Background
Human population exposed to influenza viruses exhibited wide variation in susceptibility. The ratio of neutrophils to lymphocytes (NLR) has been examined to be a marker of systemic ...inflammation. We sought to investigate the relationship between influenza susceptibility and the NLR taken before influenza virus infection.
Methods
We investigated blood samples from five independent influenza challenge cohorts prior to influenza inoculation at the cellular level by using digital cytometry. We used multi-cohort gene expression analysis to compare the NLR between the symptomatic infected (SI) and asymptomatic uninfected (AU) subjects. We then used a network analysis approach to identify host factors associated with NLR and influenza susceptibility.
Results
The baseline NLR was significantly higher in the SI group in both discovery and validation cohorts. The NLR achieved an AUC of 0.724 on the H3N2 data, and 0.736 on the H1N1 data in predicting influenza susceptibility. We identified four key modules that were not only significantly correlated with the baseline NLR, but also differentially expressed between the SI and AU groups. Genes within these four modules were enriched in pathways involved in B cell-mediated immune responses, cellular metabolism, cell cycle, and signal transduction, respectively.
Conclusions
This study identified the NLR as a potential biomarker for predicting disease susceptibility to symptomatic influenza. An elevated NLR was detected in susceptible hosts, who may have defects in B cell-mediated immunity or impaired function in cellular metabolism, cell cycle or signal transduction. Our work can serve as a comparative model to provide insights into the COVID-19 susceptibility.
We have produced stretchable lithium-ion batteries (LIBs) using the concept of kirigami, i.e., a combination of folding and cutting. The designated kirigami patterns have been discovered and ...implemented to achieve great stretchability (over 150%) to LIBs that are produced by standardized battery manufacturing. It is shown that fracture due to cutting and folding is suppressed by plastic rolling, which provides kirigami LIBs excellent electrochemical and mechanical characteristics. The kirigami LIBs have demonstrated the capability to be integrated and power a smart watch, which may disruptively impact the field of wearable electronics by offering extra physical and functionality design spaces.
Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of ...hematuria and progression of IgAN.
Retrospective cohort study.
A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months.
Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/μL (automated method) during the first 6 months of follow-up.
Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure.
Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event.
Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent.
A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated.
Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.
Magnetic modulation of lysosomes for cancer therapy Li, Yingze; Lv, Cheng; Li, Zhenguang ...
Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology,
March/April 2024, 2024 Mar-Apr, 2024-03-00, 20240301, Letnik:
16, Številka:
2
Journal Article
Recenzirano
Lysosomes play a central role in biochemical signal transduction and oxidative stress in cells. Inducing lysosome membrane penetration (LMP) to cause lysosomal‐dependent cell death (LCD) in tumor ...cells is an effective strategy for cancer therapy. Chemical drugs can destroy the stability of lysosomes by neutralizing protons within the lysosomes or enhancing the fragility of the lysosomal membranes. However, there remain several unsolved problems of traditional drugs in LMP induction due to insufficient lysosomal targeting, fast metabolism, and toxicity in normal cells. With the development of nanotechnology, magnetic nanoparticles have been demonstrated to target lysosomes naturally, providing a versatile tool for lysosomal modulation. Combined with excellent tissue penetration and spatiotemporal manipulability of magnetic fields, magnetic modulation of lysosomes progresses rapidly in inducing LMP and LCD for cancer therapy. This review comprehensively discussed the strategies of magnetic modulation of lysosomes for cancer therapy. The intrinsic mechanisms of LMP‐induced LCD were first introduced. Then, the modulation of lysosomes by diverse physical outputs of magnetic fields was emphatically discussed. Looking forward, this review will shed the light on the prospect of magnetic modulation of lysosomes, inspiring future research of magnetic modulation strategy in cancer therapy.
This article is categorized under:
Therapeutic Approaches and Drug Discovery > Emerging Technologies
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Nanotechnology Approaches to Biology > Nanoscale Systems in Biology
Magnetic modulation of lysosomes is an effective strategy for cancer therapy by inducing lysosome membrane penetration (LMP) and lysosomal‐dependent tumor cell death (LCD). Diverse strategies of magnetic modulation can generate different kinds of physical energy to lysosomes, thus leading to LMP and the leakage of lysosomal contents such as cathepsins and ions, which would induce LCD of tumor cells efficiently.
Spatial-temporal distributions, sources identification and risk assessment of polycyclic aromatic hydrocarbons (PAHs) in overlying water and surface sediments in urban river networks of Shanghai were ...studied. Analytical results showed that there was a significant seasonal variation in concentrations of ∑16PAHs in water, suspended particulate matter (SPM) and sediment phases in this study area. The PAHs pollution in these multi-phases were in the medium level compared with other areas around the world, and the levels of PAHs contamination in SPM and sediment phases in hierarchical rivers showed TS (the third-order stream) > FS (the first-order stream) > SS (the second-order stream). Two manners of isomer ratios and principal component analysis (PCA) were used to identify PAHs origins, and suggested that combustion processes are dominant for PAHs sources. The ratios of PAHs origins by fossil fuels combustion, coke burning and crude oil in hierarchical rivers were determined with FS > SS > TS in SPM and sediment phases, and the ratio of PAHs origins by traffic emissions was analyzed with TS > SS > FS. PAHs in water samples have a certain impact on aqueous ecological system especially due to the fact that the ∑ceq values of nine PAHs were calculated from 0.715 to 15.831 μg/L in winter, which inferred serious ecological risk to some special aquatic organisms. The calculations of MERMQ in sediment samples showed that the MERMQ values ranged from 0.021 to 1.209 in winter and 0.019 to 0.643 in summer, which suggested high toxicity at six sampling sites in winter and only one location in summer due to high levels of PAHs. Furthermore, the toxicity degree of sediments were demonstrated with TS > FS > SS.
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•There was a significant seasonal variation in ∑16PAHs concentrations in water, SPM and sediment phases in this study area.•Some variation of PAHs origins in hierarchical rivers were determined with FS > SS > TS in SPM and sediment phases.•Toxicity of PAHs in water and sediment samples has a certain impact on the aquatic ecological system.
PAHs levels and sources in urbanized river networks in Shanghai showed some differences and patterns between inputs and river types.
Nanomachines with active propulsion have emerged as an intelligent platform for targeted cancer therapy. Achieving an efficient locomotion performance using an external energy conversion is a key ...requirement in the design of nanomachines. In this study, inspired by diverse spiky structures in nature, a photomagnetically powered nanomachine (PMN) with a spiky surface and thermally dependent viscosity tunability is proposed to facilitate mechanical motion in lysosomes for cancer mechanotherapy. The hybrid nanomachine is integrated with magnetic nanoparticles as the core and covered with gold nanotips. Physical simulations and experimental results prove that the spiky structure endows nanomachines with an obvious photomagnetic coupling effect in the NIR‐II region through the alignment and orienting movement of plasmons on the gold tips. Using a coupling‐enhanced magnetic field, PMNs are efficiently assembled into chain‐like structures to further elevate energy conversion efficiency. Notably, PMNs with the thermal control of viscosity are efficiently propelled under simultaneously applied dual external energy sources in cell lysosomes. Enhanced mechanical destruction of cancer cells via PMNs is confirmed both in vitro and in vivo under photomagnetic treatment. This study provides a new direction for designing integrated nanomachines with active adaptability to physiological environments for cancer treatment.
A two‐pronged driving strategy of nanomachines by simultaneously enhancing magnetic forces and reducing viscous forces is proposed here. The photomagnetically powered nanomachines with spiky surface exhibit a thermally dependent viscosity tunability and coupling‐enhanced magnetic perception, which facilitate mechanical motion in lysosomes for enhanced cancer mechanotherapy. This work shines a light on designing intelligent nanomachine‐based mechanotherapy for clinical translation.
•Investigate the Su-Schriefferheeger (SSH) and Kitaev hybrid fermion model.•Detecting topological phases by Berry phase and the entanglement entropy.•Characterizing the K1-type phases by the non-zero ...Berry phase and low energy spectra.•Find a new fully occupied phase with attractive inter and intra Coulomb interactions.
Based on the Su-Schriefferheeger (SSH) and Kitaev hybrid fermion model, we study the Berry phase in detecting different types of topological phases. We find that, under the twist boundary condition, the low energy spectra play remarkable roles in determining the Berry phase value. The non-zero Berry phase combined with the low energy spectra can be used to distinguish different types of topological quantum states. Furthermore, we consider the influence of interactions on the system. Through analysis of the Berry phase, the entanglement entropy, and the electron occupation, a new quantum phase is found and the influence law of the interactions on different types of topological phases are revealed. The quantum phase diagram of the system under these interactions is finally given.
Umbilical cord mesenchymal stem cells (UCMSCs) have been proposed as an ideal source for cell-based therapy to promote endometrial repair and regeneration. Furthermore, increasing evidence has ...indicated that UCMSC-derived exosomes (UCMSC-exos) act as important paracrine mediators to recapitulate the features of MSCs and may play a vital role in this process. UCMSCs and human endometrial stromal cells (ESCs) were isolated and characterized. ESCs were cocultured with UCMSCs and further assessed by flow cytometry and EdU incorporation assays. UCMSC-exos were extracted by differential ultracentrifugation and identified by western blots, transmission electron microscopy, and nanoparticle tracking analysis. The internalization of UCMSC-exos by ESCs was observed under a confocal microscope. ESCs were treated with UCMSC-exos at different concentrations and for different durations, with cell viability evaluated by CCK-8 assays. The cell cycle analysis showed that the percentage of ESCs in S phase significantly increased after coculture with UCMSCs, whereas it significantly decreased after inhibition of UCMSC-exo secretions. EdU incorporation assays also showed a similar trend. The isolated UCMSC-exos had a typical cup-shaped morphology with a monolayer membrane, expressed the specific exosomal markers Alix, CD63, and TSG101 and were approximately 60 to 200 nm in diameter. The PKH26-labeled UCMSC-exos were incorporated into ESCs. Moreover, UCMSC-exos enhanced the cell growth and viability of ESCs in a dose-dependent manner, and the effects occurred in a short period of time. UCMSC-exos promote the proliferation of ESCs in a dose-dependent manner; thus, they could be used as a potential treatment to promote endometrial repair.
The precise prevention and control of air pollution is a great challenge faced by environmental experts in recent years. Understanding the air quality evolution in the urban agglomeration is ...important for coordinated control of air pollution. However, the complex pollutant interactions between different cities lead to the collaborative evolution of air quality. The existing statistical and machine learning methods cannot well support the comprehensive analysis of the dynamic air quality evolution. In this study, we propose AirLens, an interactive visual analytics system that can help domain experts explore and understand the air quality evolution in the urban agglomeration from multiple levels and multiple aspects. To facilitate the cognition of the complex multivariate spatiotemporal data, we first propose a multi‐run clustering strategy with a novel glyph design for summarizing and understanding the typical pollutant patterns effectively. On this basis, the system supports the multi‐level exploration of air quality evolution, namely, the overall level, stage level and detail level. Frequent pattern mining, city community extraction and useful filters are integrated into the system for discovering significant information comprehensively. The case study and positive feedback from domain experts demonstrate the effectiveness and usability of AirLens.
Artemisia annua is a well-known traditional Chinese medicine. Due to its highest antimalarial efficacy, China has a long history of cultivating A. annua, and it is used for “clearing heat and ...detoxicating”. Several, studies have shown that the A. annua extract exerts cytotoxicity. In order to clarify the basis of the cytotoxic effect of A. annua, 18 sesquiterpenes were isolated from the herb, including 2 new sesquiterpenes and 16 known analogues. The structures of new compounds were elucidated by comprehensive spectroscopic analyses, including HR-ESI-MS, NMR experiments, single-crystal X-ray, and DP4+ and electronic circular dichroism (ECD) calculations. Cytotoxic activity screening revealed three compounds that exhibited cytotoxicity in a dose-dependent manner. Additional exploration showed that compound 5 significantly inhibited the proliferation of CT26 and HCT116 cells and induced apoptosis of HCT116 cells after 24 h. These chemical constituents contributed to elucidating the mechanism of action of the cytotoxic activity of A. annua.
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