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The window for high-resolution imaging of the lung (WHRIL) enables longitudinal imaging of the same region of murine lung tissue over a period of weeks, and this enables the visualization of spontaneous cancer metastasis from the earliest stages.Stable, high-resolution intravital imaging of the lung has become possible through the utilization of vacuum-stabilized imaging windows. However, this technique is extremely invasive and limited to only hours in duration. Here we describe a minimally invasive, permanently implantable window for high-resolution intravital imaging of the murine lung that allows the mouse to survive surgery, recover from anesthesia, and breathe independently. Compared to vacuum-stabilized windows, this window produces the same high-quality images without vacuum-induced artifacts; it is also less invasive, which allows imaging of the same lung tissue over a period of weeks. We further adapt the technique of microcartography for reliable relocalization of the same cells longitudinally. Using commonly employed experimental, as well as more clinically relevant, spontaneous metastasis models, we visualize all stages of metastatic seeding, including: tumor cell arrival; extravasation; growth and progression to micrometastases; as well as tumor microenvironment of metastasis function, the hallmark of hematogenous dissemination of tumor cells.

Background Breast cancer, the most common cancer in women, also affects men. However, detailed assessments of the disease burden and future projections for male breast cancer (MBC) remain limited. Methods Data on global male breast cancer mortality, disability-adjusted life years (DALYs), prevalence, and incidence from 1990 to 2021 were analyzed. We used the Estimated Annual Percentage Change (EAPC) to assess MBC trends and analyzed regional and age impacts on disease burden. The Slope Inequality Index (SII), Concentration Index (C-I), and Frontier analysis delineated inequalities and future trends. The Age-Period-Cohort (APC) model clarified population dynamics. We also identified risk factors and applied the ARIMA model to forecast disease burden changes over the next 30 years. Results Between 1990 and 2021, MBC deaths and DALYs showed a global increase. The EAPC for deaths was 0.66 (0.56–0.76), with the middle Socio-Demographic Index (SDI) region experiencing the most significant rise at 2.0 (1.76–2.24). DALYs had an EAPC of 0.85 (0.75–0.95), and the Middle SDI region saw the most notable increase with an EAPC of 2.16 (1.89–2.42). The global prevalence and incidence also increased, with EAPCs of 2.3 (2.13–2.46) and 2.21 (2.05–2.37) respectively. Disease burden was high and decreasing in low SDI regions, but low and stable in high SDI regions. The Age-standardized rate(ASR)-Deaths correlated negatively with SDI. ASR-Prevalence showed a negative correlation with SDI when SDI was below 0.5, a positive correlation when SDI was between 0.5 and 0.8, and a negative correlation again when SDI exceeded 0.8. Disease burden increased with age initially, peaking in the 65–69 age group for deaths, prevalence, and incidence, then decreasing. DALYs peaked in the 60–64 age group. High red meat consumption was associated with increased mortality risk. Projections suggest that while the total MBC burden will rise over the next 30 years, ASR-Deaths and DALYs will decline globally, and prevalence and incidence will increase. Conclusion Global male breast cancer deaths and DALYs are rising. Low SDI regions bear a higher disease burden, which is decreasing over time, while high SDI regions maintain a lower, stable burden. Over the next 30 years, the total disease burden is projected to increase further. Given these trends, male breast cancer remains a significant global health concern, and emerging disease patterns must inform new control policies.

Metastases are initiated by disseminated tumor cells (DTCs) that colonize distant organs. Growing evidence suggests that the microenvironment of the primary tumor primes DTCs for dormant or proliferative fates. However, the manner in which this occurs remains poorly understood. Here, using the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find that spontaneously DTCs have increased levels of retention, increased speed of extravasation, and greater survival after extravasation, compared to experimentally metastasized tumor cells. Detailed analysis reveals that a subset of macrophages within the primary tumor induces a pro-dissemination and pro-dormancy DTC phenotype. Our work provides insight into how specific primary tumor microenvironments prime a subpopulation of cells for expression of proteins associated with dissemination and dormancy. The understanding of the mechanisms underlying the ability of disseminated tumor cells (DTCs) to form metastasis is incomplete. Here, by using high-resolution intravital imaging of the murine lung to track the fate of breast-derived DTCs, the authors show that macrophages within the primary tumor induce a pro-dissemination and pro-dormancy phenotype in tumor cells, favouring their extravasation in the lung.

Background During the COVID-19 outbreak, most Chinese college students were home-quarantined to prevent the spread of the virus. COVID-19-associated impact has been shown to be a risk factor for the development of post-traumatic symptoms disorder (PTSD). However, little is known about the psychological processes that mediate this association. This study investigated the association between COVID-19-associated impact and PTSD and examined whether past stressful events, psychological resilience, and social support have mediating effects on this association. Methods The 12,397 valid responses from 31cities in China via an online survey assessed PTSD symptoms, past stressful events, psychological resilience, social support and social-demographic variables. AMOS was used to test the hypotheses of mediating effects. Results On the 39th day of the declared COVID-19 epidemic in China, 6.75% of the surveyed sample showed PTSD symptoms. A positive mediating effect of past stressful events was found between COVID-19-associated impact and PTSD, whereas psychological resilience and social support had negative mediating effects. The fit indices for the path model were found to be significant (β = 0.28, p  < 0.001), COVID-19-associated impact indirectly affects the risk of PTSD through mediating pathways (past stressful events → psychological resilience → social support) on PTSD. Conclusions Attention should be paid to the effects of past stressful events of Chinese college students who were home-quarantined during the COVID-19 epidemic, and strategies should also be implemented to improve social support and develop psychological resilience. Trial registration The study was approved by the ethics committee of the Southwest Minzu University.

Cancer stem cells (CSCs) play an important role during metastasis, but the dynamic behavior and induction mechanisms of CSCs are not well understood. Here, we employ high-resolution intravital microscopy using a CSC biosensor to directly observe CSCs in live mice with mammary tumors. CSCs display the slow-migratory, invadopod-rich phenotype that is the hallmark of disseminating tumor cells. CSCs are enriched near macrophages, particularly near macrophage-containing intravasation sites called Tumor Microenvironment of Metastasis (TMEM) doorways. Substantial enrichment of CSCs occurs on association with TMEM doorways, contributing to the finding that CSCs represent >60% of circulating tumor cells. Mechanistically, stemness is induced in non-stem cancer cells upon their direct contact with macrophages via Notch-Jagged signaling. In breast cancers from patients, the density of TMEM doorways correlates with the proportion of cancer cells expressing stem cell markers, indicating that in human breast cancer TMEM doorways are not only cancer cell intravasation portals but also CSC programming sites. Intravital imaging reveals macrophage-driven de novo induction of cancer stem cells in vivo, and their dramatic enrichment on dissemination through TMEM doorways. These findings provide a mechanism for the validated ability of TMEM doorway density to be prognostic for distant recurrence of metastatic tumors in breast cancer patients.

To monitor the illegal used of furaltadone, a highly sensitive indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and fluorescence-linked immunosorbent assay (FLISA) based on a monoclonal antibody (mAb) were developed for the detection of 3-amino-5-methylmorpholino-2-oxazolidinone (AMOZ), the major metabolite of furaltadone in animal tissues. The highly specific mAb, which was very sensitive to a nitrophenyl derivative of AMOZ (2-NP-AMOZ) with IC50 values of 0.11 and 0.09 ng/mL for ic-ELISA and FLISA, respectively, was selected for the development of immunoassays. For both the ic-ELISA and FLISA for AMOZ-spiked experiments, acceptable recovery rates of 81.1–105.3% and coefficients of variation of 4.7–9.8% were obtained. In addition, results from both ic-ELISA and FLISA methods for spiked samples’ data showed excellent correlation coefficients ranging from 0.9652 to 0.9927. Meanwhile, the proposed ic-ELISA and FLISA for thirty spiked samples were confirmed by standard LC-MS/MS with high correlation coefficients of 0.9911 and 0.9921, respectively. These results suggest that the developed ic-ELISA and FLISA are valid and cost-effective tools for high-throughput monitoring methods for AMOZ residues in animal tissues.

Anxiety and depression-like symptoms occur in the early stages of Alzheimer's disease. Hippocampal Sirtuin 1 (SIRT1) signaling mediates anxiety- and depression-like behavior. Exercise training improves anxiety and depression-like behavior in various disease models, such as the rat chronic restraint stress model, rat model of posttraumatic stress disorder, and rat model of fetal alcohol spectrum disorders. Here, we aimed to investigate whether exercise ameliorates anxiety- and depression like behaviors in APP/PS1 mice and explore the potential mechanisms. After eight weeks of exercise intervention, we assessed anxiety- and depression-like behaviors in Alzheimer's disease (AD) model mice. We then measured the levels of SIRT1, peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and mitochondrial biogenesis (CO2, ATP6, and mitochondrial content) using immunofluorescence, reverse transcription-quantitative real-time PCR, and transmission electron microscopy. Finally, we investigated the effects of pharmacological activation of SIRT1 on anxiety- and depression-like behaviors, the SIRT1/PGC-1α/NRF1/TFAM signaling axis, and mitochondrial biogenesis. We first observed that treadmill exercise improved anxiety- and depression-like behaviors in six-month-old APP/PS1 mice and increased SIRT1 levels in the hippocampus. Pharmacological activation of hippocampal SIRT1 function also reduced anxiety and depression-like behaviors in APP/PS1 mice. Meanwhile, both treadmill exercise and pharmacological activation of hippocampal SIRT1 increased the levels of PGC1α, NRF1, TFAM, and enhanced mitochondrial biogenesis (CO2, ATP6, or mitochondrial content) in the hippocampus of APP/PS1 mice. These findings reveal that treadmill exercise reduces anxiety- and depression-like behaviors in six-month-old APP/PS1 mice by enhancing the SIRT1-dependent PGC-1α/NRF1/TFAM axis, promoting mitochondrial biogenesis in the hippocampus.

Background Ziziphi Spinosae Semen (ZSS) is a plant widely used as medicine and food in Asian countries due to its numerous health benefits. γ-aminobutyric acid (GABA), a non-proteinaceous amino acid, is one of the major inhibitory neurotransmitters with a relaxant function. In this study, a system pharmacology approach was employed to assess the effects of a mixture composed of ZSS and GABA (ZSSG) on sleep improvement. Methods Mice were divided into five groups (n = 10) and received either no treatment, sodium pentobarbital, or sodium barbital with diazepam or ZSSG. The effects of ZSSG on sleep quality were evaluated in mice, and differential metabolites associated with sleep were identified among the control, ZSS, GABA, and ZSSG groups. Additionally, network-based ingredient-insomnia proximity analysis was applied to explore the major ingredients. Results ZSSG significantly improved sleep quality by decreasing sleep latency and prolonging sleep duration in sodium pentobarbital-induced sleeping mouse model ( P  < 0.05). ZSSG significantly enhanced the brain content of GABA in mice. Furthermore, ZSSG also significantly decreased sleep latency-induced by sodium barbital in mice ( P  < 0.05). Metabolic analysis revealed significant differences in 10 metabolites between ZSSG group and the groups administering ZSS or GABA. Lastly, using the network-based ingredient screening model, we discovered potential four active ingredients and three pairwise ingredient combinations with synergistic effect on insomnia from ZSSG among 85 ingredients identified by UPLC-Q/TOF–MS. Also, we have constructed an online computation platform. Conclusion Our data demonstrated that ZSSG improved the sleeping quality of mice and helped to balance metabolic disorders-associated with sleep disorders. Moreover, based on the network-based prediction method, the four potential active ingredients in ZSSG could serve as quality markers-associated with insomnia. The network-based framework may open up a new avenue for the discovery of active ingredients of herbal medicine for treating complex chronic diseases or symptoms, such as insomnia.

In nature, the molecules of real gas have a certain volume and have interaction force with each other. It is difficult to find the molecular motion law of real gas because of its complex properties. An ideal gas is an imaginary substance that does not exist in reality. Its molecules are elastic, non volume particles, and there is no interaction among them. This kind of gas is simple in nature and easy to be analyzed and calculated by simple mathematical relation. The introduction of the concept of ideal gas greatly simplifies the analysis of some thermodynamic problems.

In the steam power plant, the working medium used for energy transformation is water vapor. The thermodynamic properties of water vapor are usually obtained by using water vapor tables and charts. Adiabatic process of water vapor is widespread in engineering applications. The adiabatic process is realized without heat addition or rejection and the entropy of the working medium during a reversible adiabatic process remains constant. During an adiabatic expansion process, superheated steam turns into saturated vapor , and further into wet vapor, the pressure and the temperature of the steam decreases. The entropy during a irreversible adiabatic process increases. In general, when analyzing the thermodynamic process of water vapor, we first determine the state parameters by using charts and tables, and then make relevant calculations according to the first law of thermodynamics.