Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis.

BACKGROUND: Pancreatic cancer remains one of the most lethal malignancies, and has limited effective treatment. Gemcitabine (GEM), a chemotherapeutic agent, is commonly used for clinical treatment of pancreatic cancer, but it has characteristics of low drug delivery efficiency and significant side effects. The study tested the hypothesis that human bone marrow mesenchymal stem cell (MSC)-derived exosomes loaded with GEM (Exo-GEM) would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis. AIM: To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro. METHODS: Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis. Exo-GEM through electroporation, sonication, or incubation, and the loading efficiency was evaluated. The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays. RESULTS: The isolated exosomes had an average size of 76.7 nm. The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation. The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02 µM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells. Moreover, Exo-GEM enhanced the frequency of GEM-induced apoptosis in both cell lines. CONCLUSION: Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis, offering a promising drug delivery system for improving therapeutic outcomes.

Immune remodulation in pediatric inherited metabolic liver diseases.

Inherited metabolic liver diseases arise from genetic mutations that lead to disruptions in liver metabolic pathways and are predominantly observed in pediatric populations. The spectrum of genetic metabolic liver disorders is diverse, encompassing a range of conditions associated with aberrations in iron, copper, carbohydrate, lipid, protein, and amino acid metabolism. Historically, research in the domain of genetic metabolic liver diseases has predominantly concentrated on hepatic parenchymal cell alterations. Nevertheless, emerging studies suggest that inherited metabolic liver diseases exert significant influences on the immune microenvironment, both within the liver and systemically. This review endeavors to encapsulate the immunological features of genetic metabolic liver diseases, aiming to expand the horizons of researchers in this discipline, and to elucidate the underlying pathophysiological mechanisms pertinent to hereditary metabolic liver diseases and to propose innovative therapeutic approaches.

Mutual Influence Between Allergic Rhinitis and Sleep: Factors, Mechanisms, and interventions-A Narrative Review.

Patients with allergic rhinitis (AR) have a high incidence of sleep disorders, such as insomnia, which can easily exacerbate nasal symptoms. The aggravation of nasal symptoms further promotes the deterioration of sleep disorders, forming a vicious cycle. Severe cases may even trigger psychological and neurological issues, such as anxiety, depression, and cognitive impairment, causing significant distress to patients, making clinical diagnosis and treatment difficult, and increasing costs. Furthermore, satisfactory therapeutics remain lacking. As the pathogenesis of AR-associated sleep disorders is not clear and research is still insufficient, paying attention to and understanding AR-related sleep disorders is crucial in clinical practice. Multiple studies have shown that the most crucial issues in current research on AR and sleep are analyzing the relationship between AR and sleep disorders, searching for the influencing factors, and investigating potential targets for diagnosis and treatment. This review aimed to identify and summarize the results of relevant studies using "AR" and "sleep disorders" as search terms. In addition, we evaluated the correlation between AR and sleep disorders and examined their interaction and potential mechanisms, offering a foundation for additional screening of potential diagnostic biomarkers and therapeutic targets.

Canadian Veterans' Experiences of Living with Chronic Pain: A Descriptive Qualitative Study.

Background: An estimated 30% of veterans live with chronic pain, compared to 20% of Canadians in the general population. Veterans face health care challenges upon release from the military, increasing difficulties in obtaining chronic pain care. Aims: We explored experiences of Canadian Armed Forces veterans living with chronic pain, their transition from military to civilian care, perceived barriers and facilitators to chronic pain care, and impacts of their pain on the domains of well-being. Methods: We conducted a qualitative descriptive study using semistructured interviews. We used a deductive/inductive approach to derive themes and concepts from interview transcripts. Results: Thirty-five veterans living with chronic pain participated. Participants reported that pain affected their lives in numerous ways, including negatively impacting relationships and limiting activities of daily living and leisure. They identified barriers to care, including lack of access to family doctors or health care services, reluctance to ask for help, and challenges in obtaining coverage for services from Veterans Affairs Canada. Facilitators included support from other veterans and online resources. Chronic pain had bidirectional effects on domains of well-being. Conclusions: Experiences of pain varied among Canadian veterans, and military culture played a role in perceptions and management of pain. Barriers and facilitators to chronic pain care were highlighted from their time in the military into their transition to civilian care. Participants described the impact of chronic pain on their overall well-being. Determining whether these findings are relevant to a larger population of Canadian veterans will be important for future research and knowledge translation to improve chronic pain care for Canadian veterans.

Contexte : On estime que 30 % des anciens combattants souffrent de douleur chronique, contre 20 % des Canadiens dans la population générale Les vétérans sont confrontés à des défis en matière de soins de santé lorsqu'ils quittent l'armée, ce qui augmente les difficultés pour obtenir des soins pour la douleur chronique.Objectifs : Nous avons exploré les expériences des vétérans des Forces armées canadiennes vivant avec une douleur chronique, leur transition des soins militaires aux soins civils, les obstacles et les facilitateurs perçus en matière de soins pour la douleur chronique, ainsi que les effets de cette douleur sur les différents aspects de leur bien-être.Méthodes : Nous avons réalisé une étude qualitative descriptive en utilisant des entretiens semi-structurés. Une approche à la fois déductive et inductive a été utilisée pour extraire des thèmes et des concepts à partir des transcriptions des entretiens.Résultats : Trente-cinq anciens combattants souffrant de douleur chronique ont participé à l'étude. Les participants ont déclaré que la douleur affectait leur vie de nombreuses façons, notamment en ayant un impact négatif sur leurs relations en limitant les activités de la vie quotidienne ainsi que les loisirs. Ils ont recensé des obstacles aux soins, notamment le manque d'accès à des médecins de famille ou aux services de soins de santé, la réticence à demander de l'aide, et les difficultés à obtenir une couverture pour les services d'Anciens Combattants Canada. Les facilitateurs comprennent le soutien d'autres anciens combattants et les ressources en ligne. La douleur chronique a eu des effets bidirectionnels sur différents aspects de leur bien-être.Conclusions : Les expériences de la douleur varient parmi les anciens combattants canadiens, et la culture militaire joue un rôle dans les perceptions et la prise en charge de la douleur. Les obstacles aux soins pour la douleur chronique, ainsi que les facilitateurs, ont été mis en évidence depuis leur temps dans l'armée jusqu'à leur transition vers les soins civils. Les participants ont décrit l'effet de la douleur chronique sur leur bien-être général. Il sera important de déterminer si ces résultats sont pertinents pour une population plus large d'anciens combattants canadiens dans le cadre de recherches futures et de l'application des connaissances, afin d'améliorer les soins pour la douleur chronique chez les anciens combattants canadiens.

Experimental Validation of Enhanced Information Capacity by Quantum Switch in Accordance with Thermodynamic Laws.

We experimentally probe the interplay of the quantum switch with the laws of thermodynamics. The quantum switch places two channels in a superposition of orders and may be applied to thermalizing channels. Quantum-switching thermal channels has been shown to give apparent violations of the second law. Central to these apparent violations is how quantum switching channels can increase the capacity to communicate information. We experimentally show this increase and how it is consistent with the laws of thermodynamics, demonstrating how thermodynamic resources are consumed. We use a nuclear magnetic resonance approach with coherently controlled interactions of nuclear spin qubits. We verify an analytical upper bound on the increase in capacity for channels that preserve energy and thermal states, and demonstrate that the bound can be exceeded for an energy-altering channel. We show that the switch can be used to take a thermal state to a state that is not thermal, while consuming free energy associated with the coherence of a control system. The results show how the switch can be incorporated into quantum thermodynamics experiments as an additional resource.

Self-injury and suicide among people living with HIV/AIDS in China: a systematic review and meta-analysis.

BACKGROUND: The prevalence of self-injury and suicide is higher than the general population of people living with HIV/AIDS (PLWHA). However, the results reported in existing studies are highly variable in China. The purpose of this systematic review and meta-analysis was to synthesize the currently available high-quality evidence to explore the prevalence and influence factors of self-injury and suicide among PLWHA in China. METHOD: We retrieve literature written in Chinese and English through databases such as PubMed, Embase, Web of Science, Cochrane Library, SinoMed, CNKI, WanFang Database, and CQVIP from inception to 1 September 2022. Sata 16.0 software was used for analysis. RESULTS: A total of 28 studies were included with a sample size of 1,433,971 and had a satisfactory quality score of ≥ 5. The prevalence among PLWHA in China were 30% for suicidal ideation (SI), 5% for suicide attempt (SA), 8% for suicide plan (SP), 7% for attempted suicide (AS), and 3‰ for completed suicide. High stigma (OR = 2.94, 95%CI: 1.90 - 4.57), depression (OR, 3.17; 95%CI, 2.20 - 4.57), anxiety (OR, 3.06; 95%CI, 2.23 - 4.20), low self-esteem (OR, 3.82, 95%CI, 2.22 - 6.57), high HIV related stress (OR, 2.53; 95%CI, 1.36 - 4.72), and unemployment (OR, 2.50; 95%CI, 1.51 - 4.15) are risk factors for SI; high social support (OR, 0.61; 95%CI, 0.44 - 0.84) and spouse infected with HIV (OR, 0.39; 95%CI, 0.21 - 0.74) are protective factors for SI; depression (OR, 1.62; 95%CI, 1.24 - 2.13), high aggression (OR, 4.66; 95%CI, 2.59 - 8.39), and more negative life events (OR, 2.51; 95%CI, 1.47 - 4.29) are risk factors for AS; high level of education (OR, 1.31; 95%CI, 1.21 - 1.43) is risk factor for CS. CONCLUSION: Figures indicate that approximately one-third of PLWHA had suicidal ideation, and three out of 1,000 completed suicide in China. Positive events are protective factors for self-injury and suicide among PLWHA, while negative events are risk factors. This suggests that psychosocial support and risk assessment should be integrated into the care of PLWHA.

Machine learning developed a macrophage signature for predicting prognosis, immune infiltration and immunotherapy features in head and neck squamous cell carcinoma.

Macrophages played an important role in the progression and treatment of head and neck squamous cell carcinoma (HNSCC). We employed weighted gene co-expression network analysis (WGCNA) to identify macrophage-related genes (MRGs) and classify patients with HNSCC into two distinct subtypes. A macrophage-related risk signature (MRS) model, comprising nine genes: IGF2BP2, PPP1R14C, SLC7A5, KRT9, RAC2, NTN4, CTLA4, APOC1, and CYP27A1, was formulated by integrating 101 machine learning algorithm combinations. We observed lower overall survival (OS) in the high-risk group and the high-risk group showed elevated expression levels in most of the immune checkpoint and human leukocyte antigen (HLA) genes, suggesting a strong immune evasion capacity. Correspondingly, TIDE score positively correlated with risk score, implying that high-risk tumors may resist immunotherapy more effectively. At the single-cell level, we noted macrophages in the tumor microenvironment (TME) predominantly stalled in the G2/M phase, potentially hindering epithelial-mesenchymal transition and playing a crucial role in the inhibition of tumor progression. Finally, the proliferation and migration abilities of HNSCC cells significantly decreased after the expression of IGF2BP2 and SLC7A5 reduced. It also decreased migration ability of macrophages and facilitated their polarization towards the M1 direction. Our study constructed a novel MRS for HNSCC, which could serve as an indicator for predicting the prognosis, immune infiltration and immunotherapy for HNSCC patients.

Genomic Alterations and Clinical Characterization in Chinese Patients with Metastatic Colorectal Cancer.

BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as RAS, BRAF, and microsatellite instability (MSI). Novel genomic changes, including ERBB2 amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies. METHODS: A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated. RESULTS: The cohort's genomic profiling revealed TP53 mutations in 78%, APC in 60%, and KRAS in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. ERBB2/HER2 amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent KRAS mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except TP53) that could be targeted therapeutically. The KRAS (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a BRAF V600E mutation. Notably, survival analysis showed no significant differences in OS between KRAS mutant loci and NRAS mutations (p = 0.436). However, BRAF V600E mutations were associated with a poorer prognosis than BRAF wild-type and non-V600E mutations (16.3 months vs. 29.5 and 31.1 months, respectively; p < 0.001). CONCLUSIONS: This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Experimental Realization of Self-Contained Quantum Refrigeration.

A fundamental challenge in quantum thermodynamics is the exploration of inherent dimensional constraints in thermodynamic machines. In the context of two-level systems, the most compact refrigerator necessitates the involvement of three entities, operating under self-contained conditions that preclude the use of external work sources. Here, we build such a smallest refrigerator using a nuclear spin system, where three distinct two-level carbon-13 nuclei in the same molecule are involved to facilitate the refrigeration process. The self-contained feature enables it to operate without relying on net external work, and the unique mechanism sets this refrigerator apart from its classical counterparts. We evaluate its performance under varying conditions and systematically scrutinize the cooling constraints across a spectrum of scenarios, which sheds light on the interplay between quantum information and thermodynamics.

IL-6 mediates olfactory dysfunction in a mouse model of allergic rhinitis.

BACKGROUND: Immune-inflammatory response is a key element in the occurrence and development of olfactory dysfunction (OD) in patients with allergic rhinitis (AR). As one of the core factors in immune-inflammatory responses, interleukin (IL)-6 is closely related to the pathogenesis of allergic diseases. It may also play an important role in OD induced by diseases, such as Sjögren's syndrome and coronavirus disease 2019. However, there is no study has reported its role in OD in AR. Thus, this study aimed to investigate the role of IL-6 in AR-related OD, in an attempt to discover a new target for the prevention and treatment of OD in patients with AR. METHODS: Differential expression analysis was performed using the public datasets GSE52804 and GSE140454 for AR, and differentially expressed genes (DEGs) were obtained by obtaining the intersection points between these two datasets. IL-6, a common differential factor, was obtained by intersecting the DEGs with the General Olfactory Sensitivity Database (GOSdb) again. A model of AR mice with OD was developed by sensitizing with ovalbumin (OVA) to verify the reliability of IL-6 as a key factor of OD in AR and explore the potential mechanisms. Furthermore, a supernatant and microglia co-culture model of nasal mucosa epithelial cells stimulated by the allergen house dust mite extract Derp1 was established to identify the cellular and molecular mechanisms of IL-6-mediated OD in AR. RESULTS: The level of IL-6 in the nasal mucosa and olfactory bulb of AR mice with OD significantly increased and showed a positive correlation with the expression of olfactory bulb microglia marker Iba-1 and the severity of OD. In-vitro experiments showed that the level of IL-6 significantly increased in the supernatant after the nasal mucosa epithelial cells were stimulated by Derp1, along with significantly decreased barrier function of the nasal mucosa. The expression levels of neuroinflammatory markers IL-1ß and INOS increased after a conditioned culture of microglia with the supernatant including IL-6. Then knockdown (KD) of IL-6R by small interfering RNA (siRNA), the expression of IL-1ß and INOS significantly diminished. CONCLUSION: IL-6 plays a key role in the occurrence and development of OD in AR, which may be related to its effect on olfactory bulb microglia-mediated neuroinflammation.

Hepatic Portal Venous Gas Associated with Acute Upper Gastrointestinal Hemorrhage: A Case Report and Literature Review.

BACKGROUND: Hepatic portal venous gas (HPVG) is very rare; it is associated with multiple gastrointestinal etiologies, with pathophysiology not yet fully understood. It is characteristically fast-progressing and has a high mortality rate. Treatment choice depends on the etiology, including conservative and surgical management. CASE PRESENTATION: We report an adult patient (less than 25 years old) of HPVG combined with acute upper gastrointestinal hemorrhage, in which massive gas in the hepatic portal vein system by computed tomography of the abdomen was rapidly dissipated by nasogastric decompression conservative management. CONCLUSION: Nasogastric decompression can be an effective treatment approach for HPVG when timely surgical treatment is not required.

Ultrasensitive detection of tyrosinase with click reaction-combined dark-field imaging platform.

Tyrosinase (TYR) is an essential oxidase that is responsible for the regulation of multiple physiological processes and diseases. Achieving the trace and reliable detection of TYR in complex biological samples is of great significance for the diagnosis of TYR-related diseases, but which faces a great challenge. In this study, we developed an ingenious and powerful method for the ultrasensitive detection of TYR by click reaction-combined dark-field microscopy. This method begins with the formation of cuprous ions (Cu+) based on the reduction of copper ions (Cu2+) by ascorbic acid (AA). Subsequently, the formed Cu+ can catalyze the crosslinking between azide- and alkyne-functionalized gold nanoparticles, causing a significant red-shift in the scattering spectrum. However, AA can chelate with TYR, which inhibits the generation of Cu+ and subsequent click reaction, thus achieving TYR-controlled scattering spectral shift. The proposed sensing platform shows a good linear detection range of 0.01-0.8 U/L with a low detection limit of 0.003 U/L, which is three orders of magnitude lower than the best performance of TYR sensing probes reported to date. Most importantly, the strategy has the ability to reliably and accurately detect TYR in serum sample, suggesting its potential clinical application in diagnosing TYR-related diseases. This visual sensing platform offers promising prospects for future research in enzymatic analysis and biomedical diagnostics.

Unraveling the rapid ion migration in perovskite solar cells by circuit-switched transient photoelectric technique.

Ion migration activated by illumination is a critical factor responsible for the performance decline and stability degradation of perovskite solar cells (PSCs). While ion migration has been widely believed to be much slower than charge transport, recent research suggests that, despite the lack of understanding of the mechanism, it may also be involved in a series of rapid photoelectric responses of PSCs. Here, we report an improved circuit-switched transient photoelectric technique with nanosecond temporal resolution, which enables quantitative characterization of ion migration dynamics in PSCs across a fairly broad time window. Specifically, ion migration occurring within microseconds after illumination (corresponding to a diffusion length of ∼10-7 cm) is unambiguously identified. In conjunction with the composition engineering protocol, we justify that it arises from the short-range migration of halide anions and organic cations around the contact/perovskite interface. The rapid ion migration kinetics revealed in this work strongly complement the well-established ion migration model, which offers new insights into the mechanism of ion-carrier interaction in PSC devices.

Therapeutic potential of HUC-MSC-exos primed with IFN-γ against LPS-induced acute lung injury.

Objectives: Human umbilical cord mesenchymal stem cells (HUC-MSCs) are pluripotent stem cells with anti-inflammatory and immunomodulatory properties used in the treatment of acute lung injury (ALI). However, the treatment of ALI using exosomes derived from HUC-MSCs (HUC-MSC-exos) primed with interferon-gamma (IFN-γ-exos) has not been described. This study investigated the effects of IFN-γ-exos on ALI. Materials and Methods: IFN-γ primed and unprimed HUC-MSC-exos (IFN-γ-exos and CON-exos, respectively) were extracted, identified, and traced. A549 cells and mice subjected to lipopolysaccharide (LPS)-induced inflammation were treated with IFN-γ-exos or CON-exos. Viability; interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and reactive oxygen species (ROS) levels; NF-κB p65, and NLRP3 expression and histology and lung injury scores were measured in cell, supernatant or lung tissue. Results: Indoleamine 2,3-dioxygenase (IDO) mRNA expression was elevated in HUC-MSCs primed with 5 ng/mL IFN-γ (P<0.001), and IFN-γ-exos and CON-exos were successfully extracted. LPS-induced inflammation resulted in decreased cell viability in A549 cells, and increased IL-1ß, IL-6, TNF-α and ROS levels and NF-κB p65 and NLRP3 expression in A549 cells and mice(P<0.05 to P<0.001). Treatment with IFN-γ-exos and CON-exos increased cell viability and decreased the concentrations of IL-1ß, and ROS, expression of NF-κB p65 and NLRP3, and the lung injury score, and these effects were more obvious for IFN-γ-exos(P<0.05 to P<0.001). Conclusion: IFN-γ-exos reduced oxidative stress and inflammatory responses in LPS-induced A549 cells and mice. The result demonstrated the therapeutic potential of IFN-γ-exos in LPS-induced ALI.

Chemical components with antibacterial properties found in sanchen powder from traditional Tibetan medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Sanchen powder is a traditional Tibetan medicine comprising Bambusae Concretio Silicea, Carthami Flos, and Bovis Calculus Artifactus. Bambusae Concretio Silicea is the dried mass of secreted fluid in the stalks of Gramineae plants such as Bambusa textilis McClure or Schizostachyum chinense Rendle. Carthami Flos is the dried flower of Carthamus tinctorius L. in the Compositae plant. Bovis Calculus Artifactus is made from ox bile powder, cholic acid, hyodeoxycholic acid, taurine, bilirubin, cholesterol, and trace elements. Research has evidenced the antibacterial efficacy of Sanchen powder, albeit its active constituents for this effect are yet to be established. AIM OF THE STUDY: To investigate effective compounds, potential targets, and molecular mechanism of Sanchen powder for its antibacterial properties by using network pharmacology combined with in vitro validation, with the aims of observing the action of effective compounds in Sanchen powder and exploring new therapeutic strategies for antibacterial. MATERIALS AND METHODS: In this study, UPLC-Q-TOF-MS was utilized to identify the chemical composition in Sanchen powder and its blood-borne chemical ingredients post-oral intake. A network pharmacology analysis was used to establish the chemical compound in the blood following oral administration-target-disease network. The study aimed to identify antibacterial active ingredients, which were then subjected to molecular docking and pharmacodynamic experiments to verify their efficacy. RESULTS: The findings demonstrate that following oral administration, the blood contains seven key components of Sanchen powder, including bilirubin, glycochenodeoxycholic acid, glycocholic acid, taurocholic acid, phenylalanine, safflomin A, and tryptophan. Additionally, the network pharmacology and molecular docking study results indicate the potential antibacterial effects of bilirubin, glycocholic acid, and glycochenodeoxycholic acid. In vitro antibacterial experiments revealed that bilirubin, glycocholic acid, and glycochenodeoxycholic acid could restrict the growth of the Staphylococcus aureus cell membrane at a certain concentration. Moreover, they exhibited antibacterial effects on Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Escherichia coli. CONCLUSIONS: Bilirubin, glycocholic acid, and glycochenodeoxycholic acid could be effective therapeutic ingredients for the antibacterial effects of Sanchen powder. These results offer a foundation for further clinical application and research on the antibacterial effect of Sanchen powder, a Traditional Tibetan Medicine.

Exosomes Derived from hucMSCs Primed with IFN-γ Suppress the NF-κB Signal Pathway in LPS-Induced ALI by Modulating the miR-199b-5p/AFTPH Axis.

Exosomes (exos) are primarily responsible for the process of mesenchymal stem cells (MSCs) treatment for acute lung injury (ALI), but the mechanism remains unclear, particularly in altered microenvironment. Therefore, this study aimed to investigate the potential mechanism of exos derived from human umbilical cord mesenchymal stem cells (hucMSCs) primed with interferon-gamma (IFN-γ) on ALI and to propose a promising and cell-free strategy. This study extracted exos from hucMSCs supernatant primed and unprimed with IFN-γ marked with IFN-γ-exos and CON-exos, which were identified and traced. IFN-γ-exos administration to ALI models suppressed the NF-κB signaling pathway compared to CON-exos, which were quantified through western blot and immunohistochemical staining. Reverse transcription-quantitative polymerase chain reaction validated miR-199b-5p expression in the IFN-γ-exos and CON-exos treatment groups. Data analysis, a dual-luciferase reporter assay, and cell transfection were conducted to investigate the target binding between miR-199b-5p and Aftiphilin (AFTPH), with AFTPH expression analyzed via cell immunofluorescence and western blot. Co-immunoprecipitation was conducted for the interaction between AFTPH and NF-κB p65. The result revealed that miR-199b-5p was down-regulated in the IFN-γ-exos treatment group, which had a target binding site with AFTPH, and an interaction with NF-κB p65. Consequently, IFN-γ-exos inhibited the NF-κB signaling pathway in ALI in vitro and in vivo through the miR-199b-5p/AFTPH axis. Our results demonstrated new directions of novel and targeted treatment for ALI.

Single-shot local measurement of terahertz correlated second harmonic generation in laser air plasma filaments.

We present a single-shot detection method of terahertz correlated second harmonic generation in plasma-based sources by directly mixing an optical probe into femtosecond laser-induced plasma filaments in air. The single-shot second harmonic trace is obtained by measuring a second harmonic generation on a conventional CCD with a spatiotemporally distorted probe beam. The system shows a spectrometer resolution of 22 fs/pixel on the CCD and a true resolution on the order of the probe pulse duration. With considerable THz peak electric field strength, this formalism can open the door to single-shot THz detection without bandwidth limitations.

Single-Cell Mapping of Brain Myeloid Cell Subsets Reveals Key Transcriptomic Changes Favoring Neuroplasticity after Ischemic Stroke / 神经科学通报·英文版

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.