or rivaroxaban (a full course of oral rivaroxaban for 2 months), with 30 cases in each group. After a treatment period of up to 6 months, a comparative analysis was performed to assess the efficacy and safety of both groups. Volumetric changes in PVT were monitored dynamically using enhanced computed tomography scans before treatment at week 2 and month 6., Results: There were no statistically significant differences in the clinical characteristics of the patients between the two groups. Rivaroxaban treatment reduced PVT median volume from 1.83 cm3 at week 2 to 0.0 cm3 at month 6 and prevented the worsening of PVT after 6 months of treatment with LMWH-Ca (P < 0.001). On the other hand, warfarin treatment increased PVT median volume from 1.95 cm3 at week 2 to 3.78 cm3 at month 6 (P = 0.002). None of the 30 patients in the rivaroxaban group had clinically significant gastrointestinal bleeding, while 2 of the 30 patients (7%) in the warfarin group had gastrointestinal bleeding (P = 0.317)., Conclusion: Rivaroxaban followed by LMWH-Ca is an effective anticoagulant treatment strategy for PVT in cirrhosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Coronavirus disease 2019 (COVID-19) is a highly contagious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in a global health crisis. The primary diagnostic method for COVID-19 is quantitative reverse transcription PCR, which is time-consuming and requires expensive instrumentation. Here, we developed an electrochemical biosensor for detecting SARS-CoV-2 biomarkers using a 3D porous polyacrylamide/polyaniline hydrogel (PPG) electrode prepared by UV photopolymerization and in situ polymerization. The electrochemical immunosensor for detecting SARS-CoV-2 N protein via the immune sandwich principle demonstrated a lower detection limit of 42 pg/mL and comparable specificity to a commercial enzyme-linked immunosorbent assay, which was additionally validated in pseudoviruses. The electrochemical sensor for hydrogen peroxide showed a low detection limit of 0.5 μM and excellent selectivity, which was further confirmed in cancer cells under oxidative stress. The biomarkers of SARS-CoV-2 were successfully detected due to the signal amplification capability provided by 3D porous electrodes and the high sensitivity of the antigen-antibody specific binding. This study introduces a novel three-dimensional electrode with great potential for the early detection of SARS-CoV-2., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: This study explored the mechanism of irrigation and nitrogen (N) coupling on spring maize yield and soil greenhouse gas (GHG) emissions, with the objective of achieving water saving, high yield and emission reduction. Field experiments were conducted to analyze the effects of multiple irrigation and N management strategies on GHG emissions and to determine the optimal balance between GHG, water conservation and grain yield. The experiments were conducted on spring maize with three irrigation levels (low, IL; medium, IM; and high, IH) and 4 N application levels (N40, N80, N120 and N160 kg N ha -1 )., Results: The IL treatment exhibited the lowest N 2 O and CO 2 emission fluxes and the lowest CH 4 uptake fluxes. The N40 treatment exhibited the lowest N 2 O and CO 2 emission fluxes and the highest CH 4 uptake flux. Significant positive correlations were observed among N 2 O and CO 2 emission fluxes, CH 4 uptake fluxes, and soil moisture and inorganic N content. Maize yield initially increased and then decreased with rising levels of irrigation and N management. By employing the TOPSIS method to assess yield and greenhouse effects, we identified the IMN120 treatment as optimal given that this treatment achieved the highest yield (14 686.26 kg ha -1 ) and water use efficiency (3.51 kg m -3 ) while maintaining relatively low global warming potential (573.30 kg CO2 eq ∙ ha -1 ) and GHG intensity (0.0390 kg CO2 eq ∙ kg -1 )., Conclusion: Irrigation optimization and N management are key to reducing GHG emissions, enhancing yield, and promoting both the sustainable development of agriculture and environmental protection. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

P4HA2 has been implicated in various malignant tumors; however, its expression and functional role in colorectal cancer (CRC) remain poorly elucidated. This study aims to investigate the involvement of P4HA2 in CRC metastasis and progression, uncovering the underlying mechanisms. In colorectal cancer (CRC), P4HA2 exhibited overexpression, and elevated levels of P4HA2 expression were associated with an unfavorable prognosis. Functional assays demonstrated P4HA2's regulation of cell proliferation, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Additionally, the AGO1 expression was correlated with P4HA2, and depletion of AGO1 reversed the proliferation and EMT function induced by P4HA2. Chromatin immunoprecipitation (ChIP) and luciferase assays suggested that the transcription factor SP1 binds to the promoter sequence of P4HA2, activating its expression in CRC. This study unveiled SP1 as a transcriptional regulator of P4HA2 in CRC and AGO1 is a probable target of P4HA2. In conclusion, P4HA2 emerges as a potential prognostic biomarker and promising therapeutic target in colorectal cancer.

Background: Data on long-term cancer survivors treated with apatinib are lacking. This study aimed to describe the characteristics of long-term cancer survivors after apatinib-based therapy, and to know about their satisfaction degree with apatinib and severity of depression and insomnia., Methods: Patients with solid tumors who had received apatinib-based therapy for at least 5 years were invited to complete an online questionnaire. Characteristics of patients and treatment, knowledge of apatinib, satisfaction degree, and severity of depression and insomnia assessed by Patient Health Questionnaire-9 and Insomnia Severity Index were collected., Results: Between December 8, 2023 and March 1, 2024, a total of 436 patients completed the online questionnaire. Most patients were satisfied with the efficacy (96.6%) and safety (93.1%) of apatinib, were willing to continue apatinib treatment (99.5%), and would recommend apatinib to other patients (93.3%). Continuous apatinib treatment resulted in significant negative impact on daily life, work, or study in only two (0.5%) patients. Almost all patients currently had no or mild depression (97.0%) and insomnia (97.9%) problems. The most common patient-reported adverse events were hand-foot syndrome (21.3%) and hypertension (18.3%)., Conclusions: Our survey showed a high satisfaction degree with apatinib in long-term cancer survivors. Long-term apatinib treatment resulted in almost no negative impact on patient's quality of life., (© 2024. The Author(s).)

Traditional gait analysis systems are typically complex to operate, lack portability, and involve high equipment costs. This study aims to establish a musculoskeletal dynamics calculation process driven by Azure Kinect. Building upon the full-body model of the Anybody musculoskeletal simulation software and incorporating a foot-ground contact model, the study utilized Azure Kinect-driven skeletal data from depth videos of 10 participants. The in-depth videos were prepossessed to extract keypoint of the participants, which were then adopted as inputs for the musculoskeletal model to compute lower limb joint angles, joint contact forces, and ground reaction forces. To validate the Azure Kinect computational model, the calculated results were compared with kinematic and kinetic data obtained using the traditional Vicon system. The forces in the lower limb joints and the ground reaction forces were normalized by dividing them by the body weight. The lower limb joint angle curves showed a strong correlation with Vicon results (mean ρ values: 0.78 ~ 0.92) but with root mean square errors as high as 5.66°. For lower limb joint force prediction, the model exhibited root mean square errors ranging from 0.44 to 0.68, while ground reaction force root mean square errors ranged from 0.01 to 0.09. The established musculoskeletal dynamics model based on Azure Kinect shows good prediction capabilities for lower limb joint forces and vertical ground reaction forces, but some errors remain in predicting lower limb joint angles.

Converging evidence indicates that extra-embryonic yolk sac is the source of both macrophages and endothelial cells in adult mouse tissues. Prevailing views are that these embryonically derived cells are maintained after birth by proliferative self-renewal in their differentiated states. Here we identify clonogenic endothelial-macrophage (EndoMac) progenitor cells in the adventitia of embryonic and postnatal mouse aorta, that are independent of Flt3-mediated bone marrow hematopoiesis and derive from an early embryonic CX 3 CR1 + and CSF1R + source. These bipotent progenitors are proliferative and vasculogenic, contributing to adventitial neovascularization and formation of perfused blood vessels after transfer into ischemic tissue. We establish a regulatory role for angiotensin II, which enhances their clonogenic and differentiation properties and rapidly stimulates their proliferative expansion in vivo. Our findings demonstrate that embryonically derived EndoMac progenitors participate in local vasculogenic responses in the aortic wall by contributing to the expansion of endothelial cells and macrophages postnatally., (© 2024. The Author(s).)

Objective: To describe the changes in sleep pattern throughout pregnancy and to evaluate the relationship between sleep and adverse perinatal outcomes., Methods: Pregnant women at Qianfoshan Hospital completed questionnaires regarding their sleep during each of the three trimesters. Additionally, a subset of participants engaged in objective sleep monitoring using actigraphy devices. In the perinatal period, the following data were collected: pregnancy complications; gestational age; mode of delivery; Apgar scores for the neonate; and birth weight., Results: The total night sleep time in the second trimester was about 15 minutes shorter than that in the first trimester (P=0.024), and about 31 minutes shorter in the third trimester than in the second trimester (P<0.001). The sleep efficiency in the second trimester was about 10.23% lower than in the first trimester (P<0.001), and the efficiency in the third trimester was about 5.16% lower than in the second trimester (P<0.001). The occurrence of pregnancy-induced hypertension (PIH) was associated with sleep duration (P=0.019), sleep efficiency (P<0.001) and PSQI scores (P<0.001) in the first trimester. Furthermore, the mode of delivery was also found to be associated with sleep duration (P=0.011), sleep efficiency (P<0.001) and PSQI scores (P<0.001) in the first trimester., Conclusion: With the development of the pregnancy process, the sleep situation gets worse. Pregnant women's sleep situation in the first trimester of pregnancy is associated with the occurrence of PIH and delivery mode., Competing Interests: None., (AJTR Copyright © 2024.)

Background: Ofloxacin (OFL) is often abused in medicine and animal husbandry, which poses a great threat to human health and ecological environment. Therefore, it is necessary to establish efficient method to detect OFL. Electrochemical sensor has attracted widespread attention due to the advantages of low cost and fast response. However, most electrochemical sensors usually use one response signal to detect the target, which makes it sensitive to the variable background noise in the complex environment, resulting in low robustness and selectivity. The ratio detection mode and employing molecularly imprinted polymer (MIP) are two strategies to solve these problems., Results: A novel molecular imprinting polymer-ratiometric electrochemical sensor (MIP-RECS) based on Fe-MOF-NH 2 /CNTs-NH 2 /MXene composite was prepared for the rapid and sensitive detection of OFL. The positively charged Fe-MOF-NH 2 and CNTs-NH 2 as interlayer spacers were introduced into the negatively charged MXene through a simple electrostatic self-assembly technique, which effectively prevented the agglomeration of MXene and increased the electrocatalytic activity. A glass carbon electrode was modified by the composite and a MIP film was electropolymerized on it using o-phenylenediamine and β-cyclodextrin as bifunctional monomers and OFL as template. Then a MIP-RECS was designed by adding dopamine (DA) into the electrolyte solution as internal reference, and OFL was quantified by the response current ratio of OFL to DA. The current ratio and the concentration of OFL displayed a satisfying linear relationship in the range of 0.1 μM-100 μM, with a limit of detection (LOD) of 13.2 nM., Significance: Combining molecular imprinting strategy and ratio strategy, the MIP-RECS has impressive selectivity compared with the non-imprinted polymer-RECS, and has better repeatability and reproducibility than non-ratiometric sensor. The MIP-RECS has high sensitivity and accuracy, which was applied for the detection of OFL in four different brands of milk and was verified by HPLC method with satisfactory results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Qianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce., Objective: To explore QGHJ's osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration., Methods: QGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-qPCR and Western blot. BMSCs' responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays., Results: UPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ's key compounds. In vivo , QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARγ, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro , it preserved BMSCs' viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARγ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress., Conclusion: In T2DOP rat and BMSCs oxidative stress models, QGHJ's bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Dang, Wang, Yang, Zhang, Yang, Yuan, Xu, Dang and Nan.)

The extensive application of pesticides and antibiotics in agricultural production makes it possible for them to coexist in farmland, and the interaction of the two pollutants can lead to changes in environmental behavior and toxicity, creating uncertainty risks to soil and soil organisms. In this study, we explored the environmental behavior and the effects of earthworms under co-exposure to amoxicillin and boscalid and further explored the accumulation and toxic effects on earthworms. The results showed that amoxicillin increased the adsorption of boscalid in soil and inhibited its degradation. In addition, we noticed that the co-exposure of amoxicillin and boscalid caused intestinal barrier damage, which increased the bioaccumulation of earthworms for boscalid and led to more severe oxidative stress and metabolic disorders in earthworms. In summary, our findings indicate that amoxicillin can increase the ecological risk of boscalid in the environment and imply that the encounter between antibiotics and pesticides in the environment can amplify the toxic effects of pesticides, which provides new insights into the ecological risks of antibiotics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Traditional surface-enhanced Raman scattering (SERS) sensors rely heavily on the use of plasmonic noble metals, which have limitations due to their high cost and lack of physical and chemical stability. Hence, it is imperative to explore new materials as SERS platforms that can withstand high temperatures and harsh conditions. In this study, the SERS effect of molybdenum boride ceramic powders is presented with an enhancement factor of 5 orders, which is comparable to conventional noble metal substrates. The molybdenum boride powders synthesized through liquid-phase precursor and carbothermal reduction have β-MoB, MoB 2 , and Mo 2 B 5 phases. Among these phases, β-MoB demonstrates the most significant SERS activity, with a detection limit for rhodamine 6G (R6G) molecules of 10 -9  m. The impressive SERS enhancement can be attributed to strong molecule interactions and prominent charge interactions between R6G and the various phases of molybdenum boride, as supported by theoretical calculations. Additionally, Raman measurements show that the SERS activity remains intact after exposure to high temperature, strong acids, and alkalis. This research introduces a novel molybdenum boride all-ceramic SERS platform capable of functioning in harsh conditions, thereby showing the promising of boride ultrahigh-temperature ceramics for detection applications in extreme environments., (© 2024 Wiley‐VCH GmbH.)

The aim of this study was to develop new discarded enoki mushroom root-derived multifunctional chrome-free chitosan-based tanning agents that can be used for eco-leather manufacturing. In this study, oligochitosan (OCS) was prepared from chitosan extracted from the enoki mushrooms and chemically modified using reactive dye R19 and epichlorohydrin (ECH) to prepare chromium-free tanning agent (OCS-R19-ECH) with both tanning and dyeing functions. FT-IR, XRD, and NMR ( 1 H) confirmed the successful synthesis of the product. The molecular weight of OCS-R19-ECH is 6355 g/mol, with an average particle size of 1249.37 nm and an epoxy value of 0.276 mol/100 g. OCS-R19-ECH was used for tanning experiments on bated sheepskin, and the results showed that the leather tanned with OCS-R19-ECH not only exhibited excellent wet-heat stability (shrinkage temperature = 81 °C), but also superior dyeing uniformity, resistance to dry and wet abrasion, mechanical strength (tensile strength = 12.4 MPa, tear strength = 57.3 N/mm), and outstanding antimicrobial properties. Most importantly, compared with traditional tanning agents, OCS-R19-ECH has a higher pH (9.0), tanning-dyeing integration, non-acid soaking, and non-basifying can be achieved in leather making, which can greatly simplify the tanning processes. This new multifunctional chrome-free chitosan-based tanning agent facilitates high-value utilization of waste resources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Wearing face masks is the best way to stop the spread of respiratory infections. However, if masks are not sterilized, changing them too frequently can actually increase the risk of cross-contamination. Herein, the construction of an antipathogen photocatalytic mask with carbon vacancy-modified carbon nitride nanosheets (g-C 3 N 4 -V C Ns) coated on the non-woven fabrics of the out layer of the mask, offering effective and long-term protection against damaging pathogens when exposed to light is reported. The introduced carbon vacancies are found capable of creating energy-disordered sites and inducing energetic electric force to overcome the Coulomb interactions between electron-hole pairs, thus promoting the electron-hole separation to achieve a high generation of reactive oxygen species (ROS). Thanks to its high activity in generating ROS upon exposure to light, the as-prepared photocatalytic mask shows high pathogen sterilization performance. This, in turn, prolongs the mask's protective lifetime, decreases the need for regular replacement, and decreases medical waste production. The work demonstrated here opens new viewpoints in designing pathogens biocidal protective devices for health protection, offering significant promise in specific environment self-protection., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Previously, several studies have indicated that pediatric IgA nephropathy (IgAN) might be different from adult IgAN, and treatment strategies might be also different between pediatric IgAN and adult IgAN., Methods: We analyzed two prospective cohorts established by pediatric and adult nephrologists, respectively. A comprehensive analysis was performed investigating the difference in clinical and pathological characteristics, treatment, and prognosis between children and adults with IgAN., Results: A total of 1015 children and 1911 adults with IgAN were eligible for analysis. More frequent gross hematuria (88% vs. 20%, p < 0.0001) and higher proteinuria (1.8 vs. 1.3 g/d, p < 0.0001) were seen in children compared to adults. In comparison, the estimated glomerular filtration rate (eGFR) was lower in adults (80.4 vs. 163 ml/min/1.73 m 2 , p < 0.0001). Hypertension was more prevalent in adult patients. Pathologically, a higher proportion of M1 was revealed (62% vs. 39%, p < 0.0001) in children than in adults. S1 (62% vs. 28%, p < 0.0001) and T1-2 (34% vs. 8%, p < 0.0001) were more frequent in adults. Adjusted by proteinuria, eGFR, and hypertension, children were more likely to be treated with glucocorticoids than adults (87% vs. 45%, p < 0.0001). After propensity score matching, in IgAN with proteinuria > 1 g/d, children treated with steroids were 1.87 (95% CI 1.16-3.02, p = 0.01) times more likely to reach complete remission of proteinuria compared with adults treated with steroids., Conclusions: Children present significantly differently from adults with IgAN in clinical and pathological manifestations and disease progression. Steroid response might be better in children., (© 2024. The Author(s).)

Background: We aimed to investigate the clinical features, antimicrobial susceptibility and pvl gene expression in Staphylococcus aureus causing acute hematogenous bone and joint infections (BJIs) in children in Vietnam., Methods: In this prospective study, the demographics, microbiology and clinical outcomes of pediatric patients with acute hematogenous BJIs were collected from September 2022 to September 2023. Antimicrobial susceptibility profiles were determined using VITEK2 Compact system. The pvl gene encoding the Panton-Valentine leukocidin (PVL) toxin was detected by using polymerase chain reaction. Mann-Whitney, χ 2 and Fisher test were used for statistical analysis., Results: In total, 78 patients (46 boys) with S. aureus acute hematogenous BJIs were recruited at the National Children's Hospital, Hanoi, Vietnam. Of all S. aureus isolates, 84.6% were methicillin-resistant S. aureus . All S. aureus isolates were susceptible to vancomycin, ciprofloxacin and levofloxacin; 97% of methicillin-resistant S. aureus isolates was resistant to clindamycin (minimum inhibitory concentration ≥8 μg/mL). The pvl gene was detected in 83.3% of isolates, including 57 methicillin-resistant S. aureus isolates. Patients in the pvl -positive group had significantly higher C-reactive protein levels than those in the pvl -negative group ( P = 0.04). In addition, all 8 children with septic shock were infected with pvl -positive S. aureus ., Conclusions: PVL is a prevalent virulence factor of S. aureus in Vietnam. Furthermore, high inflammatory parameters (C-reactive protein) may be present at the time of diagnosis in PVL positivity-related acute hematogenous BJIs. Further research is necessary to enhance our understanding of the varying correlations between virulence factors and outcomes of S. aureus BJIs., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRAS G12C inhibitor, has shown promising antitumour activity in patients with KRAS G12C -mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRAS G12C -mutated NSCLC., Methods: This open-label, multicentre, single-arm, phase 2 trial enrolled adult patients with KRAS G12C -mutated NSCLC who had previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors from 43 hospitals in China. Participants received 600 mg garsorasib orally twice per day. Tumour assessments were performed at baseline, at the end of every two cycles (of 21 days) for the first eight cycles, and at the end of every three cycles thereafter. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC) following the guidelines in Response Evaluation Criteria in Solid Tumours, version 1.1. Efficacy and safety were assessed in all patients who received at least one dose of garsorasib. This trial is registered at ClinicalTrials.gov, NCT05383898, and is active but no longer recruiting., Findings: From June 17, 2022, to May 17, 2023, of 225 patients screened for eligibility, 123 patients were enrolled and treated with garsorasib. Of these 123 participants, the median age was 64 years (IQR 59-68), 108 (88%) were male and 15 (12%) were female. At data cutoff (Nov 17, 2023), the median follow-up duration was 7·9 months (IQR 6·3-10·4), and 82 (67%) of 123 patients had discontinued treatment. The IRC-confirmed ORR was 50% (61 of 123 patients; 95% CI 41-59). 117 (95%) of 123 patients reported treatment-related adverse events, with 61 (50%) experiencing grade 3 or higher events. The most common types of adverse events of grade 3 or higher associated with garsorasib were hepatic and gastrointestinal events, including increased liver enzymes, such as aspartate aminotransferase (21 [17%] of 123 participants), alanine aminotransferase (19 [15%] of 123 participants), and gamma-glutamyltransferase (28 [23%] of 123 participants); nausea (2 [2%] of 123 participants); and vomiting (2 [2%] of 123 participants). No new safety signals were identified, and most of the adverse events were well managed., Interpretation: The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRAS G12C -mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population., Funding: InventisBio., Competing Interests: Declaration of interests ZL has received speaker fees from AstraZeneca, Roche, and Hansoh. SL has received research grants from AstraZeneca, Hutchison, BMS, Heng Rui, and Roche; has received consulting fees from AstraZeneca, Boehringer Ingelheim, Hutchison MediPharma, Simcere, ZaiLab, GenomiCare, and Roche; and has received speaker fees from AstraZeneca, Roche, and Hansoh. LJ, JZ, and PW have received research grants and speaker fees from InventisBio, and have served as advisors and consultants for InventisBio. LinZ is employed by InventisBio and report stocks in InventisBio. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Rainbow trout is an important fish species for Peruvian artisanal aquaculture, comprising over 60 % of the total aquaculture production. However, their industry has been highly affected by several bacterial agents such as Yersinia ruckeri. This pathogen is the causative agent of Enteric Redmouth Disease, and causes high mortality in fingerlings and chronic infection in adult rainbow trout. To date, the immune response of rainbow trout against Y. ruckeri has been well studied in laboratory-controlled infection studies (i.e. intraperitoneal infection, bath immersion), however, the immune response during natural infection has not been explored. To address this, in this study, 35 clinically healthy O. mykiss without evidence of lesions or changes in behavior and 32 rainbow trout naturally infected by Y. ruckeri, were collected from semi-intensive fish farms located in the Central Highlands of Peru. To evaluate the effect on the immune response, RT-qPCR, western blotting, and ELISA were conducted using head kidney, spleen, and skin tissues to evaluate the relative gene expression and protein levels. Our results show a significant increase in the expression of the pro-inflammatory cytokines il1b, tnfa, and il6, as well as ifng in all three tissues, as well as increases in IL-1β and IFN-γ protein levels. The endogenous pathway of antigen presentation showed to play a key role in defense against Y. ruckeri, due to the upregulation of mhc-I, tapasin, and b2m transcripts, and the significant increase of Tapasin protein levels in infected rainbow trout. None of the genes associated with the exogenous pathway of antigen presentation showed a significant increase in infected fish, suggesting that this pathway is not involved in the response against this intracellular pathogen. Finally, the transcripts of immunoglobulins IgM and IgT did not show a modulation, nor were the protein levels evaluated in this study., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Atmospheric sulfate aerosols contribute significantly to air pollution and climate change. Sulfate formation mechanisms during winter haze events in northern China have recently received considerable attention, with more than 10 studies published in high-impact journals. However, the conclusions from in-field measurements, laboratory studies, and numerical simulations are inconsistent and even contradictory. Here, we propose a physically based yet simple method to clarify the debate on the dominant sulfate formation pathway. Based on the hazes evolving in the synoptic scale, first, a characteristic sulfate formation rate is derived using the Eulerian mass conservation equation constrained by in situ observations. Then, this characteristic value is treated as a guideline to determine the dominant sulfate formation pathway with a 0D chemical box model. Our observation-derived results establish a linkage between studies from laboratory experiments and chemical transport model simulations. A convergent understanding could therefore be reached on sulfate formation mechanisms in China's wintertime haze. This method is universal and can be applied to various haze conditions and different secondary products., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Bcr-Abl is successfully applied to drug discovery as a CML therapeutic target, but point mutation resistance has become a major challenge in the clinical treatment of CML. Our previous studies have shown that the introduction of amino acids as flexible linkers and heterocyclic structures as HBMs can achieve potent inhibition of Bcr-Abl T315I . In continuation of these studies, we further enriched the linker types by developing a library of compounds with tert -leucine or serine as a linker. Biological results showed that these compounds exhibited enhanced inhibition against Bcr-Abl WT and Bcr-Abl T315I kinases as well as improved antiproliferative activity in leukemia cell assays compared to previously disclosed compounds. In particular, compounds TL8, TL10, BS4, BS10, SR5 and SR11 exhibited potent inhibitory activities against Ba/F3 cells bearing a T315I mutant. Additionally, compounds TL8, BS4 and SR5 effectively induced K562 cell apoptosis, arrested the cell cycle at the S or G2/M phase, and inhibited the phosphorylation of Bcr-Abl and STAT5 in a dose-dependent manner. Docking studies verified the rationality of tert -leucine or serine as a flexible linker and indicated that phenylpyridine with an amide side chain favored the potency of these inhibitors. Moreover, ADME prediction suggested that the tested compounds had a favorable safety profile. Thus, tert -leucine or serine can be used as a promising class of flexible linkers for Bcr-Abl inhibitors with heterocyclic structures as HBMs, and compounds BS4, SR5, and especially TL8, can be used as starting points for further optimization., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Osteoarthritis (OA) is a disease that affects the entire joint. To treat OA, it may be beneficial to inhibit the activity of TGF-β in the subchondral bone. However, delivering drugs to the subchondral bone using conventional methods is challenging. In this study, we developed an extracellular vesicle delivery system. The utilization of macrophage-derived extracellular vesicles as a drug-carrying platform enables drugs to evade immune clearance and cross biological barriers. By incorporating targeting peptides on the surface of extracellular vesicles, the drug platform becomes targeted. The combination of these two factors results in the successful delivery of the drug to the subchondral bone. The study evaluated the stability, cytotoxicity, and bone targeting capability of the engineered extracellular vesicle platform (BT-EV-G). It also assessed the effects of BT-EV-G on the differentiation, proliferation, and migration of bone mesenchymal stem cells (BMSCs). Additionally, the researchers administered BT-EV-G to anterior cruciate ligament transection (ACLT)-induced OA mice. The results showed that BT-EV-G had low toxicity and high bone targeting ability both in vitro and in vivo. BT-EV-G can restore coupled bone remodeling in subchondral bone by inhibiting pSmad2/3-dependent TGF-β signaling. This work provides new insights into the treatment of OA., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

The fabrication of supramolecular light-harvesting systems (LHS) with sequential energy transfer is of significance in utilizing light energy. In this study, we report the non-covalent self-assembly of a sequential LHS by pillar[5]arene-based host-guest interaction in water and its applications in white light-emitting diode (LED) device and latent fingerprint imaging. The host-guest complex WP5 ⊃ ${ \supset }$ G self-assembles into nanoparticles in water and shows enhanced aggregation-induced emission (AIE) effect. The nanoparticles can be further used to construct sequential LHS with fluorescent dyes 4,7-di(2-thienyl)-benzo[2,1,3]thiadiazole (DBT) and sulforhodamine 101 (SR101). Impressively, the system shows white-light emission when the molar ratio of WP5 ⊃ ${ \supset }$ G/DBT/SR101 is 1100/2/16. The material can be coated on a LED bulb to achieve white-light emission. In addition, the sequential LHS exhibit multicolor fluorescence including red emission, which have been successfully applied to high-resolution imaging of latent fingerprints. Therefore, we demonstrated a general strategy for the construction of sequential LHS in water based on macrocyclic host-guest interaction and explored its multi-functional applications in white-light LED device and imaging of latent fingerprints, which will promote future development and application of supramolecular LHSs., (© 2024 Wiley-VCH GmbH.)