Several orphan solute carriers functionally identified as organic cation transporters: substrates specificity compared with known cation transporters.

Organic cations comprise a significant part of medically relevant drugs and endogenous substances. Such substances need organic cation transporters (OCT) for efficient transfer via cell membranes. However, the membrane transporters of most natural or synthetic organic cations the membrane transporters are still unknown. To identify these transporters, genes of 10 known OCTs and 18 orphan solute carriers (SLC) were overexpressed in HEK293 cells and characterized concerning their transport activities with a broad spectrum of low molecular weight substances emphasizing organic cations. Several SLC35 transporters and SLC38A10 significantly enhanced the transport of numerous relatively hydrophobic organic cations. Significant organic cation transport activities have been found in gene families classified as transporters of other substance classes. For instance, SLC35G3 and SLC38A10 significantly accelerated the uptake of several cations, such as clonidine, 3,4-methylenedioxymethamphetamine, and nicotine, which are known as substrates of a thus far genetically unidentified proton/organic cation antiporter. The transporters SLC35G4 and SLC35F5 stood out by their significantly increased choline uptake, and several other SLC transported choline together with a broader spectrum of organic cations. Overall, there are many more polyspecific organic cation transporters than previously estimated. Several transporters had one predominant substrate but accepted some other cationic substrates, and others showed no particular preference for one substrate but transported several organic cations. The role of these transporters in biology and drug therapy remains to be elucidated.

Water-soluble organic compounds (WSOC) from atmospheric aerosols in Bou-Ismail (Algeria).

In this contribution, we report the study of nuclear resonance magnetic spectroscopy techniques (1H-NMR, 13C-NMR, and 2D-NMR) efficiency in the characterisation of the functional composition of water-soluble organic compounds (WSOC) from atmospheric aerosols. The chosen site was our scientific and technical center of research (CRAPC) situated in Algerian Bou-Ismail city. where the concentrations of PM10 were found to be between 15.66 and 142.19 µg.m-3. As results, 1H-NMR analysis showed the coexistence of biological material and emissions from urban and biomass burning. The dominant source was identified by quantitative integration of each 1H NMR spectral region. By using the HSQC technique, many peaks are revealed in biogenic samples including biomass burning. On the other hand, the identification of the source of various organic compounds and their functional composition is possible through specific NMR spectra, which can also be used to adjust the surrounding organic aerosol sources.

Animal Reproduction journal and International Symposium on Animal Biology of Reproduction: Historical and personal reflections on two decades of exciting amalgamation of young and old science and scientists.

In 2024, the Brazilian College of Animal Reproduction (CBRA in Portuguese) is proudly celebrating its golden 50th anniversary. Founded in 1974, CBRA has had a very productive and challenging journey of five decades, achieving many important milestones that have established it as a major society and its journal as a major reference in the field of animal reproduction, both in Brazil and internationally. Coincidentally, the Animal Reproduction journal and the International Symposium on Animal Biology (ISABR), both created and sponsored by CBRA, are also celebrating their 20th and 10th anniversary and edition, respectively, this year. These remarkable events are being celebrated in the city of Fortaleza, Brazil, during the 10th edition of ISABR. As someone who had the privilege of playing a leading role in the creation and establishment of both Animal Reproduction journal and ISABR, I am honored to describe here the favorable circumstances that led to these significant achievements. The crucial steps and combined efforts required to make these institutions successful were unconditionally supported by the CBRA. Additionally, significant global networking and scientific collaborations, both individual and collective, have been pivotal in advancing the science and connecting the scientific community, spanning both young and experienced members, for decades. Finally, I hope that this historical article will inspire future generations of scientists in the field to continue CBRA's journey and leadership, ensuring the growth of Animal Reproduction and ISABR advancement to even higher standards.

Insights from a COVID-era health needs assessment of rural Midwestern Latinos.

Latino health and well-being are crucial to the growth and vibrancy of rural areas across the United States, particularly at a time when the demographics of many rural communities are transitioning from minority Latino to majority Latino populations. This manuscript details the findings of a study that explored the health and healthcare benefit status of 524 Latino households in rural Indiana during the COVID-19 pandemic. Via 20-minute, door-to-door interviews conducted by bilingual researchers, survey participants answered questions about access to healthcare services and benefits, dietary and safety habits, medical issues, and vaccination status. The study found that slightly more than half of those surveyed were enrolled in healthcare benefit plans; approximately a third were unsatisfied with their health/health status; almost two-thirds had not received a flu shot and were eating fast food/processed food on a daily basis. Top health concerns reported included: stress (52%), vision problems (34%), neck and back pain (30%), headaches/migraines (28%), anxiety and depression (28%) and weight problems (26%). The study also discovered that half of the respondents could not identify a primary healthcare provider (PCP) by name and that pregnant women faced a lack of resources for maternal health in the county where the study was conducted. The results indicate that Latinos in rural communities continue to endure significant health issues and barriers to healthcare. The study provides an excellent model of how a rural community can monitor the health of its residents, which can inform health interventions for underserved populations.

Micro-costing of genetic diagnostics in acute leukemia in Sweden: from standard-of-care to whole-genome sequencing.

AIMS AND BACKGROUND: Whole-genome sequencing (WGS) is increasingly applied in clinical practice and expected to replace standard-of-care (SoC) diagnostics in hematological malignancies. This study aims to assess and compare the fully burdened cost ('micro-costing') per patient for Swedish laboratories using WGS and SoC, respectively, in pediatric and adult patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). METHODS: The resource use and cost details associated with SoC, e.g. chromosome banding analysis, fluorescent in situ hybridization, and targeted sequencing analysis, were collected via activity-based costing methods from four diagnostic laboratories. For WGS, corresponding data was collected from two of the centers. A simulation-based scenario model was developed for analyzing the WGS cost based on different annual sample throughput to evaluate economy of scale. RESULTS: The average SoC total cost per patient was €2,465 for pediatric AML and €2,201 for pediatric ALL, while in adults, the corresponding cost was €2,458 for AML and €1,207 for ALL. The average WGS cost (90x tumor/30x normal; sequenced on the Illumina NovaSeq 6000 platform) was estimated to €3,472 based on an annual throughput of 2,500 analyses, however, with an annual volume of 7,500 analyses the average cost would decrease by 23% to €2,671. CONCLUSION: In summary, WGS is currently more costly than SoC, however the cost can be reduced by utilizing laboratories with higher throughput and by the expected decline in cost of reagents. Our data provides guidance to decision-makers for the resource allocation needed when implementing WGS in diagnostics of hematological malignancies.

TRPV4 facilitates the reprogramming of inflamed macrophages by regulating IL-10 production via CREB.

BACKGROUND: Transient receptor potential vanilloid type 4 (TRPV4) is a versatile ion channel with diverse roles in immune cells, including macrophages. While its function in inflammation remains debated, we investigated its role in regulating IL-10 production and its impact on macrophage reprogramming during inflammation. METHODS: We investigated the connection between TRPV4 activation and CREB-mediated IL-10 production during inflammation. Notably, this signaling pathway was found to reprogram macrophages and enhance their ability to resist inflammatory damage. The experiments were conducted on primary macrophages and were further corroborated by animal studies. RESULTS: In response to TRPV4 activation during inflammation, we observed a significant increase in intracellular Ca2+ levels, which triggered the activation of the transcription factor CREB, subsequently upregulating IL-10 production. This IL-10 played a pivotal role in reprogramming macrophages to withstand inflammatory damage. Using a mouse model of acute lung injury (ALI), we confirmed that TRPV4 activation during ALI led to IL-10 secretion, but this increase did not significantly contribute to inflammation resolution. Moreover, we found that TRPV4 prevented the accumulation of dysfunctional mitochondria in macrophages through the CREB-IL-10 axis during inflammation. Suppression of CREB or TRPV4 inhibition exacerbated mitochondrial dysfunction, while treatment with recombinant IL-10 mitigated these effects. Additionally, IL-10 induced mitophagy and cleared dysfunctional mitochondria in LPS-exposed cells. CONCLUSION: Our study highlights the essential role of TRPV4 in regulating IL-10 production and mitochondrial health in macrophages during inflammation. These findings contribute to understand the role of TRPV4 in immune responses and suggest potential therapeutic targets for modulating inflammation-induced cellular dysfunction.

Real-life data of etanercept efficacy and safety in juvenile idiopathic arthritis: a 24-month retrospective study at a single center.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA). METHODS: The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports. RESULTS: The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it had worsened to 7.3 ± 7.8. ACR50 response was achieved in 79.6% of patients at 3 months, 67.1% at 6 months, 79.3% at twelfth months, 70.7% at the twenty-fourth month. During ETA treatment, 10 patients required hospitalization for serious infections. CONCLUSION: Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.

Healthcare resource utilization and costs associated with hepatitis A in the United States: a retrospective database analysis.

AIM: To investigate hepatitis A-related healthcare resource use and costs in the US. METHODS: The Merative Marketscan Commercial Claims and Encounters database was retrospectively analyzed for hepatitis A-related inpatient, outpatient, and emergency department (ED) claims from January 1, 2012 to December 31, 2018. We calculated the hepatitis A incidence proportion per 100,000 enrollees, healthcare resource utilization, and costs (in 2020 USD). Results were stratified by age, gender, and select comorbidities. RESULTS: The overall hepatitis A incidence proportion was 6.1 per 100,000 enrollees. Among individuals with ≥1 hepatitis A-related claim, the majority (92.6%) had ≥1 outpatient visit related to hepatitis A; 9.1% were hospitalized and 4.2% had ≥1 ED visit. The mean (standard deviation [SD]) length of hospital stay was 5.2 (8.1) days; the mean (SD) number of outpatient and ED visits were 1.3 (1.3) and 1.1 (0.6), respectively. The incidence proportion per 100,000 was higher among adults than children (7.5 vs. 1.5), individuals with HIV than those without (126.7 vs. 5.9), and individuals with chronic liver disease than those without (143.6 vs. 3.8). The total mean (SD)/median (interquartile range, IQR) per-patient cost for hepatitis A-related care was $2,520 ($10,899)/$156 ($74-$529) and the mean cost of hospitalization was 18.7 times higher than that of outpatient care ($17,373 vs. $928). LIMITATIONS: The study data included only a commercially insured population and may not be representative of all individuals. CONCLUSIONS: In conclusion, hepatitis A is associated with a substantial economic burden among privately insured individuals in the US.

Hepatitis A is an acute liver infection caused by the hepatitis A virus. In the US, safe and effective vaccines for hepatitis A have been available since 1996. Vaccination recommendations include children (all children aged 12­23 months and previously unvaccinated children aged 2­18 years old) and adults at risk of infection or severe disease (e.g. international travelers, men who have sex with men, persons experiencing homelessness, persons with chronic liver disease or persons with HIV infection). Since 2016, the US has experienced person-to-person outbreaks of hepatitis A, primarily affecting unvaccinated individuals who use drugs or are experiencing homelessness. To better understand the impact of hepatitis A in the US, we assessed healthcare resource use and costs in 15,435 patients with hepatitis A from 2012 to 2018 in the Merative Marketscan Commercial Claims and Encounters database. We found that slightly more than 6 per 100,000 enrollees had hepatitis A from 2012 to 2018 and the number of people treated for hepatitis A per 100,000 was highest for people living with HIV or with chronic liver disease. The majority (92.6%) of people reported at least an outpatient visit, 9.1% were hospitalized, and 4.2% had an emergency department visit. The average cost for hepatitis A-related care was $2,520 per patient and was 18.7 times higher for hospitalized patients ($17,373) than for patients treated in outpatient care ($928). Our results are limited by the generalizability of the dataset, which is a convenience sample of private insurance claims, and are therefore unlikely to capture groups at high-risk for hepatitis A, such as individuals experiencing homelessness. In conclusion, hepatitis A leads to considerable healthcare costs for privately insured individuals in the US.

Estimation of Attributable Risk and Direct Medical and Non-Medical Costs of Major Mental Disorders Associated With Air Pollution Exposures Among Children and Adolescents in the Republic of Korea, 2011-2019.

BACKGROUND: Recent studies have reported the burden of attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and depressive disorder. Also, there is mounting evidence on the effects of environmental factors, such as ambient air pollution, on these disorders among children and adolescents. However, few studies have evaluated the burden of mental disorders attributable to air pollution exposure in children and adolescents. METHODS: We estimated the risk ratios of major mental disorders (ADHD, ASD, and depressive disorder) associated with air pollutants among children and adolescents using time-series data (2011-2019) obtained from a nationwide air pollution monitoring network and healthcare utilization claims data in the Republic of Korea. Based on the estimated risk ratios, we determined the population attributable fraction (PAF) and calculated the medical costs of major mental disorders attributable to air pollution. RESULTS: A total of 33,598 patients were diagnosed with major mental disorders during 9 years. The PAFs for all the major mental disorders were estimated at 6.9% (particulate matter < 10 µm [PM10]), 3.7% (PM2.5), and 2.2% (sulfur dioxide [SO2]). The PAF of PM10 was highest for depressive disorder (9.2%), followed by ASD (8.4%) and ADHD (5.2%). The direct medical costs of all major mental disorders attributable to PM10 and SO2 decreased during the study period. CONCLUSION: This study assessed the burden of major mental disorders attributable to air pollution exposure in children and adolescents. We found that PM10, PM2.5, and SO2 attributed 7%, 4%, and 2% respectively, to the risk of major mental disorders among children and adolescents.

Analysis of the intensity of engagement with CuidaTEXT, a text message intervention for dementia caregiver support among Latinos/as.

OBJECTIVES: To examine the associations between participant intensity of engagement with a text message intervention, CuidaTEXT, and socio-demographic factors, acceptability measures, and clinical outcomes among Latino/a caregivers of individuals with dementia. METHODS: CuidaTEXT is a six-month, bilingual, and bidirectional intervention. We enrolled 24 Latino/a caregivers in a one-arm feasibility trial. Participants received approximately one automatic daily text message and could engage with the intervention by texting specific keywords (e.g. STRESS to receive messages about stress-coping), and by chat-texting with a live coach. We used metrics and psychometric scales to quantify variables. RESULTS: Participants sent a total of 1847 messages to CuidaTEXT. Higher intensity of engagement was associated with higher intervention satisfaction (r = 0.6, p = 0.007), as were several other acceptability outcomes. We found no associations between intensity of engagement with CuidaTEXT and sociodemographic or clinical outcomes (p > 0.05). CONCLUSION: Encouraging more intense engagement with CuidaTEXT might lead to higher levels of satisfaction with the intervention. However, it is possible that those who are highly satisfied, engage more intensely with CuidaTEXT. Future research should determine the directionality of these associations to optimize text message interventions. CLINICAL IMPLICATIONS: Creating more opportunities to increase the intensity of text message engagement with caregiver support interventions may improve caregiver satisfaction with them.

IL-10+ regulatory B cells mitigate atopic dermatitis by suppressing eosinophil activation.

Atopic dermatitis (AD) presents significant therapeutic challenges due to its poorly understood etiology. Eosinophilia, a hallmark of allergic inflammation, is implicated in AD pathogenesis. Interleukin-10 (IL-10)-producing regulatory B (Breg) cells exhibit potent anti-inflammatory effects. However, their role in controlling AD-related eosinophilia is not well understood. To investigate the impact of eosinophils on AD, we employed IL-5Rα-deficient (Il5ra-/-) mice, which lack functional eosinophils. Induction of AD in these mice resulted in attenuated disease symptoms, underscoring the critical role of eosinophils in AD development. Additionally, the adoptive transfer of purified Breg cells into mice with AD significantly alleviated disease severity. Mechanistic studies revealed that IL-10 produced by Breg cells directly inhibits eosinophil activation and infiltration into the skin. In vitro experiments further confirmed that Breg cells inhibited eosinophil peroxidase secretion in an IL-10-dependent manner. Our collective findings demonstrate that IL-10 from Breg cells alleviates AD by suppressing eosinophil activation and tissue infiltration. This study elucidates a novel regulatory mechanism of Breg cells, providing a foundation for future Breg-mediated therapeutic strategies for AD.

Complications of chest wall around malignant tumors: differences based on reconstruction strategy.

BACKGROUND: Malignant chest wall tumors need to be excised with wide resection to ensure tumor free margins, and the reconstruction method should be selected according to the depth and dimensions of the tumor. Vascularized tissue is needed to cover the superficial soft tissue defect or bone tissue defect. This study evaluated differences in complications according to reconstruction strategy. METHODS: Forty-five patients with 52 operations for resection of malignant tumors in the chest wall were retrospectively reviewed. Patients were categorized as having superficial tumors, comprising Group A with simple closure for small soft tissue defects and Group B with flap coverage for wide soft tissue defects, or deep tumors, comprising Group C with full-thickness resection with or without mesh reconstruction and Group D with full-thickness resection covered by flap with or without polymethyl methacrylate. Complications were evaluated for the 52 operations based on reconstruction strategy then risk factors for surgical and respiratory complications were elucidated. RESULTS: Total local recurrence-free survival rates in 45 patients who received first operation were 83.9% at 5 years and 70.6% at 10 years. The surgical complication rate was 11.5% (6/52), occurring only in cases with deep tumors, predominantly from Group D. Operations needing chest wall reconstruction (p = 0.0016) and flap transfer (p = 0.0112) were significantly associated with the incidence of complications. Operations involving complications showed significantly larger tumors, wider areas of bony chest wall resection and greater volumes of bleeding (p < 0.005). Flap transfer was the only significant predictor identified from multivariate analysis (OR: 10.8, 95%CI: 1.05-111; p = 0.0456). The respiratory complication rate was 13.5% (7/52), occurring with superficial and deep tumors, particularly Groups B and D. Flap transfer was significantly associated with the incidence of respiratory complications (p < 0.0005). Cases in the group with respiratory complications were older, more frequently had a history of smoking, had lower FEV1.0% and had a wider area of skin resected compared to cases in the group without respiratory complications (p < 0.05). Preoperative FEV1.0% was the only significant predictor identified from multivariate analysis (OR: 0.814, 95%CI: 0.693-0.957; p = 0.0126). CONCLUSIONS: Surgical complications were more frequent in Group D and after operations involving flap transfer. Severe preoperative FEV1.0% was associated with respiratory complications even in cases of superficial tumors with flap transfer.

Liraglutide improves follicle development in polycystic ovary syndrome by inhibiting CXCL10 secretion.

BACKGROUND: At present, a number of clinical trials have been carried out on GLP-1 receptor agonist liraglutide in the treatment of polycystic ovary syndrome (PCOS). However, the effect of liraglutide on follicle development and its specific mechanism are still unclear. METHODS: RNA sequencing was used to explore the molecular characteristics of granulosa cells from patients with PCOS treated with liraglutide. The levels of C-X-C motif chemokine ligand 10 (CXCL10) in follicular fluid were detected by ELISA, the expression levels of ovulation related genes and inflammatory factor genes in follicles and granulosa cells were detected by qPCR and the protein levels of connexin 43 (Cx43), Janus Kinase 2 (JAK2) and phosphorylated JAK2 were detected by Western blot. The mouse ovarian follicles culture system in vitro was used to detect the status of follicle development and ovulation. RESULTS: In the present study, we found that liraglutide inhibited the secretion of inflammatory factors in PCOS granulosa cells, among which CXCL10 was the most significant. In addition, CXCL10 was significantly higher in granulosa cells and follicular fluid in PCOS patients than in non-PCOS patients. We applied in vitro follicle culture and other techniques to carry out the mechanism exploration which revealed that CXCL10 disrupted the homeostasis of gap junction protein alpha 1 (GJA1) between oocyte and granulosa cells before physiological ovulation, thus inhibiting follicular development and ovulation. Liraglutide inhibited CXCL10 secretion in PCOS granulosa cells by inhibiting the JAK signaling pathway and can improved dehydroepiandrosterone (DHEA)-induced follicle development disorders, which is reversed by CXCL10 supplementation. CONCLUSIONS: The present study suggests that liraglutide inhibits CXCL10 secretion in granulosa cells through JAK signaling pathway, thereby improving the homeostasis of GJA1 between oocyte and granulosa cells before physiological ovulation and ultimately improving the follicular development and ovulation of PCOS, which provides more supportive evidence for the clinical application of liraglutide in the treatment of ovulatory disorders in PCOS. TRIAL REGISTRATION: Not applicable.

Antioxidants for Skin Health.

Antioxidants play a pivotal role in maintaining skin health and integrity, combating the deleterious effects of oxidative stress induced by environmental aggressors such as UV ra-diation, pollution, and lifestyle factors. This paper reviews the contributions of key antioxidants, including Vitamin C, Vitamin E, Vitamin A, green tea extract, Coenzyme Q10, Resveratrol, Selenium, and Polyphenols, in skin health care. Vitamin C, known for its collagen synthesis promotion and photoprotection properties, alongside Vitamin E, a lipid-soluble antioxidant, syn-ergistically works to neutralize free radicals and repair damaged skin cells. Vitamin A, in the form of retinol, plays a critical role in skin cell regeneration and the maintenance of skin integ-rity. Green tea extract, rich in Polyphenols, offers anti-inflammatory and anticarcinogenic prop-erties, making it a potent ingredient for skin protection. Coenzyme Q10, a naturally occurring antioxidant in the body, aids in energy production for cell repair and regeneration, while Resveratrol, found in grapes and berries, provides anti-ageing benefits by enhancing skin's re-sistance to oxidative stress. Selenium, an essential mineral, contributes to the protection of skin cells from oxidative damage. The incorporation of these antioxidants in skincare products and dietary sources is discussed, highlighting the importance of a holistic approach in skincare re-gimes. The paper emphasizes the synergy between topical applications and dietary intake of antioxidants, advocating for a comprehensive strategy for promoting skin health and preventing age-related skin alterations. Method: For the review article, a variety of search engines and databases were used to identify relevant articles. Furthermore, for biomedical literature focusing on antioxidants and their ef-fects on skin health, PubMed was used. Moreover, to access a wide range of scholarly articles, including those related to dermatology and skincare, Google Scholar was used. Scopus provides comprehensive coverage of peer-reviewed literature across various scientific disciplines. Web of Science identifies high-impact articles and research on antioxidants in skincare. In addition, for accessing full-text articles on antioxidants and their applications in dermatology, Science Direct was used. The inclusion criteria for the review paper were as follows: only studies pub-lished in peer-reviewed journals were included to ensure the credibility and reliability of the information. Articles published in English were considered, to avoid language-related biases and ensure comprehension. Studies published within the last 10 years were included to provide the most current insights into antioxidant research in skincare. Articles must specifically focus on the role of antioxidants (Vitamin C, Vitamin E, Vitamin A, green tea extract, Coenzyme Q10, Resveratrol, Selenium, Polyphenols) in skin health care. Both experimental studies (in vivo and in vitro) and clinical trials were included to provide a comprehensive overview of the antioxidant effects. Full-text articles were included to allow for thorough data extraction and analysis. The exclusion criteria for the review paper were as follows: Publications that were not peer-re-viewed, such as editorials, opinion pieces, and non-scholarly articles, were excluded. Articles published in languages other than English were excluded due to potential translation challenges and to maintain consistency. Studies that did not focus on the specified antioxidants or their impact on skin health were excluded. Duplicate publications were excluded to avoid redundancy in the review. Articles with insufficient or incomplete data were excluded to ensure the quality and reliability of the review findings.

p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death.

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

Results on fixed points in b-metric space by altering distance functions.

We discuss the existence of a fixed point for a self mapping and its uniqueness satisfying ( ϕ ˙ , η ˙ ) -generalized contractive condition including altering distance functions of rational terms in an ordered b-metric space. It is also discussed whether the two self-maps under the same contraction condition can be coincident and coupled coincident. The results are backed up by a dearth of numerical examples and application to nonlinear quadratic integral equation.

Application of the Marshall-Olkin-Weibull logarithmic distribution to complete and censored data.

In contemporary statistical research, there has been a notable surge of interest surrounding a suggested extension of the Marshall-Olkin-G distributions. The present extension exhibits a higher degree of flexibility in comparison to its parent distributions. In a similar manner, we present in this context an expansion of the Marshall-Olkin-G distributions proposed by statistical scholars. This study utilizes a specific variant of the extension known as the Marshall-Olkin-Weibull Logarithmic model, which is applied to both complete and censored data sets. It is evident that the aforementioned model has strong competitiveness in accurately characterizing both complete and censored observations in lifetime reliability issues, when compared to other comparative models discussed in this research work.

Reconstructive management of a patient with Tessier number 10 cleft.

Tessier number 10 cleft is one of the rarest facial clefts. Surgical treatment of this type of cleft is challenging due to the complexity of periorbital and temporal soft tissue deformities. A 23-year-old male patient presented with typical facial deformities of Tessier number 10 cleft. The surgical procedure involved using a free anterolateral thigh flap to reconstruct the eye socket, while the superficial temporal artery pedicle scalp flap was used to reconstruct the eyebrow deformity. The patient had no complications and 16 months after surgery, the patient had good aesthetic results. A hair-bearing scalp flap with a pedicle of the frontal branch of the superficial temporal artery combined with an anterolateral thigh-free flap can effectively resolve most soft tissue deformities of Tessier number 10 cleft and reconstruct the orbital socket in a single surgery. At the same time, it augments the soft tissue of the frontotemporal area and provides good aesthetic results.

Yangyin Huowei mixture alleviates chronic atrophic gastritis by inhibiting the IL-10/JAK1/STAT3 pathway.

BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear. AIM: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model. METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1ß, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3. RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1ß, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1ß, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both). CONCLUSION: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.