Search

Lipids play crucial roles in many biological processes. Mapping spatial distributions and examining the metabolic dynamics of different lipid subtypes in cells and tissues are critical to better understanding their roles in aging and diseases. Commonly used imaging methods (such as mass spectrometry-based, fluorescence labeling, conventional optical imaging) can disrupt the native environment of cells/tissues, have limited spatial or spectral resolution, or cannot distinguish different lipid subtypes. Here we present a hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. Using this platform, we visualize and identify high density lipoprotein particles in human kidney, a high cholesterol to phosphatidylethanolamine ratio inside granule cells of mouse hippocampus, and subcellular distributions of sphingosine and cardiolipin in human brain. Our PRM-SRS displays unique advantages of enhanced chemical specificity, subcellular resolution, and fast data processing in distinguishing lipid subtypes in different organs and species.

Raman microscopy is a vibrational imaging technology that can detect molecular chemical bond vibrational signals. Since this signal is originated from almost every vibrational mode of molecules with different vibrational energy levels, it provides spatiotemporal distribution of various molecules in living organisms without the need for any labeling. The limitations of low signal strength in Raman microscopy have been effectively addressed by incorporating a stimulated emission process, leading to the development of stimulated Raman scattering (SRS) microscopy. Furthermore, the issue of low spatial resolution has been resolved through the application of computational techniques, specifically image deconvolution. In this article, we present a comprehensive guide to super-resolution SRS microscopy using an Adam-based pointillism deconvolution (A-PoD) algorithm, complemented by a user-friendly graphical user interface (GUI). We delve into the crucial parameters and conditions necessary for achieving super-resolved images through SRS imaging. Additionally, we provide a step-by-step walkthrough of the preprocessing steps and the use of GUI-supported A-PoD. This complete package offers a user-friendly platform for super-resolution SRS microscopy, enhancing the versatility and applicability of this advanced microscopy technique to reveal nanoscopic multimolecular nature. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Super-resolution stimulated Raman scattering microscopy with graphical user interface-supported A-PoD Support Protocol: Deuterium labeling on cells with heavy water for metabolic imaging.

Polymeric spherulites are typically formed by melt crystallization: spherulitic growth in solution is rare and requires complex polymers and dilute solutions. Here, we report the mild and unique formation of luminescent spherulites at room temperature via the simple molecule benzene-1,4-dithiol (BDT). Specifically, BDT polymerized into oligomers (PBDT) via disulfide bonds and assembled into uniform supramolecular nanoparticles in aqueous buffer; these nanoparticles were then dissolved back into PBDT in a good solvent (i.e., dimethylformamide) and underwent chain elongation to form spherulites (rPBDT) in 10 min. The spherulite geometry was modulated by changing the PBDT concentration and reaction time. Due to the step-growth polymerization and reorganization of PBDT, these spherulites not only exhibited robust structure but also showed broad clusterization-triggered emission. The biocompatibility and efficient cellular uptake of the spherulites further underscore their value as traceable drug carriers. This system provides a new pathway for designing versatile superstructures with value for hierarchical assembly of small molecules into a complicated biological system.

"Zibo Barbecue," "Village Premier League," "Erbin Phenomenon," "Tianshui Spicy Hot Pot," "Wang Po Matchmaking," "Chengdu Disney," "London's Canary Wharf," and other phenomenal events at home and abroad have become popular on the Internet, shaping a new landscape of online and offline network technology and a new form of social space. The new comprehensive spatial effects of network technology and traffic orientation have led to clear changes in daily life, spatiotemporal structure, social organizational forms, relationships, placeness, and identity. However, academic research on this phenomenon has been insufficient. Against the backdrop of new media technology that promotes social change and frequently affects people's daily lives, further discussion is necessary. This study organized well-known experts and young scholars to conduct academic analysis of the digital practice of Internet-famous sites and the production of new spatial forms. Presenting scholars' understanding of and reflections on the phenomenal events of Internet-famous sites from different perspectives is conducive to enhancing deep understanding of new phenomena in academia. In practice, the presentation of this research can both be a reference and provide inspiration for network technology, spatial-order guidance, local construction, and socioeconomic development.

Studies have shown that brain lipid metabolism is associated with biological aging and influenced by dietary and genetic manipulations; however, the underlying mechanisms are elusive. High-resolution imaging techniques propose a novel and potent approach to understanding lipid metabolic dynamics in situ. Applying deuterium water (D2O) probing with stimulated Raman scattering (DO-SRS) microscopy, we revealed that lipid metabolic activity in Drosophila brain decreased with aging in a sex-dependent manner. Female flies showed an earlier occurrence of lipid turnover decrease than males. Dietary restriction (DR) and downregulation of insulin/IGF-1 signaling (IIS) pathway, two scenarios for lifespan extension, led to significant enhancements of brain lipid turnover in old flies. Combining SRS imaging with deuterated bioorthogonal probes (deuterated glucose and deuterated acetate), we discovered that, under DR treatment and downregulation of IIS pathway, brain metabolism shifted to use acetate as a major carbon source for lipid synthesis. For the first time, our study directly visualizes and quantifies spatiotemporal alterations of lipid turnover in Drosophila brain at the single organelle (lipid droplet) level. Our study not only demonstrates a new approach for studying brain lipid metabolic activity in situ but also illuminates the interconnection of aging, dietary, and genetic manipulations on brain lipid metabolic regulation.

The reclaimed water of municipal sewage plant after advanced treatment in a power plant is used as makeup of circulating water system. Due to the problems in the advanced treatment system of reclaimed water，such as the output of the mechanical acceleration clarification tank failing to reach the designed value，poor effluent quality，the sludge dewatering system failing to operate normally，the feeding blockage of the lime system，the widespread leakage of the dosing device and no chain control，etc.，the requirements for normal use of reclaimed water in the power plant can’t be met. After the diagnosis of the problems，the optimization scheme was put forward. The internal structure of the mechanical acceleration clarification tank and the bottom sludge discharge pipeline system were modified respectively to restore the processing capacity of the mechanical acceleration clarification tank and meet the requirements of the water required of the system. The sludge dewatering system was modified to restore the sludge dewatering unit. The lime dosing system was modified to improve the problems of lime dosing and material blockage then restored the stable operation of the lime system. After optimization and transformation，the output of the clarification tank was improved，and the effluent quality of the system was optimized，effectively ensuring the normal operation of the deep treatment system for recycled water and the safety of water use in the power plant.

A new approach for early detection of multiple cancers is presented by integrating SERS spectroscopy of serum molecular fingerprints and machine learning.

Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-programmed cell death 1 and anti-cytotoxic T lymphocyte antigen-4 antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI myocarditis and emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI myocarditis all exhibited down-regulation of MANF (mesencephalic astrocyte-derived neurotrophic factor) and HSPA5 (heat shock 70-kDa protein 5) in the heart; this down-regulation was particularly notable in female mice. ICI myocarditis was amplified by heart-specific genetic deletion of mouse Manf and was attenuated by administration of recombinant MANF protein, suggesting a causal role. Ironically, both MANF and HSPA5 were transcriptionally induced by liganded estrogen receptor β and inhibited by androgen receptor. However, ICI treatment reduced serum estradiol concentration to a greater extent in female compared to male mice. Treatment with an estrogen receptor β-specific agonist and androgen depletion therapy attenuated ICI-associated cardiac effects. Together, our data suggest that ICI treatment inhibits estradiol-dependent expression of MANF/HSPA5 in the heart, curtailing the cardiomyocyte response to immune injury. This endocrine-cardiac-immune pathway offers new insights into the mechanisms of sex differences in cardiac disease and may offer treatment strategies for ICI myocarditis.

Objective To compare the disinfection effect of three different disinfectants for oral dental chair water lines (DUWLs). Methods Selection of seven independent water source integrated treatment tables in the Stomatology Department of Beijing No. 2 Hospital before opening of the clinic in 2019, divided into 4 groups (3 experimental + 1 control). The experimental group used 500mg/L chlorine-containing disinfectant respectively (2 integrated treatment chairs in group A)、3% hydrogen peroxide (Group B, 2 comprehensive treatment chairs)、60 g/L silver ion peroxide disinfectant (2 comprehensive treatment chairs in group C) and purified municipal water purified water (1 comprehensive treatment chair in control group D). The DUWLs were disinfected by three different disinfectants, and then water samples from each group of triple lances and high-speed hand pieces were collected for bacterial cultures. To compare the total number of bacterial colonies in each group of DUWLs before disinfection and immediately, 1d, 3d, and 7d after disinfection. Results The bacterial colony counts of pre-disinfection DUWLs had exceeded the standard ( all＞4500 cfu/mL). The total number of bacterial colonies of the three disinfectants immediately after disinfection and 1 day after disinfection decreased remarkably, and were lower than that of the pre-disinfection and control group. Three days after disinfection, except for experimental group C, the total number of bacterial colonies in experimental groups A and B exceeded the standard for oral healthcare water as stipulated in the Beijing "Technical specification for the disinfection of water circuits in comprehensive oral treatment tables (DB11_T 1703-2019)". The total number of bacterial colonies in groups A, B and C were close to or exceeded the pre-disinfection level 7 days after disinfection. Conclusion Short duration of time to maintain the effect of 500 ml/L chlorine disinfectant and 3% hydrogen peroxide disinfectant on waterway disinfection. Long-term use causes irreparable damage to the inner wall of the pipeline. Silver ionic disinfectant with 60 g/L hydrogen peroxide was optimal in controlling the total number of bacterial colonies and inhibiting bacterial growth time in oral dental chair water lines (DUWLs). (目的 比较3种不同消毒剂对口腔综合治疗台水路(DUWLs)的消毒效果。方法 选取本院2019年装修后待开诊前7台采用独立水源的综合治疗台, 分为4组(3组实验组+1组对照组), 实验组分别采用500 mg/L含氯消毒剂(A组2台综合治疗椅)、3%过氧化氢(B组2台综合治疗椅)、60 g/L过氧化氢银离子消毒剂(C组2台综合治疗椅)和净化后市政用水纯水(D组对照组1台综合治疗椅), 通过3种不同的消毒剂对DUWLs进行消毒, 然后收集各组三用枪和高速手机水样进行细菌培养, 比较各组DUWLs消毒前及消毒后即刻、1d、3d、7d细菌菌落总数。结果 消毒前DUWLs各组细菌菌落总数均严重超标(均＞4500 cfu/mL)。3种消毒剂消毒后即刻和消毒后1 d细菌菌落总数明显下降, 低于消毒前及对照组。消毒后3 d, 除实验C组外, 实验A、B两组细菌菌落总数均超过北京市《口腔综合治疗台水路消毒技术规范(DB11/T 1703-2019)》规定的口腔医疗卫生用水标准。消毒后7 d, A、B、C三组细菌菌落总数均接近或超过消毒前水平。结论 500 mg/L含氯消毒剂和3%过氧化氢消毒剂对水路消毒效果维持时间短, 长期使用对管路内壁造成不可修复的危害。60g/L过氧化氢银离子消毒剂在控制口腔牙椅水路(DUWLs)细菌落数总数和抑制细菌生长时间方面效果最优。)

The growing population of older adults has attracted concern from policymakers due in part to the fact that they are at higher risk of costly and potentially injurious falls. Responding to this concern, this study investigated fall-related hospitalizations among those aged 65 and older. Hospitalizations rose from 49,299 to 58,931, with charges and costs (estimated based on charges) increasing from $2.5 billion to $3.6 billion and under $900 million to over $1.1 billion, respectively. The intraclass correlation coefficients from linear mixed-effect models (with charges and costs serving as dependent variables) indicated differences in hospitals accounted for nearly half or more of medical cost variation among older adults suffering a fall-related hospitalization. Nonmetropolitan residence, being aged 65-69 (versus older), and higher risk-of-mortality on admission indicated higher costs. Identifying trends of fall-related hospitalizations over time allows for key stakeholders to not only track the burden of falls among older adults but to also use this information to attract funding for fall prevention strategies from policy makers at various levels (e.g., locally, at the state). Further, identifying characteristics of individuals (e.g., age, race, sex) and places (e.g., rural areas) that carry a higher relative cost can serve to inform the targeted allocation of finite resources including local, state, or federal funding, but also existing evidence-based practices such as community and clinical interventions.

Lipid metabolism plays crucial roles during aging processes, but how it is regulated by diets and how it interplays with aging still remain unclear. We proposed a new optical imaging platform by integrating heavy water (D2 O) probing with stimulated Raman scattering (DO-SRS) microscopy, for the first time, to directly visualize and quantify lipid metabolism regulated by different diets and insulin signaling pathway in Drosophila fat body during aging. We found that calorie restriction, low protein diet, and (moderately) high protein and high sucrose diets enhanced lipid turnover in flies at all ages, while (moderately) high fructose and glucose diets only promoted lipid turnover in aged flies. The measured lipid turnover enhancements under diverse diets were due to different mechanisms. High protein diet shortened the lifespan while all other diets extended the lifespan. Downregulating the insulin signaling pathway enhanced lipid turnover, which is likely related to lifespan increase, while upregulating insulin signaling pathway decreased lipid turnover that would shorten the lifespan. Our study offers the first approach to directly visualize spatiotemporal alterations of lipid turnover in aging Drosophila in situ, for a better understanding of the interconnections between lipid metabolism, diets, and aging.

Microtubules are self-assembling biological nanotubes made of the protein tubulin that are essential for cell motility, cell architecture, cell division, and intracellular trafficking. They demonstrate unique mechanical properties of high resilience and stiffness due to their quasi-crystalline helical structure. It has been theorized that this hollow molecular nanostructure may function like a quantum wire where optical transitions can take place, and photoinduced changes in microtubule architecture may be mediated via changes in disulfide or peptide bonds or stimulated by photoexcitation of tryptophan, tyrosine, or phenylalanine groups, resulting in subtle protein structural changes owing to alterations in aromatic flexibility. Here, we measured the Raman spectra of a microtubule and its constituent protein tubulin both in dry powdered form and in aqueous solution to determine if molecular bond vibrations show potential Fano resonances, which are indicative of quantum coupling between discrete phonon vibrational states and continuous excitonic many-body spectra. The key findings of this work are that we observed the Raman spectra of tubulin and microtubules and found line shapes characteristic of Fano resonances attributed to aromatic amino acids and disulfide bonds.

Background Valproic acid, as a mood stabilizer, has been extensively used for the treatment of bipolar disorder and other psychiatric conditions. Although therapeutic drug monitoring (TDM) of valproic acid has been carried out at home and abroad for many years, controversies persist regarding the influence of age, sex and other factors on its plasma concentration. Objective To analyze the TDM results of valproic acid, providing a reference for rationalized individualized treatment of bipolar disorders or other psychiatric conditions. Methods Through the laboratory information system of Ruimei Medical Laboratory, information on TDM of valproic acid in outpatients and inpatients (including the patient's age, sex, TDM raw data, monitoring samples, and monitoring frequency) was obtained from Xi'an Mental Health Center from 2019 to 2021. The plasma concentration of valproic acid was classified into three categories (100 mg/L) according to the therapeutic window range recommended in the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology (hereinafter referred to as AGNP Consensus) , and the percent of each category was calculated. And subsequent data analysis was performed using MedCalc 5.2. Results A total of 2 431 patients were monitored 2 992 times for understanding valproic acid treatment status, of which 1 637 were for men, and 1 355 for women. The frequencies of TDM of valproic acid increased by 54.93% in 2020 and 44.00% in 2021 compared to those reported in 2019. The proportion of patients who received only once was about 74.41%. Compared with inpatients, outpatients had higher prevalence of receiving one TDM of valproic acid (χ2=95.15, P0.05) . For each study year 2019-2021, the proportion of plasma concentration of valproic acid within the therapeutic window was 57.72%, which was significantly higher than that of the proportion of below and above the therapeutic window (χ2=155.38, 1 216.68, P100 mg/L) had statistically significant differences between different age and gender groups, and over the years (P