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Abstract The lung is one of the most frequently metastasized organs from various cancer entities, especially colorectal cancer (CRC). The occurrence of lung metastasis correlates with worse prognosis in CRC patients. Here, we aimed to investigate the role of IL-10 in lung metastasis development and identify the cellular source and target cells of IL-10 during lung metastatic establishment. To induce lung metastasis in mice, we injected MC38 murine colon cancer cells intravenously. Mice with Il10-deficiency were used to test the role of IL-10. The lung metastatic burden was assessed both macroscopically and histologically. IL-10- and Foxp3-reporter mice were employed to identify the cellular source and target cells of IL-10 in lung metastasis using flow cytometry. These findings were further confirmed using mice with cell-specific deletion of Il10- and IL-10 receptor (Il10ra). Interestingly, Il10 ablation led to reduced lung metastasis formation, suggesting a pathogenic role of IL-10 in lung metastasis. Moreover, using reporter mice, we identified Foxp3 + regulatory T cells (Tregs) as the predominant cellular source of IL-10 in lung metastasis. Accordingly, Foxp3 + Treg-specific deletion of Il10 resulted in decreased lung metastasis formation. In terms of target cells, myeloid cells and Foxp3 + Tregs expressed high IL-10Ra levels. Indeed, IL-10 signaling blockade in these two immune cell populations resulted in reduced lung metastatic burden. In conclusion, Foxp3 + Treg-derived IL-10 was found to act on Foxp3 + Tregs and myeloid cells, thereby promoting lung metastasis formation. These findings provide insights into lung metastasis-related immunity and establish the groundwork for optimizing metastasis-targeting immunotherapies through targeting of IL-10 as a novel therapeutic strategy.

This study aimed to explain the criteria of managers at different levels of nursing in selecting effective nursing diagnosis.

There are only a few works you can find in Piranesi's Etching that are not related to the "past". In his work, "ruin" is the most frequent theme. This article targets the ways ruin is depicted in Piranesi's work. Thus, by considering Piranesi’s prime and typical works and moving through his varying embodiments of ruin, this article will explain the different aspects of these representations and describes, the visuals of the way ruin is shown in his works. Based on Kant's theory of aesthetics in "The Critique of Judgment" and describing the concept of "sublimity" within that theoretical framework, it’s been attempted to provide the ground for answering "why" this type of representation reflects sublimity.The descriptive-analytical findings from this research indicate that fragmentality is the main feature in showing "the past" in Piranesi's work. Some of his works have archaeological approach, and by them, Piranesi tries to give us an "image" from the past. The dominance of the visual aspect and the frequency of the designs and their expansive range, from fireplace details to monuments and urban design, show that, in Piranesi's view, these pictures are beside each other in a sequence to build a complete picture of "the past". Although "phrases" come in to help the visual with accuracy and detail in some of these pictures, the fragmented quality of the contents of these depictions and the distance between the different types of them are not explained, as if this past would always represent itself as "lost". The recurring theme of "ruin" is also confirming of such an approach. Shape-wise, the most prominent manifestation of Piranesi's "ruins" is their enormous dimensions. Such depictions of memorials are recounting of the "mathematically sublime" in Kant's aesthetic system. As if in the face of "the sublimity" of these ruins, imagination fails to comprehend the mounting perceptual apprehensions. Also, ruins, in different ways, bespeak the power of the passing of time as a natural force. The sign of decadence on these ruins, in the forms of distortion of segments and growth of moss and greens, on another level, can intrigue experiencing sublimity in the audience. This experience is reminding of the "dynamically sublime" in Kant's aesthetics, where the subject feels fear when confronted by the power of nature. This fear, existing in Piranesi’s memorial, can be especially observed in Piranesi’s prison series. Prisons have nested spaces that evoke the impossibility of escaping such powers. In addition, by reviewing the content of the pictures and Piranesi’s text, it is apparent that this failure to comprehend is caused by facing the sublimity of the Roman Empire. Piranesi, in his different works, has attempted to depict this lost glory through pictures and words. However, this civilization and its example in Rome are so “sublime” in his view that they are depicted as a “fragmented” matter.

Abstract This study aimed to compare the effects of photobiomodulation therapy (PBMT) with 660 and 980 nm diode lasers on differentiation of periodontal ligament mesenchymal stem cells (PDLMSCs). In this in vitro, experimental study, PDLMSCs were obtained from the Iranian Genetic Bank and cultured in osteogenic medium. They were then subjected to irradiation of 660 and 980 nm diode lasers, and their viability was assessed after one, two, and three irradiation cycles using the methyl thiazolyl tetrazolium (MTT) assay. The cells also underwent DAPI staining, cell apoptosis assay by using the Annexin V/PI, Alizarin Red staining, and real-time polymerase chain reaction (PCR) for assessment of the expression of osteogenic genes. Data were analyzed by two-way ANOVA. The two laser groups had no significant difference in cell apoptosis according to the results of DAPI staining. Both laser groups showed higher cell viability in the MTT assay at 4 and 6 days compared with the control group. Annexin V/PI results showed higher cell viability in both laser groups at 4 days compared with the control group. Rate of early and late apoptosis was lower in both laser groups than the control group at 4 days. Necrosis had a lower frequency in 980 nm laser group than the control group on day 6. Alizarin Red staining showed higher cell differentiation in both laser groups after 3 irradiation cycles than the control group. The highest expression of osteopontin (OPN), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2) was noted in 660 nm laser group with 3 irradiation cycles at 14 days, compared with the control group. PBMT with 660 and 980 nm diode lasers decreased apoptosis and significantly increased PDLMSC differentiation after 3 irradiation cycles.

As a part of the host-defense system of many organisms, defensins are considered a suitable option for treating infection agents. Using the molecular dynamics simulation, this work studied the effects of two important human antimicrobial peptides, human β-defensin 2 and human α-defensin 5 on the SARS-CoV-2 membrane. The results demonstrate that defensin peptides notably alter the bilayer membrane's structure and physicochemical activity leading to a hydrophobic mismatch that impacts transmembrane protein channel function. This study elucidates the antiviral mechanisms of defensins and their therapeutic potential, offering valuable insights for researchers in virology and public health seeking novel medications.

Introduction: Salmonella, a zoonotic pathogen causing gastroenteritis, lacks a preventive vaccine. Passive immunization with IgY antibodies derived from immunized chickens has shown potential for treating bacterial infections. This study investigated the therapeutic efficacy of entrapped IgY targeting recombinant SipD and LptD proteins from Salmonella Typhimurium. Methods: The recombinant protein was expressed in E. coli BL21 (DE3) and purified using Ni-NTA affinity chromatography. Hens were immunized with the purified protein, and the resulting IgY was entrapped into alginate nanoparticles. The shape of spherical nanoparticles and their size in the nanometer range were determined by SEM and DLS analysis. The therapeutic efficacy of free and alginate-entrapped IgY against S. Typhimurium was evaluated in mice at 1, 50, and 100 LD50 bacterial doses. Results: The purified IgY concentration in each egg yolk was 6 mg/ml (35 mg/egg). Physicochemical and structural characterization revealed spherical nanoparticles with a diameter of 157.1 nm and a negatively charged surface (zeta potential of −35.6 mV). The loading efficiency of IgY into alginate nanoparticles was 95.5 %. In a challenge test with 100 LD50 of S. Typhimurium, all mice receiving alginate-entrapped IgY survived, whereas half of the mice receiving non-entrapped IgY died within 7 days. Conclusion: Our results indicate that IgY antibodies entrapped in alginate nanoparticles may offer therapeutic effect against S. Typhimurium infection.

Perihilar cholangiocarcinoma, a formidable adversary in the field of hepatobiliary surgery, presents multifaceted challenges. This paper reviews its historical context, classification criteria, and regional variations in definition. It emphasizes the critical role of preoperative assessment, including hepatic hilum anatomy, biliary infiltration characteristics, and residual liver volume evaluation. The impact of the Bismuth-Corlette classification on surgical approach selection is elucidated, providing insights into tailored surgical options for each subtype based on the authors’ center experience in the last ten years. The article also touches upon laparoscopic and robotic surgery potential, underscoring the need for further research in this domain. Finally, it explores the potential role of liver transplantation as a treatment option for select patients ineligible for conventional surgery.

We propose simple scenarios where the observed dark matter abundance arises from decays and scatterings of heavy quarks through freeze-in of an axion-like particle with mass in the 10keV−1MeV range. These models can be tested by future X-ray telescopes, and in some cases will be almost entirely probed by searches for two-body decays K→π+invis. at NA62. As a byproduct, we discuss the cancellation of IR divergencies in flavor-violating scattering processes relevant for thermal axion production, and derive the general contribution to axion-photon couplings from all three light quarks.

Background: Fatigue is a challenging problem for nurses working in the emergency department and makes them dissatisfied with their jobs.Objectives: This study examined the effects of a mindfulness training intervention on fatigue and job satisfaction in emergency nurses.Methods: A quasi-experimental study was conducted with 80 emergency department nurses in 2022. Participants were randomly assigned into an intervention group (n=40) and a control group (n=40). The intervention group received eight mindfulness training sessions, while the control group received no intervention. Data was collected using the Minnesota Satisfaction Questionnaire and the Multidimensional Fatigue Inventory a few days before the start and immediately after the end of the intervention. Descriptive statistics, t-test, paired t-test, and analysis of covariance (ANCOVA) were used to analyze the data.Results: The two groups did not differ significantly in their pretest fatigue mean scores. However, all posttest fatigue mean scores decreased in the intervention group, and the between-group differences were statistically significant (P < 0.05). The two groups also did not differ significantly in their pretest scores for internal, external, and general job satisfaction (P> 0.05). However, all posttest job satisfaction mean scores increased in the intervention group, and the between-group differences were statistically significant (P < 0.05). The ANCOVA showed that the nurses’ pretest scores had no significant effect on the posttest scores for fatigue and job satisfaction.Conclusion: This study supports the potential benefits of the mindfulness intervention in overcoming fatigue and improving job satisfaction of nurses working in emergency department. Nurses are recommended to learn and implement mindfulness-based interventions to reduce their fatigue and improve their job satisfaction.

Ideal cascades for binary mixtures of isotopes are specified by no-mixing at confluent points and minimum total flows. Studies show that there is another type of cascade called an optimum cascade. These cascades have total flows lower than ideal cascades while separation factors are greater than unity and mixings are allowed. In this paper, using a Co-evolutionary Particle Swarm Optimization (CPSO) algorithm, the ideal and optimum cascades are compared in different operating regimes. The CPSO is a metaheuristic algorithm that uses the concept of co-evolution to deal with constrained engineering optimization problems. In this study, it is used to find the parameters of the optimum cascade. In this work, three test cases are considered to compare ideal and optimum cascades. The first test case includes two distinct symmetrical separation cascades. In the first cascade, the minimum total flow for the ideal type 3 cascade and its corresponding optimum cascade is obtained as ∑L⁄P=176.7128, and in the second one for the ideal type 1 cascade and its corresponding optimum cascade, it is obtained as ∑L⁄P=202.7828. The results show that for symmetric separation, the ideal cascade coincides with the optimum cascade. In test case 2, the minimum total flows for the ideal type 1 cascade of non-symmetrical separation elements and its corresponding optimum cascade (CPSO) are obtained as ∑L⁄P=477.6170 and ∑L⁄P=228.6997, respectively. In test case 3, for the ideal type 2 cascade of non-symmetrical elements and its corresponding optimum cascade, the minimum total flows are obtained as ∑L⁄P=299.99 and ∑L⁄P=191.6584, respectively.

Background and Objectives: Providing a clear and practical definition of advocacy would help nurse increase their involvement in advocacy and preserving the patients’ rights. This study deepens the understanding of the features of advocacy among Muslim nurses. Methods: This study was conducted using the qualitative content analysis approach. The data were gathered through conducting in-depth semi-structured interviews with a purposeful sample of 18 nurses and they were analyzed using the thematic analysis approach. Results: The main characteristics of patient advocacy include protecting the religious aspect of care (avoiding treatments that are contrary to the religious beliefs of patients, and paying attention to religious issues in the care of unconscious patients), providing dignified care (being non-judgmental, providing patient comfort using methods appropriate to their religion, maintaining patients’ privacy, and respecting patient’s cultural and religious values), and giving hope to the patient (reminding patient’s sources of strength and hope, and paying attention to the patient’s concerns). Conclusion: In this study, the main characteristics of patient advocacy from the point of view of Muslim nurses have been determined. The results of this study will help Muslim nurses to understand more deeply what they should do to help their patients.

BackgroundIn estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults.MethodsUsing the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults.FindingsThere were 1·19 million (95% UI 1·11-1·28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5-65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8-57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9-15·6] per 100 000 person-years) and middle SDI (13·6 [12·6-14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9-25·2) DALYs to the global burden of disease, of which 2·7% (1·9-3·6) came from YLDs and 97·3% (96·4-98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally.InterpretationAdolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts.FundingBill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.