HyGAnno: hybrid graph neural network-based cell type annotation for single-cell ATAC sequencing data.

Reliable cell type annotations are crucial for investigating cellular heterogeneity in single-cell omics data. Although various computational approaches have been proposed for single-cell RNA sequencing (scRNA-seq) annotation, high-quality cell labels are still lacking in single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) data, because of extreme sparsity and inconsistent chromatin accessibility between datasets. Here, we present a novel automated cell annotation method that transfers cell type information from a well-labeled scRNA-seq reference to an unlabeled scATAC-seq target, via a parallel graph neural network, in a semi-supervised manner. Unlike existing methods that utilize only gene expression or gene activity features, HyGAnno leverages genome-wide accessibility peak features to facilitate the training process. In addition, HyGAnno reconstructs a reference-target cell graph to detect cells with low prediction reliability, according to their specific graph connectivity patterns. HyGAnno was assessed across various datasets, showcasing its strengths in precise cell annotation, generating interpretable cell embeddings, robustness to noisy reference data and adaptability to tumor tissues.

The white lupin trehalase gene LaTRE1 regulates cluster root formation and function under phosphorus deficiency.

Under phosphorus (P) deficiency, white lupin (Lupinus albus L.) forms specialized root structure, called cluster root (CR), to improve soil exploration and nutrient acquisition. Sugar signaling is thought to play a vital role in the development of CR. Trehalose and its associated metabolites are the essential sugar signal molecules that link growth and development to carbon metabolism in plants, however, their roles in the control of CR are still unclear. Here, we investigated the function of the trehalose metabolism pathway by pharmacological and genetic manipulation of the activity of trehalase in white lupin, the only enzyme that degrades trehalose into glucose. Under P deficiency, validamycin A treatment, which inhibits trehalase, led to the accumulation of trehalose and promoted the formation of CR with enhanced organic acid production, whereas overexpression of the white lupin TREHALASE1 (LaTRE1) led to decreased trehalose levels, lateral rootlet density, and organic acid production. Transcriptomic and virus-induced gene silencing (VIGS) results revealed that LaTRE1 negatively regulates the formation of CRs, at least partially, by the suppression of LaLBD16, whose putative ortholog in Arabidopsis (Arabidopsis thaliana) acts downstream of ARF7- and ARF19-dependent auxin signaling in lateral root formation. Overall, our findings provide an association between the trehalose metabolism gene LaTRE1 and CR formation and function with respect to organic acid production in white lupin under P deficiency.

The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

Cell-in-cell-mediated intercellular communication exacerbates the pro-inflammatory progression in asthma.

Cell-in-cell (CIC) structures have been suggested to mediate intracellular substance transport between cells and have been found widely in inflammatory lung tissue of asthma. The aim of this study was to investigate the significance of CIC structures in inflammatory progress of asthma. CIC structures and related inflammatory pathways were analyzed in asthmatic lung tissue and normal lung tissue of mouse model. In vitro, the activation of inflammatory pathways by CIC-mediated intercellular communication was analyzed by RNA-Seq and verified by Western blotting and immunofluorescence. Results showed that CIC structures of lymphocytes and alveolar epithelial cells in asthmatic lung tissue mediated intercellular substance (such as mitochondria) transfer and promoted pro-inflammation in two phases. At early phase, internal lymphocytes triggered inflammasome-dependent pro-inflammation and cell death of itself. Then, degraded lymphocytes released cellular contents such as mitochondria inside alveolar epithelial cells, further activated multi-pattern-recognition receptors and NF-kappa B signaling pathways of alveolar epithelial cells, and thereby amplified pro-inflammatory response in asthma. Our work supplements the mechanism of asthma pro-inflammation progression from the perspective of CIC structure of lymphocytes and alveolar epithelial cells, and provides a new idea for anti-inflammatory therapy of asthma.

Electrocatalytic Coenhancement of Bimetallic Polyphthalocyanine-Anchored Ru Nanoclusters Enabling Efficient Overall Water Splitting at Ampere-Level Current Densities.

Efficient electrocatalysts capable of operating continuously at industrial ampere-level current densities are crucial for large-scale applications of electrocatalytic water decomposition for hydrogen production. However, long-term industrial overall water splitting using a single electrocatalyst remains a major challenge. Here, bimetallic polyphthalocyanine (FeCoPPc)-anchored Ru nanoclusters, an innovative electrocatalyst comprising the hydrogen evolution reaction (HER) active Ru and the oxygen evolution reaction (OER) active FeCoPPc, engineered for efficient overall water splitting are demonstrated. By density functional theory calculations and systematic experiments, the electrocatalytic coenhancement effect resulting from unique charge redistribution, which synergistically boosts the HER activity of Ru and the OER activity of FeCoPPc by optimizing the adsorption energy of intermediates, is unveiled. As a result, even at a large current density of 2.0 A cm-2 , the catalyst exhibits low overpotentials of 220 and 308 mV, respectively, for HER and OER. It exhibits excellent stability, requiring only 1.88 V of cell voltage to achieve a current density of 2.0 A cm-2 in a 6.0 m KOH electrolyte at 70 °C, with a remarkable operational stability of over 100 h. This work provides a new electrocatalytic coenhancement strategy for the design and synthesis of electrocatalyst, paving the way for industrial-scale overall water splitting applications.

Ultrahigh Heat/Fire-Resistant, Mechanically Robust, and Closed-Loop Chemical Recyclable Polycarbonate Enabled by Facile Bond Dissociation Energy Modulation.

Plastics serve as an essential foundation in contemporary society. Nevertheless, meeting the rigorous performance demands in advanced applications and addressing their end-of-life disposal are two critical challenges that persist. Here, an innovative and facile method is introduced for the design and scalable production of polycarbonate, a key engineering plastic, simultaneously achieving high performance and closed-loop chemical recyclability. The bisphenol framework of polycarbonate is strategically adjusted from the low-bond-dissociation-energy bisphenol A to high-bond-dissociation-energy 4,4'-dihydroxydiphenyl, in combination with the incorporation of polysiloxane segments. As expected, the enhanced bond dissociation energy endows the polycarbonate with an extremely high glow-wire flammability index surpassing 1025 °C, a 0.8 mm UL-94 V-0 rating, a high LOI value of 39.2%, and more than 50% reduction of heat and smoke release. Furthermore, the π-π stacking interactions within biphenyl structures resulted in a significant enhancement of mechanical strength by as more as 37.7%, and also played a positive role in achieving a lower dielectric constant. Significantly, the copolymer exhibited outstanding closed-loop chemical recyclability, allowing for facile depolymerization into bisphenol monomers and the repolymerized copolymer retains its high heat and fire resistance. This work provides a novel insight in the design of high-performance and closed-loop chemical recyclable polymeric materials.

The Effects of Daily-Living Risks on Breast Cancer-Related Lymphedema.

BACKGROUND: Conventional advice to reduce the risk of breast cancer-related lymphedema (BCLE) suggests avoidance of daily-living risks, and limited research has investigated these risks. OBJECTIVE: This study aimed to examine the occurrence, patterns, and effects of daily-living risks on BCLE. METHODS: A cross-sectional design was used to collect data from 567 patients at a metropolitan cancer center in the United States. The Lymphedema Risk-Reduction Behavior Checklist was used to assess the occurrence of 11 daily-living risks. Descriptive, regression, and factor analyses were performed. RESULTS: Significant odds of BCLE were associated with infection (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.95-3.42), cuts/scratches (OR 2.65, 95% CI 1.97-3.56), sunburn (OR 1.89, 95% CI 1.39-3.56), oil splash or steam burns (OR 2.08, 95% CI 1.53-3.83), and insect bites (OR 1.59, 95% CI 1.18-2.13). The daily-living risks were clustered into factors related to skin trauma and carrying objects. Skin trauma risk was significantly associated with BCLE (B = 0.539, z = 3.926, OR 1.714, 95% CI 1.312-2.250; p < 0.001). Having three, four, or five skin trauma risks significantly increased the odds of BCLE to 4.31, 5.14, and 6.94 times, respectively. The risk of carrying objects had no significant or incremental effects on BCLE. CONCLUSION: Complete avoidance of daily-living risks is challenging given 52.73% of patients incurred more than five daily-living risks. Our study findings underscore the importance of 'what to do' strategies to minimize infection and skin trauma.

Pulse pattern manipulation of dichromatic soliton complexes by a twistable tapered-fiber filter.

Soliton complexes highlight the particle-like dynamics of dissipative pulses. However, simple and reliable manipulation of bound solitons remains challenging, particularly for all-polarization-maintaining (PM) configurations that are free from random polarization perturbations. Here, we report controllable pulse patterns of robustly coexisting dichromatic soliton complexes in an all-PM fiber laser based on a twistable tapered-fiber filter. According to the twist angle, dichromatic pulses are switched between different patterns, and components at each wavelength can be independently manipulated, extending encodings from the time to the frequency domain. To the best of our knowledge, it is the first experimental demonstration of dual-wavelength soliton complexes that different pulse patterns coexist at separated wavebands.

Coherent beam combining of femtosecond third-harmonic generators: towards high-power, high-beam-quality UV light generation.

Coherent beam combining (CBC) of two femtosecond third-harmonic (TH) generators is proposed and demonstrated. By applying phase modulation to one of the fundamental laser pulses, the feedback loop effectively eliminates both phase and pointing errors between the two TH femtosecond laser beams. The system delivers 345-nm femtosecond laser pulses with 22-W average power at 1-MHz repetition rate. The average combining efficiency is 91.5% over approximately 1 h of testing. The beam quality of the combined ultraviolet (UV) laser beam is near-diffraction-limited with M2 factors of M X2=1.36, M Y2=1.24, which are similar to those of the individual channels. This scheme exhibits promising potential for increasing high-beam-quality UV laser power.

Pump-power-controlled L-band wavelength-tunable mode-locked fiber laser utilizing nonlinear polarization evolution in all-polarization-maintaining fibers.

We present for the first time, to the best of our knowledge, the pump-power-controlled, all-polarization-maintaining (all-PM), all-fiber configured, wavelength-tunable mode-locked fiber laser in the L-band (1565 to 1625 nm). A tuning range over 20 nm (1568.2  to 1588.9 nm) is attained simply by varying the pump power between 45 and 115 mW. Our work represents the first demonstration of wavelength tuning in all-PM configured nonlinear polarization evolution (NPE) lasers. The non-mechanical and electrically controllable tuning method offers ease of use and cost efficiency within an advanced all-PM, all-fiber design, indicating promising adaptability to diverse wavelength bands.

Efficacy and safety of second-line therapies for advanced hepatocellular carcinoma: a network meta-analysis of randomized controlled trials.

BACKGROUND: The selection of appropriate second-line therapy for liver cancer after first-line treatment failure poses a significant clinical challenge due to the lack of direct comparative studies and standard treatment protocols. A network meta-analysis (NMA) provides a robust method to systematically evaluate the clinical outcomes and adverse effects of various second-line treatments for hepatocellular carcinoma (HCC). METHODS: We systematically searched PubMed, Embase, Web of Science and the Cochrane Library to identify phase III/IV randomized controlled trials (RCTs) published up to March 11, 2024. The outcomes extracted were median overall survival (OS), median progression-free survival (PFS), time to disease progression (TTP), disease control rate (DCR), objective response rate (ORR), and adverse reactions. This study was registered in the Prospective Register of Systematic Reviews (CRD42023427843) to ensure transparency, novelty, and reliability. RESULTS: We included 16 RCTs involving 7,005 patients and 10 second-line treatments. For advanced HCC patients, regorafenib (HR = 0.62, 95%CI: 0.53-0.73) and cabozantinib (HR = 0.74, 95%CI: 0.63-0.85) provided the best OS benefits compared to placebo. Cabozantinib (HR = 0.42, 95%CI: 0.32-0.55) and regorafenib (HR = 0.46, 95% CI: 0.31-0.68) also offered the most significant PFS benefits. For TTP, apatinib (HR = 0.43, 95% CI: 0.33-0.57), ramucirumab (HR = 0.44, 95% CI: 0.34-0.57), and regorafenib (HR = 0.44, 95% CI: 0.38-0.51) showed significant benefits over placebo. Regarding ORR, ramucirumab (OR = 9.90, 95% CI: 3.40-42.98) and S-1 (OR = 8.68, 95% CI: 1.4-154.68) showed the most significant increases over placebo. Apatinib (OR = 3.88, 95% CI: 2.48-6.10) and cabozantinib (OR = 3.53, 95% CI: 2.54-4.90) provided the best DCR benefits compared to placebo. Tivantinib showed the most significant advantages in terms of three different safety outcome measures. CONCLUSIONS: Our findings suggest that, in terms of overall efficacy and safety, regorafenib and cabozantinib are the optimal second-line treatment options for patients with advanced HCC.

Superior Adsorptive Removal of Anionic Azo Dyes from Aqueous Solutions Using Sulfonic Acid Group-Modified MIL-101@Graphene Oxide Composite.

It is critical to remove organic contaminants from wastewater released by the printing and dyeing industry for addressing water pollution issue. Therefore, the fabrication of new adsorbents with excellent removal efficiencies is an urgent task. A composite of MIL-101 partially functionalized with -SO3H (MIL-101-SO3H) and graphene oxide (GO) was prepared by assembling MIL-101-SO3H truncated octahedrons on the GO framework. The synthesized MIL-101-SO3H@GO has a superior adsorption efficiency for anionic azo dyes. The maximum adsorption capacities of MIL-101-SO3H@GO-1 for Congo red, methyl orange, acid orange 7, and acid orange G reached 2711.3, 818.8, 551.2, and 319.8 mg/g, respectively, which are considerably higher than those obtained using unmodified MIL-101. This is because additional interactions that promote azo dye adsorption, such as hydrogen bonding between the dye and the sulfonic acid groups of MIL-101-SO3H or the carboxyl groups of GO, were induced, and agglomerate pores that accommodated the dye were formed in the composite. The ultrahigh removal efficiency of the composite for azo dyes is mainly driven by hydrogen bonding, electrostatic interactions, π-π stacking between the MIL-101-SO3H@GO and dye molecules, synergistic interactions at the interface of GO and MIL-101-SO3H microcrystals, and the pore-filling effect. Understanding these driving forces for dye adsorption can contribute to the development of sustainable and functionally modified metal-organic framework composite adsorbents.

IL20Rb aggravates pulmonary fibrosis through enhancing bone marrow derived profibrotic macrophage activation.

Idiopathic pulmonary fibrosis (IPF) is one of the most fatal chronic interstitial lung diseases with unknown pathogenesis, current treatments cannot truly reverse the progression of the disease. Pulmonary macrophages, especially bone marrow derived pro-fibrotic macrophages, secrete multiple kinds of profibrotic mediators (SPP1, CD206, CD163, IL-10, CCL18…), thus further promote myofibroblast activation and fibrosis procession. IL20Rb is a cell-surface receptor that belongs to IL-20 family. The role of IL20Rb in macrophage activation and pulmonary fibrosis remains unclear. In this study, we established a bleomycin-induced pulmonary fibrosis model, used IL4/13-inducing THP1 cells to induce profibrotic macrophage (M2-like phenotype) polarization models. We found that IL20Rb is upregulated in the progression of pulmonary fibrosis, and its absence can alleviate the progression of pulmonary fibrosis. In addition, we demonstrated that IL20Rb promote the activation of bone marrow derived profibrotic macrophages by regulating the Jak2/Stat3 and Pi3k/Akt signaling pathways. In terms of therapeutic strategy, we used IL20Rb neutralizing antibodies for animal administration, which was found to alleviate the progression of IPF. Our results suggest that IL20Rb plays a profibrotic role by promoting profibrotic macrophage polarization, and IL20Rb may become a potential therapeutic target for IPF. Neutralizing antibodies against IL20Rb may become a potential drug for the clinical treatment of IPF.

Cell-in-cell promotes lung cancer malignancy by enhancing glucose metabolism through mitochondria transfer.

Heterotypic cell-in-cell structure (CICs) is the definition of the entry of one type of living cells into another type of cell. CICs between immune cells and tumor cells have been found to correlate with malignancy in many cancers. Since tumor immune microenvironment promotes non-small cell lung cancer (NSCLC) progression and drug resistance, we wondered the potential significance of heterotypic CICs in NSCLC. Heterotypic CICs was analyzed by histochemistry in an expanded spectrum of clinical lung cancer tissue specimens. In vitro study was performed using the mouse lung cancer cell line LLC and splenocytes. Our results revealed that CICs formed by lung cancer cells and infiltrated lymphocytes were correlated with malignancy of NSCLC. In addition, we found CICs mediated the transfer of lymphocyte mitochondria to tumor cells, and promoted cancer cell proliferation and anti-cytotoxicity by activating MAPK pathway and up-regulating PD-L1 expression. Furthermore, CICs induces glucose metabolism reprogramming of lung cancer cells by upregulating glucose intake and glycolytic enzyme. Our findings suggest that CICs formed by lung cancer cell and lymphocyte contribute to NSCLC progression and reprogramming of glucose metabolism, and might represent a previously undescribed pathway for drug resistance of NSCLC.

Pure rotational and rovibrational spectroscopy of cyclopropylamine in the far-infrared region: -NH2 torsion.

The pure rotational and rovibrational spectra of the ν27 -NH2 torsion of cyclopropylamine (CPA) in the far-infrared region were measured with a high-resolution Fourier transform infrared coupled to a synchrotron. The complex spectra reflect the presence of both trans and gauche conformers. Analysis of the pure rotational spectra (34-64 cm-1) yielded accurate rotational and centrifugal distortion constants of the ground and first two torsional excited states of trans-CPA. The fundamental, hot bands and weak overtones were identified and assigned in the 200-550 cm-1 range. Global analysis of over 19 000 transitions provides accurate energy levels of the torsional polyads up to vT = 3. The torsional levels and their rotational constants were in agreement with the theoretical results from quasiadiabatic channel reaction path Hamiltonian (RPH) calculations, emphasizing the need for molecular-specific theoretical treatments for large amplitude motions. Tunneling components of the torsional fundamental of gauche-CPA were assigned based on the RPH results and symmetry considerations, differing from previous experimental and theoretical work. This comprehensive spectroscopic characterization of CPA is crucial for its potential detection in the interstellar medium as a precursor to complex prebiotic molecules, providing essential data for future astronomical searches and advancing our understanding of nitrogen-containing organic molecules in space.

MicroRNA-122 protects against interferon-α-induced hepatic inflammatory response via the Janus kinase-signal transducer and activator of transcription pathway.

Significant overlap in the epidemiology and coinfection of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) has been identified, which accelerates the development of severe liver cirrhosis and hepatocellular carcinoma worldwide. Interferon-α (IFN-α), a cytokine with antiviral properties, exerts profound physiological effects on innate immunity by regulating interferon-stimulated genes (ISGs) within cells. However, the underlying mechanism of IFN-α in hepatic inflammation remains to be fully elucidated. Here, we utilized LO2 cells treated with the recombinant IFN-α protein and conducted microRNA (miR) sequencing. MiR-122-3p and miR-122-5p_R+1 were the most enriched miRNAs involved in the pathogenesis of IFN-α-induced inflammatory responses and were significantly downregulated by IFN-α treatment. Furthermore, we identified interferon induced protein with tetratricopeptide repeats 1 (IFIT1) as a potential target gene of miR-122. IFN-α markedly increased the expression of proinflammatory cytokines and fibrogenic genes but decreased the mRNA expression of ISGs. Additionally, IFN-α significantly activated the NF-κB p-p65, MAPK p-p38, and Jak/STAT pathways to trigger inflammation. Importantly, supplementation with a miR-122 mimic significantly alleviated IFN-α-induced inflammation and induced IFIT1 expression in LO2 cells. Conversely, the suppression of miR-122 markedly exacerbated the inflammatory response triggered by IFN-α. Furthermore, silencing IFIT1 via an siRNA elicited an inflammatory response, whereas IFIT1 overexpression ameliorated hepatic inflammation and fibrosis in a manner comparable to that induced by IFN-α treatment. Taken together, our findings suggest that miR-122 and its target, IFIT1, reciprocally regulate the inflammatory response associated with IFN through the Jak/STAT pathway.

Establishing and applying an adaptive framework for imported malaria: a field practice in Anhui Province, China from 2012 to 2022.

BACKGROUND: Anhui Province is currently facing an increase in imported malaria cases as a result of globalization and international travel. In response, Anhui Province has implemented a comprehensive adaptive framework to effectively address this threat. METHODS: This study collected surveillance data from 2012 to 2022 in Anhui Province. Descriptive statistics were used to analyze the epidemiological characteristics of imported malaria cases. Additionally, multivariate logistic regression was employed to identify factors associated with severe malaria. Documents were reviewed to document the evolution of the adaptive framework designed to combat imported malaria. The effectiveness of the adaptive framework was evaluated based on the rates of timely medical visits, timely diagnosis, and species identification. RESULTS: During the study period, a total of 1008 imported malaria cases were reported across 77 out of 105 counties in Anhui Province, representing a coverage of 73.33%. It was found that 10.52% of imported cases went undiagnosed for more than seven days after onset. The multivariate analysis revealed several potential risk factors for severe malaria, including increasing age (OR = 1.049, 95%CI:1.015-1.083), occupation (waitperson vs. worker, OR = 2.698, 95%CI:1.054-6.906), a longer time interval between onset and the initial medical visit (OR = 1.061, 95%CI:1.011-1.114), and misdiagnosis during the first medical visit (OR = 5.167, 95%CI:2.535-10.533). Following the implementation of the adaptive framework, the rates of timely medical visits, timely diagnosis, and species identification reached 100.00%, 78.57%, and 100.00%, respectively. CONCLUSIONS: Anhui Province has successfully developed and implemented an adaptive framework for addressing imported malaria, focusing on robust surveillance, prompt diagnosis, and standardized treatment. The experiences gained from this initiative can serve as a valuable reference for other non-endemic areas.

Innovative indenone-derivative colorimetric fluorescent probe: A approach for copper ion detection in water.

Copper (Cu2+) is a metal chemical element closely related to human life and is widely used in many fields. However, with the discharge of copper wastewater, the water quality will be seriously affected, leading to excessive intake of Cu2+ and a variety of diseases. Hence, there is a pressing need for an effective detection method for Cu2+ in aqueous environments. Leveraging the remarkable attributes of GFP chromophores and indenone derivatives, we have created a novel colorimetric fluorescent probe P-Cu2+, tailored for efficient copper ion detection. The addition of Cu2+ causes the solution to visibly change from colorless to a pronounced yellow, enabling naked-eye detection and offering promise for real sample analysis.

Succinate and mitochondrial DNA trigger atopic march from atopic dermatitis to intestinal inflammation.

BACKGROUND: Atopic march has long been recognized as the progression from atopic dermatitis (AD) to food allergy and asthma during infancy and childhood. However, effective blocking is hampered by the lack of specific biomarkers. OBJECTIVES: We aimed to investigate the pathologic progression of atopic march trajectories from skin to gut. METHODS: We built an atopic march mouse model by mechanical skin injury and percutaneous sensitization to peanut allergen. Anaphylaxis from the skin to the small intestine was then investigated by ELISA, RNA sequencing, quantitative real-time PCR, histopathologic analysis, and flow cytometry. The findings from the mice results were also verified by the serum samples of allergic pediatric patients. RESULTS: After modeling, inflammation in the skin and small intestine manifested as a mixed type of TH2 and TH17. Further analysis identified elevated succinate in the circulation and expanded tuft cells with upregulated IL-25 in the small intestine, resulting in increased intestinal type 2 innate lymphoid cells and an enhanced type 2 inflammatory response. In addition, free mitochondrial DNA (mtDNA) released after tissue damage was also involved in inflammation march from injured skin to small intestine through the STING pathway. Analysis of clinical samples verified that serum concentrations of succinate and mtDNA were higher in AD allergic children than non-AD allergic children. CONCLUSIONS: Succinate and mtDNA play key roles in skin-to-gut cross talk during the atopic march from AD to food allergy, and can be considered as biomarkers for risk assessment or targets for atopic march prevention strategies.